Recurrent subluxation and dislocation of the patella in association with athletic injuries.
Seventy-one patients with 81 operations for correction of patellar instability are reviewed. Follow-up was for at least five years. The various preoperative symptoms, signs, and radiographic findings are presented. Two types of patellar instability become clear. One type is usually bilateral and secondary to general ligamentous laxity. A second type, usually unilateral with distinct physical findings, is secondary to trauma. The operative technique and results of surgery and physical therapy are discussed. A new rational approach to the operative treatment of recurrent subluxation and dislocation of the patella is proposed. The operative procedure would depend on the Q angle. For a Q angle of less than 14 degrees, a proximal realignment is sufficient. For a Q angle greater than 14 degrees, a distal realignment would be necessary in addition.


[Mechanism of gold solid extraction from aurocyanide solution using D3520 resin impregnated with TRPO].
Trialkyphosphine oxides (TRPO) was successfully used for the impregnation of D3520 resin to prepare an extractant-impregnated resin (EIR). Solid extraction of Au(I) from alkaline cyanide solution was studied using this extractant-impregnated resin (EIR), with addition of cetyltrimethylammonium bromide (CTMAB), directly into the aurous aqueous phase in advance. The mechanism of solid extraction was further investigated by means of FTIR, XPS and SEM. The column separation studies have shown that cationic surfactant CTMAB played a key role in the solid phase extraction, and the resin containing TRPO were effective for the extraction of gold when the molar ratio of CTMAB: Au( I ) reached 1:1. FTIR spectroscopy of gold loaded EIR showed that the frequency of C[triple bond]N stretching vibration was at 2144 cm(-1), and the frequency of P=O stretching vibration shifted to lower frequency from 1153 to 1150 cm(-1). The XPS spectrum of N(1s), Au(4f7/2) and Au(4f5/2) sugges- ted that the coordination environment of gold did not change before and after extraction, and gold was still as the form of Au (CN)2(-) anion exiting in the loaded resin; O(1s) spectrum showed that the chemically combined water significantly increased after solid extraction from 30.74% to 42.34%; Comparing to the P(2p) spectrum before and after extraction, the binding energy increased from 132. 15 to 132. 45 eV, indicating there maybe existing hydrogen-bond interaction between P=O and water molecule, such as P=O...H-O-H. The above results obtained established that in the solid extraction process, the hydrophobic ion association [CTMA+ x Au(CN)] diffused from the bulk solution into the pores of the EIR, and then be solvated by TRPO adsorbed in the pores through hydrogen bonding bridged by the water molecules.


Clinical trial: the efficacy of open-label prucalopride treatment in patients with chronic constipation - follow-up of patients from the pivotal studies.
Prucalopride is approved in Europe for symptomatic treatment of chronic constipation in women with inadequate relief from laxatives. To evaluate efficacy of prucalopride during long-term treatment of patients with chronic constipation. Patients from three pivotal double-blind, placebo-controlled, 12-week studies with prucalopride could continue treatment in open-label studies up to 24 months. Efficacy was evaluated every 3 months using the Patient Assessment of Constipation-Quality of Life (PAC-QOL) satisfaction scale. Laxative use and reasons for study discontinuation were recorded. Eighty-six percent of patients who completed the pivotal studies continued prucalopride treatment in the open-label studies (n = 1455, 90% female). Improvement in average PAC-QOL satisfaction score observed after 12-week, double-blind prucalopride was maintained during open-label treatment for up to 18 months; in each 3 month period, 40-50% of patients did not use any laxatives. Most frequent adverse events (AEs) resulting in discontinuation were gastrointestinal events (3.3%) and headache (1.0%). Only 10% of patients who had normalized bowel function on prucalopride at the end of pivotal trials discontinued due to insufficient response during open-label treatment. Satisfaction with bowel function is maintained for up to 18 months of treatment with prucalopride. Gastrointestinal events and headache cause discontinuation of prucalopride treatment in ∼5% of patients (ClinicalTrials.gov identifiers: NCT01070615 and NCT00987844).


Retrospective study of sensitivity and specificity of EEG in the elderly compared with younger age groups.
Following a recommendation from a Good Practice Guide published in Scotland stating that EEG should not be routinely used in the diagnosis of epilepsy in the elderly, we conducted a retrospective study to ascertain the effects this recommendation had. We found that predating the recommendation, there had already been a decline in the use of EEG in people aged 65 and over. Detailed examination of a 3.5-year epoch which straddled 2 years before the recommendation and 1.5 years after its publication revealed no evidence of a change in the type of referrals but just in the number of referrals. Comparison with 2 younger cohorts showed that EEG in the elderly had the same specificity and sensitivity as in the younger age groups and was of particular use in picking up previously unsuspected non-convulsive status. We conclude the EEG remains an important diagnostic adjunct in the elderly.


Requests for information by family and friends of cancer patients calling the National Cancer Institute's Cancer Information Service.
To characterize their information needs, we examined the main topics of inquiry and discussion (subjects of interaction, SOI) of calls made by family and friends of cancer patients to the National Cancer Institute's Cancer Information Service's (CIS) 1-800-4-CANCER telephone information service and summarized differences by sociodemographic characteristics. Data from 26 789 family or friends of cancer patients calling the CIS between September 2002 and August 2003 were analyzed. Frequencies, chi(2)'s, and logistic regressions were conducted to ascertain sample characteristics and sociodemographic correlates of each SOI. The greatest proportion of calls concerned specific treatment information (54.9%) and general cancer site information (36.9%). Calls about specific treatment information were more likely among Asians, Hawaiian Natives, and Pacific Islanders (OR = 1.23, 1.04-1.45), and those with higher education (OR = 1.21, 1.18-1.25). As age increased, the odds of calls about specific treatment information also increased (OR = 1.05, 1.03-1.07). Females (OR = 0.78, 0.72-0.84), Hispanics (OR = 0.77, 0.67-0.89), African-Americans (OR = 0.68, 0.61-0.76), and American-Indians and Alaskan Natives (OR = 0.74, 0.58-0.93) were less likely to inquire about specific treatment information. Inquiries about general cancer site information were more likely among females (OR = 1.14, 1.06-1.23) and less likely among younger callers (OR = 0.95, 0.93-0.97) and African-Americans (OR = 0.87, 0.78-0.98). Differences in inquiries made by sociodemographic subgroups can inform the CIS' and other cancer-related organizations' efforts to develop and disseminate cancer information for family and friends of cancer patients.


A randomized controlled trial with bright light and melatonin for delayed sleep phase disorder: effects on subjective and objective sleep.
Delayed sleep phase disorder (DSPD) is assumed to be common amongst adolescents, with potentially severe consequences in terms of school attendance and daytime functioning. The most common treatment approaches for DSPD are based on the administration of bright light and/or exogenous melatonin with or without adjunct behavioural instructions. Much is generally known about the chronobiological effects of light and melatonin. However, placebo-controlled treatment studies for DSPD are scarce, in particular in adolescents and young adults, and no standardized guidelines exist regarding treatment. The aim of the present study was, therefore, to investigate the short- and long-term effects on sleep of a DSPD treatment protocol involving administration of timed bright light and melatonin alongside gradual advancement of rise time in adolescents and young adults with DSPD in a randomized controlled trial and an open label follow-up study. A total of 40 adolescents and young adults (age range 16-25 years) diagnosed with DSPD were recruited to participate in the study. The participants were randomized to receive treatment for two weeks in one of four treatment conditions: dim light and placebo capsules, bright light and placebo capsules, dim light and melatonin capsules or bright light and melatonin capsules. In a follow-up study, participants were re-randomized to either receive treatment with the combination of bright light and melatonin or no treatment in an open label trial for approximately three months. Light and capsules were administered alongside gradual advancement of rise times. The main end points were sleep as assessed by sleep diaries and actigraphy recordings and circadian phase as assessed by salivary dim light melatonin onset (DLMO). During the two-week intervention, the timing of sleep and DLMO was advanced in all treatment conditions as seen by about 1 h advance of bed time, 2 h advance of rise time and 2 h advance of DLMO in all four groups. Sleep duration was reduced with approximately 1 h. At three-month follow-up, only the treatment group had maintained an advanced sleep phase. Sleep duration had returned to baseline levels in both groups. In conclusion, gradual advancement of rise time produced a phase advance during the two-week intervention, irrespective of treatment condition. Termination of treatment caused relapse into delayed sleep times, whereas long-term treatment with bright light and melatonin (three months) allowed maintenance of the advanced sleep phase.


Biological versus mineralogical chromium reduction: potential for reoxidation by manganese oxide.
Hexavalent chromium (Cr(vi), present predominantly as CrO4(2-) in water at neutral pH) is a common ground water pollutant, and reductive immobilization is a frequent remediation alternative. The Cr(iii) that forms upon microbial or abiotic reduction often co-precipitates with naturally present or added iron (Fe), and the stability of the resulting Fe-Cr precipitate is a function of its mineral properties. In this study, Fe-Cr solids were formed by microbial Cr(vi) reduction using Desulfovibrio vulgaris strain RCH1 in the presence of the Fe-bearing minerals hematite, aluminum substituted goethite (Al-goethite), and nontronite (NAu-2, Clay Minerals Society), or by abiotic Cr(vi) reduction by dithionite reduced NAu-2 or iron sulfide (FeS). The properties of the resulting Fe-Cr solids and their behavior upon exposure to the oxidant manganese (Mn) oxide (birnessite) differed significantly. In microcosms containing strain RCH1 and hematite or Al-goethite, there was significant initial loss of Cr(vi) in a pattern consistent with adsorption, and significant Cr(vi) was found in the resulting solids. The solid formed when Cr(vi) was reduced by FeS contained a high proportion of Cr(iii) and was poorly crystalline. In microcosms with strain RCH1 and hematite, Cr precipitates appeared to be concentrated in organic biofilms. Reaction between birnessite and the abiotically formed Cr(iii) solids led to production of significant dissolved Cr(vi) compared to the no-birnessite controls. This pattern was not observed in the solids generated by microbial Cr(vi) reduction, possibly due to re-reduction of any Cr(vi) generated upon oxidation by birnessite by active bacteria or microbial enzymes. The results of this study suggest that Fe-Cr precipitates formed in groundwater remediation may remain stable only in the presence of active anaerobic microbial reduction. If exposed to environmentally common Mn oxides such as birnessite in the absence of microbial activity, there is the potential for rapid (re)formation of dissolved Cr(vi) above regulatory levels.


Induced unilateral vocal fold paralysis and recovery rapidly modulate brain areas related to phonatory behavior: a case study.
Peripheral and behavioral effects of voice disorders are well documented in the literature; yet, there is little information regarding the central neural biomarkers and mechanisms underlying these disorders. Understanding the details of brain function changes in disordered voice production is a critical factor for developing better treatment strategies that result in more robust patient outcomes. To examine a model of induced unilateral vocal fold paralysis (iUVFP) to demonstrate and characterize the form of activity changes within central mappings of the larynx to the induced paralysis. The induced paralysis model allowed the participant to serve as his or her own control when comparing baseline results of normal voice with results during the paralysis and subsequent recovery. Prospective, case-study design. Functional magnetic resonance imaging was used to examine central laryngeal representations during three time points: pre-iUVFP, during iUVFP, and postrecovery from iUVFP. iUVFP was induced using a lidocaine with epinephrine nerve block unilaterally. Percent changes in blood oxygenation level-dependent (BOLD) activity served as the dependent variable. Results indicated an overall reduced activity level in sensorimotor, subcortical, and cerebellar regions during paralysis. Recovery from paralysis led to augmented responses, particularly in sensory, association, and cerebellar zones. The decrease in activity during iUVFP and the significantly increased activity during the recovery phase likely represent immediate neuroplastic events occurring within minutes of nerve blockade. Recovery-related changes in the BOLD response are hypothesized to be associated with a recalibration of the system after return of normal laryngeal function.


[Arboviral diseases: a field where research and public health call for international cooperation (author's transl)].
Arboviral diseases constitute a group of infections transmitted to man by hematophagous arthropods: mosquitoes, ticks, sand flies and culicoides. A long period of research has provided only partial insight into their mode of transmission. Arboviruses can cause influenza-like diseases, haemorrhagic fevers, and encephalitides. As a result of the different clinical manifestations and their complex mode of transmission, they give rise to public health problems which are usually severe and difficult to solve, and which may result in extensive and deadly epidemics. Fortunately, these problems have motivated international cooperation in scientific research and in the solution of public health problems, a unique example in the field of virology.


Normal pregnancy is associated with an increase in thrombin generation from the very early stages of the first trimester.
Pregnancy is a hypercoagulable state associated with an increased risk of venous thrombosis, which begins during the first trimester, but the exact time of onset is unknown. Thrombin generation, a laboratory marker of thrombosis risk, increases during normal pregnancy but it is unclear exactly how early this increase occurs. We assessed thrombin generation by Calibrated Automated Thrombography in women undergoing natural cycle in vitro fertilization, who subsequently gave birth at term following a normal pregnancy (n=22). Blood samples were taken just prior to conception and repeated five times during very early pregnancy, up to Day 59 estimated gestation. Mean Endogenous Thrombin Potential (ETP), peak thrombin generation and Velocity Index (VI) increased significantly from pre-pregnancy to Day 43 gestation (p=0.024-0.0004). This change persisted to Day 59 gestation. The mean of the percentage change from baseline, accounting for inter-individual variation, in ETP, peak thrombin and VI increased significantly from pre-pregnancy to Day 32 gestation (p=0.0351-<0.0001) with the mean increase from baseline persisting to Day 59 gestation. Thrombin generation increases significantly during the very early stages of normal pregnancy when compared to the pre-pregnancy state. The increased risk of venous thrombosis therefore likely begins very early in a woman's pregnancy, suggesting that women considered clinically to be at high thrombotic risk should start thromboprophylaxis as early as possible after a positive pregnancy test.


Nocardiosis in HIV-positive patients: an autopsy study in West Africa.
There are many reports of nocardiosis associated with HIV infection in industrialized and developing countries, but its true prevalence is unknown. An autopsy study was performed of HIV-positive and HIV-negative patients dying on the general medical wards of a large hospital in Abidjan, Ivory Coast, in 1991. 247 HIV-positive adult cadavers were examined. 10 (4%) had nocardiosis of the lung, of whom 6 showed disseminated disease. 8 patients had one or more AIDS-defining pathologies, and 5 had nocardiosis as the main cause of death. Pulmonary tuberculosis was found in 87 cadavers (35%), giving a ratio of pulmonary nocardial to tuberculous disease of 1:9. No nocardiosis was seen in 42 HIV-negative cadavers. This is the highest recorded prevalence of HIV-associated nocardiosis in a representative sample. The prevalence of nocardiosis varies geographically, and in zones where HIV-associated tuberculosis is common, it is possible that some patients diagnosed as smear-negative pulmonary tuberculosis actually have nocardiosis. A revised strategy of sputum examination with gram stain is suggested to detect nocardia.


Early versus delayed, provisional eptifibatide in acute coronary syndromes.
Glycoprotein IIb/IIIa inhibitors are indicated in patients with acute coronary syndromes who are undergoing an invasive procedure. The optimal timing of the initiation of such therapy is unknown. We compared a strategy of early, routine administration of eptifibatide with delayed, provisional administration in 9492 patients who had acute coronary syndromes without ST-segment elevation and who were assigned to an invasive strategy. Patients were randomly assigned to receive either early eptifibatide (two boluses, each containing 180 microg per kilogram of body weight, administered 10 minutes apart, and a standard infusion > or = 12 hours before angiography) or a matching placebo infusion with provisional use of eptifibatide after angiography (delayed eptifibatide). The primary efficacy end point was a composite of death, myocardial infarction, recurrent ischemia requiring urgent revascularization, or the occurrence of a thrombotic complication during percutaneous coronary intervention that required bolus therapy opposite to the initial study-group assignment ("thrombotic bailout") at 96 hours. The key secondary end point was a composite of death or myocardial infarction within the first 30 days. Key safety end points were bleeding and the need for transfusion within the first 120 hours after randomization. The primary end point occurred in 9.3% of patients in the early-eptifibatide group and in 10.0% in the delayed-eptifibatide group (odds ratio, 0.92; 95% confidence interval [CI], 0.80 to 1.06; P=0.23). At 30 days, the rate of death or myocardial infarction was 11.2% in the early-eptifibatide group, as compared with 12.3% in the delayed-eptifibatide group (odds ratio, 0.89; 95% CI, 0.79 to 1.01; P=0.08). Patients in the early-eptifibatide group had significantly higher rates of bleeding and red-cell transfusion. There was no significant difference between the two groups in rates of severe bleeding or nonhemorrhagic serious adverse events. In patients who had acute coronary syndromes without ST-segment elevation, the use of eptifibatide 12 hours or more before angiography was not superior to the provisional use of eptifibatide after angiography. The early use of eptifibatide was associated with an increased risk of non-life-threatening bleeding and need for transfusion. (ClinicalTrials.gov number, NCT00089895.)


Strong Prognostic Value of Microsatellite Instability in Intestinal Type Non-cardia Gastric Cancer.
The clinical role of microsatellite instability (MSI) in gastric cancer (GC) is controversial. A large series of patients submitted to respective surgery for primary GC with a long follow-up time was evaluated. 472 patients with prospectively collected frozen samples of normal mucosa and tumor tissue stored in a biological tissue bank were included. Microsatellite analysis was evaluated using 5 quasi monomorphic mononucleotide repeats (BAT-26, BAT-25, NR-24, NR-21, and NR-27). The presence of MSI in 2 or more loci was classified as MSI-H, whereas all other cases were included in the microsatellite-stable (MSS) group. MSI-H phenotype was found in 111 of 472 patients (23.5%). MSI-H status was related significantly with older age, female gender, non-cardia location, WHO histotype, non-cardia Lauren intestinal type, and less advanced stages. Cancer-related 5-year survival was significantly higher in MSI-H versus MSS group (67.6% vs. 35%, p < 0.001). Stratified analysis revealed a significant impact of MSI on prognosis in non-cardia tumors of intestinal type or tubular/poorly differentiated histology, particularly in stages II and III; multivariate Cox regression analysis confirmed MSS status as a strong predictor of poor prognosis (hazard ratio 2.65, 95% CI 1.56-4.51, p < 0.001) in non-cardia intestinal type. No prognostic value of MSI in the diffuse-mixed type and signet-ring cell/mucinous histotypes was observed. MSI was confirmed as a significant predictor of long term outcome in a large series of GC with a long follow-up time, but the prognostic value is limited to selected histotypes of non-cardia tumors.


Authoritarian parenting attitudes and social origin: The multigenerational relationship of socioeconomic position to childrearing values.
Support for authoritarian approaches to parenting, including corporal punishment, is known to be elevated among individuals with low current levels of socioeconomic attainment. The objectives of this study are: (1) to determine whether authoritarian parenting dispositions are related to disadvantages in one's social background, in addition to one's present socioeconomic standing; and (2) to distinguish, in this regard, between support for spanking and other authoritarian parenting dispositions. Ordered logit models, applied to General Social Survey data concerning a nationally representative sample of US adults, are used to examine relationships of authoritarian parenting dispositions to the socioeconomic positions that respondents currently occupy and in which they were raised. It is found that support for spanking (N=10,725) and valuing of obedience (N=10,043) are inversely related to the socioeconomic status (SES) of one's family of origin, and that these associations are robust to controls for one's current SES. A disadvantaged family background is found to increase support for spanking most among those with high current SES. Strong associations (robust to controls for SES indicators) are additionally found between African-American racial identity and support for authoritarian parenting. Prior research indicates that authoritarian parenting practices such as spanking may be harmful to children. Thus, if the parenting attitudes analyzed here translate into parenting practices, then this study's findings may point to a mechanism for the intergenerational transmission of disadvantages.


SOX-1 autoantibodies in patients with paraneoplastic neurological syndromes.
Paraneoplastic neurological syndromes (PNS) are tumour-associated disorders, which are not caused by the tumour itself or its metastases. Since antineuronal autoantibodies can be detected in these patients, an autoimmune pathogenesis is suspected. Recently, autoantibodies against cerebellar Bergmann glia were found in patients with paraneoplastic Lambert-Eaton myasthenic syndrome and other paraneoplastic neurological syndromes associated with small cell lung cancer, and SOX1 has been identified as the corresponding antigen. SOX1-antibodies have been reported to be highly specific for paraneoplastic neurological disorders. However, increasing evidence exists that they may also be associated with other neuroimmunological disorders without an underlying tumour.


[Adenocarcinoma of the rete testis. Apropos of a case].
In the light of a case report, the authors recall the clinical signs of adenocarcinoma of the rete testis and the precise histological and immunohistochemical features allowing confirmation of this very rare diagnosis. They emphasize the persistent controversies concerning the treatment of this testicular tumour.


Mutations affecting the delayed rectifier potassium current in Drosophila.
Mutations and pharmacological agents have been used to resolve and analyze several K(+) currents in Drosophila. Mutations that affect channels carrying the voltage-activated I(A) and the Ca(2+) -activated I(CF) have helped greatly in analyzing the structure, function and regulation of these channels. We now report mutations that selectively affect the delayed rectifier current, I(K). Flies mutagenized with ethylmethanesulfonate were screened for temperature-induced paralysis. Paralytic mutants identified in the screen were examined for K(+) currents in the larval body-wall muscles. The z66 mutant larvae showed a significant reduction in I(K). The mutation did not affect other K(+) currents (I(A), I(CF), or I(CS) ) or the Ca(2+) channel current in the muscles. Another mutation, z4, which showed reduced I(K), failed to complement z66. Genetic analysis localized the gene disrupted by z66 and z4 to the left arm of chromosome 3, in the 63A1-63B6 region on polytene chromosomes. The z66 and the z4 mutations, which lie in the Shab K(+) channel gene, provide an opportunity to undertake analysis of the functioning of these channels and to study the role of these channels in membrane excitability.


Odd-parity superconductivity in Sr2RuO4.
Phase-sensitive measurements were made on Sr2RuO4 to establish unambiguously the odd-parity pairing in this material. The critical current of Au(0.5)In(0.5)-Sr2RuO4 superconducting quantum interference devices prepared on Sr2RuO4 single crystals was found to be a maximum for devices with junctions on the same side of the crystal and a minimum for devices with junctions on opposite sides, in the limit of zero magnetic flux; these findings indicate that the phase of the superconducting order parameter in Sr2RuO4 changes by pi under inversion. This result verifies the odd-parity pairing symmetry and the formation of spin-triplet Cooper pairs in Sr2RuO4.


Fibrolamellar carcinoma in a young patient.
This is a twenty two years old male patient with weight loss, abdominal pain, hepatomegaly and elevated liver function tests. The serological markers for viral B, C hepatitis and tumoral markers were normal. The CT scan demonstrated a hipodense, nodular lesion in the liver and the histological examination was reported as a typical fibrolamellar hepatocarcinoma


Early Wound Morbidity after Open Ventral Hernia Repair with Biosynthetic or Polypropylene Mesh.
Recently introduced slow-resorbing biosynthetic and non-resorbing macroporous polypropylene meshes are being used in hernias with clean-contaminated and contaminated wounds. However, information about the use of biosynthetic meshes and their outcomes compared with polypropylene meshes in clean-contaminated and contaminated cases is lacking. Here we evaluate the use of biosynthetic mesh and polypropylene mesh in elective open ventral hernia repair (OVHR) and investigate differences in early wound morbidity after OVHR within clean-contaminated and contaminated cases. All elective, OVHR with biosynthetic mesh or uncoated polypropylene mesh from January 2013 through October 2016 were identified within the Americas Hernia Society Quality Collaborative. Association of mesh type with 30-day wound events in clean-contaminated or contaminated wounds was investigated using a 1:3 propensity-matched analysis. Biosynthetic meshes were used in 8.5% (175 of 2,051) of elective OVHR, with the majority (57.1%) used in low-risk or comorbid clean cases. Propensity-matched analysis in clean-contaminated and contaminated cases showed no significant difference between biosynthetic mesh and polypropylene mesh groups for 30-day surgical site occurrences (20.7% vs 16.7%; p = 0.49) or unplanned readmission (13.8% vs 9.8%; p = 0.4). However, surgical site infections (22.4% vs 10.9%; p = 0.03), surgical site occurrences requiring procedural intervention (24.1% vs 13.2%; p = 0.049), and reoperation rates (13.8% vs 4.0%; p = 0.009) were significantly higher in the biosynthetic group. Biosynthetic mesh appears to have higher rates of 30-day wound morbidity compared with polypropylene mesh in elective OVHR with clean-contaminated or contaminated wounds. Additional post-market analysis is needed to provide evidence defining best mesh choices, location, and surgical technique for repairing contaminated ventral hernias.


Oral manifestations of giant cell arteritis.
Giant cell arteritis is a systemic disease of unknown origin characterized by vasculitis of medium-sized and larger vessels, found mainly in elderly women. It presents with a variety of symptoms, including temporal pain and tenderness, headache, and neuroophthalmic features. This report describes a case of giant cell arteritis in a 78-year-old woman with a large ulceration on the right side of the tongue, painful lesion in the right temporal area, and recent visus loss of the right eye.


Selective and sensitive detection of chromium(VI) in waters using electrospray ionization mass spectrometry.
From 2000 through 2011, there were 14 criminal cases of violations of the Clean Water Act involving the discharge of chromium, a toxic heavy metal, into drinking and surface water sources. As chromium(VI), a potential carcinogen present in the environment, represents a significant safety concern, it is currently the subject of an EPA health risk assessment. Therefore, sensitive and selective detection of this species is highly desired. This study reports the analysis of chromium(VI) in water samples by electrospray ionization mass spectrometry (ESI-MS) following its reduction and complexation with ammonium pyrrolidinedithiocarbamate (APDC). The reduction and subsequent complexation produce a characteristic [Cr(III)O]-PDC complex which can be detected as a protonated ion of m/z 507 in the positive ion mode. The detection is selective to chromium(VI) under acidic pH, even in the presence of chromium(III) and other metal ions, providing high specificity. Different water samples were examined, including deionized, tap, and river waters, and sensitive detection was achieved. In the case of deionized water, quantification over the concentration range of 3.7 to 148ppb gave an excellent correlation coefficient of 0.9904 using the enhanced MS mode scan. Using the single-reaction monitoring (SRM) mode (monitoring the characteristic fragmentation of m/z 507 to m/z 360), the limit of detection (LOD) was found to be 0.25ppb. The LOD of chromium(VI) for both tap and river water samples was determined to be 2.0ppb. A preconcentration strategy using simple vacuum evaporation of the aqueous sample was shown to further improve the ESI signal by 15 fold. This method, with high sensitivity and selectivity, should provide a timely solution for the real-world analysis of toxic chromium(VI).


Ecogeography, genetics, and the evolution of human body form.
Genetic resemblances among groups are non-randomly distributed in humans. This population structure may influence the correlations between traits and environmental drivers of natural selection thus complicating the interpretation of the fossil record when modern human variation is used as a referential model. In this paper, we examine the effects of population structure and natural selection on postcranial traits that reflect body size and shape with application to the more general issue of how climate - using latitude as a proxy - has influenced hominin morphological variation. We compare models that include terms reflecting population structure, ascertained from globally distributed microsatellite data, and latitude on postcranial phenotypes derived from skeletal dimensions taken from a large global sample of modern humans. We find that models with a population structure term fit better than a model of natural selection along a latitudinal cline in all cases. A model including both latitude and population structure terms is a good fit to distal limb element lengths and bi-iliac breadth, indicating that multiple evolutionary forces shaped these morphologies. In contrast, a model that included only a population structure term best explained femoral head diameter and the crural index. The results demonstrate that population structure is an important part of human postcranial variation, and that clinally distributed natural selection is not sufficient to explain among-group differentiation. The distribution of human body form is strongly influenced by the contingencies of modern human origins, which calls for new ways to approach problems in the evolution of human variation, past and present.


Processing fly ash stabilized hydrogen titanate nano-sheets for industrial dye-removal application.
We report a new method for the processing of fly ash (FA) stabilized hydrogen titanate nano-sheets in the form of aggregated microspheres. The industrial silica-based FA has been utilized for this purpose which has been surface-modified by coating with the anatase-titania (TiO(2)) via sol-gel. The anatase-TiO(2) coated FA particles are subjected to the hydrothermal treatment in an autoclave under high temperature and pressure conditions in a highly alkaline solution. The hydrothermal conditions cause dissolution of silica resulting in the disintegration of other constituents of FA which are adsorbed in ionic and/or oxidized form on the surface of intermediate product of the hydrothermal treatment of anatase-TiO(2), specifically the hydrogen titanate. The adsorption of FA constituents has resulted in the stabilization of hydrogen titanate in the nano-sheet morphology instead of nanotubes. The FA stabilized hydrogen titanate nano-sheets exhibit higher specific surface-area than that of the hydrogen titanate nanotubes and have been successfully utilized for the removal of an organic synthetic-dye from an aqueous solution via surface-adsorption, involving the electrostatic-attraction and ion-exchange mechanisms operating, in the dark-condition.


Effects of septal grafts on acetylcholine release from rat hippocampus after 192 IgG-saporin lesion.
The cholinergic inputs to the rat hippocampus were lesioned by intraseptal injections of 192 IgG-saporin. After 15 days, fetal septal cells were grafted into the hippocampus. Thirteen months later, hippocampal acetylcholine (ACh) release was studied by microdialysis. Lesioning reduced basal ACh release (100%) to 20% of normal, which was compensated for by the graft (71%). Infusion of the serotonin uptake inhibitor citalopram (100 microM) enhanced ACh release to the same extent (% of basal release) in all rat groups. Systemic injection of 8-OH-DPAT (0.5 mg/kg, SC), an agonist of 5-HT1A receptors, caused a smaller ACh release than citalopram. Acetylcholinesterase (AChE) staining and densitometric quantification revealed that the lesion-induced reduction of the AChE-staining density was compensated for by septal grafting. In conclusion, both histochemical and biochemical methods showed that cholinergic hippocampal parameters were drastically impaired by 192 IgG-saporin lesions, but were almost completely restored by septal grafting. The graft responded to intrinsic serotonergic regulation.


Role of acute pain service in optimizing postoperative pain relief in a tertiary care teaching hospital.
To assess the frequency and types of adjustments that acute pain service makes to postoperative analgesic regimes to improve pain relief or treat side effects. The prospective observational study was conducted at the Aga Khan University Hospital, Karachi, from December 1, 2012, to March 31, 2013. Data was collected from Acute Pain Service register four hours after the pain rounds by a Service member not involved in rounds. Data was collected on a standardised form and analysed using SPSS 19. Of the 323 patients, 209(65%) were receiving epidural infusions and 114(35%) were receiving intravenous patient-controlled analgesia. Overall, 114(35%) required action by Acute Pain Service; 76(66.6%) with epidural infusions and 38(33.3%) intravenous analgesia. Besides, 98(85.9%) had inadequate pain relief, 61(62%) with epidural and 37(38%) with analgesia. Post-intervention, motor block occurred in 13(11.4%) patients, who were managed by change of patient\'s position and/or lowering the concentration of epidural solution. Improvement was seen in all patients after the adjustments. Acute Pain Service played an important role in improving the quality of postoperative pain relief and management of analgesia-related side effects. Regular feedback to the primary anaesthesiologist can lead to improved practices.


Fate and effects of 3,4-dichloroaniline (DCA) in marine plankton communities in experimental enclosures.
The fate and effects of single doses of 3,4-dichloroaniline (DCA) on North Sea coastal plankton communities enclosed by large plastic bags (contents 1.5 m3) were studied in two experiments lasting 5 and 6 weeks, respectively. The biodegradation of DCA was also studied in laboratory experiments, which were carried out simultaneously, using water from the enclosed model ecosystems. DCA was not degraded in the laboratory tests and probably also not degraded in the enclosed plankton communities, although concentrations in the water decreased during the experiments. This decrease appeared to be partly caused by diffusion of DCA through the walls of the enclosures. After the addition of single doses of 2, 10, and 25 microgram liter-1 DCA no effects on the enclosed plankton community could be detected. The addition of 0.1 mg liter-1 DCA had a clear influence on the species composition and the biomass development of the phytoplankton, changed the relative species composition of the zooplankton, and resulted in lower numbers of bacteria. In addition to these effects 1 mg liter-1 DCA limited the phytoplankton growth and resulted in mortality and inhibition of growth of the copepods.


Evaluation of myocardium in ischemic heart disease by ultrafast computed tomography.
In this study we evaluated quantitatively the contrast enhancement of the myocardium of 27 patients with infarction and ischemia by ultrafast CT (Imatron C-100) with a scan time of 100 msec. We defined three parameters from the CT numbers of the myocardium and the ventricle in both the early and the late phase (about 4 min) after the injection of non-ionic contrast material; the difference of the CT numbers of myocardium between the early and the late phase (delta CT#), and the ratios of the CT numbers of the myocardium and the ventricular lumen (M/L) in both the early phase and the late phase. The delta CT# for myocardial infarction and severe ischemia were -20 +/- 10HU and -8 +/- 10HU, respectively. These values were significantly lower than the mild ischemic myocardium and normal myocardium (p less than 0.001). The average M/L values for myocardial infarction and ischemia in the early phase were 19 +/- 8% and 16 +/- 6%, respectively. These values were significantly lower than those in normal myocardium (p less than 0.001). The average M/L values for infarction and severe ischemia in the late phase were 90 +/- 18% and 63 +/- 20%, respectively. These M/L were significantly dissociated (p less than 0.001). Our results indicate that with contrast UFCT it is feasible to detect quantitatively the myocardial characteristics of ischemia and infarction.


A 2-Year Follow-up Study of an Absorbable Implant to Treat Nasal Valve Collapse.
The safety and effectiveness of an absorbable implant for lateral cartilage support have been recently demonstrated in subjects with nasal valve collapse (NVC) at 12 months postprocedure. This follow-up study aimed to assess whether the safety and effectiveness of the implant persist in these patients for 24 months after the procedure. Thirty subjects with Nasal Obstruction Symptom Evaluation (NOSE) score ≥ 55 and isolated NVC were treated; 14 cases were performed in an operating suite under general anesthesia and 16 cases were performed in a clinic-based setting under local anesthesia. The implant, a polylactic acid copolymer, was placed with a delivery tool within the nasal wall to provide lateral cartilage support. Subjects were followed up through 24 months postprocedure. Fifty-six implants were placed in 30 subjects. The mean preoperative NOSE score was 76.7 ± 14.8, with a range of 55 to 100. At 24 months, the mean score was 32.0 ± 29.3, reflecting an average within-patient reduction of -44.0 ± 31.1 points. There were no device-related adverse events in the 12 to 24 months period. There were five subjects who exited the study prior to the 24-month follow-up. Four of the five subjects who exited were elected for further intervention and one subject was lost to follow-up. This study demonstrates safety of an absorbable implant for lateral nasal wall support and symptom improvement in some subjects with NVC at 24 months postprocedure.


[Screening for retinopathy of prematurity: results of one centre between 1991 and 2002].
The aim of this study was to analyse the results of retinopathy of prematurity (ROP) screening, stage of disease and time of treatment from one tertiary care centre. Between 1991 and 2001, 666 infants with a gestational age (GA) < 33 weeks or birth weight (BW) less than < 1501 g were examined. Coagulation treatment was performed in accordance with the Cryo-ROP study, after reaching the threshold. All infants were followed-up until a stable retinal situation was reached. Mean GA of the 666 infants was 28.5 +/- 2.3 weeks. Mean BW was 1180 +/- 372 g. During the years of screening, the GA and BW significantly decreased, but no significant change in the yearly incidence of ROP was detected. 460 (69.1 %) of the infants did not develop any stage of ROP. Maximum stage of ROP in the worse eye was stage one in 51 (7.6 %) infants, stage two in 59 (8.9 %) infants and stage three below threshold in 62 (9.3 %) infants. 34 (5.1 %) infants were treated with coagulation treatment. Mean time of treatment was 36.5 weeks postmenstrual age, or 10.7 weeks postnatal age. Postnatal age showed a better correlation to treatment time than postmenstrual age. No infant was treated before seven weeks of life and not before 32 weeks postmenstrual age. In spite of the increasing survival of children with lower GA and BW the incidence of ROP has not increased, and the incidence of ROP in our centre appears to be comparable to other international studies. In contrast to the Cryo-ROP study, treatment time correlates better to postnatal age than to postmenstrual age. All infants who underwent treatment were detected at an appropriate time using German screening guidelines.


Platinum complexes bearing a boron-based PBP pincer ligand: synthesis, structure, and application as a catalyst for hydrosilylation of 1-decene.
Four platinum(II) complexes bearing a boron-based PBP pincer ligand and chloride, hydride, triflate, and bis(trifluoromethanesulfonyl)imide were synthesized and structurally characterized. PBP-platinum chloride was proven to be an active catalyst for the hydrosilylation reaction using 1-decene and triethylsilane.


Impacts of (14)C discharges from a nuclear fuel reprocessing plant on surrounding vegetation: Comparison between grass field measurements and TOCATTA-χ and SSPAM(14)C model computations.
This article compares and discusses the ability of two different models to reproduce the observed temporal variability in grass (14)C activity in the vicinity of AREVA-NC La Hague nuclear fuel reprocessing plant in France. These two models are the TOCATTA-χ model, which is specifically designed for modelling transfer of (14)C (and tritium) in the terrestrial environment over short to medium timescales (days to years), and SSPAM(14)C, which has been developed to model the transfer of (14)C in the soil-plant-atmosphere with consideration over both short and long timescales (days to thousands of years). The main goal of this article is to discuss the strengths and weaknesses of the models studied, and to investigate if modelling could be improved through consideration of a much higher level of detail of plant physiology and/or higher number of plant compartments. These models have been applied here to the La Hague field data as it represents a medium term data set with both short term variation and a sizeable time series of measurements against which to compare the models. The two models have different objectives in terms of the timescales they are intended to be applied over, and thus incorporate biological processes, such as photosynthesis and plant growth, at different levels of complexity. It was found that the inclusion of seasonal dynamics in the models improved predictions of the specific activity in grass for such a source term of atmospheric (14)C.


[A case of Marchiafava-Bignami disease suggesting vasogenic edema].
A 61-year-old alcoholic man was admitted to our hospital because of disturbance of consciousness. He also exhibited external ophthalmoplegia, diplopia and mild rigidity, but tendon reflex was normal. On brain MRI, diffusion weighted images (DWI) and apparent diffusion coefficient (ADC) map depicted high intensity in the splenium of the corpus callosum. DWI showed high intensity, but ADC map depicted iso-intensity in bilateral precentral gyri. Marchiafava-Bignami disease (MBD) was diagnosed. After intravenous drip of vitamin, his symptoms improved rapidly and the abnormal MRI findings in the splenium of the corpus callosum and bilateral precentral gyri disappeared gradually. MBD is pathologically characterized by demyelination and necrosis in the corpus callosum, which are generally caused by cytotoxic edema. Our case suggests that vasogenic edema may occur at the early stage of the MBD.


Distribution of a novel binding site for angiotensins II and III in mouse tissues.
A novel binding site for angiotensins II and III that is unmasked by parachloromercuribenzoate has been reported in rat, mouse and human brains. Initial studies of this binding site indicate that it is not expressed in the adrenal, liver or kidney of the rat and mouse. To determine if this binding site occurs in other mouse tissues, 8 tissues were assayed for expression of this binding site by radioligand binding assay and compared with the expression of this binding site in the forebrain. Particulate fractions of homogenates of testis, epididymis, seminal vesicles, heart, spleen, pancreas, lung, skeletal muscle, and forebrain were incubated with (125)I-sarcosine(1), isoleucine(8) angiotensin II in the presence or absence of 0.3mM parachloromercuribenzoate plus 10microM losartan and 10microM PD123319 (to saturate AT(1) and AT(2) receptors). Specific (3microM angiotensin II displaceable) high affinity binding occurred in the testis>forebrain>epididymis>spleen>pancreas>lung when parachloromercuribenzoate was present. Binding could not be reliably observed in heart, skeletal muscle and seminal vesicles. High affinity binding of (125)I-sarcosine(1), isoleucine(8) angiotensin II was observed in the absence of parachloromercuribenzoate in the pancreas on occasion. This suggests that this novel angiotensin binding site may have a functional role in these tissues.


Hydroxylation of p-substituted phenols by tyrosinase: further insight into the mechanism of tyrosinase activity.
A study of the monophenolase activity of tyrosinase by measuring the steady state rate with a group of p-substituted monophenols provides the following kinetic information: k(cat)(m) and the Michaelis constant, K(M)(m). Analysis of these data taking into account chemical shifts of the carbon atom supporting the hydroxyl group (δ) and σ(p)(+), enables a mechanism to be proposed for the transformation of monophenols into o-diphenols, in which the first step is a nucleophilic attack on the copper atom on the form E(ox) (attack of the oxygen of the hydroxyl group of C-1 on the copper atom) followed by an electrophilic attack (attack of the hydroperoxide group on the ortho position with respect to the hydroxyl group of the benzene ring, electrophilic aromatic substitution with a reaction constant ρ of -1.75). These steps show the same dependency on the electronic effect of the substituent groups in C-4. Furthermore, a study of a solvent deuterium isotope effect on the oxidation of monophenols by tyrosinase points to an appreciable isotopic effect. In a proton inventory study with a series of p-substituted phenols, the representation of [Formula: see text] / [Formula: see text] against n (atom fractions of deuterium), where [Formula: see text] is the catalytic constant for a molar fraction of deuterium (n) and [Formula: see text] is the corresponding kinetic parameter in a water solution, was linear for all substrates. These results indicate that only one of the proton transfer processes from the hydroxyl groups involved the catalytic cycle is responsible for the isotope effects. We suggest that this step is the proton transfer from the hydroxyl group of C-1 to the peroxide of the oxytyrosinase form (E(ox)). After the nucleophilic attack, the incorporation of the oxygen in the benzene ring occurs by means of an electrophilic aromatic substitution mechanism in which there is no isotopic effect.


Near-infrared light triggered liposomes combining photodynamic and chemotherapy for synergistic breast tumor therapy.
Photodynamic therapy (PDT) as a promising noninvasive and effective treatment modality has been clinically approved for cancer therapy. However, the poor selectivity of tumor and hypoxia-induced resistance constrain PDT efficacy immensely. To further enhance PDT's potency, we developed a drug delivery system based on liposome combining PDT and chemotherapeutics. The lipophilic IR780 was loaded into the lipid bilayer while hydrophilic chemotherapeutic agent tirapazamine (TPZ) was encapsulated in the hydrophilic core. IR780 could generate reactive oxygen species and hypoxic microenvironment in local site because of the continuous consumption of oxygen, resulting in the TPZ encapsulated in the aqueous liposome chamber brings out TPZ radicals to cause DNA double-strand breaks and chromosome aberrations. In vivo studies demonstrated that the liposomes which encapsulate IR780 and TPZ showed great antitumor efficacy via combining photodynamic therapy with chemotherapy. Therefore, the investigation combines PDT and hypoxia-activated chemotherapy from the TPZ. It is a simple but effective liposome platform to achieve multiple synergistic antitumor efficacy and shows potential for clinical use.


The effect of storage conditions on samples for the evaluation of copper status in blesbok (Damaliscus pygargus phillipsi).
Investigaltions to determine the effect of sample storage on the concentration of copper in liver tissue and on the activity of erythrocyte superoxide dismutase were undertaken in preparation for a study of blesbok (Damaliscus pygargus phillipsi) that were suspected to be suffering from copper deficiency. Two liver samples were collected from each of 20 culled blesbok in a manner that simulated the collection of biopsies from the live animal. These samples were stored either in 10% formalin or frozen at -20 degrees C until analysed 4 1/2 months later. The effect of different methods of sample storage on superoxide dismutase activity was determined. Erythrocytes collected from 3 Jersey cows and 5 culled blesbok were washed and divided into 0.5 ml portions, stored at room temperature (approximately 20 degrees C), in a refrigerator (4 degrees C), frozen at -20 degrees C in a freezer, and in liquid nitrogen (-200 degrees C). An analysis of superoxide dismutase activity was undertaken using a commercial assay kit at intervals of 2-4 days until the levels of activity had fallen significantly. The copper concentration in formalin-preserved liver samples was significantly lower than that measured in frozen liver tissue apparently as a result of leaching. The activity of superoxide dismutase in cattle blood was unchanged for 4 days at room temperature but fell appreciably after 2 days at 4 degrees C and -20 degrees C. Enzyme activity remained unchanged for 200 days in erythrocytes stored in liquid nitrogen. Superoxide dismutase activity levels in healthy blesbok were considerably lower than those measured in Jersey cows and remained unaffected for up to 6 days in samples stored at 4 degrees C and 20 degrees C. The level of activity fell significantly thereafter. Samples stored in liquid nitrogen were unchanged after 40 days.


Role of Aspergillus niger in recovery enhancement of valuable metals from produced red mud in Bayer process.
Annual worldwide growth rate of red mud (RM) as a hazardous waste has caused serious environmental problems for its disposal in the mining and metallurgy industries. Accordingly, the aim of this study was to investigate biological leaching of RM and recovery of metals using organic acids exerted by Aspergillus niger. Experiments using A. niger were conducted in batch cultures with a pulp density of 2% (w/v) RM under one-step, two-step and spent-medium bioleaching. Based on HPLC results, the major lixiviant was the secretion of organic acids (citric, gluconic, oxalic and malic) by A. niger. Leaching efficiency of metals in the one-step process was the highest and the amounts of leached metals were 69.8%, 60% and 25.4% for Al, Ti and Fe, respectively. The fungal leaching technique demonstrated an adequate recovery of metals, with an efficient and cost-effective means and respect to a reuse of RM for economic and environmental purposes.


Role of PTEN promoter methylation in tamoxifen-resistant breast cancer cells.
Tamoxifen (TAM) resistance is a serious clinical problem in the treatment of breast cancer. Here, we found that S-adenosylmethionine (SAM) and DNA methyltransferase1 (DNMT1) expression are up-regulated in TAM-resistant breast cancer (TAMR-MCF-7) cells. We further focused on whether increased SAM with DNMT1 overexpression in TAMR-MCF-7 cells lead to aberrant methylation of the PTEN gene promoter and its therapeutic potential. Methylation-specific PCR analyses revealed that two sites within the PTEN promoters were methylated in TAMR-MCF-7 cells, which resulted in down-regulation of PTEN expression and increase in Akt phosphorylation. Both the loss of PTEN expression and the increased Akt phosphorylation in TAMR-MCF-7 cells were completely reversed by 5-aza-2'-deoxycytidine (5-Aza), a DNMT inhibitor. 5-Aza inhibited the basal cell proliferation rate of TAMR-MCF-7 cells and intraperitoneal injection of 5-Aza significantly suppressed TAMR-MCF-7 tumor growth in a xenograft study. Immunohistochemistry showed that PTEN expression in TAM-resistant human breast cancer tissues was lower than in TAM-responsive cases. These results suggest that methylation of the PTEN promoter related to both SAM increase and DNMT1 activation contributes to persistent Akt activation and are potential therapeutic targets for reversing TAM resistance in breast cancer.


Induction and modulation of cerebellar granule neuron death by E2F-1.
Growing evidence suggests that certain cell cycle regulators also mediate neuronal death. Of relevance, cyclin D1-associated kinase activity is increased and the retinoblastoma protein (Rb), a substrate of the cyclin D1-Cdk4/6 complex, is phosphorylated during K(+) deprivation-evoked death of cerebellar granule neurons (CGNs). Cyclin-dependent kinase (CDK) inhibitors block this death, suggesting a requirement for the cyclin D1/Cdk4/6-Rb pathway. However, the downstream target(s) of this pathway are not well defined. The transcription factor E2F-1 is regulated by Rb and is reported to evoke death in proliferating cells when overexpressed. Accordingly, we examined whether E2F-1 was sufficient to evoke death of CGNs and whether it was required for death evoked by low K(+). We show that adenovirus-mediated expression of E2F-1 in CGNs results in apoptotic death, which is independent of p53, dependent upon Bax, and associated with caspase 3-like activity. In addition, we demonstrate that levels of E2F-1 mRNA and protein increase during K(+) deprivation-evoked death. The increase in E2F-1 protein is blocked by the CDK inhibitor flavopiridol. Finally, E2F-1-deficient neurons are modestly resistant to death induced by low K(+). These results indicate that E2F-1 expression is sufficient to promote neuronal apoptosis and that endogenous E2F-1 modulates the death of CGNs evoked by low K(+).


Postnatal development of adrenergic innervation in the tibial and vagus nerves of Fischer-344 rats.
Adrenergic innervation of rat tibial and vagus nerves was studied in male Fischer-344 rats between 1 and 84 days of age, using sucrose-phosphate-glyoxylic acid (SPG) histochemistry and the formaldehyde-induced fluorescence (FIF) method. Adrenergic nerve fibers were found in epi-perineurial blood vessels of the vagus nerve at one day of age, whereas blood vessels in the tibial nerve received the first adrenergic nerve fibers at 3 days. A few adrenergic nerve fibers were seen in the endoneurium of both tibial and vagus nerves at 7 days. The densities of adrenergic innervation increased gradually during the first 4 postnatal weeks, and at 21 days the distributions of adrenergic innervation in both nerves resembled those in adult animals. The results suggest that development of adult adrenergic innervation in rat peripheral nerves occurs during the first postnatal month and that sympathetic innervation becomes available to regulate nerve blood flow within this period.


Dendrigraft poly-L-lysine: a non-immunogenic synthetic carrier for antibody production.
An easily synthesized DendriGraft poly-lysine DGL-G3 (third generation) was shown to act as an efficient carrier for raising antibodies directed against small molecules. The immunological properties of three different forms of DGL-G3 were investigated: the native form (molecular weight 22 kDa bearing a mean number of 123 surface amino groups as TFA salts), a form modified at the C-terminus by fluorescein (fluorescein-DGL-G3), and last a surface-modified form bearing histamine (DGL-G3-Histamine). Our studies demonstrate the native DGL-G3 to be inefficient in eliciting antibody production in rabbits. Immunizations of rabbits using the core-modified fluorescein-DGL-G3 or the surface-modified DGL-G3-histamine conjugate failed in eliciting antibody production. Conversely, following a primary immunization using a BSA-histamine conjugate, a second immunization with DGL-G3-histamine conjugate improved the production of specific hapten-directed antibodies, which demonstrates the utility of DGL-G3 as a carrier for the production of highly specific antibody against haptens.


In vitro and in vivo effects of neem tree (Azadirachta indica A. Juss) products on larvae of the sheep nose bot fly (Oestrus ovis L. Díptera: Oestridae).
Two studies were carried out in order to test the effects of neem tree extracts (Azadirachta indica A. Juss) on sheep bot fly larvae (Oestrus ovis L. Diptera: Oestridae). First, aqueous extracts from neem seeds (ASNE) at 0, 5 y 10% (w/v) concentrations were tested on larval mortality in vitro. In a second study, the effect of oral administration with neem seed meal (0, 100 y 200mg/kg) and neem leaves (1% of diet) on number of larvae found at necropsy and larval development was evaluated in experimentally O. ovis-infected sheep. Results in Experiment 1 showed a significant (P<0.05) effect of ASNE on time to L1 mortality in a dosis-dependent manner. In Experiment 2, oral administration of seeds or leaves did not affect the number of larvae found at necropsy of the sheep, but interfered with larval development and there was a tendency to reduce larval weight at the end of the infection period (55d).


Locating the optic nerve in retinal images: comparing model-based and Bayesian decision methods.
In this work we compare two methods for automatic optic nerve (ON) localization in retinal imagery. The first method uses a Bayesian decision theory discriminator based on four spatial features of the retina imagery. The second method uses a principal component-based reconstruction to model the ON. We report on an improvement to the model-based technique by incorporating linear discriminant analysis and Bayesian decision theory methods. We explore a method to combine both techniques to produce a composite technique with high accuracy and rapid throughput. Results are shown for a data set of 395 images with 2-fold validation testing.


cea5, a structurally divergent member of the murine carcinoembryonic antigen gene family, is exclusively expressed during early placental development in trophoblast giant cells.
The carcinoembryonic antigen (CEA) gene family encodes a large family of glycoproteins. Some are probably involved in the homeostasis/development of epithelial cells and granulocyte activation, while others e.g. the pregnancy-specific glycoproteins, are expressed in the placenta and are essential for a positive outcome of pregnancy. In this paper, we have characterized cea5, a member of the murine CEA gene family. RNase protection and in situ hybridization analyses revealed that Cea5 mRNA is exclusively synthesized in primary and secondary trophoblast giant cells of the placenta only during early stages of development. Full-length Cea5 cDNA was obtained by a reverse transcription-polymerase chain reaction using day 10.5 post-coitum placental RNA. The 1.6-kilobase pair (kb) Cea5 mRNA encodes a secreted glycoprotein with a predicted size of 30 kDa. It is composed of a leader peptide (L), one immunoglobulin (Ig) variable or N, and one Ig constant-like or A domain. This domain organization is unique within the human and murine CEA families. Two overlapping cosmid clones covering 54 kb of the cea5 gene locus were mapped. cea5 consists of three exons (L, N, A/3'-untranslated region exon) located within a 4-kb region. rnCGM2, the rat cea5 counterpart, exhibits the same restricted expression pattern. This together with their exceptional conservation within the rat and murine CEA families and their absence from the human CEA family suggests that cea5 and rnCGM2 are of functional importance for rodent placental development.


[Hemorheologic effects following ergometric-controlled physical exercise].
In collaboration with the Laboratory of Physiology, the Unity of Biorheology realized hemorheological studies on healthy volunteers who performed four kinds of well-controlled exercises on a cycle ergometer. Blood was always collected just before exercise and just after exercise. Rheological measurements were performed (blood and plasma viscosities, blood thixotropy and blood viscoelasticity) as well as biological (plasma proteins) and biophysical (osmolarity, pH) measurements. In all the cases, results show the importance of a hemoconcentration and its hemorheology consequences.


miRNAs: whys and wherefores of miRNA-mediated regulation.
MiRNAs are assumed to be important in animal development and physiology, but their specific roles in vivo are still poorly understood. New bioinformatic and genetic studies are setting the stage for unraveling the specific biological functions of miRNAs.


Retinal hemorrhages: advances in understanding.
Retinal hemorrhage is a cardinal manifestation of abusive head injury characterized by repetitive acceleration-deceleration with or without blunt head impact. Detailed description of the hemorrhages and documentation are critical to diagnosis. Vitreoretinal traction appears to be the major causative factor. Outcome is largely dependent on brain and optic nerve injury.


Bilateral Erector Spinae Plane Block for Surgery on the Posterior Aspect of the Neck: A Case Report.
The erector spinae plane block is an interfascial plane block whereby local anesthetic is injected within the plane deep to the erector spinae muscle and superficial to the transverse process. To date, it has been used to provide analgesia in thoracic, abdominal, and lumbar regions. We present the first reported case of bilateral erector spinae plane block being used to provide surgical anesthesia in the cervical region.


Effects of Na+/H+ exchange inhibitors in cardiac ischemia.
To investigate a possible protective role of Na+/H+ exchange inhibition under ischemic conditions isolated rat hearts were subjected to regional ischemia and reperfusion. In these experiments all 6 untreated hearts suffered ventricular fibrillation on reperfusion. Addition of 1 x 10(-5) mol/l amiloride or 3 x 10(-7) mol/l 5-(N-ethyl-N-isopropyl)amiloride (EIPA) markedly decreased the incidence and duration of ventricular fibrillation or even suppressed fibrillation completely as in the case of 1 x 10(-6) mol/l EIPA. Both compounds diminished the activities of lactate dehydrogenase and creatine kinase in the venous effluent of the hearts during ischemia. At the end of the experiments tissue contents of glycogen, ATP and creatine phosphate were increased in the treated hearts as compared to control hearts. In an additional experiment the beneficial effects of Na+/H+ exchange inhibition during ischemia was confirmed in vivo with anaesthetized rats undergoing coronary artery ligation. In these animals amiloride or EIPA pretreatment caused a marked reduction of ventricular premature beats and ventricular tachycardia as well as a complete suppression of ventricular fibrillation. The concentration dependent inhibition of Na+ influx via Na+/H+ exchange by amiloride and EIPA was investigated in erythrocytes from hypercholesterolemic rabbits with Na+/H+ exchange activated by exposure to hyperosmotic medium. Furthermore the inhibition of Na+ influx by EIPA after intracellular acidification was studied in cardiac myocytes of neonatal rats. Both agents were effective in the same order of potency in the ischemic isolated working rat heart as in the erythrocyte model in which they inhibited Na+/H+ exchange.(ABSTRACT TRUNCATED AT 250 WORDS)


Intraspecific variation of biological activities in venoms from wild and captive Bothrops jararaca.
The venom of Bothrops jararaca is composed of complex mixture of molecules, mainly lectins, metalloproteinases, serinoproteinases, desintegrins, phospholipases, and peptides. This composition may vary according to the snake's age, gender, and region of origin. The aim of the was to determine individual variation in Bothrops jararaca venom in the Botucatu region, Sao Paulo State, Brazil, by means of enzymatic, biochemical, and pharmacological characterization, utilizing in vitro tests and biological assays. The activities were compared with those of Brazilian Reference Venom (BRV). Protein concentration varied between adult and juvenile groups. The electrophoretic profiles were similar, with molecular masses ranging between 25 and 50 kD, but with intraspecific variations. Reverse-phase high-performance liquid chromatography (RP-HPLC) revealed protein concentration differences. Coagulant activity did not differ significantly among adult groups, but there was a large variation between juvenile venom and BRV, which coagulated more extensively. Venoms from adults displayed greater hemorrhagic activity, especially in males recently obtained from the wild. In contrast, juveniles kept in captivity and adult males showed higher values. Edematogenic activity displayed an increase in edema in all groups. At the mean lethal dose (LD₅₀), toxicity varied significantly between groups, with venom from captive females being threefold more toxic than juvenile venom. Data illustrate the intra- and interspecific complexity that occurs in snake venoms, which may be attributed to ontogenetic, sexual, and environmental factors that affect variability in Bothrops jararaca venom. Further, it is proposed that Brazilian public health authorities document the constitution of pooled venom employed in the immunization of serum-producing animals due to this variability in venom properties. Given the large Brazilian territory, this variability requires regional monitoring and evaluation of the efficacy of bothropic antivenom in treatment of snakebite and consequent permanent sequelae observed.


Critical pulmonary stenosis: challenges following surgical correction.
A 20-day-old girl was diagnosed with critical pulmonary valvular stenosis with patent ductus arteriosus (PDA). She underwent surgical pulmonary valvotomy and infundibular resection. A trial snaring of the PDA resulted in significant systemic desaturation, and the PDA was left undivided. A continuous infusion of prostaglandin was used to keep the PDA open for the next 8 days. The PDA acted as a "natural systemic-to-pulmonary shunt" to provide pulmonary blood flow until right ventricular compliance and function improved. The various causes of persistent desaturation following pulmonary valvotomy are discussed.


Redox-responsive molecular nanoreservoirs for controlled intracellular anticancer drug delivery based on magnetic nanoparticles.
A novel redox responsive controlled drug release system based on magnetic nanoparticles for efficient intracellular anticancer drug delivery is fabricated. Disulfide bonds are employed as intermediate linkers to immobilize PEI/β-CD molecules as nanoreservoirs for drug loading onto magnetic nanoparticles. The endocytotic pathway and endosomal escape of the smart controlled drug release system is proposed.


Dyspnea in COPD: New Mechanistic Insights and Management Implications.
Dyspnea is the most common symptom experienced by patients with chronic obstructive pulmonary disease (COPD). To avoid exertional dyspnea, many patients adopt a sedentary lifestyle which predictably leads to extensive skeletal muscle deconditioning, social isolation, and its negative psychological sequalae. This "dyspnea spiral" is well documented and it is no surprise that alleviation of this distressing symptom has become a key objective highlighted across COPD guidelines. In reality, this important goal is often difficult to achieve, and successful symptom management awaits a clearer understanding of the underlying mechanisms of dyspnea and how these can be therapeutically manipulated for the patients' benefit. Current theoretical constructs of the origins of activity-related dyspnea generally endorse the classical demand-capacity imbalance theory. Thus, it is believed that disruption of the normally harmonious relationship between inspiratory neural drive (IND) to breathe and the simultaneous dynamic response of the respiratory system fundamentally shapes the expression of respiratory discomfort in COPD. Sadly, the symptom of dyspnea cannot be eliminated in patients with advanced COPD with relatively fixed pathophysiological impairment. However, there is evidence that effective symptom palliation is possible for many. Interventions that reduce IND, without compromising alveolar ventilation (VA), or that improve respiratory mechanics and muscle function, or that address the affective dimension, achieve measurable benefits. A common final pathway of dyspnea relief and improved exercise tolerance across the range of therapeutic interventions (bronchodilators, exercise training, ambulatory oxygen, inspiratory muscle training, and opiate medications) is reduced neuromechanical dissociation of the respiratory system. These interventions, singly and in combination, partially restore more harmonious matching of excessive IND to ventilatory output achieved. In this review we propose, on the basis of a thorough review of the recent literature, that effective dyspnea amelioration requires combined interventions and a structured multidisciplinary approach, carefully tailored to meet the specific needs of the individual.


Sodium-glucose co-transporter 2 inhibitors: evidence and place in therapy.
Type 2 diabetes effects millions of people yet remains difficult to treat with oral pharmacotherapy. Metformin is the first line recommended therapy, and current guidelines suggest individualized therapy for second line selection. Sodium-glucose co-transporter 2 (SGLT-2) inhibitors are the newest class of agents in treating type 2 diabetes via an insulin independent mechanism to lower blood glucose. Currently marketed agents, including canagliflozin, dapagliflozin, empagliflozin, and luseogliflozin, reduce hemoglobin A1c (HbA1c) ~0.8-1%, reduce fasting and post prandial glucose, and have little hypoglycemia associated with them when added to therapies including metformin, a sulfonylurea, pioglitazone, or insulin. Patients receiving SGLT-2 inhibitors have reduced weight and blood pressure, but are more susceptible to urinary tract infections and genital mycotic infections. This review summarizes current literature regarding the SGLT-2 inhibitors.


Distribution and resorption of polymeric microparticles in visceral organs of laboratory animals after intravenous injection.
Microparticles obtained by using (14)C-labeled resorbable hydroxyaminobutyric acid polymer were injected into the caudal vein of laboratory animals without negative aftereffects for their growth and development and without changes in the macro- and microstructure of organs and tissues. The distribution of microparticles in the viscera and the dynamics of accumulation of carbon-containing polymer degradation products in the viscera were studied. The main targets for the particles are liver tissues, as well as renal and splenic tissues. The polymeric matrix of the microparticles is most actively destroyed in the spleen and liver. The presence of high-molecular-weight polymeric matrix in organs indicates the integrity of microparticles and the possibility of long-term (up to 12 weeks) functioning of polymeric particles in vivo.


Interactions between fetal HLA-DQ alleles and maternal smoking influence birthweight.
Maternal smoking during pregnancy inhibits fetal growth, and is a major cause of childhood and adult morbidity, including increased risks of cardiovascular disease and diabetes. However, the use of birthweight as a proxy for future smoking-related morbidity is hindered by its wide variability, suggesting a role for other birthweight-modifying factors. We report here, for the first time, that interactions between specific fetal HLA-DQA1 and DQB1 alleles and maternal smoking can influence birthweight. We compared mean birthweights of a series of term, HLA-DQ typed white UK newborns (n = 552) whose mothers had either smoked (n = 211) or not smoked (n = 341) during pregnancy. Maternal smoking during pregnancy resulted in an average birthweight reduction of 244 g, but the combined effects of maternal smoking and fetal DQA1*0101 or DQB1*0501 alleles resulted in a 230 and 240 g further reduction in mean birthweight, respectively, resulting from interactions between smoking and these DQ types. Other fetal DQ allele-specific interactions with maternal smoking are suggested by a "protective" effect on smoking-associated birthweight reduction in newborns typing for DQA1*0201 and DQB1*0201. Our results suggest biological interactions between maternal cigarette smoking during pregnancy and specific fetal DQ alleles that affect fetal growth. The precise nature of these interactions merits further investigation, as knowledge of fetal HLA-DQ type may be useful in refining risk estimates of severe fetal growth restriction because of maternal smoking during pregnancy.


Retrieval of the optical depth using an all-sky CCD camera.
A new method is presented for retrieval of the aerosol and cloud optical depth using a CCD camera equipped with a fish-eye lens (all-sky imager system). In a first step, the proposed method retrieves the spectral radiance from sky images acquired by the all-sky imager system using a linear pseudoinverse algorithm. Then, the aerosol or cloud optical depth at 500 nm is obtained as that which minimizes the residuals between the zenith spectral radiance retrieved from the sky images and that estimated by the radiative transfer code. The method is tested under extreme situations including the presence of nonspherical aerosol particles. The comparison of optical depths derived from the all-sky imager with those retrieved with a sunphotometer operated side by side shows differences similar to the nominal error claimed in the aerosol optical depth retrievals from sunphotometer networks.


Microarrays and high-throughput transcriptomic analysis in species with incomplete availability of genomic sequences.
Microarrays produce a measurement of gene expression based on the relative measures of dye intensities that correspond to the amount of target RNA. This technology is fast developing and its application is expanding from Homo sapiens to a wide number of species, where enough information on sequences and annotations exist. Anyway, the number of species for which a dedicated platform exists is not high. The use of heterologous array hybridization, screening for gene expression in one species using an array developed for another one, is still quite frequent, even though cross-species microarray hybridization has raised many arguments. Some methods which are high throughput and do not rely on knowledge of the DNA/RNA sequence exist, namely serial analysis of gene expression (SAGE), Massively Parallel Signature Sequencing (MPSS) and deep sequencing of full transcriptome. Although very powerful, particularly the latter, they are still quite costly and cumbersome methods. In some species where genome sequences are largely unknown, several anonymous sequences are deposited in gene banks as a result of Expressed Sequence Tags (ESTs) sequencing projects. The ESTs databases represent a valuable knowledge that can be exploited with some bioinformatic effort to build species-specific microarrays. We present here a method of high-density in situ synthesized microarrays starting from available EST sequences in, Ovis aries. Our data indicate that the method is very efficient and can be easily extended to other species of which genetic sequences are present in public databases, but neglected so far with advanced devices like microarrays. As a perspective, the approach can be applied also to species of which no sequences are available to date, thanks to high-throughput deep sequencing methods.


White matter integrity affected by depressive symptoms in migraine without aura: a tract-based spatial statistics study.
Previous studies have proven that migraine and depression are bidirectionally linked. However, few studies have investigated white matter (WM) integrity affected by depressive symptoms in patients suffering from migraine without aura (MWoA). Forty patients with MWoA were divided into two groups according to their self-rating depression scale (SDS) score in the present study, including 20 in the SDS (+) (SDS > 49) group and 20 in the SDS (-) (SDS ≤ 49) group. Forty healthy participants were also recruited as the control group. Tract-based spatial statistics analyses with multiple diffusion tensor imaging-derived indices [fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), axial diffusivity (AD)] were employed collectively to investigate WM integrity between all patients with MWoA and all healthy controls, between each subgroup (SDS (-) group and SDS (+) group) and healthy controls, and between the SDS (-) and SDS (+) groups. Compared with healthy controls, decreased AD was shown in several WM tracts of the whole MWoA group, SDS (-) group and SDS (+) group. In addition, compared with the SDS (-) group, the SDS (+) group showed decreased FA and increased MD and RD, with conserved AD, including the genu, body and splenium of the corpus callosum, bilateral superior longitudinal fasciculi, the right anterior corona radiata and some other WM tracts, similar to previous findings in depression disorder. Furthermore, mean FA and RD in some of the above-mentioned WM tracts in the SDS (+) group were correlated significantly with SDS scores, including the genu and splenium of the corpus callosum, the right anterior corona radiata and the superior longitudinal fasciculi. Our results suggest that WM integrity may be affected by both depression symptoms (more sensitive as RD) and migraine (more sensitive as AD). The findings may serve as a sensitive biomarker of depression severity in MWoA.


Recombinant BCG expressing a PspA-PdT fusion protein protects mice against pneumococcal lethal challenge in a prime-boost strategy.
Pneumococcal proteins have been evaluated as genetically-conserved potential vaccine candidates. We have previously demonstrated that a fragment of PspA in fusion with PdT (rPspA-PdT) induced protective immune responses in mice. However, purified proteins have shown poor immunogenicity and often require the combination with strong adjuvants and booster doses. Here, we investigated the use of a Bacillus Calmette-Guérin (BCG) strain, a well-established prophylactic vaccine for tuberculosis with known adjuvant properties, for delivery of the PspA-PdT fusion protein. Immunization of mice in a prime-boost strategy, using rPspA-PdT as a boost, demonstrated that rBCG PspA-PdT/rPspA-PdT was able to induce an antibody response against both proteins, promoting an IgG1 to IgG2 antibody isotype shift. Sera from rBCG PspA-PdT/rPspA-PdT immunized mice showed antibodies able to bind to the pneumococcal surface and promoted higher complement deposition when compared with WT-BCG/rPspA-PdT or a single dose of rPspA-PdT. In addition, these antisera inhibited the cytolytic activity of Ply. Production of interleukin-6 (IL-6), gamma interferon (IFN-γ), and tumor necrosis factor alpha (TNF-α) was increased in splenocytes culture. Furthermore, a higher expression of CD69 early activation molecule was observed on splenic CD4+ T cells from mice immunized with rBCG PspA-PdT before and after the protein booster dose. Finally, immunization with rBCG PspA-PdT/rPspA-PdT protected mice against pneumococcal lethal challenge. These results support the further investigation of recombinant BCG strains to express pneumococcal proteins, which could be administered in early stages of life and lead to protective pneumococcal immunity in infants and children.


Dynamic properties of the backbone of an integral membrane polypeptide measured by 2H-NMR.
The 2H-NMR spectrum of the exchangeable hydrogens of the synthetic amphiphilic polypeptide, lys2-gly-leu24-lys2-ala-amide, was measured for the solid peptide at room temperature and, as a function of temperature, for the peptide incorporated into hydrated dipalmitoylphosphatidylcholine (DPPC) bilayers. This study is a prototype of a similar class of experiments which can be carried out on integral membrane proteins to characterize, quantitatively, the dynamic properties of integral membrane proteins. At temperatures below the DPPC gel-liquid crystalline phase transition, the 2H NMR spectrum was very similar to that of the solid peptide indicating that the peptide was immobilized in the lipid bilayer on the time scale (approximately equal to 10(-5) s) of the 2H-NMR measurements. The 2H-NMR spectrum above the phase transition corresponded to that expected from a peptide in the alpha-helical conformation reorienting rapidly about the symmetry axis of the alpha-helix. Measurements of the quadrupolar echo relaxation time, T2e, gave a quantitative measure of the correlation time, tau c, for this motion. The value of tau c decreased rapidly with increasing temperature as the fraction of DPPC molecules in the liquid crystalline phase increased, reaching a value of 2 X 10(-7) s above the phase transition. The observation of a characteristic minimum in T2e as the temperature was raised provided a definitive, quantitative interpretation of the T2e measurements. Using the known geometry of the peptide and the theory of uniaxial rotational diffusion, a value of eta = 1.1 poise was obtained for the effective viscosity of the membrane in close agreement with values obtained previously from transient linear dichroism measurements.


Profiling gene expression in citrus fruit calyx abscission zone (AZ-C) treated with ethylene.
On-tree storage and harvesting of mature fruit account for a large proportion of cost in the production of citrus, and a reduction of the cost would not be achieved without a thorough understanding of the mechani sm of the mature fruit abscission. Genome-wide gene expression changes in ethylene-treated fruit calyx abscission zone (AZ-C) of Citrus sinensis cv. Olinda were therefore investigated using a citrus genome array representing up to 33,879 citrus transcripts. In total, 1313 and 1044 differentially regulated genes were identified in AZ-C treated with ethylene for 4 and 24 h, respectively. The results showed that mature citrus fruit abscission commenced with the activation of ethylene signal transduction pathway that led to the activation of ethylene responsive transcription factors and the subsequent transcriptional regulation of a large set of ethylene responsive genes. Significantly down-regulated genes included those of starch/sugar biosynthesis, transportation of water and growth promoting hormone synthesis and signaling, whereas significantly up-regulated genes were those involved in defense, cell wall degradation, and secondary metabolism. Our data unraveled the underlying mechanisms of some known important biochemical events occurring at AZ-C and should provide informative suggestions for future manipulation of the events to achieve a controllable abscission for mature citrus fruit.


[Transformation of phospholipids by cabbage phospholipase D in mixed micelles containing 3-[(3-cholamidopropyl)dimethylammonio]propanesulfonate].
We compared the activities of cabbage phospholipase D during hydrolysis and transesterification of phosphatidylcholine in mixed micelles of surface-active compounds with various physicochemical properties. Mixed micelles of phospholipids and 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate (ratio, 1:2) were among the best substrates. Hydrolysis and transphosphatidylation were studied in micelles containing 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate. Mixed micelles of phosphatidylcholine and 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate may serve as a new substrate for measurements of phospholipase D activity and preparative isolation of phospholipids using this enzyme.


New anesthesia techniques.
Advances in anesthesia involve refinements in understanding, technique, and technology. These refinements have led to better control of the anesthetic state, effective anesthesia for a wider variety of situations, and the ability to bring sicker patients to the operating room. Although the molecular mechanisms underlying the general anesthetic state are unknown, evidence suggests a specific, receptor-based effect. This concept has allowed anesthesiologists to treat anesthetic end points of immobility, lack of awareness, and autonomic control separately. It is likely that anesthesia and naturally occurring sleep interact physiologically. New, processed EEG monitors may allow anesthesiologists to titrate more finely anesthetic dose, with possible benefits in terms of speed of recovery and detection of intraoperative awareness. Since the 1990s, new anesthetic drugs (propofol, desflurane/sevoflurane, cisatracurium) have enhanced greatly control of the anesthetic state. The new intravenous anesthetic agent dexmedetomidine offers sedation with preserved respiration and cognitive function. Although its role has yet to be defined fully, it currently plays a role in ICU sedation and monitored anesthesia care. New anesthesia ventilators have better monitoring and better flow delivery at high airway pressures. These improvements significantly narrow the performance gap between anesthesia and ICU ventilators. In patients with COPD, pulmonary hypertension, or severe hypoxemia, heliox may improve gas flow, and NO may reduce pulmonary vascular resistance and improve oxygenation.


Congenitally unguarded tricuspid orifice: its differentiation from Ebstein's malformation in association with pulmonary atresia and intact ventricular septum.
Dysplasia of the leaflets is a well-known integral part of Ebstein's malformation. It is less well-recognized that occasionally the septal leaflet may be completely absent and not simply displaced from its usual annular attachment. This may make it difficult to differentiate by echocardiography between Ebstein's malformation and the rare lesion in which the tricuspid orifice is completely devoid of leaflet tissue ("congenitally unguarded orifice"). A neonatal case is described in which a partially unguarded orifice was present in association with pulmonary atresia and intact ventricular septum but misdiagnosed as Ebstein's malformation. In addition we reviewed the morphologic features of all 46 cases of pulmonary atresia and intact septum in the Cardiopathological Collection of the Children's Hospital of Pittsburgh: 17 also had Ebstein's malformation, while three had a congenitally unguarded tricuspid orifice. We found that the differential diagnosis occurred when the right ventricle was dilated rather than being a hypoplastic cavity, as was a feature of all the cases with unguarded orifice and five of those with Ebstein's malformation. The difference between the lesions is best demonstrated by examining the mural leaflet of the valve, which is absent when the orifice is unguarded but displaced in association with Ebstein's malformation. This feature should be recognizable by cross-sectional echocardiography. We have confirmed previous studies that dilatation of the chambers of the right heart indicates a very poor prognosis in cases with pulmonary atresia and an intact ventricular septum.


Authoritative school climate, number of parents at home, and academic achievement.
School climate is widely recognized as an important factor in promoting student academic achievement. The current study investigated the hypothesis that a demanding and supportive school climate, based on authoritative school climate theory, would serve as a protective factor for students living with 1 or no parents at home. Using a statewide sample of 56,508 middle school students from 415 public schools in 1 state, results indicated that student perceptions of disciplinary structure, academic demandingness, and student support all had positive associations with student self-reported grade point average (GPA). In addition, findings showed that academic expectations and student support were more highly associated with GPA for students not living with any parent. Implications for policy and practice are discussed. (PsycINFO Database Record


High levels of mercury and low levels of persistent organic pollutants in a tropical seabird in French Guiana, the Magnificent frigatebird, Fregata magnificens.
In the present study, trace elements and persistent organic pollutants (POPs) were quantified from Magnificent frigatebirds (Fregata magnificens) breeding at a southern Atlantic island. Stable isotope ratio of carbon (δ(13)C) and nitrogen (δ(15)N) were also measured to infer the role of foraging habitat on the contamination. For another group from the same colony, GPS tracks were recorded to identify potential foraging areas where the birds may get contaminated. Fourteen trace elements were targeted as well as a total of 40 individual POPs, including organochlorine pesticides (OCPs), polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs). The concentration of Hg in the blood was up to 6 times higher in adults (5.81 ± 1.27 μg g(-1) dw.) than in nestlings (0.99 ± 0.23 μg g(-1) dw.). A similar pattern was found for POPs. ∑PCBs was the prevalent group both in adults (median 673, range 336-2801 pg g(-1) ww.) and nestlings (median 41, range 19-232 pg g(-1) ww.), followed by the sum of dichlorodiphenyltrichloroethanes and metabolites (∑DDTs), showing a median value of 220 (range 75-2342 pg g(-1) ww.) in adults and 25 (range 13-206 pg g(-1) ww.) in nestlings. The isotope data suggested that the accumulation of trace elements and POPs between adults and nestlings could be due to parental foraging in two different areas during incubation and chick rearing, respectively, or due to a shift in the feeding strategies along the breeding season. In conclusion, our work showed high Hg concentration in frigatebirds compared to non-contaminated seabird populations, while other trace elements showed lower values within the expected range in other seabird species. Finally, POP exposure was found generally lower than that previously measured in other seabird species.


Changes in thalamic projection to the barrelfield of rat after neonatal lesions sparing one whisker.
The thalamic input to the barrelfield of rats with a solitary mystacial vibrissa (C3) intact was examined using succinic dehydrogenase techniques. Rats were lesioned on postnatal day (PD) 1 and brains examined at either 7, 12, 21 or 28 days later. The resultant segmentation in the hemisphere contralateral to the lesioned muzzle consisted of fused rows (A to E). At all ages row C differed from the other rows in that the center of the row was enlarged and separated from the row on either side of it. Thus the presence of a single vibrissa is sufficient to organize the thalamic input to its barrel.


A strategic approach of enzyme engineering by attribute ranking and enzyme immobilization on zinc oxide nanoparticles to attain thermostability in mesophilic Bacillus subtilis lipase for detergent formulation.
The present study envisaged rationalized protein engineering approach to attain thermostability in a mesophilic Bacillus subtilis lipase. Contributing amino acids for thermostability were analyzed from homologous thermophilic-mesophilic protein dataset through relative abundance and generated ranking model. Analyses divulged priority of charged amino acids for thermostability. Ranking model was used to predict thermostabilizing mutations. Three lipase mutants, bsl_the1 (V149K, Q150E), bsl_the2 (F41K, W42E, V149K, Q150E) and bsl_the3 (F41K, W42E, P119E, Q121K, V149K, Q150E) were generated and validated through in silico and in vitro approaches for improved activity and thermostability. ZnO nanoparticles were synthesized by precipitation method and functionalized using polyethylenimine, APTES and glutaraldehyde for lipase immobilization. The immobilization was confirmed through various analytical techniques. Analysis revealed bsl_wt showed optimum activity at 35 °C and pH 8 which was increased to 60 °C and pH 10 in case of ZnO-bsl_the3. The ZnO-bsl_the3 showed 80% of their initial activity after 60 days of storage stability and retained 78% of activity after 20 cycles of reuse. Lipases were applied for oil and grease stain removal from fabric. ZnO-bsl_the3 removed 90% and 82% of oil and grease stains, respectively. Conclusively, it revealed a promising perspective of low-cost nanobiocatalysts in detergent formulation.


Homology modeling of GPCRs.
Over 1,000 sequences likely to encode G protein-coupled receptors (GPCRs) are currently available in publicly accessible and proprietary databases and this number may grow with the refinement of a number of different genomes. However, despite recent efforts in the crystallization of these proteins, homology modeling approaches are becoming widely used as a method for obtaining quantitative and qualitative information for structure-based drug design as well as the interpretation of experimental data.


Ecstasy: an important cause of acute liver failure.
A twenty year old female was referred to hospital by her GP, after he received the results of blood tests taken earlier in the day. She had presented to him complaining of malaise, nausea and anorexia over a 3 day period. On the day of referral she had also become jaundiced with dark urine, but normal stool colour. There was no abdominal pain. She had no significant past medical history with no history of jaundice, liver disease or autoimmune conditions, and no apparent risk factors for blood-borne hepatitis infection. There was no relevant family history. She was taking no prescribed medication, had not taken any over the counter medication or herbal remedies. She denied excessive alcohol use or use of intravenous drugs in the past, although she was not specifically questioned on the use of other recreational drugs. She was a single mother and admitted to being under considerable stress recently. On examination she appeared well, apart from marked jaundice. There were no signs of hepatic encephalopathy or chronic liver disease. Abdominal examination revealed mild left upper quadrant tenderness, but no significant hepatomegaly. Liver function tests (LFTs) taken by her GP are shown in Table 1, revealing marked elevation of the Alanine Transaminase (ALT) (Table 1), with a relatively preserved albumin. Unfortunately her International Normalised Ratio (INR) had not been measured. An Ultrasound of the abdomen demonstrated a normal size liver with normal contour and texture with no other abnormality.


Polycyclic Aromatic Hydrocarbons (PAHs) in Exposed-Lawn Soils from 28 Urban Parks in the Megacity Guangzhou: Occurrence, Sources, and Human Health Implications.
Polycyclic aromatic hydrocarbons (PAHs) in urban soils may pose a serious threat to human health via oral ingestion, dermal absorption, and particulate inhalation, especially in public parks and playgrounds, with children and senior citizens showing the highest susceptibility. Several studies have been undertaken identifying PAHs in urban soils, but no studies to date have assessed PAHs in urban parks, in particular in exposed-lawn soils. In recent decades, unprecedented rates of urbanization and industrialization in China have resulted in significant levels of urban environmental pollution. However, concentrations, sources, and the health risk associated with PAH exposure via urban park lawn soils in China remain unknown. The concentrations, sources, and health risk of exposure to 16 PAHs in surface-exposed lawn soils were studied in 28 urban parks in Guangzhou. Concentrations of Σ16PAHs ranged from 76.44 to 890.85 ng/g with a mean of 286.11 ng/g. PAH composition was mostly characterized by 2- and 4-ring PAHs in most sampling parks; Nap, Flua, Pyr, Phe, and Chr were the dominant constituents. Principle component analysis coupled with multivariate linear regression indicated that vehicular and coal combustion emissions contributed to 50.53 and 49.46% of PAHs in Guangzhou's urban park soils, respectively. Total cancer risk (TCR) analysis found that 22 parks (accounting for 78.57% total parks) designed for children's use and general-use park areas presented a potentially high risk (>1 × 10-4) for all users.