A return-based alternative to IRR (internal rates of return) evaluations.
A dilemma often faced by healthcare financial managers is whether to describe a potential investment project to organizational decision-makers in terms of the projects' internal rates of return (IRR) or to use the net present value (NPV) method. The IRR represents an intuitively appealing method of measuring investment value, but a number of conceptual and methodological problems associated with IRR measurement would seem to argue the use of the NPV method. Unfortunately, while the NPV measure is theoretically valid, it lacks the intuitive appeal of the IRR in communicating the value of investment alternatives. This article details an alternative method of measuring return that incorporates all the intuitive appeal of the conventional IRR, but few of the shortcoming associated with that measure.


A YAC mouse model for Huntington's disease with full-length mutant huntingtin, cytoplasmic toxicity, and selective striatal neurodegeneration.
We have produced yeast artificial chromosome (YAC) transgenic mice expressing normal (YAC18) and mutant (YAC46 and YAC72) huntingtin (htt) in a developmental and tissue-specific manner identical to that observed in Huntington's disease (HD). YAC46 and YAC72 mice show early electrophysiological abnormalities, indicating cytoplasmic dysfunction prior to observed nuclear inclusions or neurodegeneration. By 12 months of age, YAC72 mice have a selective degeneration of medium spiny neurons in the lateral striatum associated with the translocation of N-terminal htt fragments to the nucleus. Neurodegeneration can be present in the absence of macro- or microaggregates, clearly showing that aggregates are not essential to initiation of neuronal death. These mice demonstrate that initial neuronal cytoplasmic toxicity is followed by cleavage of htt, nuclear translocation of htt N-terminal fragments, and selective neurodegeneration.


Stem/progenitor cell proliferation factors FGF-2, IGF-1, and VEGF exhibit early decline during the course of aging in the hippocampus: role of astrocytes.
Dentate neurogenesis, important for learning and memory, declines dramatically by middle age. Although studies have shown that this age-related decrease can be reversed to some extent by exogenous applications of mitogenic factors, it is unclear whether one or more of these factors exhibits decline by middle age. We hypothesize that multiple stem/progenitor cell proliferation factors exhibit early decline during the course of aging in the hippocampus, and some of these declines are linked to age-related alterations in hippocampal astrocytes. We measured the concentrations of fibroblast growth factor-2 (FGF-2), insulin-like growth factor-1 (IGF-1), and vascular endothelial growth factor (VEGF) in the hippocampus of young, middle-aged, and aged F344 rats, using enzyme-linked immunosorbent assay (ELISA). In addition, we quantified the total number of FGF-2 immunopositive (FGF-2+) and glial fibrillary acidic protein immunopositive (GFAP+) cells in the dentate gyrus and the entire hippocampus. Our results provide new evidence that the concentrations of FGF-2, IGF-1, and VEGF decline considerably by middle age but remain steady between middle age and old age. Further, decreased concentrations of FGF-2 during aging are associated with decreased numbers of FGF-2+ astrocytes. Quantification of GFAP+ cells, and GFAP and FGF-2 dual immunostaining analyses, reveal that aging does not decrease the total number of astrocytes but fractions of astrocytes that express FGF-2 decline considerably by middle age. Thus, dramatically decreased dentate neurogenesis by middle age is likely linked to reduced concentrations of FGF-2, IGF-1, and VEGF in the hippocampus, as each of these factors can individually influence the proliferation of stem/progenitor cells in the dentate gyrus. Additionally, the results demonstrate that decreased FGF-2 concentration during aging is a consequence of age-related impairment in FGF-2 synthesis by astrocytes.


Hostility and doctor-patient interaction in chronic pelvic pain.
Interaction in medical consultations is of interest for many reasons and has long been thought an important variable in determining outcomes. Relatively few methods or instruments exist that attempt to access this phenomenon. The design, validation and possible application of a simple instrument to assess doctor-patient interaction are reported. Rapport and hostility may be related and we hypothesised that interaction between doctor and patient would be related in part to hostility. A simple instrument to assess doctor-patient interaction was designed based on 4 areas related to interaction and perception of 'the other'. These were the areas of communication, rapport, trust and sense of ease. The instrument was compared with an external previously validated measure of hostility. Data were obtained from 74 women attending initial and follow-up consultations for chronic pelvic pain during the course of a larger study. The instrument had acceptable reliability and a single-factor structure. Patients' assessment of the initial consultation as unsatisfactory correlated with inwardly directed hostility (Spearman correlation coefficient, r = 0.30, p = 0.011). Patients' tendency to rate the consultation worse than the doctor was correlated with inwardly directed hostility (r = 0.42, p < 0.001). Pain outcomes were not directly related to the variables studied. This instrument offers a simple method of assessing some interactional aspects of a medical consultation.


Negative hyperconjugation in phosphorus stabilized carbanions.
The electronic Fukui function is used to give qualitative electronic proof on the existence of back-bonding from the carbon lone pair toward the sigma* P-Y and P-O orbitals in phosphorus stabilized carbanions. NBO analyses are used to investigate the energetic, electronic, and structural impacts of this negative hyperconjugation interaction. The observed energetic stabilization can indeed be attributed to the electronic delocalization of the lone pair toward the antibonding orbitals. This delocalization is furthermore responsible for the shorter P-C bonds, longer P-Y (P-O) bonds, and wider Y-P-Y angles observed for the anionic compounds compared to their neutral counterparts. From the electronic NBO analysis it becomes clear that phosphorus containing functional groups are best described as sigma donor/pi acceptors.


Worsening of pre-existing TMJ dysfunction following sagittal split osteotomy: a study of three cases.
When patients seeking treatment for malocclusion also suffer from temporomandibular joint (TMJ) disorders, it is hard to predict the result of simultaneous treatment of both conditions, or to plan for its different goals, because of unpredictable changes in the relationship between the disk, the fossa and the condylar head. Prediction is harder in cases of presurgical TMJ hypomobility, especially those with adhesion in the upper TMJ compartment. Authors differ widely on the likely effect of orthognathic surgery on TMJ disorders. This paper reports three cases in which TMJ disorders worsened after treatment of malocclusion by sagittal split osteotomy. It examines how presurgical diagnosis of TMJ disorders could assist treatment planning in such cases. The results suggest that microbleeding in the upper TMJ compartment during orthognathic surgery, as well as long-term postoperative intermaxillary fixation, carries a risk of creating worse adhesion that adversely affects the outcome for patients. Therefore, preoperative diagnosis of disk position and pathological conditions in the upper TMJ compartment, as well as careful choice of method and term of postoperative fixation, are essential in planning the treatment of malocclusion with sagittal split osteotomy.


A mild copper-catalyzed aerobic oxidative thiocyanation of arylboronic acids with TMSNCS.
A facile and efficient transformation of arylboronic acids to their corresponding aryl thiocyanates has been successfully developed. Based on the CuCl-catalyzed oxidative cross-coupling reaction between arylboronic acids and trimethylsilylisothiocyanate (TMSNCS) under oxygen atmosphere, the transformation can be readily conducted at ambient temperature. The newly-developed protocol provided a competitive synthetic approach to aryl thiocyanates that can tolerate a broad range of reactive functional groups and/or strong electron-withdrawing groups.


Intimate Partner Violence and HIV Status among Ever-Married and Cohabiting Zimbabwean Women: An Examination of Partners' Traits.
This study examines the connection between intimate partner violence (IPV) and Human Immunodeficiency Virus status among married and cohabitating women in Zimbabwe using an African feminist framework. Stata 13.0 was used to analyze data from the 2010-2011 Zimbabwe Demographic and Health Survey, which used a national probability sample of households in the country of Zimbabwe. This study used logistic regression to analyze the 2,830 ever-married or cohabitating women who also answered the violence and spousal traits questionnaire as well as provided blood samples. The logistic regression revealed that women who had experienced any type of intimate partner violence (odds ratio=1.29, CI [1.00, 1.67]) or broken bones (odds ratio=2.39, CI [1.19, 4.77]) were more likely to be HIV positive; relative to those with bruises bruises (odds ratio=- .64 CI [.41, .99]) were less likely. Women with partners who are trackers (odds ratio=1.28, CI [1.04, 1.59]) were more likely to be HIV positive. Patriarchal, hypermasculist culture, shown through violence against women, contributes to the likelihood of HIV in wives and partners. A cultural shift at the highest levels may help to prevent IPV and reduce the spread of HIV.


Differential effects of amphetamines-induced neurotoxicity on appetitive and aversive Pavlovian conditioning in mice.
The abuse of substituted amphetamines such as methamphetamine (METH) and 3,4-methylenedioxymethamphetamine (MDMA/Ecstasy) can result in neurotoxicity, manifested as the depletion of dopamine (DA) and 5-hydroxytriptamine (5-HT; serotonin) axon terminal markers in humans and animal models. Human METH and MDMA users exhibit impairments in memory and executive functions, which may be a direct consequence of the neurotoxic potential of amphetamines. The objective of this study was to investigate the influence of amphetamines-induced neurotoxicity on Pavlovian learning. Using mouse models of selective DA neurotoxicity (METH; 5 mg/kg x 3), selective 5-HT neurotoxicity (fenfluramine /FEN; 25 mg/kg x 4) and dual DA and 5-HT neurotoxicity (MDMA; 15 mg/kg x 4), appetitive and aversive conditioning were investigated. Dopaminergic neurotoxicity significantly impaired METH and cocaine conditioned place preference (CPP), but had no effect on LiCl-induced conditioned place aversion (CPA). In contrast, serotonergic neurotoxicity significantly enhanced CPP, and had no effect on CPA. Dual dopaminergic/serotonergic neurotoxicity had no apparent effect on CPP; however, CPA was significantly attenuated. Postmortem analysis revealed that significantly diminished levels of DA and 5-HT markers persisted in the striatum, frontal cortex, hippocampus, and amygdala. These findings suggest that amphetamines-induced dopaminergic and serotonergic neurotoxicity exert opposing influences on the affective state produced by subsequent drug reward, while dual dopaminergic/serotonergic neurotoxicity impairs associative learning of aversive conditioning. Furthermore, results revealed that amphetamines-induced DA and 5-HT neurotoxicity modulates appetitive Pavlovian conditioning similar to other DA and 5-HT neurotoxins. Modulation of Pavlovian conditioning by amphetamines-induced neurotoxicity may be relevant to compulsive drug-seeking behavior in METH and MDMA abusers.


HPV16 infection regulates RASSF1A transcription mediated by p53.
Human papillomavirus (HPV) 16 infection and RASSF1A expression play important roles in tumor development and progression. However, the precise mechanisms underlying their concerted function in the development of reproductive system tumors still remain to be elucidated. In the present study, we showed that HPV16-E6 selectively upregulates RASSF1A expression via degradation of p53, which interacts with the RASSF1A promoter and regulates apoptosis. Overexpression of p53 triggered a decrease in endogenous RASSF1A in SiHa cells, accompanied by apoptosis. Similarly, knockdown of endogenous HPV16-E6 in SiHa cells with RNA interference (RNAi) led to downregulation of RASSF1A mediated by p53 and the subsequent induction of apoptosis. These findings collectively suggest that HPV16 infection regulates p53-mediated RASSF1A expression and suppresses apoptosis. Moreover, RASSF1A may form an element of the negative autoregulatory feedback loops that act on the HPV16 response and are involved in p53-dependent apoptosis. Our results provide novel insights into the cellular mechanism of tumor development, and present a starting point for the development of novel strategies in cancer treatment and effective diagnosis.


[Efficacy of various methods for preoperative vaginal antisepsis].
In a prospective clinical study we investigated 115 patients prior to vaginal surgical interventions to determine the antimicrobial efficacy of six different procedures for vaginal antisepsis. To sample the microorganisms we used a cotton swab moistened with a neutralising fluid. Immediately after the time of action of the antiseptic procedures (3 minutes), providone-iodine solution, applied undiluted or diluted 1:10, yielded the strongest median reduction of the vaginal flora (log RF 3.60 and 2.68, respectively). Of three detergents with antiseptic efficacy, octenidine 0.1% was the most efficient formula (log RF 2.32). After 30 minutes the log reduction factors (log RF) of almost all procedures (log RF 2.79-3.25) were in a fairly close range, excepting chlorohexidine 0.05% (log RF 2.07). Overall, the antiseptic detergents showed a marked residual effect, which was less pronounced, if at all, with providone-iodine solutions. A germ-reducing effect of povidone-iodine vaginal suppositories, applied 2 to 3 hrs prior to surgery, was not confirmed, while additional findings indicated that providone-iodine solution applied with the help of a vaginal douche yields a similarly strong germ reduction as the application by means of a ball swabs.


Nucleus-independent chemical shift analysis of the electronic states of the (CO)4, (CS)4, and (CSe)4 molecules.
NICS(1) calculations have been performed on the 8π and 10π singlet states and the 9π triplet state of (CO)4, (CS)4, and (CSe)4. The results show that transfer of electrons from the b2g σ MO into the a2u π MO decreases the NICS(1) value, indicating an increase in the diamagnetic ring current. The decreases in the calculated NICS(1) values are substantially larger in (CO)4 than in (CS)4 or (CSe)4. This finding is rationalized by the larger coefficients on the carbons in the a2u MO of (CO)4 than in the a2u MOs of (CS)4 and (CSe)4.


[Sinonasal mucosal malignant melanoma].
Mucosal melanomas are rare tumors, and primary sinonasal malignant melanomas uncommon tumors that are frequently misclassified. Differential diagnosis should rule out other sinonasal malignancies, including carcinoma, lymphoma, sarcoma, and olfactory neuroblastoma. We report two new cases of sinonasal melanoma. One involved a 68-year-old man being followed for chronic sinusitis, despite antibiotics; he presented a tumor of the right nasal cavity. The second case was that of a 77-year-old woman, referred for painful gingival swelling shown to involve osteolytic growth in the left maxillary sinus. In both cases, pathologic examination of the biopsy samples concluded that these were sinonasal malignant melanomas. Histologically, the diagnosis is very difficult because of the polymorphic features of this tumor, and immunohistochemical studies are very important. The relative inaccessibility of the mucosa to self-examination often delays diagnosis and leads to late detection and poor prognosis.


Fovea-sparing internal limiting membrane peeling versus complete internal limiting membrane peeling for myopic traction maculopathy.
To compare the outcomes of vitrectomy with fovea-sparing internal limiting membrane peeling (FSIP) and complete internal limiting membrane peeling (ILMP) for myopic traction maculopathy (MTM). A retrospective, observational study. In this study, we included 22 eyes of 21 consecutive patients who underwent vitrectomy with FSIP or ILMP for MTM and were monitored for at least 6 months. Eleven eyes were treated with FSIP, and 11, with ILMP. With FSIP, the postoperative best-corrected visual acuity (BCVA) significantly improved from 0.61 (20/82) to 0.34 (20/44; P = .009) logarithm of the minimum angle of resolution (logMAR) units. With ILMP, the postoperative BCVA improved from 0.65 (20/89) to 0.52 (20/66) logMAR units, but was not significant (P = .106). The postoperative final central foveal thickness (CFT) reduced significantly after FSIP (from 557.6 to 128.8 µm, P = .003) and ILMP (from 547.3 to 130.3 µm, P = .008). The postoperative incidence of a macular hole was 0% (0/11 eyes) with FSIP and 27.3% (3/11 eyes) with ILMP. All patients with a macular hole had foveal detachment in association with a thin fovea preoperatively. With ILMP, postoperative BCVA with a macular hole worsened by -3.5 letters; in contrast, postoperative BCVA without a macular hole improved by +10.5 letters. With FSIP, postoperative BCVA without a macular hole significantly improved by +13.5 letters (P = .009). FSIP resulted in significant improvement in MTM and prevented postoperative macular hole development.


Comparative safety and costs of transparent versus gauze wound dressings in intravenous catheterization.
The type of dressing selected for intravascular catheters may influence costs and complications. We carried out a clinical trial to compare the safety and costs of transparent and gauze dressings. We did not find differences in complication rates between transparent (34.1%) and gauze (26.5%) dressings (P = .62). The total cost per patient was $24.82 for transparent and $38.85 for gauze. The results indicate similar safety but increased cost associated with gauze dressings.


TCR gene recombination and alpha beta-gamma delta lineage divergence: productive TCR-beta rearrangement is neither exclusive nor preclusive of gamma delta cell development.
Two types of T lymphocytes can be generated intrathymically, distinguishable by either TCR-gamma delta or -alpha beta surface expression. Regulation of the intrathymic divergence of these cells is unresolved, at least in part because thymically derived gamma delta cells have rarely been studied. We used quantitative Southern blotting together with PCR-based cloning/sequencing and restriction fragment length polymorphism to analyze TCR-alpha and -beta gene recombination in thymically derived gamma delta cells. We found that TCR-beta gene recombination is a frequent occurrence in thymic gamma delta cells. Furthermore, not only do complete (V-D-J) TCR-beta gene rearrangements occur in thymic gamma delta cells, but the frequency of in-frame rearrangements is greater than would be predicted based upon random occurrence. In contrast, we show that thymically derived gamma delta cells do not make detectable rearrangements of the TCR-alpha locus. These studies clearly demarcate a point for alpha beta vs gamma delta commitment in the thymus, after TCR-beta but before TCR-alpha gene recombination. Further, while our data support gamma delta lineage commitment as a consequence of successful TCR-gamma and -delta gene rearrangement, we do not find support for a competitive model of lineage commitment, since productive TCR-beta gene rearrangement does not necessarily relegate cells to the alpha beta lineage.


The role of biliary scanning in the investigation of the surgically jaundiced patient.
The diagnostic accuracy of biliary scanning using 99mTc-pyridoxylideneglutamate has been determined in a series of 51 surgically jaundiced patients. This noninvasive technique was found to be safe, reliable and universally applicable in all instances of jaundice, regardless of the serum bilirubin value or prothrombin time. The results were found to compare favorably with those of other investigative procedures. It is suggested that the 99mTc-pyridoxylideneglutamate biliary scan is most advantageously carried out after clinical assessment and full biochemical evaluation of the patient. The scan result will indicate the next logical step in the management of the patient whether it be endoscopic retrograde cholangiopancreatography, percutaneous transhepatic cholangiography, biopsy of the liver or laparotomy.


Kruppel-like factor 2 controls T cell trafficking by activating L-selectin (CD62L) and sphingosine-1-phosphate receptor 1 transcription.
Krüppel-like factor 2 (KLF2) is a member of zinc-finger transcription factors. Based on its expression in naive and memory T cells and the activated phenotype of few T cells in mice lacking KLF2 in the lymphoid lineage, KLF2 is postulated to regulate T cell homeostasis by promoting cell quiescence. In this study, we show that in reporter gene assays KLF2 directly activates the promoters of both CD62L and sphingosine-1-phosphate receptor 1 (S1P1), whose expression is critical for T cell egress from the thymus and homing to the lymph nodes. Correspondingly, exogenous KLF2 expression in primary T cells significantly up-regulates both CD62L and S1P1. Following adoptive transfer, KLF2-transduced T cells are much more efficient in homing to lymphoid organs than nontransduced T cells. These findings suggest that KLF2 regulates T cell homeostasis at least partly by controlling CD62L and S1P1 expression, and therefore T cell egress from the thymus and circulation in the periphery.


Extent of resection and radiotherapy in GBM: A 1973 to 2007 surveillance, epidemiology and end results analysis of 21,783 patients.
Surgery, radiation and chemotherapy are the standard of care for GBM patients, however, the impact of extent of resection (EOR) and radiotherapy (RT) on patient survival across age groups has not been established. Therefore, we present the current largest study on EOR and RT in GBM over the past three decades. Using the population based Surveillance, Epidemiology and End Results (SEER) registry, we identified a total of 21,783 GBM patients (1973-2007). Survival analysis based on EOR and RT was performed by means of factor analysis, Kaplan-Meier survival and Cox proportional hazard's ratio. Age, RT and EOR were highly prognostic (p<0.00001). Combined gross total resection (GTR) and RT showed the longest median survival (11 months) compared to subtotal resection (STR) and RT (9 months). Survival times after monotherapy with RT, GTR and STR were 5, 3 and 2 months, respectively. Patients without therapy showed a median survival of 1 month. RT and GTR demonstrated highest median survival. Interestingly, survival advantage of GTR versus STR amounted to only 1-2 months. Monotherapy (GTR, STR or RT) showed a significantly lower survival rate compared to combination therapies. RT alone yielded significantly better survival compared to any resective approach. Relative to overall age-specific median survival, elderly patients still reasonably benefit from RT alone. However, across all age groups multimodality treatment with surgery and RT continues to provide the largest survival benefit compared to either treatment alone and, thus, should be pursued whenever feasible.


[Evaluation of the alarm reaction induced by blood pressure determination].
The purpose of this paper was to evaluate the characteristics of the alarm reaction that induces an increase of blood pressure (BP) above the "basal" when it is measured in the clinic. This "supplemental" increase that is added to the "basal" pressure was analyzed through the decrease of systolic blood pressure (SBP) along ten consecutive measurements separated by 3 minutes intervals in 85 patients with BP values within a wide range (Table I). 91% of the patients showed a decrease in consecutive measurements and only 9% showed increases or no significant change in SBP values. The decrease showed good correlation with the exponential decay (r = 0.99). The asymptote was for the SBP of -8.7 +/- .81 mmHg (P < 0.01) (Fig. 2) with a time constant T (tau) of 4.7 +/- 1.3 minutes. There was no correlation between the magnitude of the decrease and the BP levels, which does not support the idea that this reaction would be increased in hypertensives. The decrease of DBP was lower (3.87 +/- .71 mmHg (P < 0.01) but with similar characteristics (Fig. 3). If we consider the characteristics of the exponential decay and the fact that after 4 or 5 measurements we arrive at values near the asymptote, basal BP could be simply determined by the average of 2 or 3 determinations with 3 minutes intervals measured after discarding the first two or three readings obtained in the same conditions or by calculating the exponential decay from the equation SBP = Po.e-1/T + As (Fig. 6).(ABSTRACT TRUNCATED AT 250 WORDS)


Synthesis of NAC capped near infrared-emitting CdTeS alloyed quantum dots and application for in vivo early tumor imaging.
The synthesis of water-soluble near-infrared (NIR)-emitting quantum dots (QDs) has recently received extensive attention for non-invasive detection of biological information in living subjects. Highly fluorescent CdTeS alloyed QDs for biological application are introduced in this paper. QDs were synthesized by a hydrothermal method and coated with N-acetyl-l-cysteine (NAC) as both bioactive ligand and sulfur source for biocompatibility and biological stability. The optical properties, morphology and structure of CdTeS alloyed QDs were characterized. The in vitro and in vivo toxicity was intensively investigated. Furthermore, the dynamics and bio-distribution of CdTeS alloyed QDs on living mice were studied. To explore biomedical application, folate-polyethylene glycol (FA-PEG) was used to decorate the CdTeS alloyed QDs (FP-CdTeS QDs) for targeted imaging of tumors over-expressing the folate receptor (FR). The tumor targeting capability of FP-CdTeS QDs on tumor bearing nude mice was demonstrated. The results showed that the prepared CdTeS QDs have excellent optical properties and low toxicity, which makes them an ideal inorganic material for biomedical imaging. In addition, the folate-PEG conjugated NIR-QDs displayed good biocompatibility as well as excellent sensitivity and specificity for optical imaging of tumors which can extend the application of CdTeS QDs.


Use of a quartz crystal microbalance platform to study protein adsorption on aluminum hydroxide vaccine adjuvants: Focus on phosphate-hydroxide ligand exchanges.
Aluminum hydroxide (AH) salts are widely used as vaccine adjuvants and controlling antigen-AH interactions is a key challenge in vaccine formulation. In a previous work, we have developed a quartz crystal microbalance (QCM) platform, based on stable AH-coated sensors, to explore the mechanisms of model antigen adsorption. The QCM study of bovine serum albumin (BSA) adsorption at different pH and ionic strength (I) values showed that protein adsorption on AH adjuvant at physiological pH cannot be explained mainly by electrostatic interactions, in contrast with previous reports. Here, we exploit further the developed QCM platform to investigate the role of phosphate-hydroxyl ligand exchanges in the adsorption mechanism of BSA, human serum albumin (HSA) and ovalbumin (OVA) on two commercial AH adjuvants. BSA adsorption decreased on immobilized AH particles previously treated with KH2PO4, highlighting the role of exchangeable sites on AH particles in the adsorption process. BSA and OVA were dephosphorylated by treatment with an acid phosphatase to decrease their phosphate content by about 80% and 25%, respectively. Compared to native BSA, adsorption of dephosphorylated BSA decreased significantly on one AH adjuvant at pH 7. Adsorption of dephosphorylated OVA was comparable to the one of native OVA. Further QCM assays showed that phospho-amino acids (PO4-serine and PO4-threonine) displaced previously adsorbed BSA and OVA from AH particles in conditions that were depending on the protein and the AH. Taken together, these observations suggest that phosphate-hydroxyl ligand exchange is an important adsorption mechanism of proteins on AH. These results moreover confirm that the developed AH-coated QCM sensors offer a new platform for the study of antigen adsorption, to the benefit of vaccine formulation.


The application of faith-based principles. Mission leaders can facilitate an organization's cultural transformation.
Cultural factors account for a high percentage of the less-than-successful mergers, partnerships, and joint ventures that are taking place in today's healthcare marketplace. Culture is found wherever people live and work together in relative stability. Those in the Catholic healthcare ministry are in need of faith-based wisdom to deal with the challenges of cultural transformation. Five principles may be helpful: Take time as a team to return in a reflective way to the wellsprings of our ministry. Remember that this is a three-way undertaking--you, your co-workers, and God. Remember that to hear God speak to us, to recognize God's presence, we need to keep ourselves centered and deeply attentive. Help one another sort out motivations and maintain a clean heart. Appreciate the affective potential in the cultural elements of symbol, myth, and ritual. Using these principles, leaders can begin to focus on how they can positively affect culture change through the following conceptual model of culture: The symbolic dimension of symbols, myths, and rituals. The dimension of espoused beliefs, purpose, and values. The mini-expressive dimension of revealing everyday comments and behaviors. The hidden dimension of sentiments, convictions, and commitments.


Long-term effects of radiotherapy on cardiovascular risk factors in acromegaly.
Radiation therapy (RT) is a useful adjuvant tool for acromegalic patients not cured by surgery and/or not responding to pharmacotherapy. However, its specific effects on cardio- and cerebrovascular morbidity are still on debate. Retrospective analysis of 42 acromegalic patients cured after conventional radiotherapy (CRT, n=31) or radiosurgery by gamma-knife (GKRS, n=11) followed for a median period of 16.5 years (range: 2-40). Totally, 56 patients cured by surgery alone, with similar GH/IGF1 levels and duration of disease remission, served as control group. Changes in cardiovascular risk factors, such as body mass index, glucose metabolism, insulin resistance, blood pressure, and lipid profile (pre-defined primary end point) and occurrence of new major cardio- and cerebrovascular events (secondary end point) during follow-up. The number of obese, hypertensive, and dyslipidemic subjects increased over time only in patients cured with RT. In contrast, the glucose response to the oral glucose tolerance test and the percentage of subjects with glucose alterations improved only in controls. As expected, the percentage of patients with pituitary failure was deeply higher among RT patients than among controls (86 vs 30%, P<0.0005). Despite these findings, a similar number of RT patients and controls developed major cardio- or cerebrovascular events (4/42 vs 3/56, P: NS). No differences were found between CRT and GKRS subgroups. Previous RT seems to be associated with a worse metabolic profile in acromegalic patients studied after a long-term follow-up. Nevertheless, a direct link between RT and cardiovascular events remains to be proven.


Genetic parameters estimation for preweaning traits and their relationship with reproductive, productive and morphological traits in alpaca.
The aim of this study was to estimate the genetic parameters for preweaning traits and their relationship with reproductive, productive and morphological traits in alpacas. The data were collected from 2001 to 2015 in the Pacomarca experimental farm. The data set contained data from 4330 females and 3788 males corresponding to 6396 and 1722 animals for Huacaya and Suri variants, respectively. The number of records for Huacaya and Suri variants were 5494 and 1461 for birth weight (BW), 5429 and 1431 for birth withers height (BH), 3320 and 896 for both weaning weight (WW) and average daily gain (DG) from birth to weaning, 3317 and 896 for weaning withers height (WH), and 5514 and 1474 for survival to weaning. The reproductive traits analyzed were age at first calving and calving interval. The fiber traits were fiber diameter (FD), standard deviation of FD (SD), comfort factor and coefficient of variation of FD and the morphological traits studied were density, crimp in Huacaya and lock structure in Suri, head, coverage and balance. Regarding preweaning traits, model of analysis included additive, maternal and residual random effects for all traits, with sex, coat color, number of calving, month-year and contemporary group as systematic effects, and age at weaning as linear covariate for WW and WH. The most relevant direct heritabilities for Huacaya and Suri were 0.50 and 0.34 for WW, 0.36 and 0.66 for WH, 0.45 and 0.20 for DG, respectively. Maternal heritabilities were 0.25 and 0.38 for BW, 0.18 and 0.32 for BH, 0.29 and 0.39 for WW, 0.19 and 0.26 for WH, 0.27 and 0.36 for DG, respectively. Direct genetic correlations within preweaning traits were high and favorable and lower between direct and maternal genetic effects. The genetic correlations of preweaning traits with fiber traits were moderate and unfavorable. With morphological traits they were high and positive for Suri but not for Huacaya and favorable for direct genetic effect but unfavorable for maternal genetic effect with reproductive traits. If the selection objective was meat production, the selection would have to be based on the direct genetic effect for WW but not on the maternal genetic effect that has been shown to have less relevance. Other weaning traits such as WH or DG would be indirectly selected.


Endocrine activities of alexamorelin (Ala-His-d-2-methyl-Trp-Ala-Trp-d-Phe-Lys-NH2), a synthetic GH secretagogue, in humans.
Peptidyl and non-peptidyl synthetic GH secretagogues (GHS) possess significant GH-, prolactin (PRL)- and ACTH/cortisol-releasing activity after i.v. and even p.o. administration, acting via specific hypothalamo-pituitary receptors in both animals and humans. The hexapeptide hexarelin (HEX) is a paradigmatic GHS whose activities have been widely studied in humans. The heptapeptide Ala-His-d-2-methyl-Trp-Ala-Trp-d-Phe-Lys-NH(2) (alexamorelin, ALEX) is a new synthetic molecule which inhibits GHS binding in vitro, but its endocrine activity has never been studied in humans. In six young adults we studied the effects of 1.0 and 2.0 microgram/kg i.v. ALEX or HEX on GH, PRL, ACTH, cortisol and aldosterone levels and those of 20mg p.o. ( approximately 300 microgram/kg) on GH levels. Basal GH, PRL, ACTH, cortisol and aldosterone levels in all testing sessions were similar. ALEX and HEX (1.0 and 2.0 microgram/kg i.v.) induced the same dose-dependent increase of GH and PRL levels. Both ALEX and HEX induced a dose-dependent increase of ACTH and cortisol levels. The ACTH and cortisol responses to the highest ALEX dose were significantly higher than those after HEX. Aldosterone levels significantly increased after both i.v. ALEX doses, but not after HEX. The GH response to 20mg p.o. ALEX was higher, though not significantly, than that to the same HEX dose. ALEX, a new GHS, shows the same GH-releasing activity as HEX. On the other hand, ALEX seems endowed with an ACTH-releasing activity more marked than that of HEX; this evidence could explain the significant increase of aldosterone levels after its i.v. administration.


Conservative surgical treatment of endometriosis.
In the period 1979-1983, 102 patients with endometriosis underwent conservative surgery at Ia Clinica Ostetrica e Ginecologica, Milan University. Treatment indications, techniques and results are presented. 34.3% of the women were in stage I, 51% in stage II and 14.7% in stage III of the American Fertility Society classification. Postoperatively, the incidence of dysmenorrhea fell from 63.7% to 15.7%, deep dyspareunia from 53.3% to 17.6% and chronic pelvic pain 21.6% to 11.8%. In 1-6 years' follow-up of the 53 women wanting children, the postoperative birth-rate was 68.3% in stage I patients, 59% in stage II and 37.5% in stage III. Endometriosis treatment is still only symptomatic, and conservative surgery, using atraumatic procedures, should aim at restoring fertility and resolving pain symptomatology.


The results of intracapsular cataract extraction with a Binkhorst iris clip lens implant 34 to 40 months after surgery.
A series of 300 consecutive intracapsular cataract extractions with a Binkhorst iris clip lens implant was evaluated 34 to 40 months after surgery, except for those patients who died before this time (30 patients) and those lost to follow-up (13 patients). Eighty-eight percent of the 257 patients achieved 20/40 or better visual acuity. The results were similar to those series previously reported by the authors where the final examination time for each patient was not uniform.


Is RIRS Safe and Efficient In Patients With Kidney Stones Who Had Previous Open ,Endoscopic,Percutaneous Kidney Stone Surgery? One Center Retrospective Study.
In our study, we assessed the efficiency and reliability of retrograde intrarenal surgery secondary to open surgery for kidney stone treatment. Moreover, we compared the efficiency and safety of retrograde intrarenal surgery for the patients with previous history of open surgery, Percutaneous nephrolithotomy, secondary RIRS and primary RIRS. Data was retrospectively reviewed. Patients who had kidney anomalies,who had been stented due to ureteral stricture in the operation and who were < 18 years old, were excluded. There were 30 patients who underwent RIRS secondary to open surgery. The demographic and stone characteristic as well as intraoperative and postoperative data of the patients were recorded. 30 patients with similar demographic and stone characteristics to those patients were selected by match pairing method from patients who had previous PNL, RIRS history and had been undergone primary RIRS . Total 120 patients, in total 4 groups, were included in the study. Statistically significant difference was detected among the groups with regards to shock wave lithotripsy history and preoperative JJ stent rate, either. There was no statistically significant difference in terms of stone characteristics ,intraoperative and postoperative dataConclusions: RIRS is an efficient and safe method for kidney stone treatment of the patients with previous history of open surgery, Percutaneous nephrolithotomy and retrograde intrarenal surgery. It has a similar efficiency and safety for the patients who have undergone retrograde intrarenal surgery firstly. This is the first study that compares the patients especially with different previous surgery methods.


[The internal picture of the disease in subjects with a history of a heart valve prosthetic operation under artificial circulation].
Sensitive, emotional, intellectual, motivation, preoperative and postoperative aspects of the disease pattern were studied in 93 patients who had acquired valvular defects and underwent replacement of the valves in conditions of artificial circulation. The findings provided evidence in support of psychic correction for preoperative preparation of the patients and postoperative restoration of their personality and social status.


Federal civil service adult survivor annuitants and Social Security, December 1975.
This article reviews the recent experience of adult survivor annuitants under the Federal civil service retirement program. Data are presented for such persons in terms of their status in December 1975 as primary beneficiaries, secondary beneficiaries, or nonbeneficiaries under the Old-Age, Survivors, and Disability Insurance (OASDI) program. Analysis reveals that 63 percent of the survivor annuitants were dual beneficiaries-that is, they received an OASDI benefit as well as an annuity payment. About half the remaining annuitants were permanently insured under the OASDI program, so it can be anticipated that at least four-fifth of the Federal civil service survivor annuitants ultimately will also receive an OASDI benefit. The survivor annuity replaced 27 percent of a decreased spouse's Federal civil service salary at the median. The median replacement rate of annuity plus OASDI benefit was 48 percent of civil service salary.


Source, profile, and carcinogenic risk assessment for cohorts occupationally exposed to dust-bound PAHs in Lahore and Rawalpindi cities (Punjab province, Pakistan).
In this study, the occurrence and concentrations of PAHs in dust samples, which were collected from the traffic police cabins/working spots, located on the main busy roads of Lahore (TP-L) and Rawalpindi (TP-R) cities (Punjab province, Pakistan) and from the public transport vehicles in the same cities (named as AM-L and AM-R, respectively) were determined. The mean and median concentrations of ∑PAHs were observed in the following descending order: AM-L (1340 and 774 ng g(-1) d.w., respectively), TP-L (866 and 854 ng g(-1) d.w.), TP-R (504 and 379 ng g(-1) d.w.), and AM-R (393 and 290 ng g(-1) d.w. Source apportionment of the soil/dust-bound PAHs was also performed. In all the sampling areas, the diagnostic ratios, principal component analysis (PCA) followed by multiple linear regression (MLR) analysis indicated signatures of mixed sources of PAHs (including vehicular exhaust emission, gasoline/diesel, and coal/wood combustion). Estimated results of incremental lifetime cancer risk (ILCR) indicated that the traffic policemen and drivers, especially those in the urban area of Lahore, were at high risk of cancer via routes of dust ingestion and dermal contact. The results of this research could be very useful for the local Government in order to control the exposure and promote actions to alleviate PAH contamination and to manage health both at work places in the big cities of Pakistan.


Post-translational modifications on yeast carbon metabolism: Regulatory mechanisms beyond transcriptional control.
Yeast cells have developed a variety of mechanisms to regulate the activity of metabolic enzymes in order to adjust their metabolism in response to genetic and environmental perturbations. This can be achieved by a massive reprogramming of gene expression. However, the transcriptional response cannot explain the complexity of metabolic regulation, and mRNA stability regulation, non-covalent binding of allosteric effectors and post-translational modifications of enzymes (such as phosphorylation, acetylation and ubiquitination) are also involved, especially as short term responses, all converging in modulating enzyme activity. The functional significance of post-translational modifications (PTMs) to the regulation of the central carbon metabolism is the subject of this review. A genome wide analysis of PTMs indicates that several metabolic enzymes are subjected to multiple PTMs, suggesting that yeast cells can use different modifications and/or combinations of them to specifically respond to environmental changes. Glycolysis and fermentation are the pathways where phosphorylation, acetylation and ubiquitination are most frequent, while enzymes of storage carbohydrate metabolism are especially phosphorylated. Interestingly, some enzymes, such as the 6-phosphofructo-2-kinase Pfk26, the phosphofructokinases Pfk1 and Pfk2 and the pyruvate kinase Cdc19, are hubs of PTMs, thus representing central key regulation nodes. For the functionally better characterized enzymes, the role of phosphorylations and lysine modifications is discussed. This review focuses on the regulatory mechanisms of yeast carbon metabolism, highlighting the requirement of quantitative, systematical studies to better understand PTM contribution to metabolic regulation.


Design and characterization of a surfactant-enriched tablet formulation for oral delivery of a poorly water-soluble immunosuppressive agent.
The feasibility of incorporating significant quantities of the anionic surfactant, sodium lauryl sulfate (SDS), into an immediate release tablet formulation of a poorly water-soluble immunosuppressive agent was investigated. Despite the extremely poor compressibility of SDS and poor chemical stability of the drug, a commercializable, direct-compression tablet formulation with satisfactory mechanical properties and acceptable chemical stability was achieved. Optimal in vitro release of the drug from the tablet formulation was achieved by establishing the minimum molar uptake ratio necessary to achieve complete micellar solubilization of the drug, after which formulation studies were conducted to determine the influence of formulation and process variables on the rate and extent of drug release. A model-independent analysis of dissolution results in a reduced volume (250 ml) of modified simulated gastric fluid demonstrated that the rate and extent of drug release was highly dependent on the mean particle size of the bulk drug, but independent of compression force above that required to achieve a compact of acceptable mechanical strength. Employing the Korsmeyer-Peppas model of Fickian and non-Fickian drug release, it was further shown that release of the drug from the dosage form was governed largely by surface erosion of the surfactant-enriched tablet matrix.


Computer simulations using GastroPlus to justify a biowaiver for etoricoxib solid oral drug products.
The purpose of this study was to compare the dissolution behaviour of etoricoxib in different dissolution media and to establish in vitro/in vivo correlation (IVIVC) using computer simulations. Drug solubility was measured in different media. The dissolution behaviour of etoricoxib was studied in the USP Apparatus 2 using different dissolution media. A dissolution transfer model was used to investigate if the drug stays in solution when the pH of the medium changes. Drug permeability assessment was performed using the caco-2 cell culture technique. The in vitro data were used as input functions in GastroPlus to simulate the in vivo profiles of the drug. Solubility of etoricoxib was highest at low pH, and there was no significant difference in the solubility observed between blank buffers and biorelevant media of similar pH. The drug remained solubilised when transferred into simulated intestinal fluids. Using the in vitro data as input function in Gastro Plus, an IVIVC was established. Further simulations confirmed that the drug absorption occurs similar to the absorption of an oral solution. Due to the solubility behaviour within the physiological pH gradient of the gastrointestinal tract, etoricoxib can be classified as an intermediate class 1/2 drug rather than BCS class 2. In vitro results combined with in silico simulations using GastroPlus support scientifically that a biowaiver for immediate release etoricoxib solid oral dosage forms is justified.


Nerve growth factor and autoimmune rheumatic diseases.
Nerve growth factor (NGF) is the first discovered and best known neurotrophic factor and is required for the survival and differentiation of a variety of neuronal cell types in both the peripheral and central nervous system. Recent studies indicate that NGF is synthesized by cells of immune system lineage and that its level increases during inflammatory responses, while cytokines such as interleukin-1 beta and tumor necrosis factor-alpha are potent inducers of NGF secretion. The role played by NGF on cells of the immune system was strengthened by recent evidence demonstrating that cells normally present in inflammatory tissues, such as mast cells and lymphocytes, express NGF receptors and are receptive to the action of NGF. Studies carried out in our and other laboratories showed that NGF is expressed in the synovial fluid of patients with rheumatoid arthritis and other forms of chronic arthritis, as well as in the synovium of pharmacologically-induced arthritis in animal models. Moreover, arthritic transgenic mice which carry and express the human tumor necrosis factor-gene also showed elevated levels of NGF. Significant increases in NGF levels have been found in the sera of patients with systemic lupus erythematosus and in the dermis of patients affected by systemic sclerosis. In this paper the hypothesis that NGF is involved in the pathophysiology of autoimmune rheumatic arthritis is discussed.


A rat model of childhood diet-induced obesity: Roux-en-Y gastric bypass induced changes in metabolic parameters and gastric peptide ghrelin.
Childhood morbid obesity is reaching epidemic proportions. Roux-en-Y gastric bypass (RYGB) results in many metabolic alterations, including changes in glucose and lipid metabolism, and changes in levels of the gastric hormone, ghrelin. As more children are undergoing RYGB, an animal model would be beneficial to further study RYGB and its subsequent metabolic effects. DIO Sprague Dawley rats underwent RYGB, sham jejunojejunostomy (SH), or no operation (HFC) after 6 weeks of high-fat diet. Non-obese rats fed standard chow (SC) were a final control group. Animals were post-operatively fed standard chow for 7 days before sacrifice. At sacrifice, venous blood and gastric mucosa was collected for metabolic parameters and ghrelin determination. RYGB rats weighed less than SH and HFC (361 +/- 8.8 vs. 437 +/- 9.3 and 443 +/- 6.2 g, P < 0.05). Compared to HFC, RYGB animals had decreased plasma glucose (292 +/- 23 vs. 141 +/- 10 mg/dL), cholesterol (80 +/- 12 vs. 45 +/- 5 mg/dL), triglycerides (138 +/- 37 vs. 52 +/- 7 mg/dL), HDL (43 +/- 5 vs. 20 +/- 3 mg/dL), and free fatty acids (0.72 +/- 0.14 vs. 0.23 +/- 0.02 mEq/L), all P < 0.05. Plasma ghrelin increased in RYGB rats compared to SC and HFC (116.22 +/- 32.27 vs. 31.60 +/- 2.66 and 31.75 +/- 0.75 pg/mL, P < 0.05). In a rat model of RYGB, we demonstrated improved metabolic parameters and increased plasma and gastric mRNA ghrelin levels. The rat model for RYBG appears to be a reasonable model for future study of the cellular and molecular regulatory pathways of obesity and its surgical treatment.


Microarrays of bladder cancer tissue are highly representative of proliferation index and histological grade.
The number of genes suggested to play a role in cancer biology is rapidly increasing. To be able to test a large number of molecular parameters in sufficiently large series of primary tumours, a tissue microarray (TMA) approach has been developed where samples from up to 1000 tumours can be simultaneously analysed on one glass slide. Because of the small size of the individual arrayed tissue samples (diameter 0.6 mm), the question arises of whether these specimens are representative of their donor tumours. To investigate how representative are the results obtained on TMAs, a set of 2317 bladder tumours that had been previously analysed for histological grade and Ki67 labelling index (LI) was used to construct four replica TMAs from different areas of each tumour. Clinical follow-up information was available from 1092 patients. The histological grade and the Ki67 LI were determined for every arrayed tumour sample (4x2317 analyses each). Despite discrepancies in individual cases, the grade and Ki67 information obtained on minute arrayed samples were highly similar to the data obtained on large sections (p<0.0001). Most importantly, every individual association between grade or Ki67 LI and tumour stage or prognosis (recurrence, progression, tumour-specific survival) that was observed in large section analysis could be fully reproduced on all four replica TMAs. These results show that intra-tumour heterogeneity does not significantly affect the ability to detect clinico-pathological correlations on TMAs, probably because of the large number of tumours that can be included in TMA studies. TMAs are a powerful tool for rapid identification of the biological or clinical significance of molecular alterations in bladder cancer and other tumour types.


Inhibitors of the heat shock response: biology and pharmacology.
A number of human diseases can be linked to aberrations in protein folding which cause an imbalance in protein homeostasis. Molecular chaperones, including heat shock proteins, act to assist protein folding, stability and activity in the cell. Attention has begun to focus on modulating the expression and/or activity of this group of proteins for the treatment of a wide variety of human diseases. This review will describe the progress made to date in developing pharmacological modulators of the heat shock response, including both agents which affect the entire heat shock response and those that specifically target the HSP70 and HSP90 chaperone families.


Refocusing on history-taking skills during internal medicine training.
Recognizing that skilled history-taking is in danger of becoming a lost art, the American Board of Internal Medicine calls attention to the urgent need for internal medicine residency programs to ensure that these skills are taught and assessed. Although the Board's certification examination contains standardized items that test the physician's ability to use information from a patient's medical history, the written examination cannot assess the physician's ability to elicit that history. The Board believes that history-taking skills will become even more crucial as health care delivery changes, requiring more cost efficiency without sacrificing quality. By highlighting the skills of effective history-taking and strategies for assessment, the Board offers specific recommendations for its promotion as a key element of quality patient care.


[Functional evaluation of the intrathoracic stomach after esophagectomy for esophageal cancer].
Sixteen patients underwent evaluation of duodenogastric reflux and gastric function 1 to 7 years after esophagectomy, high intrathoracic anastomosis, and pyloric divulsion for esophageal cancer. Ten patients (62%) had either postoperative digestive symptoms or endoscopic mucosal lesions, cholescintigraphy demonstrated duodenogastric reflux in 11 cases (69%). No gastric motor activity was recorded on manometry. 24-hour pH gastric monitoring showed that the area under the curve less than 4 was significantly less than in controls (p = 0.0003). The results of the present study show that duodenogastric reflux is a common event after esophageal replacement with the stomach. The interaction between acid and alkaline secretions plays a role in the pathogenesis of mucosal lesions, and it may explain the partial failure of the current therapeutic strategies.


[Value of (99m)Tc-MIBI/(18)F-FDG-dual-isotope simultaneous acquisition in diagnosis and treatment of myocardial infarction].
To investigate the value of(99m)Tc-MIBI/(18)F-FDG-dual-isotope simultaneous acquisition (DISA) in diagnosis and treatment of patients with myocardial infarction. Sixty-three patients with myocardial infarction who underwent DISA before and after treatment were enrolled in the study. All cases were divided into subgroups based on different treatment and myocardial viability: Group A1 (n = 16) with coronary revascularization and viable myocardium, A2 (n = 9) same as A1 but no viable myocardium; B1 (n = 6) with coronary revascularization + stem cell transplantation and viable myocardium, B2 (n = 7) same as B1 but no vital myocardium; C1 (n = 8) with stem cell transplantation and viable myocardium, C2 (n = 17) same as C1 but on viable myocardium. The changes of uptake rate of (99m)Tc-MIBI/(18)F-FDG before and after treatment were analyzed with SPSS 13.0 software. There were statistical significances in DF value of (99m)Tc-MIBI or (18)F-FDG imaging before and after treatment in all groups (P <0.05), except Group A2 (P>0.05). The improvement of blood perfusion and metabolism in cardiac survival groups was more marked than that in non-cardiac survival groups after treatment (P<0.05). Furthermore, Group B1 was superior to Groups A1 and C1; Group B2 was superior to Group A2 and Group C2 (P<0.05 or<0.01). (99m)Tc-MIBI/(18)F-FDG DISA can detect myocardial viability and is of value for patients with myocardial infarction to choose appropriate therapeutic strategies. The degree of cardiac improvement after treatment can be evaluated by DISA.


What's 'difficult'? A multi-stage qualitative analysis of secondary care specialists' experiences with medically unexplained symptoms.
The term 'difficult' is pervasively used in relation to medically unexplained symptoms (MUS) and patients with MUS. This article scrutinises the use of the term by analysing interview data from a study of secondary care specialists' experiences with and attitudes towards patients suffering from MUS. Qualitative design employing semi-structured open-ended interviews systematically analysed in three stages: first, data were analysed according to the principles of content analysis. The analysis subsequently focused on the use of the term 'difficult'. Iterations of the term were extracted by summative analysis and thematic coding revealed its different meanings. Finally, alternative expressions were explored. Three NHS trust secondary care hospitals in North-East England. 17 senior clinicians from seven medical and two surgical specialities. Unsolicited use of the term 'difficult' was common. 'Difficult' was rarely used as a patient characteristic or to describe the therapeutic relationship. Participants used 'difficult' to describe their experience of diagnosing, explaining, communicating and managing these conditions and their own emotional reactions. Health care system deficits and the conceptual basis for MUS were other facets of 'difficult'. Participants also reported experiences that were rewarding and positive. This study shows that blanket statements such as 'difficult patients' mask the complexity of doctors' experiences in the context of MUS. Our nuanced analysis of the use of 'difficult' challenges preconceived attitudes. This can help counter the unreflexive perpetuation of negative evaluations that stigmatize patients with MUS, encourage greater acknowledgement of doctors' emotions, and lead to more appropriate conceptualizations and management of MUS.


A controlled study of allergen production in cultures of Dermatophadoides pteronyssinus.
Allergenic substances have been isolated from cultures of Dermatophagoides pteronyssinus on wheat germ flakes and powdered yeast; as controls, non-sterile nutrient medium containing no mites, as well as sterile medium, were maintained and extracted under identical conditions. Chemical purification and analyses indicated the occurrence of skin-active allergens in all three preparations. This was confirmed by the assay of skin-reactivity in vivo and complement-inactivating capacity in vitro. Quantitatively, the medium containing bacteria and fungi contained more allergen than the sterile control, but less than the mite-infected medium. The evidence indicates that degradation reactions of nutrient components proceed faster in the non-sterile media than in the sterile control. The results of immunochemical analyses demonstrate that degradation reactions, give rise to the introduction of lysine-sugar structures inot high-molecular weight components from the medium. It is concluded that mites and micro-organisms have a role in allergen formation by promoting degradation reactions among nutrient constituents.


PPE2 protein of Mycobacterium tuberculosis may inhibit nitric oxide in activated macrophages.
Although the pathophysiological role of PE/PPE proteins of Mycobacterium tuberculosis is yet to be fully understood, recent evidence shows that these proteins play important roles in antigenic diversity, as well as in host-pathogen interactions and mycobacterial pathogenesis. Most of the PE/PPE proteins are highly expressed in pathogenic bacteria, pointing to their role in the pathogenesis of mycobacteria. Here, we provide an overview of our work in progress on a specific PPE protein, PPE2 (Rv0256c), which may inhibit nitric oxide (NO) production in activated macrophages. As NO and its by-products are considered to be toxic to bacilli, it is possible that the bacilli recruit Rv0256c in order to inhibit higher production of NO during infection.


Clinical management of motility disorders in children.
We review the current clinical evaluation and management of the most common esophageal and gastrointestinal motility disorders in children based on the literature and our experience in a pediatric motility center in the United States. The disorders discussed include esophageal achalasia, pre- and post-fundoplication motility disorders, gastroparesis, motility disorders occurring after repair of congenital atresias, motility disorders associated with gastroschisis, chronic intestinal pseudo-obstruction, motility after intestinal transplantation, motility disorders after colonic resection for Hirschsprung's disease, chronic functional constipation, and motility disorders associated with imperforate anus.


Chirality-Amplifying, Dynamic Induction of Single-Handed Helix by Chiral Guests to Macromolecular Chiral Catalysts Bearing Boronyl Pendants as Receptor Sites.
Helical chirality of poly(quinoxaline-2,3-diyl)s bearing a boronyl pendant at the 5-position of the quinoxaline ring was induced by condensation with chiral guests such as a diol, diamine, and amino alcohol. Reversible induction of a single-handed helical structure was achieved by using less than an equimolar amount of chiral amino alcohols to the boronyl pendants. Majority-rule-effect-based chiral amplification on the polyquinoxaline main chain was demonstrated with chiral amino alcohols with low enantiomeric excess (ee). The helical macromolecular scaffold whose helicity was thus induced was utilized in palladium-catalyzed asymmetric silaboration of meso-methylenecyclopropane (up to 92% ee) by introducing (diarylphosphino)phenyl pendants at their side chains.


Relationship of argyrophilic proteins of nucleolal organizer regions in Ki-67+ cells with clinical and morphological parameters in lung adenocarcinoma.
Ninety-four lung adenocarcinoma samples obtained during surgeries were examined using a combination of immunohistochemical staining for Ki-67 antigen and silver nitrate staining for argyrophilic nucleolar organizer (Ag-NOR) proteins. In lung adenocarcinoma, we studied the correlation between the area of Ag-NOR proteins in Ki-67(+) cells and clinical and morphological TNM parameters: maximum tumor diameter (T) and stage of the disease and tumor differentiation degree (N). Survival of patients with small area of Ag-NOR proteins in Ki-67(+) cells was higher that in patients with great area of these proteins. The area of Ag-NOR proteins in Ki-67(+) cells is an independent prognostic factor in lung adenocarcinoma. The area of Ag-NOR proteins in Ki-67(+) cells correlates with clinical and morphological TNM parameters and survival of patients with lung adenocarcinoma.


Amblyopia prevalence and risk factors in Australian preschool children.
To determine the prevalence of and factors associated with amblyopia in a sample of Australian preschool children. Population-based, cross-sectional study. The Sydney Paediatric Eye Disease Study examined 2461 (73.8% participation) children aged between 6 and 72 months from 2007 to 2009. Visual acuity (VA) was assessed in children aged ≥ 30 months using the Electronic Visual Acuity system, and a subset using the logarithm of the minimum angle of resolution chart. Amblyopia was categorized into unilateral and bilateral subtypes: Unilateral amblyopia was defined as a 2-line difference in reduced VA between the 2 eyes, in addition to strabismus, anisometropia, and/or visual axis obstruction; bilateral amblyopia was defined as bilateral reduced VA with either bilateral visual axis obstruction or significant bilateral ametropia. Information on ethnicity, birth parameters, and measures of socioeconomic status were collected in questionnaires completed by parents. Amblyopia. We included 1422 children aged 30 to 72 months, of whom 27 (1.9%) were found to have amblyopia or suspected amblyopia. Mean spherical equivalent for the amblyopic eyes was +3.57 diopters, with a mean VA of 20/50. Only 3 of the 27 amblyopic children had previous diagnoses or treatments for amblyopia. In regression analysis controlling for age, gender, and ethnicity, amblyopia was significantly associated with hyperopia (odds ratio [OR], 15.3; 95% confidence interval [CI], 6.5-36.4), astigmatism (OR, 5.7; 95% CI, 2.5-12.7), anisometropia (OR, 27.8; 95% CI, 11.2-69.3), and strabismus (OR, 13.1; 95% CI, 4.3-40.4). There were no significant associations of amblyopia with low birthweight (<2500 g), preterm birth (<37 weeks), maternal smoking, age, gender, ethnicity, or measures of socioeconomic status (all P>0.05). Amblyopia was found in 1.9% of this Australian preschool sample, which is comparable with prevalence rates reported by other recent studies in preschool children. Refractive errors, particularly significant hyperopia and astigmatism, in addition to anisometropia and strabismus, were the major amblyogenic factors. There was a low amblyopia detection rate in this preschool population, which suggests that different strategies are required to improve current vision screening strategies in preschoolers. The authors have no proprietary or commercial interest in any of the materials discussed in this article.


Effects of maternal serum on permeability of glomerular endothelial cell membrane.
The mechanism of injury on the human glomerular endothelial cells (ciGENC) induced by preeclampsia serum was investigated. Concentration of maternal serum sFlt-1 protein was detected by ELISA. Fluorescently-labeled bovine serum albumin infiltrating through lower chamber of Transwell was measured by multifunction microplate reader. Morphologic change of ciGENC was observed under inverted phase contrast microscope. The concentration of sflt-1 in preeclampsia groups was significantly increased as compared with control group (P<0.01). Permeability in preeclampsia groups was significantly increased as compared with control group (P<0.01). By contrast with severe preeclampsia group, the permeability of ciGENC monolayer in mild preeclampsia group was decreased significantly (P<0.05). Intervention of exogenous VEGF significantly decreased permeability of ciGENC in preeclampsia groups. It was concluded that sFlt-1 increased ciGENC permeability by damaging integrity of endothelial barrier function.


Peroxidatic oxidation of benzo[a]pyrene and prostaglandin biosynthesis.
The arachidonic acid dependent oxidation of benzo[a]pyrene to a mixture of 3,6-, 1,6-, and 6,12-quinones has been studied by using enzyme preparations from sheep seminal vesicles. Maximal oxidation is observed at 100 microM benzo[a]pyrene and 150 microM arachidonic acid. The arachidonic acid dependent oxidation is peroxidatic and utilizes prostaglandin G2 (PGG2), generated in situ from arachidonate, as the hydroperoxide substrate. 15-Hydroperoxy-5,8,11,13-eicosatetraenoic acid is equivalent to PGG2 as a hydroperoxide substrate, but hydrogen peroxide, cumene hydroperoxide, and tert-butyl hydroperoxide are much poorer substrates. Arachidonic acid dependent benzo[a]pyrene oxidation by microsomal and solubilized enzyme preparations is markedly.


Evaluation of speech disorders in children with cleft lip and palate.
We investigated the reliability of nasopharyngoscopy and auditory perception, two common clinical methods employed in examining the speech pathology of children with cleft lip and palate. Nasopharyngoscopy was performed to assess velopharyngeal closure function and nasopharyngeal morphology. The auditory examination evaluated nasality and other speech disorders such as articulatory tension, shift in articulation, and sigmatism. The study was based on the audio and video recordings of twelve patients (9.5 +/- 0.5 years) after surgical rehabilitation of their cleft lip and palate. The speech sample consisted of reading a standardized sequence of words. The recordings were analyzed by several examiners with different experience in the evaluation procedure at two time-points. Inter-rater and intra-rater reliability was determined by Cohen's Kappa coefficient and by estimation of the 95% intervals of confidence. Analysis of the visual and auditory-perceptual findings by the experienced raters was highly reliable. However, the less experienced raters' results showed greater variability, as did morphological evaluation in both groups. Comparison between visual and auditory evaluations concerning hypernasality resulted in little correlation. These two subjective methods of evaluation are recommended because of their high reliability with experienced raters. Our results suggest that "experience" is an essential criterion in determining the structural quality of the morphological and functional assessment of typical speech pathologies in children with cleft lip and palate. In addition, the data demonstrate the necessity of special multidisciplinary rehabilitation teams in so-called cleft centers.


Enlargement of the superior rectus and superior oblique muscles causes intorsion in Graves' eye disease.
To review the prevalence of preoperative and postoperative intorsion in patients with strabismus and Graves' eye disease (GED), and to correlate the intorsion with coexisting superior rectus (SR) and superior oblique (SO) muscle enlargement as a possible mechanism causing intorsion in these patients. Charts of consecutive patients with GED who underwent strabismus surgery between 1 January 2010 and 1 April 2013 were retrospectively reviewed. Of these, patients with orbital CT or MRI scan were identified for further analysis. Clinical characteristics documented included age, gender, horizontal and vertical deviation, subjective torsional deviation, specific extraocular muscles (EOMs) operated upon, EOM enlargement on CT/MRI scans and width and thickness of SO, SR group and inferior rectus (IR). Charts of 45 patients (14 males and 31 females) were reviewed. Mean age was 56.8±12.5 years. Of these, seven (15.6%) patients demonstrated intorsion, and 38 (84.4%) patients demonstrated extorsion preoperatively. But after strabismus surgery, 15 (39.5%) of the 38 patients with preoperative extorsion demonstrated postoperative intorsion and 23 (60.5%) patients continued to show postoperative extorsion. On analysis of CT/MRI scans in these patients, only an increase in the thickness of SR group and the thickness/width of SO muscle were significantly associated with preoperative and postoperative intorsion; while age, gender, preoperative horizontal or vertical deviation and IR recession were unrelated to preoperative or postoperative intorsion. Postoperative intorsion was also associated with smaller degrees of preoperative extorsion (<3.5°). Preoperative SR and/or SO muscle enlargement appear to be a primary contributing factor relating to preoperative and postoperative intorsion in patients with GED-associated strabismus. Patients with only small amounts of preoperative extorsion (<3.5°) in the presence of tight IRs should be carefully evaluated for possible SR and/or SO involvement by CT or MRI scan to predict those at risk for and plan for prevention/treatment of postoperative intorsion.


Cytotoxin from an ovine strain of Pasteurella haemolytica: characterisation studies and partial purification.
A cell-free, water-soluble cytotoxin from an ovine strain of Pasteurella haemolytica biotype A serotype 1 killed sheep bronchoalveolar macrophages at 37 degrees C, but not at 4 degrees C or 22 degrees C. The cytotoxin was stable over the pH range 2-12, resistant to heat at 60 degrees C but inactivated at 100 degrees C or by autoclaving. Trypsin also destroyed the cytotoxin, which is therefore thought to contain a protein component essential for biological activity. A preliminary purification of the crude cytotoxin using gel-filtration column chromatography resulted in the isolation of a biologically active fraction which resolved as a single protein band and one carbohydrate band on non-dissociating polyacrylamide gels. However, this fraction resolved into approximately 16 component bands on a sodium dodecyl sulphate polyacrylamide gel.


Concentrations of particulate matter emitted from large cattle feedlots in Kansas.
Particulate matter (PM) emitted from cattle feedlots are thought to affect air quality in rural communities, yet little is known about factors controlling their emissions. The concentrations of PM (i.e., PM2.5, PM10, and total suspended particulates or TSP) upwind and downwind at two large cattle feedlots (KS1, KS2) in Kansas were measured with gravimetric samplers from May 2006 to October 2009 (at KS1) and from September 2007 to April 2008 (at KS2). The mean downwind and net (i.e., downwind - upwind) mass concentrations of PM2.5, PM10, and TSP varied seasonally, indicating the need for multiple-day, seasonal sampling. The downwind and net concentrations were closely related to the moisture content of the pen surface. The PM2.5/PM10 and PM2.5/TSP ratios at the downwind sampling location were also related to the moisture content of the pen surface, humidity, and temperature. Measurement of the particle size distribution downwind of the feedlot with a cascade impactor showed geometric mean diameter ranging from 7 to 18 microm, indicating that particles that were emitted from the feedlots were generally large in size.


FDG-PET and chemotherapy for successful diagnosis and treatment of cardiac metastasis from non-small cell lung cancer.
Non-small cell lung cancer was metastasized at the septal side of right atrium in 59-year-old woman who had undergone surgery for lung cancer 11 years ago. The cardiac metastasis was found by whole-body 18F-fluoro-deoxy-glucose positron emission tomography/computed tomography (FDG-PET/CT), and cytologically confirmed by myocardial aspiration biopsy with right heart catheterization. The patient was treated with 4 cycles of carboplatin/pemetrexed followed by maintenance therapy with pemetrexed. The metastatic cardiac tumor shrank, and the atrioventricular (AV) block in ECG was improved. In this case, FDG-PET and chemotherapy were valuable for diagnosis and treatment of cardiac metastasis from non-small cell lung cancer.


Head-to-head comparison of 11C-PBR28 and 11C-ER176 for quantification of the translocator protein in the human brain.
11C-ER176 is a new PET tracer to quantify the translocator protein (TSPO), a biomarker for inflammation. The aim of this study was to perform a head-to-head comparison between 11C-ER176 and the widely used 11C-PBR28. Seven healthy volunteers had a 90-min PET scan and metabolite-corrected arterial input function with 11C-PBR28 in the morning and 11C-ER176 in the afternoon. Binding was quantified at the regional level in terms of VT with a two-tissue compartmental model. By using VND values from the literature obtained with pharmacological blockade, we derived the binding potential BPND for both tracers. 11C-ER176 was more stable in arterial blood than 11C-PBR28 (the percentages of unmetabolized parent in plasma at 90 min were 29.0 ± 8.3% and 8.8 ± 2.9% respectively). The brain time-activity curves for both tracers were well fitted by the two-tissue model, but 11C-ER176 had higher VT values than 11C-PBR28 (5.74 ± 1.54 vs 4.43 ± 1.99 ml/cm3) and a lower coefficient of variation. The BPND of 11C-ER176 was more than 4 times larger than that of 11C-PBR28 for high-affinity binders, and more than 9 times larger for mixed-affinity binders. 11C-ER176 displays a higher binding potential and a smaller variability of VT values. Thanks to these characteristics, clinical studies performed with 11C-ER176 are expected to have higher statistical power and thus require fewer subjects.


Emergent control of manual and vocal-motor activity in relation to the development of speech.
Babbling typically precedes, resembles, and conceivably facilitates development of speech, and yet there is no accepted neurobiological characterization of babbling. Here we report a study of infants' developing control of vocal behavior in relation to manual activity performed under differing conditions of audibility. We hypothesized that babbling is associated with the onset of left-lateralized motor control, as expressed in repetitive right-handed activity, and that audibility facilitates such activity. Sixty-one normally developing infants were seen before (N = 21) or at various intervals following (N = 40) the onset of babbling. In experimental trials, audible or inaudible rattles were placed in left or right hands equally often. Analysis of manual activity revealed little shaking movement in the youngest and vocally least differentiated infants, and a sharp increase in shaking in slightly older infants who had recently begun to babble. Surprisingly, audibility only marginally enhanced shaking activity. A dextral bias was evident in the shaking of infants who had recently begun to babble, but not in younger or older infants. These and other findings suggest that the left cerebral hemisphere may be disproportionately involved in the production of repetitive vocal-motor activity as occurs in babbling.


Patterns and predictive factors of long-lasting insecticidal net usage in a previously high malaria endemic area in Sri Lanka: a cross-sectional survey.
Long-lasting insecticidal nets (LLINs) have been widely distributed in Sri Lanka for malaria control. Their effectiveness depends on proper utilisation and maintenance at the household level. A cross-sectional study was performed to examine the patterns and predictive factors of LLIN maintenance and use in Anuradhapura district. Data was collected and analysed from 530 LLIN-owning households, selected by a multi-stage cluster sampling technique. Multivariable logistic regression identified factors associated with proper maintenance at the household level. Hierarchical linear modelling identified factors associated with LLIN use the previous night. Almost 75% (377/504) of households had used all their LLINs the previous night, while 82.9% (418/504) had used at least one. Only 3.2% (15/474) were maintaining the LLIN in such a way as to maximise its insecticidal efficacy. Six variables were significantly associated (p<0.05) with use the previous night: more residents, fewer plain nets, reporting practical benefits of LLINs, conical shape, newer nets and lack of side effects. Two variables were significantly associated with proper maintenance: increasing level of education and taking safety precautions while washing. Results suggest LLIN practices could improve in settings of low malaria transmission if distribution programmes took into account recipient preferences, promoted LLIN use over plain nets, and emphasised the techniques and significance of proper net maintenance.


[Methods, value and limits of prenatal hearing diagnosis].
An intrauterine sound test was developed for monitoring prenatal hearing disorders and evaluated concerning its efficacy and practical feasibility. The procedure is based on the fetesto capacity react upon exogenous sound stimulation. An acoustic stimulation was achieved by a noise generator placed directly on the maternal abdomen in the proximity of the fetal ear. Successful stimulation was monitored by sonographic means expressed as fetal child movements in 447 pregnant women at the end of the 26th to the 37th week of gestation. The most favourable time for an intrauterine hearing test is between the 30th and 32nd week of gestation. The quantity of amniotic liquor, placental location and pathological pregnancies influences the test results. Efficiency and limits of prenatal hearing diagnostics are discussed.


Influence of transmetatarsal amputation in patients requiring lower extremity distal revascularization.
When a transmetatarsal amputation (TMA) is required, successful long-term limb salvage is questioned. We evaluated the influence of TMA on limb salvage in patients undergoing lower extremity revascularization. Patients who had distal bypasses extending to the infrapopliteal arterial tree and adjunctive TMA were retrospectively reviewed. Limb salvage was determined with life-table analysis. Twenty-four patients (29 limbs) were evaluated: 15 male and 9 female. Average age was 64.2 years old. Gangrene was the indication for bypass and TMA in 25 (86.2%) patients. Seven limbs were lost to follow-up. Nine of the remaining 22 limbs required below-knee (8) or above-knee (1) amputations, seven limbs within the first 3 months. In the group of patients who had major amputations within the first 3 months, graft thrombosis was the cause of leg amputation in six (85.7%) cases. No significant predictors of early major amputation were identified. Limb salvage was 62 per cent at 1 year in the TMA group. In comparison, among historical controls requiring distal revascularization and no adjunctive toe or foot amputations, limb salvage was 76.5 per cent (P = NS). Long-term limb salvage is dependent on successful lower extremity revascularization. Requirement for TMA should not influence the decision for limb salvage.


Identification and functional characterization of sex pheromone receptors in beet armyworm Spodoptera exigua (Hübner).
In moths, males can detect a distinct blend of several pheromone components by specialized olfactory receptor neurons (ORNs) on the antennae. Four candidate pheromone receptors (PR) with seven transmembrane domains were identified by homology cloning from the antennae of Spodoptera exigua (Sexi). Phylogenetic analyses reveal that all four odorant receptors (OR) belong to pheromone receptor subtypes. Expression patterns revealed that PRs were male-specific in the antenna except for SexiOR11, which was female antenna-biased. Functional analyses of these PRs were conducted using heterologous expression in Xenopus oocytes. SexiOR13 and SexiOR16 were all broadly activated by multiple pheromone components. SexiOR13 responded robustly to the critical pheromone component, Z9, E12-14:OAc and the minor pheromone component, Z9-14:OAc at a concentration of 10(-4) M. Dose-response studies indicate that SexiOR13 was approximately 4 times more sensitive to Z9,E12-14:OAc (EC50 = 3.158 × 10(-6) M) compared to Z9-14:OAc (EC50 = 1.203 × 10(-5) M). While, SexiOR16 responded robustly to the secondary pheromone component Z9-14:OH with high sensitivity (EC50 = 9.690 × 10(-7) M). However, similar tests of the five pheromones with SexiOR6 and SexiOR11 failed to elicit any response. These results provide basic knowledge to further advance research on the molecular mechanisms of pheromone reception.


Biology and functions of the RGS9 isoforms.
Two splice isoforms of the ninth member of the regulator of G protein signaling (RGS) protein family are expressed in the nervous system, where they are engaged in such diverse functions as vision and behavior. RGS9-1 regulates phototransduction in rods and cones, while RGS9-2 regulates dopamine and opioid signaling in the basal ganglia. The main goal of this review is to illustrate how these functions are fulfilled through the interplay between the intrinsic molecular properties of RGS9 isoforms and their interactions with several key protein partners in the cells in which they are expressed.


The vertebral foramen: a report concerning its contents.
Thirteen subjects were randomly selected and embalmed according to Winckler's technique. After removal of the vertebral column and the head in one block the specimens were frozen. Transverse transpedicular cuts were performed at C6, T1, T6, L1, L3, and L5. After enlargement photography, the surface area of the vertebral foramen and its various contents were measured on a computer using the Canvas programme and analysed using the Statview programme. The mean area of the vertebral foramen occupied by the cord was 30.5% at C6, 26.1% at T1, 21.4% at T6, 12.7% at L1, 0.08% at L3. The mean area occupied by the nerve roots was 3.9% at C6, 3.3% at T1, 1.6% at T6, 14.2% at L1, 17.5% at L3, 12.2% at L5. The mean area of all the nervous tissue was 34.4% at C6, 29.5% at T1, 23% at T6, 26.9% at L1, 18.9% at L3, 19.3% at L5. The cerebrospinal fluid occupied a mean area of 25.2% at C6, 30.7% at T1, 31.6% at T6, 43% at L1, 43.5% at L3, and 28.1% at L5. The total neural tissue did not occupy more than a third of the vertebral foramen. These facts should be considered by surgeons who perform laminectomy or decompression in cases of vertebral trauma or congenital and osteoarthritic stenoses.


Extended Risk Factors for Stroke Prevention.
Stroke causes disability and high mortality, while it can be prevented by increasing public awareness of risk factors. The common known risk factors are hypertension, atrial fibrillation, heart failure, smoking, alcohol consumption, low physical activity, overweight and hypercholesterolemia. However, the deep understanding of risk factors is limited. Moreover, more risk factor emerges in recent years. To further increase the awareness of risk factors for stroke prevention, this review indicates the reasonable application of antihypertensive agents according to the age-dependent changes of hypertension, and some new risk factors including chronic kidney disease, obstructive sleep apnea, migraine with aura, working environment, genetic factors and air pollution. Therefore, internal risk factors (e.g. heredity, hypertension, hyperglycemia) and external risk factors (e.g. working environment, air pollution) are both important for stroke prevention. All of these are reviewed to provide more information for the pre-hospital prevention and management, and the future clinical studies.


Arsenic geochemistry of groundwater in Southeast Asia.
The occurrence of high concentrations of arsenic in the groundwater of the Southeast Asia region has received much attention in the past decade. This study presents an overview of the arsenic contamination problems in Vietnam, Cambodia, Lao People's Democratic Republic and Thailand. Most groundwater used as a source of drinking water in rural areas has been found to be contaminated with arsenic exceeding the WHO drinking water guideline of 10 μg·L(-1). With the exception of Thailand, groundwater was found to be contaminated with naturally occurring arsenic in the region. Interestingly, high arsenic concentrations (> 10 μg·L(-1)) were generally found in the floodplain areas located along the Mekong River. The source of elevated arsenic concentrations in groundwater is thought to be the release of arsenic from river sediments under highly reducing conditions. In Thailand, arsenic has never been found naturally in groundwater, but originates from tin mining activities. More than 10 million residents in Southeast Asia are estimated to be at risk from consuming arsenic-contaminated groundwater. In Southeast Asia, groundwater has been found to be a significant source of daily inorganic arsenic intake in humans. A positive correlation between groundwater arsenic concentration and arsenic concentration in human hair has been observed in Cambodia and Vietnam. A substantial knowledge gap exists between the epidemiology of arsenicosis and its impact on human health. More collaborative studies particularly on the scope of public health and its epidemiology are needed to conduct to fulfill the knowledge gaps of As as well as to enhance the operational responses to As issue in Southeast Asian countries.


Assessing the impact of nanomaterials on anaerobic microbial communities.
As the technological benefits of nanotechnology begin to rapidly move from laboratory to large-scale industrial application, release of nanomaterials to the environment is inevitable. Little is known about the fate and effects of nanomaterials in nature. Major environmental receptors of nanomaterials will be soil, sediment, and biosolids from wastewater treatment. Analysis of anaerobic microbial activity and communities provides needed information about the effects of nanoparticles in certain environments. In this study, biosolids from anaerobic wastewater treatment sludge were exposed to fullerene (C60) in order to model an environmentally relevant discharge scenario. Activity was assessed by monitoring production of CO2 and CH4. Changes in community structure were monitored by denaturing gradient gel electrophoresis (DGGE), using primer sets targeting the small subunit rRNA genes of Bacteria, Archaea, and Eukarya. Findings suggest that C60 fullerenes have no significant effect on the anaerobic community over an exposure period of a few months. This conclusion is based on the absence of toxicity indicated by no change in methanogenesis relative to untreated reference samples. DGGE results show no evidence of substantial community shifts due to treatment with C60, in any subset of the microbial community.


[Interaction of protein RecA with ADP (ATP): the mechanism of the ATPase reaction].
Structure of the RecA x ADP(ATP) and recA x ADP x cation(+2) complexes was studied by methods of ESR, NMR and near-ultraviolet spectroscopy. The strong hypochromism in the adenine absorption band occurs. The complexes of nucleotide with cation and with protein were independently involved in the triple recA x ADP x cation(+2) complex. The triple complex can be treated as a three-link chain with the ADP localized in the middle.


Prediction of Large Esophageal Variceal Bleeding and Subsequent Mortality.
Ruptured esophageal varices (EV) are commonly associated with bleeding in patients with portal hypertension. As previous studies have been designed to include all viral cirrhosis patients, including those with small varices, there are no definitive reports of the risk factors for large EV (LEV) bleeding and subsequent mortality. In this study we sought to investigate these risk factors. 16 patients with initial episodes of LEV bleeding and 56 patients who had undergone initial preventive treatment for LEV were examined. The Child-Pugh score, MELD score, and their component serological factors were examined. The Child-Pugh score and the MELD score were significantly lower for preventive cases. Serum albumin concentration was significantly lower in bleeding cases, as determined by univariable and multivariable analyses. In initial LEV bleeding cases, higher MELD scores and Child-Pugh scores, and lower serum albumin concentration were associated with significantly higher one-year mortality. These results indicate that control of the MELD score, the Child-Pugh score, and serum albumin concentration is key to improving the prognosis of patients with LEV. Especially, control of serum albumin concentration may be critical for the prevention of initial episodes of LEV bleeding and improving subsequent mortality.


Altered ACTH and corticosterone responses to interleukin-1 beta in male rats exposed to an alcohol diet: possible role of vasopressin and testosterone.
We have previously shown that female rats exposed to an alcohol (ethanol, E) diet exhibited a blunted ACTH response to systemically administered interleukin-1 beta (IL-1 beta). Because of the presence of gender differences in the activity of the hypothalamic-pituitary-adrenal (HPA) axis, and of the possible role played by sex steroids in modulating the inhibitory influence of E in females, we studied the ability of a 10-day E diet to alter ACTH and corticosterone secretion of intact or castrated male rats injected with IL-1 beta or endotoxin, a releaser of endogenous cytokines. Pituitary responsiveness to secretagogues that mediate the endocrine effects of IL-1 beta, namely corticotropin-releasing factor (CRF) and vasopressin (VP), was also investigated. The ACTH responses of animals fed ad libitum (C group) or pair-fed (PF group) to the intravenous administration of IL-1 beta or endotoxin were not statistically different (p > 0.05); therefore, results from these two groups were combined in the initial experiments. Subsequent experiments only used E and C animals. When compared with this latter group, intact E males showed a significant (p < 0.01) decrease in ACTH levels measured 30 and 60 min after the intravenous injection of IL-1 beta or endotoxin. In contrast, E rats released as much corticosterone as C rats in response to IL-1 beta, but significantly (p < 0.05) more following administration of endotoxin (lipopolysaccharide). The stimulatory effect of VP on ACTH release was also measurably blunted by alcohol, whereas that of CRF was not. In none of these experiments were any significant differences observed between C and PF rats.(ABSTRACT TRUNCATED AT 250 WORDS)


Simple radiological indicators for staghorn calculi response to ESWL.
To evaluate staghorn calculi response to ESWL using simple radiological indicators which are stone size, stone homogeneity, and stone density. This is a prospective study of 60 patients with staghorn calculi where the majority had ESWL. The relationship between response and size, homogeneity and density is studied. Single staghorn calculus less than 4 cm, heterogeneous with stone density similar to bone or a little denser than bone has best response to ESWL. ESWL is useful as first line therapy for staghorn calculi less than 4 cm, heterogeneous with similar density to bone or a little denser than bone.


The Stroop effect in English-Japanese bilinguals: the effect of phonological similarity.
English-Japanese bilinguals performed a Stroop color-word interference task with both English and Japanese stimuli and responded in both English and Japanese. The Japanese stimuli were either the traditional color terms (TCTs) written in Hiragana or loanwords (LWs) from English written in Katakana. Both within-language and between-language interference were found for all combinations of stimuli and responses. The between-language interference was larger for Katakana LWs (phonologically similar to English) than for Hiragana TCTs, especially with Japanese responses. The magnitude of this phonological effect increased with self-rated reading fluency in Japanese. Overall responding was slower and the Stroop effect larger with English than with Japanese stimuli. These results suggest that unintentional lexical access elicits automatic phonological processing even with intermediate-level reading proficiency.


Advances in nerve transfer surgery.
Peripheral nerve injuries are devastating injuries and can result in physical impairments, poor functional outcomes and high levels of disability. Advances in our understanding of peripheral nerve regeneration and nerve topography have lead to the development of nerve transfers to restore function. Over the past two decades, nerve transfers have been performed and modified. With the advancements in surgical management and recognition of importance of cortical plasticity, motor-reeducation and perioperative rehabilitation, nerve transfers are producing improved functional outcomes in patients with nerve injuries. This manuscript explores the recent literature as it relates to current nerve transfer techniques and advances in post-operative rehabilitation protocols, with a focus on indications, techniques and outcomes.


Coping and emotional distress in a sample of Swedish unemployed.
The study investigated the associations between coping and symptoms of emotional distress within a sample of 166 unemployed men and women (mean age 40 +/- 10 years, range 22 to 63 years, 52% males). All variables were measured with a questionnaire comprising sociodemographic background, length of unemployment, financial strain, coping style ("Ways of Coping Checklist"), and emotional distress (Hopkins Symptom Check List-25). Emotional distress was positively related to financial strain and more common among younger subjects, divorced subjects and those with foreign background, but less frequent among subjects who had been unemployed for more than three years. After controlling for age, gender, education, foreign background, length of unemployment and financial strain, hierarchical regression analyses showed that emotion-focused coping, i.e. self-blame and wishful thinking, was positively related to emotional distress. Problem-focused coping and cognitive restructuring were negatively associated with emotional distress. Younger subjects and divorced subjects made frequent use of both emotion-focused and problem-focused coping. Female subject and subjects with mandatory school made frequent use of emotion focused coping, if exposed to high financial strain. Problem-focused coping was less frequent among subjects with a low education coupled with low financial strain. Cognitive restructuring was less common among subjects who had been unemployed for more than three years. Younger subjects who were also divorced made less use of both problem-focused coping and cognitive restructuring. The results confirm that coping style has importance for the mental health of the unemployed, and indicate a differential use of coping strategies among subjects with different sociodemographic backgrounds and different levels of financial strain.


bcl-2 plays a critical role in growth and in spontaneous or induced apoptosis in myeloma cell lines.
The role of bcl-2 in spontaneous and drug-induced apoptosis in multiple myeloma (MM) is not yet established, particularly since the frequency of t(14:18) in MM is relatively low. In recent studies, we have investigated the steady-state levels of bcl-2 mRNA transcripts and bcl-2 protein in 8 MM cell lines and found inverse correlation between the levels of bcl-2 and sensitivity to dexamethasone (DEX)-induced apoptosis. Moreover, we have shown that bcl-2 was further down-regulated in DEX sensitive cell lines, but not in DEX resistance cell lines, in the course of DEX-induced apoptosis (Int J Oncol 8: 719-726, 1996). Herein, we report the results of transfection studies of 2 DEX sensitive MM cell lines, expressing relatively low levels of bcl-2, with a bcl-2 inducible gene construct expressed under the control of lac repressor operon. Thus, switching-on of bcl-2 by IPTG resulted in increased bcl-2 protein in the cells, enhancement of cell growth, and a decrease in spontaneous apoptosis, concomitant with increased resistance to DEX. Switching-off of bcl-2 protein expression by removal of IPTG resulted in restoration of sensitivity to DEX-induced apoptosis. We, therefore, conclude that bcl-2 plays a central role in cell growth and in spontaneous and induced apoptosis in MM cell lines.


A simple method for excising pulmonary venous obstruction after repair of total anomalous pulmonary venous drainage.
A simple excision of pulmonary venous obstruction (PVO) was carried out following a radical operation for total anomalous pulmonary venous drainage (TAPVD, Darling Ia). The results were quite satisfactory. This technique can be performed easily and effectively although hitherto relief of PVO has been considered to be very difficult.