Prevention of symptomatic recurrences of esophageal candidiasis in AIDS patients after the first episode: a prospective open study.
To evaluate the efficacy and safety of low-dose antifungals as prophylaxis of recurrent esophageal candidiasis after the first episode in patients with AIDS. After the first episode of esophageal candidiasis, 122 consecutive AIDS patients were randomly assigned to two different regimens of continuous long-term antifungal prophylaxis (ketoconazole 200 mg or fluconazole 50 mg/day p.o.) or no antifungal therapy over a period of 2 yr. Patients were followed up by monthly clinical controls and upper GI endoscopy in the case of recurrence of esophageal symptoms. One hundred and six patients were clinically evaluable over a mean observation time of 7.5 months. Prophylaxis with oral antifungals significantly reduced symptomatic relapses of esophageal candidiasis, the cumulative probability of relapse at 12 months being 38% in the prophylaxis group, compared with 84% in the untreated group. Both antifungals were sufficiently safe and well tolerated. The clinical response of a second episode of candidiasis to the reintroduction of standard oral antifungals was markedly worse in patients on prophylaxis (especially with ketoconazole) than in untreated patients, presumably due to the development of resistance to the antifungal. Continuous prophylaxis with both-fluconazole and ketoconazole is effective in preventing recurrences of Candida esophagitis in AIDS patients; however, the possible emergence of strains resistant to these antifungals, as well as the high cost of the therapy, should raise doubts as to whether or not this type of prophylaxis should be extended to all AIDS patients with Candida esophagitis, rather than to limit its use to specific subgroups of patients, such as those with frequent symptomatic relapses.


Rapidly fatal neuropathies and an ALS clinical presentation.
OBJECTIVES - The objective of this report is to describe patients with an unusually severe, rapidly fatal acquired polyneuropathy. METHODS - The clinical, electrodiagnostic (EDX), laboratory, and pathological findings in three patients with a distinctive form of neuropathic illness are discussed. RESULTS - Three patients, ages 67, 54, and 50, had clinical findings that met accepted clinical criteria for amyotrophic lateral sclerosis (ALS) - definite in two and probable in one. The EDX studies in these patients had abnormalities that would be highly atypical for ALS. There were features consistent with an asymmetrical, non-length-dependent process as well findings consistent with demyelination - features consistent with a chronic acquired polyneuropathy. All patients had a rapidly progressive course with death because of respiratory failure in 4-30 months. The patients did not respond to immunomodulating therapies. Extensive evaluations in these patients did not reveal a cause for the patients' neuropathies. Postmortem examination in two of the patients did not reveal evidence for ALS. In one of these patients, there were pathological findings thought possibly consistent with an immunologically mediated process. CONCLUSION - This report emphasizes the importance of considering other diagnoses in patients who clinically appear to have ALS and raise the specter of an as of yet poorly understood, severe neuropathic illness.


Real-World Evidence for Regulatory Decisions: Concomitant Administration of Zoster Vaccine Live and Pneumococcal Polysaccharide Vaccine.
The US Food and Drug Administration is charged with expanding the use of real-world evidence for regulatory decisions. As a test case for real-world evidence to support regulatory decisions, we present the scenario of concomitant vaccination with zoster vaccine live (ZVL) and 23-valent pneumococcal polysaccharide vaccine (PPSV23). The prescribing information states that these vaccines should not be given concurrently, based on a small trial using varicella zoster virus antibody levels as a correlate of ZVL efficacy, even though ZVL protects against herpes zoster via cell-mediated immunity. We conducted an observational cohort study involving more than 35,000 members of Kaiser Permanente Southern California receiving concomitant ZVL and PPSV23 versus PPSV23 prior to ZVL. Occurrence of herpes zoster was assessed through electronic health records from January 1, 2007, to June 30, 2016. The adjusted hazard ratio comparing incidence rates of herpes zoster in the concomitant vaccination cohort and the prior vaccination cohort was 1.04 (95% confidence interval: 0.92, 1.16). This real-world evidence study provides direct evidence for a lack of vaccine interference, relying on herpes zoster occurrence rather than an intermediate marker of immunity. Real-world evidence is essential for regulators and policy makers in addressing evidentiary gaps regarding safety, effectiveness, compliance, and vaccine interactions for the new recombinant zoster vaccine.


Triclosan Resistance in a Bacterial Fish Pathogen, Aeromonas salmonicida subsp. salmonicida, is Mediated by an Enoyl Reductase, FabV.
Triclosan, the widely used biocide, specifically targets enoyl-acyl carrier protein reductase (ENR) in the bacterial fatty acid synthesis system. Although the fish pathogen Aeromonas salmonicida subsp. salmonicida exhibits triclosan resistance, the nature of this resistance has not been elucidated. Here, we aimed to characterize the triclosan resistance of A. salmonicida subsp. salmonicida causing furunculosis. The fosmid library of triclosan-resistant A. salmonicida subsp. salmonicida was constructed to select a fosmid clone showing triclosan resistance. With the fosmid clone showing triclosan resistance, a subsequent secondary library search resulted in the selection of subclone pTSR-1. DNA sequence analysis of pTSR-1 revealed the presence of a chromosomal-borne fabV-encoding ENR homolog. The ENR of A. salmonicida (FabVas) exhibited significant homology with previously known FabV, including the catalytic domain YX(8)K. fabVas introduction into E. coli dramatically increased its resistance to triclosan. Heterologous expression of FabVas might functionally replace the triclosan-sensitive FabI in vivo to confer E. coli with triclosan resistance. A genome-wide search for fabVas homologs revealed the presence of an additional fabV gene (fabVas2) paralog in A. salmonicida strains and the fabVas orthologs from other gram-negative fish pathogens. Both of the potential FabV ENRs expressed similarly with or without triclosan supplement. This is the first report about the presence of two potential FabV ENRs in a single pathogenic bacterium. Our result suggests that triclosan-resistant ENRs are widely distributed in various bacteria in nature, and the wide use of this biocide can spread these triclosan-tolerant ENRs among fish pathogens and other pathogenic bacteria.


Mineralization of p-chlorophenol in water solution by AOPs based on UV irradiation.
Protection of clean aquifers requires radical minimization of water consumption, overall reduction of wastewater and, furthermore, minimization of wastewater loading. Many organic pollutants in wastewater present a specific problem because of their toxicity, bioaccumulation and poor biodegradability. The scope of this paper is to investigate and identify the benefits offered by advanced oxidation processes (AOPs) as destructive methods for treatment of wastewater loaded with recalcitrant organic pollutants. The study was performed on model wastewater containing p-chlorophenol as a representative of organic chemical industry intermediates. Several UV based AOPs were studied: UV, UV/H2O2, UV/O3, UV/H2O2/O3 and UV/Fenton. Optimal process conditions for the highest mineralization efficiency in the investigated range (pH, [H2O2] and [Fe2+]) have been determined on the basis of HPLC measurements and the following ecological parameters: total organic carbon (TOC), adsorbable organic halides (AOX), chemical oxygen demand (COD) and biochemical oxygen demand (BOD5). Toxicity is one of the most important ecological parameters in determining the level of water pollution. In this study, toxicity tests were performed on the zooplankton Daphnia magna in order to evaluate efficiency of the applied treatments. The UV/ Fenton and UV/H2O2/O3 processes were found to be the most appropriate processes for degradation and mineralization of p-chlorophenol. Complete degradation was achieved after 15 minutes ofUV/Fenton process treatment, while 92.1% TOC and 98.3% AOX removals were obtained after treatment of 60 minutes.


Stepping stones in the electron transport from cells to electrodes in Geobacter sulfurreducens biofilms.
Geobacter sulfurreducens bacteria grow on biofilms and have the particular ability of using polarized electrodes as the final electron acceptor of their respiratory chain. In these biofilms, electrons are transported through distances of more than 50 μm before reaching the electrode. The way in which electrons are transported across the biofilm matrix through such large distances remains under intense discussion. None of the two mechanisms proposed for explaining the process, electron hopping through outer membrane cytochromes and metallic like conduction through conductive PilA filaments, can account for all the experimental evidence collected so far. Aiming at providing new elements for understanding the basis for electron transport, in this perspective article we present a modelled structure of Geobacter pilus. Its analysis in combination with already existing experimental evidence gives support to the proposal of the "stepping stone" mechanism, in which the combined action of pili and cytochromes allows long range electron transport through the biofilm.


Artificial photosynthesis: closing remarks.
This paper derives from my closing remarks lecture at the 198th Faraday Discussion meeting on Artificial Photosynthesis, Kyoto, Japan, February 28-March 2. The meeting had sessions on biological approaches and fundamental processes, molecular catalysts, inorganic assembly catalysts, and integration of systems for demonstrating realistic devices. The field has had much progress since the previous Faraday Discussion on Artificial Photosynthesis in Edinburgh, UK, in 2011. This paper is a personal account of recent discussions and developments in the field, as reflected in and discussed during the meeting. First it discusses the general directions of artificial photosynthesis and some considerations for a future solar fuels technology. Then it comments on some scientific directions in the area of the meeting.


CNV-RF Is a Random Forest-Based Copy Number Variation Detection Method Using Next-Generation Sequencing.
Simultaneous detection of small copy number variations (CNVs) (<0.5 kb) and single-nucleotide variants in clinically significant genes is of great interest for clinical laboratories. The analytical variability in next-generation sequencing (NGS) and artifacts in coverage data because of issues with mappability along with lack of robust bioinformatics tools for CNV detection have limited the utility of targeted NGS data to identify CNVs. We describe the development and implementation of a bioinformatics algorithm, copy number variation-random forest (CNV-RF), that incorporates a machine learning component to identify CNVs from targeted NGS data. Using CNV-RF, we identified 12 of 13 deletions in samples with known CNVs, two cases with duplications, and identified novel deletions in 22 additional cases. Furthermore, no CNVs were identified among 60 genes in 14 cases with normal copy number and no CNVs were identified in another 104 patients with clinical suspicion of CNVs. All positive deletions and duplications were confirmed using a quantitative PCR method. CNV-RF also detected heterozygous deletions and duplications with a specificity of 50% across 4813 genes. The ability of CNV-RF to detect clinically relevant CNVs with a high degree of sensitivity along with confirmation using a low-cost quantitative PCR method provides a framework for providing comprehensive NGS-based CNV/single-nucleotide variant detection in a clinical molecular diagnostics laboratory.


[A case of carcinomatous autonomic and sensory neuropathy].
A 61-year-old male with carcinomatous autonomic and sensory neuropathy was presented. The disease started with numbness in his lower extremities and loss of sensation gradually developed over the upper extremities within two months. Finally he became unable to walk because of orthostatic hypotension and dystaxia due to loss of deep sensation. Physical examination on admission revealed mydriasis with negative light reflex, orthostatic hypotension, sensory loss of below C-4, areflexia, positive Babinski's sign and sexual impotence. Laboratory examinations revealed serum antineural antibody, elevation of protein and oligoclonal IgG band in the CSF. Sural nerve biopsy specimen showed severe loss of myelinated fibers, especially in the large-sized fibers. The pharmacological functional tests of the autonomic nerves disclosed disturbance of parasympathetic nervous system as well as the postsynaptic fibers of the sympathetic nerves. An instillation test of 2.5% mecholyl solution demonstrated contraction of both pupils. Chest X-ray showed abnormal shadow at the right hilus and transbronchial biopsy revealed small cell carcinoma (oat cell type). Plasma exchange improved orthostatic hypotension and decreased the titer of the antineural antibody. In this case, the autonomic ganglion including the ciliary ganglia and the dorsal root ganglia cells were predominantly involved and such cases have been described as a variant of paraneoplastic syndrome in the literature.


Remifentanil: a novel, short-acting, mu-opioid.
Because of remifentanil's unique pharmacokinetics, its systemic administration may be suitable for clinical settings where a potent, fast-acting, systemic mu-opioid with a rapid recovery is required, e.g., short painful intervention in the emergency room or the intensive care unit, or procedures in the day surgery or endoscopy suite. Total intravenous anesthesia for longer lasting procedures may become more promising because of the predictability of the offset of remifentanil even after long infusions. Its closest competitor, alfentanil, depends on its small volume of distribution for rapid termination of its effect, but still possesses the potential to accumulate because of its relatively long terminal elimination half-life. Remifentanil might be the first potent mu-opioid that does not accumulate in this fashion, and therefore it opens promising new clinical perspectives (52). However, as mentioned above, the relative short-lasting analgesic effect after cessation of the remifentanil infusion might require new, sophisticated techniques from the anesthetist to prevent immediate onset of postoperative pain.


Sequential molecular and cytologic analyses provides a complementary approach to the diagnosis of pancreatic cystic lesions: a decade of clinical practice.
Many pancreatic cystic lesions (PCL) are of neoplastic nature with potential to progress to pancreatic adenocarcinoma. Early stratification of patients to either clinical observation or surgical intervention can considerably increase the survival rate. Recent studies have shown the value of molecular analysis to current diagnostic modalities.The aim of this study is to evaluate the diagnostic improvement by utilizing multiple sequential cytologic and molecular cyst fluid analyses. We prospectively evaluated 58 patients for whom multiple endoscopic ultrasound-guided fine-needle aspiration of cyst fluid specimens were available. Specimens were subjected to next generation sequencing to identify any recurrent gene mutations commonly found in PCL. The molecular findings were compared with cytologic and final diagnoses. Cytologic diagnoses were classified into 3 groups: non-diagnostic (first visit: 33.9%, cumulative: 15.8%, P = 0.03), negative (1st visit: 53.6%, cumulative: 56.1%, P = 0.85) and atypical/suspicious/positive (first visit: 12.5%, cumulative: 28.1%, P = 0.06). The mutational analyses were clustered into indeterminate/failure (first visit: 1.7%, cumulative: 0%), KRAS/GNAS/VHL group (first visit: 50.0%, cumulative: 53.4%) and any mutation (first visit: 50.0%, cumulative: 53.4%). Mutational analysis identifies up to 72% and 71% whereas cytologic analysis classified up to 46% and 63% of lesions correctly in first and multiple visits, respectively. The cytology and molecular analyses provide a complementary approach to patients with PCL. Power of molecular analysis in detection of a neoplastic lesion is significantly higher in one visit (P = 0.01) with comparable detection rates (P = 0.43) for both cytologic and molecular analyses after multiple visits.


Mental health, binge drinking, and antihypertension medication adherence.
To evaluate the relationship between self-reported mental health and binge drinking, as well as health status, sociodemographic, social support, economic resource, and health care access indicators to antihypertension medication adherence. Analysis of 2003 California Health Interview Survey data. Having poor mental health days predicted medication nonadherence, whereas binge drinking did not. Nonadherence predictors included younger age, Latino, non-US citizen, uninsured, less education, and no regular medical care. Adherence predictors were older age, African American, having prescription insurance, a college degree, poor health, comorbid diabetes or heart disease, and overweight or obese. Better mental health may improve medication adherence among hypertensive individuals.


Malignant ameloblastoma metastasis to the lung: a case report.
Ameloblastoma is an odontogenic tumor, usually benign, which rarely metastasizes to distant organs. The case of a 27-year-old white woman is described, who presented a metastatic pulmonary ameloblastoma 7 years after the removal of a mandibular ameloblastoma. She presented no pulmonary symptoms, but a lung nodule was found in a chest x-ray during a routine check-up for job admission. Computed tomography (CT) revealed a 2-cm well-defined solitary round nodule without calcifications, leading to the hypothesis of a metastatic tumor. Clinical and CT investigation confirmed no ameloblastoma recurrence in the jaw and no other primary tumor. The diagnosis of metastatic ameloblastoma was confirmed by microscopic evaluation of the pulmonary nodule.


The effect of radiation therapy on normal tissue function.
As more patients are treated for their primary malignancy with cure or increased disease-free intervals, injury to normal tissues will become more detectable and an important endpoint for study. Future protocols will probably be modified based on toxicity endpoints. In Hodgkin's disease, current protocols use response-based treatment strategies to limit therapy. The objective is to provide the same level of tumor control and follow normal tissue endpoints for outcome analysis. DVH analysis has improved the ability to analyze endpoint data for normal tissues. These image-guided platforms will provide the infrastructure needed to continue efforts in improving the delivery of radiation therapy.


Magnetic response of a viscoelastic ferrodispersion: From a nearly Newtonian ferrofluid to a Jeffreys ferrogel.
The theory of orientational motion of a Brownian magnetic nanoparticle embedded in a viscoelastic medium and subjected to a time-dependent uniform magnetic field is developed. The rheology of the viscoelastic environment of the particle is modeled by the Jeffreys scheme, which under variation of a minimal number of parameters is able to resemble a wide range of soft materials: from a weakly structured (nearly Newtonian) polymer solution to a gel. It is shown that in the Jeffreys model, the diffusional orientational motion of a particle is a combination of two modes, which could be associated with a fast motion within the polymer mesh cell and a slow displacement that involves deformation of the mesh, respectively. The dependencies of the reference times of both relaxation modes on the Jeffreys viscous and elastic parameters and temperature are found. It turns out that in substantially viscoelastic media, the rate of the slow mode (it dominates in relaxation) quadratically depends on the matrix temperature. This effect does not have analogs in linearly viscous systems. For an ensemble of magnetic nanoparticles in viscoelastic and gel Jeffreys matrices: (1) the dynamic magnetic susceptibility is derived and evaluated both within an exact approach and in a simple approximation; (2) the problem of magnetic relaxometry, i.e., evolution of magnetization after step-wise turning off the field, is solved; (3) the specific power loss caused by viscous dissipation generated by the particles under an ac field is analyzed as a function of the rheological parameters. Results (1) and (2) provide simple models for magnetic nanorheology; consideration (3) advances the physics of magnetic hyperthermia in viscoelastic and gel-like media.


Occupational exposure to asthmagens and adult onset wheeze and lung function in people who did not have childhood wheeze: A 50-year cohort study.
There are few prospective studies that relate the development of adult respiratory disease with exposure to occupational asthmagens. To evaluate the risk of adult onset wheeze (AOW) and obstructive lung function associated with occupational exposures over 50years. A population-based randomly selected cohort of children who had not had asthma or wheezing illness, recruited in 1964 at age 10-15years, was followed-up in 1989, 1995, 2001 and 2014 by spirometry and respiratory questionnaire. Occupational histories were obtained in 2014 and occupational exposures determined with an asthma-specific job exposure matrix. The risk of AOW and lung function impairment was analysed in subjects without childhood wheeze using logistic regression and linear mixed effects models. All 237 subjects (mean age: 61years, 47% male, 52% ever smoked) who took part in the 2014 follow-up had completed spirometry. Among those who did not have childhood wheeze, spirometry was measured in 93 subjects in 1989, in 312 in 1995 and in 270 subjects in 2001 follow-up. For longitudinal analysis of changes in FEV1 between 1989 and 2014 spirometry records were available on 191 subjects at three time points and on 45 subjects at two time points, with a total number of 663 records. AOW and FEV1<LLN were associated with occupational exposure to food-related asthmagens (adjusted odds ratios (adjORs) 95% CI: 2.7 [1.4, 5.1] and 2.9 [1.1, 7.7]) and biocides/fungicides (adjOR 95% CI: 1.8 [1.1, 3.1] and 3.4 [1.1, 10.8]), with evident dose-response effect (p-trends<0.05). Exposure to food-related asthmagens was also associated with reduced FEV1, FVC and FEF25-75% (adjusted regression coefficients 95% CI: -7.2 [-12.0, -2.4], -6.2 [-10.9, -1.4], and -13.3[-23.4, -3.3]). Exposure to wood dust was independently associated with AOW, obstructive lung function and reduced FEF25-75%. Excess FEV1 decline of 6-8ml/year was observed with occupational exposure to any asthmagen, biocides/fungicides and food-related asthmagens (p<0.05). This longitudinal study confirmed previous findings of increased risks of adult onset wheezing illness with occupational exposure to specific asthmagens. A novel finding was the identification of food-related asthmagens and biocides/fungicides as potential new occupational risk factors for lung function impairment in adults without childhood wheeze.


Cord blood oxygen saturation in vigorous infants at birth: what is normal?
To define the normal ranges of umbilical cord blood oxygen saturation (SaO2) and acid-base status at birth and to evaluate the effect of gestational age on cord blood values in vigorous newborn infants following spontaneous vaginal birth from a vertex position. Prospective study. Department of Obstetrics and Gynaecology, University of Graz, Austria. Cord blood samples from 1281 vigorous newborn infants. Cord blood sampling was performed following on newborn infants following spontaneous vaginal birth in a vertex position. SaO2 was measured directly by a spectrophotometer and pH, base excess, pCO2 and pO2 by a pH/blood-gas analyser. Infants with a 5-minute Apgar score > or = 7 were considered vigorous. Subgroups were classified according to the gestational age: preterm, term and post-term (< 37, 37-42 and > 42 weeks, respectively). The median umbilical artery SaO2 was 24.3% and the 2.5th centile was as low as 2.7%. The median umbilical artery values were pH = 7.25, base excess = -4.3 mmol/L and pO2 = 16 mmHg. The 2.5th centiles were 7.08, -11.1 mmol/L and 5 mmHg, respectively. The median umbilical artery pCO2 was 50 mmHg and the 97.5th centile was 75 mmHg. The mean umbilical artery and vein SaO2 values were not significantly influenced by gestational age. The umbilical artery SaO2 and base excess values were strongly skewed. The mean umbilical artery pH values in preterm infants were higher than in other subgroups. The mean umbilical artery and vein base excess values were lower in post-term newborn infants than in other subgroups. The physiological range of oxygen saturation in umbilical cord of vigorous newborn infants at birth is wide and skewed. In contrast to pH and base excess, umbilical cord blood oxygen saturation is not influenced significantly by gestational age at birth.


[Chronic subdural hematoma as a cause for blindness].
The uncommon complication of bilateral blindness resulting from a decompressive neurosurgical procedure is presented by the case of a 51-year old patient suffering from a traumatic chronic subdural haematoma. A breakdown of the altered vasoregulation of the optic nerves due to papilledema at the time of intracranial pressure drop is supposed to be the etiological background of optic atrophy and consequent amaurosis. The causal relationship of accident trauma and blindness in the presented case is pointed out.


Analysis of comparative efficiencies of different transformation methods of E. coli using two common plasmid vectors.
The efficiencies of different transformation methods of E. coli DH5Qalpha train, induced by several cations like Mg2+, Mn2+ Rb+ and especially Ca2+, with or without polyethylene glycol (PEG) and dimethyl sulfoxide (DMSO) were compared using the two commonly used plasmid vectors pCAMBIA1201 and pBI121. The widely used calcium chloride (CaCl2) method appeared to be the most efficient procedure, while rubidium chloride (RbCl) method was the least effective. The improvements in the classical CaCl2 method were found to further augment the transformation efficiency (TR)E for both the vectors like repeated alternate cycles of heat shock, followed by immediate cold, at least up to the third cycle; replacement of the heat shock step by a single microwave pulse and even more by double microwave treatment and administration of combined heat shock-microwave treatments. The pre-treatment of CaCl2-competent cells with 5% (v/v) ethanol, accompanied by single heat shock also triggered the (TR)E, which was further enhanced, when combined heat shock-microwave was applied. The minor alterations or improved approaches in CaCl2 method suggested in the present study may thus find use in more efficient E. coli transformation.


Total knee replacement with a variable axis knee prosthesis.
The Variable Axis Knee Prosthesis was designed to accommodate a wide range of problems in the knee and to minimize the complication of loosening. The results of the series, which now spans over seven years at this institution, have confirmed the effectiveness of the prosthesis in providing stability and firm fixation. Patellar alignment remains critical for optimum results. A wide variety of abnormalities, including failed prostheses, severe flexion contractures, arthrodesed knees, and severely osteoporotic bone, can be effectively managed utilizing this device. As with any other total knee prosthesis, the use of this prosthesis should be restricted to those knees with definite radiographic evidence of joint impairment in addition to significant symptoms. Relative contraindications include previous sepsis, neuropathic joint disease, and gross ligamentous incompetency. If these indications and limitations are adhered to, the results from knee replacement can be expected to equal or exceed those from total hip replacement over the long term.


[Benign paroxysmal positional vertigo of the horizontal and superior semicircular canals].
The incidence of benign paroxysmal positional vertigo (BPPV) of the horizontal and superior semicircular canals is much less than that of BPPV due to affection of the posterior semicircular canal. Their diagnosis is however much more difficult and still prone to controversies. The provocative manoeuvre of the BPPV of the horizontal canal (BPPV-HSC) is the manoeuvre of rotation of the head in dorsal position. A horizontal positional nystagmus is obtained. There are two forms of BPPV-HSC: the geotropic form and the ageotropic form. In the geotropic form, the liberatory manoeuvre is a "barbecue" rotation of 180 with 360 degrees towards the healthy side. In the ageotropic form, there is no universal liberatory manoeuvre. Moreover as some cases of neurological aetiology have been recognized, it is not appropriate to apply ineffective manoeuvres. The BPPV of the superior canal (BPV-SSC) is very rare. The provocative manoeuvre is the Dix and Hallpike's manoeuvre. It causes positional torsional and vertical nystagmus with an opposite direction to that obtained for a BPPV of the contra-lateral posterior canal. The liberatory manoeuvre is a Semont manoeuvre, which is identical to that we would make for a contra-lateral BPPV of the posterior canal.


Triboelectric simulation of pacemaker malfunction.
We report the occurrence of a triboelectric phenomenon (static electricity) that mimicked malfunction of a contemporary pacemaker by creating an electrocardiograpic artifact virtually identical to the pacemaker stimuli. The diagnosis was established by observing a subtle overshoot of the questionable deflection that was absent from pacemaker stimuli.


Treatment of Waldenstrom's macroglobulinemia with very low doses of alpha interferon.
Waldenström's macroglobulinemia (WM) is a differentiated B-cell malignancy which is usually less responsive to standard chemotherapy because of low-proliferating cells. Interferon alpha has been shown to possess a therapeutic action in numerous B-cell malignancies including the early stage of chronic lymphocytic leukemia, multiple myeloma, follicular lymphoma and hairy cell leukemia. Fourteen patients with progressive WM were included in a pilot study using very low dose of interferon alpha-2a (1 Million Units 3 times a week). The mean duration of treatment was 10.3 months (range 2-44). Six of 14 (42%) patients presented an increase in the hemoglobin level (> or = 0.9 g/dL) and 4/14 (28%) had a substantial decrease of the monoclonal component (> or = 20% of reduction). Only two patients presented both types of response, while the others with an increase in the hemoglobin level had a slight decrease in the monoclonal component (MC) (1 patient), a stable MC (1 patient) or a slight increase of MC (1 patient). One additional patient had a 15% decrease of the MC with a stable hemoglobin level. Response was observed within 3 months with a median duration of 6 months. Treatment was stopped for 3 patients because of flu-like symptoms (2 patients), or thrombocytopenia (1 patient). Follow up was possible in 12 patients lasting up to a maximum of 30 months after discontinuing treatment. Seven patients died, including 4 with progressive disease, two of infection and one of cardiac failure. In the view of these results, very low dose of interferon alpha may constitute a new approach for treatment of some cases of WM.


Anatomical location of the vocal cords in relation to cervical vertebrae: A new predictor of difficult laryngoscopy?
Several anatomical factors, such as prognathism, sex, short thyromental distance and others are known to make direct laryngoscopy difficult. We investigated the hypothesis that the anatomical position of the vocal cords in relation to the cervical vertebrae correlates with difficult laryngoscopy. Existing MRI was used to identify the position of the vocal cords relative to the cervical spine in patients with and without difficult laryngoscopy. Observational study with adaptive enrichment. University hospital. A total of 142 adult patients, 91 with easy (Cormack-Lehane class 1 or 2) and 51 with difficult (Cormack-Lehane class 3 or 4) laryngoscopy. Position of the vocal cords relative to cervical vertebrae in patients with easy vs. difficult laryngoscopy. In patients with difficult laryngoscopy, we found a higher incidence of cranial position of the vocal cords in relation to the cervical spine compared with patients with easy laryngoscopy (P < 0.001). Anaesthesiologists should take advantage of existing imaging of the cervical spine when assessing the patient's airway.


Cerebroside sulfotransferase deficiency ameliorates L-selectin-dependent monocyte infiltration in the kidney after ureteral obstruction.
Mononuclear cells infiltrating the interstitium are involved in renal tubulointerstitial injury. The unilateral ureteral obstruction (UUO) is an established experimental model of renal interstitial inflammation. In our previous study, we postulated that L-selectin on monocytes is involved in their infiltration into the interstitium by UUO and that a sulfated glycolipid, sulfatide, is the physiological L-selectin ligand in the kidney. Here we tested the above hypothesis using sulfatide- and L-selectin-deficient mice. Sulfatide-deficient mice were generated by gene targeting of the cerebroside sulfotransferase (Cst) gene. Although the L-selectin-IgG chimera protein specifically bound to sulfatide fraction in acidic lipids from wild-type kidney, it did not show such binding in fractions of Cst(-/-) mice kidney, indicating that sulfatide is the major L-selectin-binding glycolipid in the kidney. The distribution of L-selectin ligand in wild-type mice changed after UUO; sulfatide was relocated from the distal tubules to the peritubular capillaries where monocytes infiltrate, suggesting that sulfatide relocated to the endothelium after UUO interacted with L-selectin on monocytes. In contrast, L-selectin ligand was not detected in Cst(-/-) mice irrespective of UUO treatment. Compared with wild-type mice, Cst(-/-) mice showed a considerable reduction in the number of monocytes/macrophages that infiltrated the interstitium after UUO. The number of monocytes/macrophages was also reduced to a similar extent in L-selectin(-/-) mice. Our results suggest that sulfatide is a major L-selectin-binding molecule in the kidney and that the interaction between L-selectin and sulfatide plays a critical role in monocyte infiltration into the kidney interstitium.


A positive charge preservation at position 116 of alpha A-crystallin is critical for its structural and functional integrity.
An autosomal dominant congenital cataract associated with a missense mutation, Arg-116 to Cys (R116C), in the coding sequence of human alphaA-crystallin has been reported. Subsequent study of this mutant, generated by site-directed mutagenesis, showed significant changes in secondary and tertiary structures, partial loss of chaperone activity, and substantially increased oligomeric size. The study presented here aims to show whether these changes are due to the loss of a positive charge at this position or due to the presence of an extra Cys. To show this, Arg-116 in alphaA-crystallin was mutated to Lys (R116K), Cys (R116C), Gly (R116G), and Asp (R116D) and expressed in Escherichia coli cells. The wild-type (alphaA-wt) and mutant proteins were purified by size exclusion chromatography and characterized by measurements of circular dichroism, intrinsic tryptophan fluorescence, and TNS fluorescence and by determination of molecular masses and chaperone function which was assessed as the ability to suppress target protein aggregation or enhance target protein refolding. Mutation of Arg-116 to a Cys or Gly showed very similar changes in structure, oligomerization, and chaperone function which suggest that the presence of this Cys per se is not the cause of the changes. The R116K mutant, on the other hand, had nearly the same structure, oligomeric size, and chaperone function as alphaA-wt, whereas the mutant with an acidic amino acid in this position, R116D, showed drastic changes in protein structure. Thus, a positive charge must be preserved at this position for the structural and functional integrity of alphaA-crystallin.


Anticoagulant therapy for venous thromboembolism during pregnancy: a systematic review and a meta-analysis of the literature.
Venous thromboembolism (VTE) is one of the most relevant causes of maternal death in industrialized countries. Low molecular weight heparin (LMWH), continued throughout the entire pregnancy and puerperium, is currently the preferred treatment for patients with acute VTE occurring during pregnancy. However, information on the efficacy and safety of anticoagulant drugs in this setting is extremely limited. We carried out a systematic review and a meta-analysis of the literature to provide an estimate of the risk of bleeding complications and VTE recurrence in patients with acute VTE during pregnancy treated with antithrombotic therapy. The weight mean incidence (WMI) of bleeding and thromboembolic events and the corresponding 95% confidence interval (CI) were calculated. Eighteen studies, giving a total of 981 pregnant patients with acute VTE, were included. LMWH was prescribed to 822 patients; the remainder were treated with unfractionated heparin. Anticoagulant therapy was associated with WMIs of major bleeding of 1.41% (95% CI 0.60-2.41%; I) antenatally and 1.90% (95% CI 0.80-3.60%) during the first 24 h after delivery. The estimated WMI of recurrent VTE during pregnancy was 1.97% (95% CI 0.88-3.49%; I(2) 39.5%). Anticoagulant therapy appears to be safe and effective for the treatment of pregnancy-related VTE, but the optimal dosing regimens remain uncertain.


Levonorgestrel-releasing intrauterine device use as an alternative to surgical therapy for uterine leiomyoma.
To evaluate the efficacy of the levonorgestrel-releasing intrauterine system (LNG-IUS) in the treatment of leiomyoma related menorrhagia and to assess the effect of LNG-IUS on uterine, leiomyoma, and ovarian volume. In this prospective before and after study, LNG-IUS was inserted in 38 women with myoma-related menorrhagia. The patients were evaluated for serum levels of hemoglobin, hematocrit and uterine, leiomyoma, and ovarian volume at the time of insertion and at six months. Significant reduction in the Pictorial Blood Loss Assessment Chart (PBAC) score and increases in serum hemoglobin levels and in amenorrhea was observed within three months. However, there was no statistically significant reduction in the myoma and uterine volume. Ovarian volume, also, did not changed significantly. The use of LNG-IUS is effective in reducing menorrhagia associated with leiomyomas with improvement in hemoglobin levels and may be a simple and effective alternative to surgical treatment of leiomyoma-related abnormal uterine bleeding (AUB-L) without significant influence on the volume of leiomyoma and ovarian and uterine volume.


Asymptomatic or mildly symptomatic effort-induced myocardial ischemia: plasma beta-endorphin and effect of naloxone.
The hypothesis that endogenous opioids may be involved in reduced exercise-induced ischemic pain or in silent ischemia was tested. Fifteen male patients with coronary artery disease were tested in a randomized, double-blind crossover study. After a preliminary screening effort test they were divided into two groups: the first group of nine patients received an i.m. injection of naloxone 0.4 mg, or saline as placebo, and the second group, comprising six patients, received 4 mg naloxone or saline i.v. Effort testing was performed at weekly intervals on an ergometric bicycle, following the Bruce protocol. ECG, heart rate, blood pressure and pain perception were monitored continually. Blood was sampled through an indwelling venous catheter for beta-endorphin determination before, at the peak of, and 10-20 min following exercise. ST depression, heart rate, blood pressure and the double product were similar after naloxone and following saline administration. Beta-endorphin concentrations in plasma were significantly increased following exercise in the second group of patients. The increase in beta-endorphin concentration was larger when the patients were pretreated with naloxone (4 mg) than with placebo. However, chest pain was not significantly altered by either dose of naloxone.


Pathological prognostic factors of recurrence in early stage lung adenocarcinoma.
Histological heterogeneity is thought to be important for prognosis of lung adenocarcinoma. We investigated to determine pathological features with prognostic value for recurrence of early stage lung cancer. A total of 368 patients who underwent curative surgical resection for early stage lung adenocarcinoma between 2009 and 2012 were enrolled. Pathologic characteristics including the presence of visceral pleural invasion, micropapillary patterns, aerogenous spread, lymphovascular invasion, perineural invasion and necrosis were examined. The correlations between pathological factors and clinical outcomes were analysed to determine prognostic significance. Mean follow-up was 43.0 months (±14.56, ranging from 0.0 to 73.9 months). Three-year overall survival was 95.2% and disease-free survival was 89.8%. The recurrence rate was 9.0% (33 patients) and the mortality rate was 6.0% (22 patients). The presence of a micropapillary pattern (P < 0.002), lymphatic invasion (P < 0.000), aerogenous spread (P < 0.000), vascular invasion (P = 0.036) and necrosis (P < 0.000) were negative prognostic factors of recurrence in univariate analysis. In multivariate analysis, only aerogenous spread had prognostic value (P = 0.020). The recurrence hazard ratio for the presence of aerogenous spread was 3.2 (95% confidence interval 1.20-8.47). The presence of aerogenous spread was an independent pathological risk factor of recurrence in stage I lung adenocarcinoma. Micropapillary pattern had prognostic importance for recurrence in univariate analysis, but not in multivariate analysis.


Ectopic ACTH syndrome.
Ectopic adrenocorticotropin secretion (EAS) accounts for 10-15% of cases of Cushing's syndrome and comprises a spectrum of tumours from undetectable isolated lesions to widespread metastatic and aggressive malignancies. EAS is often associated with severe hypercortisolaemia causing hypokalaemia, diabetes, generalized infections, hypertension and psychotic reactions. Surgical resection of the primary lesion, achievable with a curative intent in about 40% of patients with EAS, is associated with complete remission in up to 80% of such cases. It is therefore mandatory to localize the source of ectopic ACTH hypersecretion in order to stage the disease and adopt optimal treatment modalities. Modern cross-sectional imaging techniques can identify the majority of the ACTH secreting lesions, either initially or at follow-up reassessment. However, in approximately 10-20% of patients with EAS, the source of ACTH hypersecretion remains occult in spite of extensive investigation and prolonged followup. In such cases, control of the hypercortisolemia can be achieved with long-term adrenolytic medication. When conditions require a prompt and definitive resolution of the hypercortisolaemia (i.e. as in pregnancy), bilateral adrenalectomy remains an alternative option. This review focuses on the clinical features, diagnostic pitfalls, management and long-term followup of the EAS based on the extensive experience of major referral centres.


Delirium as a predictor of mortality in mechanically ventilated patients in the intensive care unit.
In the intensive care unit (ICU), delirium is a common yet underdiagnosed form of organ dysfunction, and its contribution to patient outcomes is unclear. To determine if delirium is an independent predictor of clinical outcomes, including 6-month mortality and length of stay among ICU patients receiving mechanical ventilation. Prospective cohort study enrolling 275 consecutive mechanically ventilated patients admitted to adult medical and coronary ICUs of a US university-based medical center between February 2000 and May 2001. Patients were followed up for development of delirium over 2158 ICU days using the Confusion Assessment Method for the ICU and the Richmond Agitation-Sedation Scale. Primary outcomes included 6-month mortality, overall hospital length of stay, and length of stay in the post-ICU period. Secondary outcomes were ventilator-free days and cognitive impairment at hospital discharge. Of 275 patients, 51 (18.5%) had persistent coma and died in the hospital. Among the remaining 224 patients, 183 (81.7%) developed delirium at some point during the ICU stay. Baseline demographics including age, comorbidity scores, dementia scores, activities of daily living, severity of illness, and admission diagnoses were similar between those with and without delirium (P>.05 for all). Patients who developed delirium had higher 6-month mortality rates (34% vs 15%, P =.03) and spent 10 days longer in the hospital than those who never developed delirium (P<.001). After adjusting for covariates (including age, severity of illness, comorbid conditions, coma, and use of sedatives or analgesic medications), delirium was independently associated with higher 6-month mortality (adjusted hazard ratio [HR], 3.2; 95% confidence interval [CI], 1.4-7.7; P =.008), and longer hospital stay (adjusted HR, 2.0; 95% CI, 1.4-3.0; P<.001). Delirium in the ICU was also independently associated with a longer post-ICU stay (adjusted HR, 1.6; 95% CI, 1.2-2.3; P =.009), fewer median days alive and without mechanical ventilation (19 [interquartile range, 4-23] vs 24 [19-26]; adjusted P =.03), and a higher incidence of cognitive impairment at hospital discharge (adjusted HR, 9.1; 95% CI, 2.3-35.3; P =.002). Delirium was an independent predictor of higher 6-month mortality and longer hospital stay even after adjusting for relevant covariates including coma, sedatives, and analgesics in patients receiving mechanical ventilation.


Force-frequency relationship as a predictor of long-term prognosis in patients with heart diseases.
Adequate evaluation of the nature of the residual failing myocardium, as well as the severity of myocardial injury, is important for managing patients with heart failure. The aim of this study was to investigate the myocardial function and the prognosis of patients with heart diseases using the force-frequency relationship (FFR). We enrolled 76 patients with sinus rhythm who had miscellaneous heart diseases and performed incremental right atrial pacing at the time of diagnostic cardiac catheterization. The first derivatives of left ventricular pressure (dP/dt) were recorded using a micro manometer-tipped catheter during the study. To represent properties of FFR, two parameters-the peak force rate (PFR) and force gain (FG)-were estimated. PFR was defined as the heart rate at which dP/dt became maximum. FG was defined as the difference between dP/dt at PFR and dP/dt at the basal heart rate. FG decreased as the severity of left ventricular (LV) dysfunction increased (372.0 ± 110.7, 209.5 ± 29.1 and 116.3 ± 13.1 mmHg/s for normal LV function, mild LV dysfunction and severe LV dysfunction groups, P < 0.05, respectively). PFR correlated with cardiac index (r = 0.375, P = 0.001). FG correlated with LV end systolic volume index (r = -0.297, P = 0.010) and LV ejection fraction (r = 0.539, P < 0.001). Furthermore, pulmonary arterial wedge pressure [hazard ratio (HR) 1.126, P < 0.01] and FG (HR 0.992, P = 0.061) tended to be independent predictors for cardiovascular death. Analysis of FFR, especially FG, seems to be useful to evaluate the nature of the failing myocardium and the prognosis of patients with heart diseases.


Soil carbon sequestration impacts on global climate change and food security.
The carbon sink capacity of the world's agricultural and degraded soils is 50 to 66% of the historic carbon loss of 42 to 78 gigatons of carbon. The rate of soil organic carbon sequestration with adoption of recommended technologies depends on soil texture and structure, rainfall, temperature, farming system, and soil management. Strategies to increase the soil carbon pool include soil restoration and woodland regeneration, no-till farming, cover crops, nutrient management, manuring and sludge application, improved grazing, water conservation and harvesting, efficient irrigation, agroforestry practices, and growing energy crops on spare lands. An increase of 1 ton of soil carbon pool of degraded cropland soils may increase crop yield by 20 to 40 kilograms per hectare (kg/ha) for wheat, 10 to 20 kg/ha for maize, and 0.5 to 1 kg/ha for cowpeas. As well as enhancing food security, carbon sequestration has the potential to offset fossil fuel emissions by 0.4 to 1.2 gigatons of carbon per year, or 5 to 15% of the global fossil-fuel emissions.


Thioacetamide-induced liver regeneration involves the expression of cyclooxygenase 2 and nitric oxide synthase 2 in hepatocytes.
A regeneration process intended to restore organ function follows liver hepatotoxicity induced by a necrogenic dose of thioacetamide (TAM). The expression of genes related to inflammation such as nitric oxide synthase-2 (NOS-2) and cyclooxygenase-2 (COX-2) has been analyzed in the course of the regenerative response, using NOS-2 KO mice or animals treated with selective inhibitors of COX-2. All animals lacking both activities survived to the hepatotoxic administration. However, animals deficient for NOS-2 exhibited more severe organ damage in view of the levels of hepatic serum markers of function, as well as an attenuated activation of NF-kappaB. The levels of C/EBPs were determined as markers of hepatocyte de-differentiation and regeneration, and the expression of COX-2 in TAM treated animals was concomitant with a decrease in C/EBP-alpha level. Analysis of cyclin D1, E and PCNA correlated with hepatocytes entering into the S phase of cell cycle by the effect of TAM. These data indicate that hepatocytes from TAM-treated mice express NOS-2 and COX-2 proteins and initiate the regeneration process that follows acute liver injury. However, the absence of NO delays hepatocyte regeneration, whereas COX-2-inhibition appears to decrease liver damage.


Regional blood-to-tissue transport in ethylnitrosourea-induced brain tumors.
Regional blood-to-tissue transport, expressed as a unidirectional transfer rate constant (K), was measured in experimental brain tumors using alpha-aminoisobutyric acid (AIB) labeled with carbon 14 and quantitative autoradiography. A total of sixteen oligodendrogliomas, four mixed gliomas, three astrocytomas, two diffuse gliomatosis, one anaplastic astrocytoma, one ependymoma and four malignant schwannomas were studied in 9 rats. The mean Ks for all glioma classifications were similar, averaging 2.6 +/- 0.4 (standard error of the mean) ml . kg-1 . min-1, and were only slightly higher than those for nontumorous parietal cortex (2.1 ml . kg-1 . min-1), corpus callosum (0.9 ml . kg-1 . min-1), and a comparable region of brain tissue in the contralateral hemisphere (1.3 ml . kg-1 . min-1). Values of K varied minimally in the intracerebral gliomas and were marginally correlated with tumor cell morphology in only two tumors. In some (but not all) of the larger gliomas, increased vascularity, with or without endothelial proliferation, was associated with a 3- to 15-fold increase in K. Regional K values in malignant schwannomas were highly variable (4 to 207 ml . kg-1 . min-1) and generally were not correlated with specific histological features of the tumor, except in some regions with increased vascularity. Estimates of the average fractional extraction of AIB by the intracranial gliomas and malignant schwannomas were 0.01 and 0.2, respectively; average fractional extractions for nontumorous brain were approximately 0.003.


Experimental autoallergic sialadenitis in the LEW rat. II. Target antigens are associated with cell surface and intracellular particulate fractions derived from the submandibular gland.
Experimental autoallergic sialadenitis (EAS) in the LEW rat is an autoimmune lymphocytic destruction of the submandibular gland (SMG) induced by sensitization with an SMG homogenate emulsified in adjuvant. Here we report that the antigens in the SMG homogenate involved in the induction of EAS can be localized to both cell-surface and intracellular particulate fractions. Differential centrifugation procedures were used to isolate 10,000g, 25,000g, 40,000g, and 100,000g particulate fractions from the SMG of LEW or WF rats. The particulate SMG fractions were used to sensitize female LEW rats for EAS induction. Since the protein concentrations of the fractions varied as a percentage of their composition in the whole homogenate, additional experiments were performed using equivalent protein concentrations for sensitization. Two weeks after sensitization, the SMGs of the sensitized animals were recovered and processed for histologic examination. Samples of the SMG fractions used for sensitization were also examined by electron microscopy. The 25,000g and 100,000g fractions consistently induced extensive mononuclear cell infiltrates and exocrine gland destruction in the SMGs while the 10,000g and 40,000g fractions caused infrequent and minimal inflammatory cell infiltrates in the glands. These data, combined with the electron microscopic analysis of the fractions, suggest that the target antigens in EAS reside on particulate fractions from the SMG that have the characteristics of the cell surface (25,000g) and microsomes (100,000g).


Investigating mechanical behaviour at a core-sheath interface in peripheral nerve.
As peripheral nerves bend and stretch, internal elements need to move in relation to each other. However, the way in which intraneural components interact is poorly understood. Previous work identified a distinct core and sheath in the rat sciatic nerve and provides a useful model with which to investigate this interaction. Here we have focused on identifying the mechanical and anatomical characteristics of the interface between core and sheath. Nerve samples, 15 and 20 mm long, of rat sciatic nerves were harvested and placed in a purpose-built jig, and a tensile testing machine was used to pull core from sheath. Mechanical tests of specimens in which core had been previously pulled from sheath by 25% of its initial length achieved a mean pull-out force approximately six times smaller than that achieved using intact controls. These results are consistent with the proposal that core-sheath interactions involve physical connections rather than a viscous fluid interface. Anatomical features of this interface were characterised using transmission electron microscopy. It appeared that sheath was derived from epineurium and most of the perineurium, whilst core consisted of endoneurium and a small proportion of the perineurium: the plane of cleavage appeared to involve the innermost perineurial cell layer.


Iron-Catalyzed Alkylation of Nitriles with Alcohols.
A general, efficient iron-catalyzed α-alkylation of nitriles with primary alcohols through a hydrogen-borrowing pathway has been developed, allowing a wide variety of alkylated nitriles to be readily accessible. Detailed mechanistic studies suggest that the reaction proceeds via an olefin intermediate with the turnover rate limited by the hydrogenation of the olefin with an iron hydride. Apart from participating in the alkylation, the nitrile is found to play an important role in promoting the formation of and stabilizing the active catalytic species.


Clinical and ultrasound features of segmental testicular infarction: six-year experience from a single centre.
The purpose was to analyse the aetiology and ultrasound appearances of segmental testicular infarction. Patients with focal testicular lesions underwent colour Doppler high frequency ultrasound. Segmental testicular infarction was defined as any focal area of altered reflectivity, with or without focal enlargement with absent or diminished colour Doppler flow, proven on histology or on follow-up exclusion of lesion progression. Patients were reviewed to document lesion shape, position, border definition, reflectivity and vascularity and correlated to presenting clinical symptoms and signs. Over a 6-year period 24 patients were defined as having segmental testicular infarction; median age was 37 years (range 16-82 years). All presented with a sudden onset of testicular pain. Of the patients, 14/24 (58.3%) had scrotal inflammatory disease, 5/24 (20.8%) had evidence of spermatic cord torsion, and three patients were termed idiopathic; 12/24 (50.0%) were of low reflectivity, 11/24 (45.8%) of mixed reflectivity, one of high reflectivity, 11/24 (45.8%) were wedge shaped, and 13/24 (54.2%) were round shaped. Of the patients, 8/24 (33.3%) demonstrated a mass effect, all with round-shaped lesions and with underlying epididymo-orchitis in seven. Absent colour Doppler flow was demonstrated in 20/24 (83.3%). Histology confirmed infarction in 8/24 (33.3%), and 12/24 (50.0%) had follow-up examinations without progression of the lesions. Segmental testicular infarction has characteristic ultrasound features, not always wedge-shaped, with reduced or absent vascularity of key importance. Awareness of the ultrasound features will allow for conservative management and avoid unnecessary orchidectomy.


Structural and conformational analysis of two native procyanidin trimers.
The structure and conformation of two native procyanidin trimers in water have been determined using 2D NMR and molecular mechanics. The results show the existence of four rotameric forms, one of which is predominant (60 to 80%). These four rotamers are shown to be in slow to intermediate exchange on the NMR timescale. Both trimers, whose structures vary owing to a different substitution of one carbon atom, adopt conformations in which stacking between different phenolic rings is favored.


Case report 805: Synovial sarcoma, epithelial hyperplasia in the humeral air sacs, and formation of medullary bone.
In summary, we have reported a most interesting case of synovial sarcoma, epithelial hyperplasia in the air sacs, and formation of medullary bone in the left humerus of a 5-year-old female white pigeon. The tumor showed aggressive features radiologically and caused dysfunction of the left wing. The histologic findings and immunohistochemical reactions in this report were identical in many respects to the manifestation of synovial sarcoma described in human beings and dogs. Formation of medullary bone in female birds during the reproductive phase and hyperplasia of epithelia in the air sacs were also discussed.


Short-term effects of continuous positive airway pressure on sex hormones in men and women with sleep apnoea syndrome.
Patients with sleep apnoea syndrome (SAS) suffer from symptoms of hypogonadism. Besides surgical interventions, in some cases, the standard care of SAS for most patients is continuous positive airway pressure (CPAP). Studies focusing on the long-term effects of CPAP on testosterone levels revealed conflicting results. None of the studies included female patients with SAS. The aim of our study was to analyse and compare sex hormone levels in saliva before and after a night without and with CPAP in women and men with SAS. The results were negative. One night with CPAP did not affect the dynamics of sex hormones, neither in men nor in women. Future studies should focus on long-term effects of CPAP in both genders.


A Consensus Definition and Classification System of Oncoplastic Surgery Developed by the American Society of Breast Surgeons.
Several definitions of oncoplastic surgery have been reported in the literature. In an effort to facilitate communication regarding oncoplastic surgery to patients, trainees, and among colleagues, the American Society of Breast Surgeons (ASBrS) aimed to create a consensus definition and classification system for oncoplastic surgery. We performed a comprehensive literature search for oncoplastic surgery definitions using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Following this, a consensus definition and classification system was created by the ASBrS. Overall, 30 articles defining oncoplastic surgery were identified, with several articles contradicting each other. The ASBrS definition for oncoplastic surgery defines this set of breast-conserving operations using volume displacement and volume replacement principles as: "Breast conservation surgery incorporating an oncologic partial mastectomy with ipsilateral defect repair using volume displacement or volume replacement techniques with contralateral symmetry surgery as appropriate". Volume displacement is defined as closing the lumpectomy defect and redistributing the resection volume over the preserved breast, and is divided into two levels: level 1 (< 20%) and level 2 (20-50%). Volume replacement includes those situations when volume is added using flaps or implants to correct the partial mastectomy defect. The ASBrS oncoplastic surgery definition and classification system provides language to facilitate discussion and teaching of oncoplastic surgery among breast surgeons, trainees, and patients.


Direct analysis and identification of Helicobacter and Campylobacter species by MALDI-TOF mass spectrometry.
Campylobacter jejuni, Campylobacter fetus, and Campylobacter coli were compared with Helicobacter pylori and Helicobacter mustelae by direct analysis of individual cultured colonies in 50% methanol-water with a matrix-assisted laser desorption/ionization time-of-flight mass spectrometer (MALDI-TOF MS). H. pylori and Campylobacter species from blood agar culture produced unique, complex spectra with over 25 different ions in mass/charge (m/z) range from 2,000 to 62,000. A biomarker for H. pylori was centered around m/z 58,268, and H. mustelae was distinguished from H. pylori by its ions at m/z 49,608 and 57,231. Campylobacters could be distinguished from Helicobacters by their lack of ions around m/z 58,000 and 61,000 as well as distinguishing biomarkers of lower m/z: 10,074 and 25,478 for C. coli; m/z 10,285 and 12,901 for C. jejuni; m/z 10,726 and 11,289 for C. fetus. MALDI-TOF MS is a rapid and direct method for detection of these potentially pathogenic bacteria from culture.


Methanofollis aquaemaris sp. nov., a methanogen isolated from an aquaculture fish pond.
A novel methanogen, designated strain N2F9704T, was isolated from an aquaculture fish pond near Wang-gong, Taiwan. The cells were irregular cocci, non-motile, 1.2-2.0 microm in diameter and stained gram-negative. Cells of strain N2F9704T lysed easily by SDS treatment (0.1 g l(-1)) and the S-layer protein had an Mr of 137000. The catabolic substrates used included formate and H2+CO2, but not acetate, methanol, trimethylamine or secondary alcohols. The optimal growth parameters for strain N2F9704T were pH 6.5, 37 degrees C with 0.5% NaCl. Trace amounts of tungstate not only promoted growth but also extended the range of growth conditions. Analysis of the 16S rDNA sequence revealed a phylogenetic relationship to Methanofollis species and the name Methanofollis aquaemaris sp. nov. is therefore proposed for strain N2F9704T (= OCM 746T = CCRC 16166T). Additionally, the strain was infected with a novel coccus-shaped, enveloped virus with a diameter of 200 nm.


A randomized multicenter study comparing the efficacy and bleeding pattern of a single-rod (Implanon) and a six-capsule (Norplant) hormonal contraceptive implant.
To compare the contraceptive efficacy, tolerability, and bleeding patterns, 200 healthy female volunteers received, in an open, comparative, randomized, multicenter study in China, either a single-rod (Implanon) or a six-capsule (Norplant) contraceptive implant for 2 years with an optional extension of up to 4 years. Women were exposed to Implanon for 341.6 woman-years and Norplant for 329.1 woman-years. There were no pregnancies during the study. Per 90-day reference period, the median number of bleeding/spotting days with Implanon decreased from 33.5 in the first period to 19.0-21.5 days in the last year. Similarly, with Norplant, the median number of bleeding/spotting days decreased from 34.5 to 18.0-23.0 days, respectively. The number of bleeding/spotting episodes during year 1 was 2.0 per 90-day reference period with Implanon and 3.0 per period with Norplant (p < 0.05 for periods 1-4). For the remaining 90-day periods, there was no statistical difference between the two groups. In general, there was less frequent bleeding with Implanon compared with Norplant, whereas the incidences of amenorrhea and infrequent bleeding were higher with Implanon than with Norplant. The mean overall incidence of prolonged bleeding fell markedly during the study, from 66.0% in reference period 1 to 27.3% in period 16 with Implanon and from 69.0% to 21.7% with Norplant, respectively. The most common adverse events were related to disturbed bleeding patterns, which were also the major reasons for discontinuation (Implanon n = 8; Norplant n = 14). Normal menses returned in almost all subjects within 3 months after removal of the implants. Implanon was inserted in a mean time of 0.61 min and Norplant in 3.90 min (p < 0.001). Similarly, the mean time required to remove the implant was significantly shorter for Implanon than for Norplant (2.18 min vs 11.25 min, p < 0.001). The maximum time required for removal of the implant was 10 min for the Implanon group and 60 min for the Norplant group. In both groups, blood pressure and hemoglobin were not affected, whereas body weight tended to increase. It can be concluded that both contraceptive systems demonstrated excellent contraceptive efficacy and were well tolerated. Compared with Norplant, there was less frequent bleeding with Implanon, whereas the incidence of infrequent bleeding and amenorrhea was higher. Implanon was significantly quicker to insert and to remove than was the multiple capsule system.


Redistribution of skin blood flow during leg dependency in peripheral arterial occlusive disease.
A disturbed autoregulation of cutaneous blood flow in legs with peripheral arterial occlusive disease (PAOD) has previously been demonstrated for circumscribed skin areas. In the present study, posturally-induced changes of skin perfusion distribution along ischaemic limbs were investigated topographically in 35 PAOD patients by means of fluorescein perfusography. Among the 68 legs studied, 7 had patent arteries and 61 could be assigned to FONTAINE stages I to IV. Limbs with peripheral skin lesions (stage IV) were further differentiated according to either healing (stage IV+) or non-healing (stage IV-) on conservative treatment. Sitting-up always led to prolonged calf as well as foot fluorescein appearance times (AT) except for legs in stage III or IV- disease. In the latter two groups, decreased sitting as compared to supine AT foot-to-calf ratios indicated a relative shift of dye delivery from proximal towards distal skin regions during posture. In contrast, this measure of blood flow redistribution did not change in the other groups. The redirection of fluorescein influx was significantly correlated with the systolic arterial pressure ankle-to-arm ratios. In conclusion, besides small perfusion pressure increases or passive microvessel distension, a shift of the peripheral resistance ratios may contribute to the improved blood supply of ischaemic skin regions during leg dependency. An arteriolar vasoparalysis does not regularly exist in limbs with skin lesions not primarily originating from ischaemia (stage IV+).


Evaluation of the E+V video image analysis system as a predictor of pork carcass meat yield.
This study was conducted to assess the ability of the VCS2001 (E+V, Oranienburg, Germany) video image analysis system to predict pork carcass composition. Pork carcasses (n = 278) were selected from a commercial packing plant to differ in weight, Fat-O-Meater (FOM) predicted percentage lean, and gender. Carcasses were imaged three times with the VCS2001, chilled overnight, and then sequentially fabricated into boneless subprimals. The VCS2001 accurately predicted the weight of total saleable product (R2 = 0.88, root mean square error [RMSE] = 1.84) and fat-corrected lean (R2 = 0.92, RMSE = 1.66), but autocorrelation existed between dependent and independent variables. The VCS2001 was acceptably accurate and precise in predicting weights of bone-in ham (R2 = 0.83, RMSE = 0.80), bone-in loin (R2 = 0.74, RMSE = 1.17), loin lean (R2 = 0.77, RMSE = 0.82), belly (R2 = 0.78, RMSE = 0.94), sparerib (R2 = 0.55, RMSE = 0.28), and boneless shoulder (R2 = 0.73, RMSE = 0.79). Weights were more accurately predicted than yields (as a percentage of hot carcass weight) of total saleable product (R2 = 0.47, RMSE = 1.97) or total fat-corrected lean (R2 = 0.44, RMSE = 1.89) using VCS2002, and it did not accurately predict percentages of bone-in ham (R2 = 0.45, RMSE = 1.13), ham lean (R2 = 0.32, RMSE = 1.46), bone-in loin (R2 = 0.29, RMSE = 1.36), loin lean (R2 = 0.56, RMSE = 0.90), belly (R2 = 0.43, RMSE = 1.08), sparerib (R2 = 0.08, RMSE = 0.32), or boneless shoulder (R2 = 0.30, RMSE = 0.88). New prediction models and equations were developed using VCS2001 output variables plus hot carcass weight to predict weight of total saleable product (R2 = 0.89, RMSE = 1.72) and fat-corrected lean (R2 = 0.93, RMSE = 1.55) with very minimal increases in accuracy and precision over that achieved using E+V-programmed models and equations. Use of new prediction models and equations marginally improved accuracy and precision of estimations of total saleable product yield (R2 = 0.56, RMSE = 1.81) and fat-corrected lean yield (R2 = 0.57, RMSE = 1.67) over that achieved using E+V-programmed models and equations. The VCS2001 was not able to predict pork carcass composition more accurately than existing technology; therefore, further development is needed to assure commercial viability of this instrument.


Enantioseparation of tartaric acid by ligand-exchange capillary electrophoresis using contactless conductivity detection.
A method for the determination of tartaric acid enantiomers using CE with contactless conductivity detection has been developed. Cu(II) as a central metal ion together with L-hydroxyproline were used as a chiral selector, the BGE was composed of 7 mM CuCl2, 14 mM trans-4-hydroxy-L-proline, and 100 mM ε-aminocaproic acid; the pH was adjusted to 5 by hydrochloric acid. Separation with a resolution of 1.9 was achieved in 9 min in a polyacrylamide-coated capillary to suppress the EOF. Various counterions of the BGE were studied, and migration order reversal was achieved when switching from ε-aminocaproic acid to L-histidine. With detection limits of about 20 μM, the method was applied to the analysis of wine and grape samples; only L-tartaric acid was found.


Epilepsy surgery in a pediatric population: a retrospective study of 129 children from a tertiary care hospital in a developing country along with assessment of quality of life.
To assess the outcome of a pediatric population operated for drug-resistant epilepsy from a large tertiary care center in India. Retrospectively: quality of life (QOL); prospectively: preoperative assessment included interictal EEG, MRI (as per epilepsy protocol), video-EEG. Ictal SPECT (with subtraction) and PET were performed when required. QOL scores were assessed using the HASS or SSQ for seizure severity, Quality of Life in Childhood Epilepsy (QOLCE) for QOL, and Child Behavior Check List (CBCL) for behavior. 142 were operated from January 2000 to June 2011 by the senior author. 118 patients with at least 1 year of follow-up were included in the study. Mean age at surgery was 9.8 ± 4.3 years. In addition, 40 patients underwent QOL assessment prospectively both before and after surgery. Mean duration of epilepsy was 5.3 ± 3.3 years. A class I outcome (Engel's) was seen in 79.5% patients, class II in 8.6%, class III in 10.7%, and class IV in 1 patient. As per surgical procedures, class I outcome in patients who underwent temporal resection, hemispherotomy and extratemporal resection was 76, 87 and 72%, respectively. QOL scores correlated with duration of seizures, epileptic encephalopathy and outcome of surgery, but not with side of surgery, age and sex. This study, the largest reported from India, has demonstrated satisfactory results for epilepsy surgery in children.


Angiotensin II stimulates extracellular signal-regulated kinase activity in intact pressurized rat mesenteric resistance arteries.
The activation of extracellular signal-regulated kinases 1/2 (ERK1/2) was assessed in isolated rat mesenteric resistance arteries (200-micrometer diameter) in a pressure myograph and stimulated for 5 minutes by angiotensin II (Ang II, 0.1 micromol/L) with a pressure of 70 mm Hg. ERK1/2 activity was measured by using an in-gel assay, and ERK1/2 phosphorylation was measured by Western blot analysis with use of a phospho-specific ERK1/2 antibody. Ang II (0.1 micromol/L) induced contraction (28% of phenylephrine contraction, 10 micromol/L). ERK kinase inhibitor PD98059 (10 micromol/L) attenuated this contraction by 36% but not that to phenylephrine or K(+) (60 mmol/L). In unpressurized arteries, Ang II increased ERK1/2 activity by 26%, and pressure (70 mm Hg) itself increased ERK1/2 activity by 72%. Ang II and pressure together acted synergistically, increasing ERK1/2 activity by 264%. Thus, in pressurized vessels, Ang II (0.1 micromol/L) increased ERK1/2 activity by 112%, calculated as [(364/172)-1]x100, which was confirmed by a measured 72% increase in ERK1/2 phosphorylation. Ang II type 1 receptor blockade by candesartan (10 micromol/L) abolished the Ang II-induced increase in ERK1/2 activity, but Ang II type 2 receptor blockade (PD123319, 10 micromol/L) did not. The Ang II-induced increase in ERK1/2 activity was inhibited by protein kinase C inhibitors Ro-31-8220 (1 micromol/L) and Go-6976 (300 nmol/L) and tyrosine kinase inhibitors genistein (1 micromol/L, general) and herbimycin A (1 micromol/L, c-Src family). The present findings show for the first time in intact resistance arteries that ERK1/2 activation is rapidly regulated by Ang II, is synergistic with pressure, and is involved in contraction. The ERK1/2 signaling pathway apparently includes upstream protein kinase C and c-Src.


11β-HSD1 in Human Fetal Membranes as a Potential Therapeutic Target for Preterm Birth.
Human parturition is a complex process involving interactions between the myometrium and signals derived from the placenta, fetal membranes, and fetus. Signals originating from fetal membranes are crucial components that trigger parturition, which is clearly illustrated by the labor-initiating consequence of membrane rupture. It has been recognized for a long time that among fetal tissues in late gestation the fetal membranes possess the highest capacity for cortisol regeneration by 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1). However, the exact role of this unique feature remains a mystery. Accumulating evidence indicates that this extra-adrenal source of cortisol may serve as an upstream signal for critical events in human parturition, including enhanced prostaglandin and estrogen synthesis as well as extracellular matrix remodeling. This may explain why such high capacity for cortisol regeneration develops in human fetal membranes at late gestation. Therefore, inhibition of 11β-HSD1 may provide a potential therapeutic target for prevention of preterm birth. This review summarizes the current understanding of the functional role of cortisol regeneration by 11β-HSD1 in human fetal membranes.


[Metabolism of ATP in rat tissues under different experimental states].
The content and incorporation intensity of tritium from methionine CH33-groups as well as ATP phosphorus renewal of the skeletal muscles, liver and brain were studied in albino rats as effected by proserin, nicotinic acid and the vagus cutting. It is established that the organs and tissues with a high metabolic activity of ATP are characterized by a higher level of its renewal of ATP. Proserin and the vagus cutting are most likely to affect the renewal of ATP through choline metabolism. Nicotinic acid may affect the renewal of ATP through pyridine nucleotides in the process of oxidative phosphorylation.


New Mechanism of Amyloid Fibril Formation.
Polymorphism is a specific feature of the amyloid structures. We have studied the amyloid structures and the process of their formation using the synthetic and recombinant preparations of Aβ peptides and their three fragments. The fibrils of different morphology were obtained for these peptides. We suppose that fibril formation by Aβ peptides and their fragments proceeds according to the simplified scheme: destabilized monomer → ring-like oligomer → mature fibril that consists of ringlike oligomers. We are the first who did 2D reconstruction of amyloid fibrils provided that just a ringlike oligomer is the main building block in fibril of any morphology, like a cell in an organism. Taking this into account it is easy to explain the polymorphism of fibrils as well as the splitting of mature fibrils under different external actions, the branching and inhomogeneity of fibril diameters. Identification of regions in the protein chains that form the backbone of amyloid fibril is a direction in the investigation of amyloid formation. It has been demonstrated for Aβ(1-42) peptide and its fragments that their complete structure is inaccessible for the action of proteases, which is an evidence of different ways of association of ring-like oligomers with the formation of fibrils. Based on the electron microscopy and mass spectrometry data, we have proposed a molecular model of the fibril formed by both Aβ peptide and its fragments. In connection with this, the unified way of formation of fibrils by oligomers, which we have discovered, could facilitate the development of relevant fields of medicine of common action.


Hospitalizations of Brazilian children under fiver years old: a systematic review.
to describe the causes of hospitalization of Brazilian children under five years old. this is a systematic review of articles published from 2008 to 2015, searched in the databases Medline and LILACS; selected studies were critically analyzed through a validated instrument. eleven articles were included, four of them are ecological and seven are cross-sectional studies; respiratory diseases (n=5), parasitic infections (n=4) and perinatal diseases (n=2) were the main causes for hospitalizations in the reviwed articles; in the studies that analyzed the sensitive conditions, pneumonia (n=6), gastroenteritis (n=5), and asthma (n=5) were the mais causes pointed out. respiratory, parasitic and perinatal diseases revealed to be the main causes for hospitalizations in Brazilian children; pneumonia, gastroenteritis, and asthma constitute the most important of hospitalizations, treatable in the ambulatory health care.


Advances in understanding the cyanobacterial CO2-concentrating-mechanism (CCM): functional components, Ci transporters, diversity, genetic regulation and prospects for engineering into plants.
Cyanobacteria have evolved a significant environmental adaptation, known as a CO(2)-concentrating-mechanism (CCM), that vastly improves photosynthetic performance and survival under limiting CO(2) concentrations. The CCM functions to transport and accumulate inorganic carbon actively (Ci; HCO(3)(-), and CO(2)) within the cell where the Ci pool is utilized to provide elevated CO(2) concentrations around the primary CO(2)-fixing enzyme, ribulose bisphosphate carboxylase-oxygenase (Rubisco). In cyanobacteria, Rubisco is encapsulated in unique micro-compartments known as carboxysomes. Cyanobacteria can possess up to five distinct transport systems for Ci uptake. Through database analysis of some 33 complete genomic DNA sequences for cyanobacteria it is evident that considerable diversity exists in the composition of transporters employed, although in many species this diversity is yet to be confirmed by comparative phenomics. In addition, two types of carboxysomes are known within the cyanobacteria that have apparently arisen by parallel evolution, and considerable progress has been made towards understanding the proteins responsible for carboxysome assembly and function. Progress has also been made towards identifying the primary signal for the induction of the subset of CCM genes known as CO(2)-responsive genes, and transcriptional regulators CcmR and CmpR have been shown to regulate these genes. Finally, some prospects for introducing cyanobacterial CCM components into higher plants are considered, with the objective of engineering plants that make more efficient use of water and nitrogen.


Large-scale blood substitute production using a microfluidizer.
Microfluidization has been tested as a way to disperse phospholipids in aqueous hemoglobin solutions. Spherical and stable liposomes of 2 to 3 microns were obtained. Lipid incorporation (up to 85%) and hemoglobin encapsulation (up to 15%) in liposomes have been improved with respect to previous investigations. However, results show that a more efficient dispersion system using lower concentrations of lipid is required to obtain a high liposome hemoglobin concentration (limited actually to 150 g/l) and an economically and biologically suitable process for artificial blood production at large scale.


Treatment of injectable soft tissue filler complications.
Increasing use of dermal fillers, especially with the U.S. introduction of long-term and permanent fillers, is expected to increase the number of complications seen after treatment with these materials. To provide physicians with an overview for treatment of dermal filler complications. Complications of dermal filler use can be treated successfully based on a firm understanding of the mechanisms and limitations of filler action and wound healing. Complications can be classified as immediate, early, or delayed onset; available treatment options are presented. Short- and long-term dermal fillers are increasingly becoming popular treatment options for signs of facial aging. Complications, although not common, can be treated effectively and excellent outcomes achieved.


Pharmacokinetics of rimantadine hydrochloride in patients with chronic liver disease.
Six patients with chronic liver disease and six sex-, age (+/- 5 years)-, and weight (+/- 5 kg)-matched healthy control subjects received a single dose of two 100 mg tablets rimantadine HCl. Eight additional patients with chronic liver disease who were not matched to healthy subjects received a single dose of two 100 mg tablets of rimantadine HCl. Blood and urine samples were collected and rimantadine concentrations were determined by a GCMS method. The values for maximum plasma concentration, AUC, elimination half-life, and renal clearance were not significantly different between patients and control subjects, independent of the statistical analyses (parametric and nonparametric) used. The mean apparent elimination half-life, volume of distribution, and total clearance in the matched patients with liver disease were 32 hours, 24 L/kg, and 676 ml/min, respectively. Renal clearance and the amount excreted in the urine unchanged were 63 ml/min and 10%, respectively. In conclusion, rimantadine pharmacokinetics were not appreciably altered in patients with less severe chronic liver disease.


Purification and characterization of native conventional kinesin, HSET, and CENP-E from mitotic hela cells.
We have developed a strategy for the purification of native microtubule motor proteins from mitotic HeLa cells and describe here the purification and characterization of human conventional kinesin and two human kinesin-related proteins, HSET and CENP-E. We found that the 120-kDa HeLa cell conventional kinesin is an active motor that induces microtubule gliding at approximately 30 microm/min at room temperature. This active form of HeLa cell kinesin does not contain light chains, although light chains were detected in other fractions. HSET, a member of the C-terminal kinesin subfamily, was also purified in native form for the first time, and the protein migrates as a single band at approximately 75 kDa. The purified HSET is an active motor that induces microtubule gliding at a rate of approximately 5 microm/min, and microtubules glide for an average of 3 microm before ceasing movement. Finally, we purified native CENP-E, a kinesin-related protein that has been implicated in chromosome congression during mitosis, and we found that this form of CENP-E does not induce microtubule gliding but is able to bind to microtubules.


[Apoptosis increased by bcl-2 antisense ODN in MCF-7 cell line].
To study the effects of bcl-2 antisense oligonucleotides (ODN) on the expression of bcl-2 and apoptosis in MCF-7 cell line. Artificially synthesized bcl-2 specific antisense OND was introduced into MCF-7 cells by gene pulser electroprotocol. Fluorescence microscope, electron microscope, immunocytochemical staining assay, and FCM were used to detect the effects on cell apoptosis, expressional level of bcl-2 protein and cell cycle after transfecting bcl-2 antisense ODN. The number of apoptotic cells was increased and expression of bcl-2 protein was declined (P < 0.05). FCM showed that the number of G(0)-G(1) phase cells was decreased and the number of G(2)-M, S phase cells were increased. The effective transient expression of bcl-2 antisense ODN can be obtained by gene pulser electroprotocol in MCF-7 cell, the function of bcl-2 gene was declined and the number of apoptotic cells was increased after transfecting bcl-2 antisense ODN. bcl-2 may be used as an useful target in tumor research.


The transition to regional networks. Changes in reimbursement and approaches to care favor cooperative arrangements among providers.
As costs escalate and the delivery system becomes more fragmented, organizations throughout the United States have begun to call for basic reform of the healthcare system. Several national organizations, including the American Hospital Association and the Catholic Health Association, have presented working proposals advocating coordinated regional healthcare delivery systems. The proposed networks would provide a full continuum of services from prevention through aftercare and long-term care, and from primary through tertiary care. In the past few years, providers themselves have begun to see the value of cooperative efforts. Collaborative ventures such as group purchasing and sharing mobile equipment have increased as hospitals look for ways to reduce costs and control overhead. Mergers and affiliations are also becoming more common. As they develop, different networks will allow for various kinds of interrelationships among components. In general, these systems will provide high-volume, low-cost services at a number of sites and low-volume, high-cost services at a central location. Secondary and tertiary campuses will focus increasingly on specialty care, and as volume increases at primary campuses, secondary and tertiary organizations will establish more primary affiliations. To make the transition from a competitive to a cooperative healthcare delivery system, providers will have to reexamine their mission and values and, in many cases, refocus their vision of the future.


Type 2 diabetes is not a risk factor for asymptomatic ischemic brain lesion--the Funagata study.
The purpose of this study is to clarify whether type 2 diabetes (DM) is a risk factor for asymptomatic (silent) ischemic brain lesion, which is controversial at present. The subjects (n=187), who showed normal results on both neurological and neuropsychological examinations, underwent a 75-g OGTT and were examined by brain MRI on T1-weighted, T2-weighted, and FLAIR (fluid-attenuated inversion recovery) images. Their brain MRIs were evaluated quantitatively with the ischemia rating scale defined here. The subjects were grouped based on their glucose tolerance: normal glucose tolerance (NGT) (n=48), impaired glucose tolerance (IGT) (n=62), and DM (n=65). The subjects with DM were further divided based on their duration of illness: 20 with short duration (short DM: 1.3+0.8 years) and 45 with long duration (long DM; 8.9+/-5.4 years). Ages were matched among the groups. The percentages of individuals with asymptomatic ischemic brain lesion were 81% in NGT, 74% in IGT, 65% in short DM, and 78% in long DM. No significant difference was observed among the groups in terms of the percentage. Namely, even in individuals with a long history of DM without clinical stroke, the prevalence of asymptomatic ischemic brain lesion was not different from that of the other groups. Multiple regression and multiple logistic regression analyses showed that age and hypertension were significant independent risk factors for asymptomatic ischemic brain lesion, whereas hypercholesterolemia, smoking, and glucose intolerance, including IGT, short DM and long DM, were not. DM is not a risk factor for asymptomatic ischemic brain lesion.


Macrolactin W, a new antibacterial macrolide from a marine Bacillus sp.
Bioactivity-guided isolation for the new/novel metabolites from the EtOAc extract obtained from the culture broth of a marine Bacillus sp. 09ID194 followed by chromatographic fractionations and subsequently HPLC purifications led to the isolation of two known macrolides, macrolactins A (1) and Q (2), together with a new glycosylated marcrolide, macrolactin W (3). The chemical structures of compounds 1-3 were assigned based on extensive MS and NMR spectral data analysis and literature review. Compound 3 showed potent antibacterial activity against both Gram-positive and Gram-negative pathogenic bacteria.


Elevated expression of KiSS-1 in placenta of preeclampsia and its effect on trophoblast.
The expression of KiSS-1, MMP-9 and MMP-2 mRNAs and proteins was studied in placentas of women with preeclampsia (PE, n=47) and women of normal pregnancy (NP; n=30). In addition, KiSS-1 mRNA expression as well as cell growth, proliferation and invasion were examined in JAR cells (human trophoblast cell line) transfected with pcDNA3-KiSS-1vector. Expression of KiSS-1 mRNA and protein was higher (p<0.05) in women with PE compared with that of NP women. In contrast, expression of MMP-9 and MMP-2 was lower (p<0.05) in PE than in NP women. KiSS-1 mRNA was detected in JAR cells successfully transfected with pcDNA3-KiSS-1 gene (JAR-K1, JAR-K2, JAR-K3). KiSS-1 mRNA was not detected in JAR cells transfected with pcDNA3 gene (JAR-P1, JAR-P2) and non-transfected JAR cells. No difference (p>0.05) was observed in cell growth among these three cell types. Invasion ability was significantly lower (p<0.01) in JAR-K1, JAR-K2 and JAR-K3 cells compared to JAR-P cells and non-transfected JAR cells. Overexpression of KiSS-1 and insufficient expression of MMP-9 and MMP-2 in placenta were demonstrated in women with PE. The data suggests that KiSS-1 gene plays an important role in inhibiting trophoblast invasion during placental development.


Induction of nuclear NF-kappa B DNA binding activity after exposure of lymphoid cells to soluble tax1 protein.
We demonstrate that purified HTLV-I Tax1 protein can be taken up by 70Z/3 lymphoid cells and localized in both the nuclear and cytoplasmic compartments. Introduction of the Tax1 protein into the growth medium of 70Z/3 cells resulted in the rapid and transient induction of NF-kappa B binding activity in the nuclear fraction. Tax1 activation of NF-kappa B was not sensitive to either staurosporin or prolonged stimulation with the phorbol ester 12-O-tetradecanoylphorbol-13-acetate, suggesting that Tax1-dependent NF-kappa B activation did not require the protein kinase C pathway. Purified Tax1 did not directly increase NF-kappa B binding activity in 70Z/3 cytoplasmic extracts, suggesting that NF-kappa B induction may require cellular factors. Western blot and competitive radioimmunoassays demonstrated that Tax1 protein was present in the tissue culture media of HTLV-I-transformed cell lines. These results show that extracellular Tax1 may regulate cellular gene expression in noninfected cells.


Recurarisation following a suxamethonium-alcuronium sequence in patients with atypical cholinesterase.
Alcuronium 10 mg was administered to maintain muscle relaxation in two patients before recovery from suxamethonium neuromuscular blockade to facilitate tracheal intubation. This sequence resulted in a markedly prolonged block which could not be antagonised adequately by neostigmine 0.05 mg/kg; initial antagonism was followed rapidly by prolonged recurarisation. Estimation of plasma cholinesterase activity revealed that the two patients were homozygous for the atypical and silent genes. respectively.


Cost, correlates and effects of malpractice litigation in family practice residency programmes in the United States.
A survey of family practice residency programme directors in the United States was undertaken to look at the impact of malpractice and malpractice insurance on residency education. Of 385 programmes 276 (71.7%) responded to the 20 question survey. The results indicated a mean rate of 0.043 claims per resident or faculty member in the previous year. One-fifth of the respondents did not report the type of malpractice insurance retained for residents and over half did not report the cost of insurance for residents. Current problems with liability were most often related to the region of the country, number of visits to the family practice centre, the number of residents, the number of faculty, the type of faculty employer and the type of resident employer. Programmes which anticipated future problems with liability were most likely to be those with current problems. The areas identified as most concerning to residents included: obstetrics, cost of malpractice insurance, difficulty obtaining coverage, and the general anxiety created by malpractice litigation.


Epilepsy: old drugs do the trick in childhood absence epilepsy.
A randomized, double-blind clinical trial that compared three widely used anticonvulsants for childhood absence epilepsy established that ethosuximide was the most appropriate first-line therapy for this condition. The study provides guidance for the treatment of this common childhood epilepsy where evidence-based recommendations have previously been lacking.


A pilot study of nalbuphine versus tramadol administered through continuous intravenous infusion for postoperative pain control in children.
Nalbuphine and tramadol are potent analgesic drugs. Our aim was to preliminarily assess and compare the efficacy and safety of nalbuphine and tramadol for postoperative analgesia in children. In a double-blind design, 24 ASA 1-3 children aged 1 to 10 years undergoing a scheduled surgical procedure were randomly allocated to receive either an intravenous bolus dose of nalbuphine 100 microg/kg immediately before the end of surgery followed by an infusion of 0.2 microg/kg/min for 72 hrs., or an intravenous bolus dose of tramadol 1000 microg/kg followed by an infusion of 2.0 microg/kg/min for 72 hrs. Postoperative pain control and drug-related adverse events were recorded. Three children who received nalbuphine required an extra bolus dose within the 12 hrs. of post-surgery versus one child in the tramadol group. A similar number of patients in both groups required an increment in the infusion rate within the 72 post-surgery hours. Sedation was observed in 2 children in the nalbuphine group and in 1 child in the tramadol group. Four children presented vomiting with tramadol and two with nalbuphine. Cardiovascular parameters remained within the normal ranges in both groups. In conclusion, the bolus/infusion regimen of tramadol evaluated in this study appears to have better postoperative analgesic efficacy than the bolus/infusion regimen of nalbuphine. These preliminary results require further confirmation by studies with a sample size enough to clearly identify differences in their efficacy as well as in the rate of adverse events secondary to the administration of each of them.


A program of screening and prompting improves short-term physician counseling of dependent and nondependent harmful drinkers.
Physicians in the general medical setting commonly encounter but rarely counsel patients with dependent or harmful drinking behaviors. We tested whether providing physicians with their patients' results on the alcohol module of the Diagnostic Interview Schedule and counseling directives would prompt them to counsel these patients. We randomly assigned 83 first-, second-, and third-year medical residents to receive or not to receive diagnostic information and counseling directives on 214 patients who reported at least one symptom of alcohol impairment as defined in the Diagnostic and Statistical Manual of Mental Disorders, Third Edition. Using binary logistic regression, we examined the effect of specific covariables on rates of physician counseling. These variables included physician information status, patient gender, and drinking disorder severity and recency. We also examined the effect of physician prompting on counseling of female patients, patients with inactive disorders, and nondependent but harmful drinkers. We determined counseling by post-visit patient interviews. Physician prompting, dependent drinking, and recent disorder activity were significant correlates of physician counseling (P < .05), while male gender was a marginally significant correlate (P = .08). Informed physicians counseled female patients, harmful but nondependent drinkers, and patients with inactive disorders more often than their uninformed colleagues, although only the last variable achieved statistical significance. Providing physicians with the results of the Diagnostic Interview Schedule and counseling directives resulted in short-term improvement in their rates of counseling patients with a history of dependent or nondependent but harmful drinking. Further research is necessary to determine long-term gains in rates of physician counseling and improvements in the course of these patients.