Association of homocysteine levels with blood lead levels and micronutrients in the US general population.
Even though several epidemiological studies have observed positive associations between blood lead levels and homocysteine, no study has examined whether this association differs by the levels of micronutrients, such as folate, vitamin B6, and vitamin B12, which are involved in the metabolism of homocysteine. In this study, we examined the interactions between micronutrients and blood lead on homocysteine levels. This study was performed with 4089 adults aged ≥20 years old in the US general population using the National Health and Nutrition Examination Survey 2003-2004. There were significant or marginally significant interactions between micronutrients and blood lead levels on mean homocysteine levels. Positive associations between blood lead and homocysteine were clearly observed among subjects with low levels of folate or low vitamin B6 (p-trend <0.01, respectively). However, in the case of vitamin B12, there was a stronger positive association between blood lead and homocysteine among subjects with high levels of vitamin B12, compared to those with low levels of vitamin B12. In fact, the levels of homocysteine were already high among subjects low in vitamin B12, irrespective of blood lead levels. When we used hyperhomocysteinemia (homocysteine>15 µmol/L) as the outcome, there were similar patterns of interaction, though p-values for each interaction failed to reach statistical significance. In the current study, the association between blood lead and homocysteine differed based on the levels of folate, vitamin B6, or vitamin B12 present in the blood. It may be important to keep sufficient levels of these micronutrients to prevent the possible harmful effects of lead exposure on homocysteine levels.


Distribution of actin and tubulin in outer hair cells isolated from developing rat cochlea: a quantitative study.
In the organ of Corti, outer hair cells (OHCs) are sensory effectors responsible for the high sensitivity and sharp tuning of the cochlea. Whilst the distribution and organization of actin and tubulin in adult OHCs have been extensively studied, less is known about developing OHCs. In this study we use a quantitative cytometric approach on rat isolated OHCs to measure the distribution of these cytoskeletal proteins from the first stages of development (postnatal day 5) to the adult stage. We report a general decrease in both actin and tubulin concentrations during OHC maturation. Actin first decreases in the apical domain, and then in the medio-basal domain. In the apical domain, this could be related to the physiological reduction in the number of stereocilia occurring during ciliogenesis. In the medio-basal domain, the decrease, accompanied by a redistribution of actin toward the lateral wall, is possibly related to the general reorganization of cytoplasmic organelles, to the maturation of the cortical lattice, and to cell growth. Tubulin concentration decreases regularly in both the apical and the medio-basal domains. This developmental change in tubulin concentration could be due to the regression of the kinocilium that occurs by the end of ciliogenesis, and, as argued for actin, to the general reorganization of cytoplasmic organelles, and to cell growth.


Modeling ternary fluids in contact with elastic membranes.
We present a thermodynamically consistent model of a ternary fluid interacting with elastic membranes. Following a free-energy modeling approach for the fluid phases, we derive the governing equations for the dynamics of the ternary fluid flow and membranes. We also provide the numerical framework for simulating such fluid-structure interaction problems. It is based on the lattice Boltzmann method for the ternary fluid (Eulerian description) and a finite difference representation of the membrane (Lagrangian description). The ternary fluid and membrane solvers are coupled through the immersed boundary method. For validation purposes, we consider the relaxation dynamics of a two-dimensional elastic capsule placed at a fluid-fluid interface. The capsule shapes, resulting from the balance of surface tension and elastic forces, are compared with equilibrium numerical solutions obtained by surface evolver. Furthermore, the Galilean invariance of the proposed model is proven. The proposed approach is versatile, allowing for the simulation of a wide range of geometries. To demonstrate this, we address the problem of a capillary bridge formed between two deformable capsules.


The role of HCN channels in ventricular repolarization.
Hyperpolarization-activated cyclic nucleotide gated (HCN) channels pass a cationic current (I(h)/I(f)) that crucially contributes to the slow diastolic depolarization (SDD) of sinoatrial pacemaker cells and, hence, is a key determinant of cardiac automaticity and the generation of the heartbeat. However, there is growing evidence that HCN channels are not restricted to the spontaneously active cells of the sinoatrial node and the conduction system but are also present in ventricular cardiomyocytes that produce an action potential lacking SDD. This observation raises the question of the principal function(s) of HCN channels in working myocardium. Our recent analysis of an HCN3-deficient (HCN3-/-) mouse line has shed new light on this central question. We propose that HCN channels contribute to the ventricular action potential waveform, specifically during late repolarization. In this review, we outline this new concept.


Helical computed tomographic scan in the evaluation of mediastinal gunshot wounds.
The standard evaluation of mediastinal gunshot wounds usually requires angiography and either esophagoscopy or esophagography. In the present study, we have evaluated the role of helical computed tomographic (CT) scanning in reducing the need for angiographic and esophageal studies. This was a prospective study of patients with mediastinal gunshot wounds who were hemodynamically stable and would otherwise require angiography and esophageal evaluation. All patients underwent CT scan of the chest with intravenous contrast to delineate the missile trajectory. If the missile tract was in close proximity to the aorta, great vessels, or esophagus, then traditional evaluation with angiographic or esophageal evaluation was pursued. A total of 24 patients met the inclusion criteria and underwent CT scan evaluation of their mediastinal gunshot wounds. One patient was taken for sternotomy to remove a missile embedded in the myocardium solely on the basis of the result of the CT scan. Because of proximity of the bullet tract, 12 patients required additional evaluation with eight angiograms and nine esophageal studies. One of these patients had a positive angiogram (bullet resting against the ascending aorta) and underwent sternotomy for missile removal; all other studies were negative. The remaining 11 patients were found to have well-defined missile tracts that approached neither the aorta nor the esophagus, and no additional evaluation was pursued. There were no missed mediastinal injuries in this group. Overall, 12 of 24 patients (50%) had a change in management (either received an operation or avoided additional radiographic or endoscopic evaluation) on the basis of the CT scan. The helical CT scan provides a rapid, readily available, noninvasive means to evaluate missile trajectories. This permits accurate assessment of potential mediastinal injury and reduces the need for routine angiographic and esophageal studies.


Alcohol and drug use among adolescents: and the co-occurrence of mental health problems. Ung@hordaland, a population-based study.
The use of alcohol and drugs is prevalent among adolescents, but too little is known about the association between debut of alcohol and drug use, problematic use and concurrent mental health. The aim of the study was to investigate the cross-sectional association between debut of any alcohol or drug use and alcohol-related and drug-related problems and mental health. We also wanted to examine potential interactions between gender and age, and alcohol-related and drug-related variables. Cross-sectional study. Population-based sample of Norwegian adolescents. Data stem from the large population-based ung@hordaland study (N=9203), where all adolescents aged 17-19 years living in Hordaland county (Norway) were invited to participate. The main independent variables were debut of alcohol and drug use, alcohol consumption and the presence of alcohol and drug problems as measured by CRAFFT. The dependent variables were self-reported symptoms of anxiety, depression, inattention and hyperactivity. Statistical analyses included logistic regression models. Debut of alcohol and drug use were associated with symptoms of depression, inattention and hyperactivity (crude ORs 1.69-2.38, p<0.001), while only debut of drug use was associated with increased symptoms of anxiety (OR=1.33, CI 95% 1.05 to 1.68, p=0.017). Alcohol-related and drug-related problems as measured by CRAFFT were associated with all mental health problems (crude ORs 1.68-3.24, p<0.001). There was little evidence of any substantial age or gender confounding on the estimated associations between alcohol-related and drug-related measures and mental health problems. Early debut of alcohol and drug use and drug problems is consistently associated with more symptoms of mental health problems, indicating that these factors are an important general indicator of mental health in adolescence.


DNA polymerase zeta is essential for hexavalent chromium-induced mutagenesis.
Translesion synthesis (TLS) is a unique DNA damage tolerance mechanism involved in the replicative bypass of genetic lesions in favor of uninterrupted DNA replication. TLS is critical for the generation of mutations by many different chemical and physical agents, however, there is no information available regarding the role of TLS in carcinogenic metal-induced mutagenesis. Hexavalent chromium (Cr(VI))-containing compounds are highly complex genotoxins possessing both mutagenic and clastogenic activities. The focus of this work was to determine the impact that TLS has on Cr(VI)-induced mutagenesis in Saccharomyces cerevisiae. Wild-type yeast and strains deficient in TLS polymerases (i.e. Polzeta (rev3), Poleta (rad30)) were exposed to Cr(VI) and monitored for cell survival and forward mutagenesis at the CAN1 locus. In general, TLS deficiency had little impact on Cr(VI)-induced clonogenic lethality or cell growth. rad30 yeast exhibited higher levels of basal and induced mutagenesis compared to Wt and rev3 yeast. In contrast, rev3 yeast displayed attenuated Cr(VI)-induced mutagenesis. Moreover, deletion of REV3 in rad30 yeast (rad30 rev3) resulted in a significant decrease in basal and Cr(VI) mutagenesis relative to Wt and rad30 single mutants indicating that mutagenesis primarily depended upon Polzeta. Interestingly, rev3 yeast were similar to Wt yeast in susceptibility to Cr(VI)-induced frameshift mutations. Mutational analysis of the CAN1 gene revealed that Cr(VI)-induced base substitution mutations accounted for 83.9% and 100.0% of the total mutations in Wt and rev3 yeast, respectively. Insertions and deletions comprised 16.1% of the total mutations in Cr(VI) treated Wt yeast but were not observed rev3 yeast. This work provides novel information regarding the molecular mechanisms of Cr(VI)-induced mutagenesis and is the first report demonstrating a role for TLS in the fixation of mutations induced by a carcinogenic metal.


Effectiveness and characteristics of interventions to improve work participation in adults with chronic physical conditions: a systematic review.
Chronic physical conditions often negatively affect work participation. The objective of this systematic review is to investigate the effectiveness and characteristics of vocational rehabilitation interventions for people with a chronic physical condition. Searches in five databases up to April 2020 identified 30 studies meeting our inclusion criteria. Two reviewers independently assessed and extracted data. The Grading of Recommendation, Assessment, Development and Evaluation (GRADE) framework was used to evaluate quality of evidence for three outcome measures related to work participation. All vocational rehabilitation interventions consisted of multiple components, but their characteristics varied widely. Analysis of 22 trials yielded a moderate positive effect with moderate certainty of interventions on work status; analysis of five trials with low risk of bias showed a large positive effect with moderate certainty (risk ratio 1.33 and 1.57, respectively). In addition, in eight studies we found a moderate to small positive effect with low certainty on work attitude (standardized mean difference = 0.59 or 0.38, respectively). We found no effect on work productivity in nine studies. The systematic review of the literature showed positive effects of vocational rehabilitation interventions on work status and on work attitude; we found no effect on work productivity.Implications for rehabilitationIn rehabilitation, addressing work participation of persons with a chronic physical condition using targeted interventions is beneficial to improve or sustain work participation, irrespective of the intervention characteristics and diagnosis.Interventions that include multiple components and offer individual support, whether or not combined with group sessions, are likely to be more effective in improving work participation in persons with a chronic physical condition.The overview of vocational interventions in this systematic review may assist healthcare professionals in making informed decisions as to which intervention to provide.Vocational rehabilitation, as well as studies on work participation in chronic disease, should include a long follow-up period to explore if work participation is sustainable and contributes to health and wellbeing.


Prediction of behavioural and cognitive deficits in patients with traumatic brain injury at an acute rehabilitation setting.
The goal of this study was to identify factors that would predict short-term neuropsychological outcome in patients with traumatic brain injury (TBI) hospitalized in an acute rehabilitation setting. Data was collected in the context of an acute early rehabilitation setting of a trauma centre. A brief neuropsychological assessment was carried out for 348 patients within a month following their trauma. Length of post-traumatic amnesia (PTA) was the best predictor of behavioural, memory and executive function variables within a month post TBI. The odds of being agitated, labile, irritable and disinhibited at one month post trauma were almost six times higher for those with PTA that lasted more than 7 days compared to those with a PTA of less than 24 hours. Also, the odds of having a higher mental manipulation score (less significant executive function impairment) were almost two times lower for those with frontal lesions, and three to six times lower for those with PTA of more than 24 hours. In addition, TBI severity, education and age were considered good predictors of some aspects of neuropsychological outcome. This model may help clinicians and administrators recognize the probable post-traumatic deficits as quickly as possible and to plan interventions as well as post-acute discharge orientation accordingly and early on.


Expression and properties of two types of protein kinase C: alternative splicing from a single gene.
Two complementary DNA's, encoding the complete sequences of 671 and 673 amino acids for subspecies of rat brain protein kinase C, were expressed in COS 7 cells. The complementary DNA sequence analysis predicted that the two enzymes are derived from different ways of splicing and differ from each other only in the short ranges of their carboxyl-terminal regions. Both enzymes showed typical characteristics of protein kinase C that responded to Ca2+, phospholipid, and diacylglycerol. The enzymes showed practically identical physical and kinetic properties and were indistinguishable from one of the several subspecies of protein kinase C that occurs in rat brain but not in untransfected COS 7 cells. Partial analysis of the genomic structure confirmed that these two subspecies of protein kinase C resulted indeed from alternative splicing of a single gene.


Beyond Marcus theory and the Landauer-Büttiker approach in molecular junctions. II. A self-consistent Born approach.
Marcus and Landauer-Büttiker approaches to charge transport through molecular junctions describe two contrasting mechanisms of electronic conduction. In previous work, we have shown how these charge transport theories can be unified in the single-level case by incorporating lifetime broadening into the second-order quantum master equation. Here, we extend our previous treatment by incorporating lifetime broadening in the spirit of the self-consistent Born approximation. By comparing both theories to numerically converged hierarchical-equations-of-motion results, we demonstrate that our novel self-consistent approach rectifies shortcomings of our earlier framework, which are present especially in the case of relatively strong electron-vibrational coupling. We also discuss circumstances under which the theory developed here simplifies to the generalized theory developed in our earlier work. Finally, by considering the high-temperature limit of our new self-consistent treatment, we show how lifetime broadening can also be self-consistently incorporated into Marcus theory. Overall, we demonstrate that the self-consistent approach constitutes a more accurate description of molecular conduction while retaining most of the conceptual simplicity of our earlier framework.


Role of Mitochondrial Stress Protein HSP60 in Diabetes-Induced Neuroinflammation.
Diabetes mellitus is the most common metabolic disorder characterized by hyperglycemia and associated malfunctions of the metabolism of carbohydrates, proteins, and lipids. There is increasing evidence of a relationship between diabetes and vascular dementia. Interestingly, hyperglycemia-linked neuroinflammation in the central nervous system is considered to play a key role during vascular dementia in diabetic patients. However, the mechanisms responsible for the relationship between hyperglycemia and neuroinflammation is not clearly understood. Diabetes-induced alternations in the blood-brain barrier permit high glucose influx into the brain cells via glucose transporters and promote oxidative stress through overproduction of reactive oxygen species. Despite many studies demonstrating a link between oxidative stress and mitochondrial dysfunction, the relationship between mitochondrial dysfunction and neuron inflammation during hyperglycemia remains to be established. In this review, we will focus on diabetes-induced changes in the central nervous system and the role of mitochondrial heat shock protein 60 (HSP60) as an initiator of oxidative stress and potential modulator of neuroinflammation. We suggest that oxidative stress-mediated mitochondrial dysfunction stimulates the upregulation of mitochondrial heat shock protein 60 (HSP60) and ultimately initiates inflammatory pathways by activating pattern recognition receptors. HSP60 also could be a focal point in the development of a biomarker of neuroinflammation as HSP60 is known to be significantly elevated in diabetic patients. Interestingly, extracellular secretion of HSP60 via exosomes suggests that inflammation could spread to neighboring astrocytes by activating pattern recognition receptors of astrocytes via neuronal exosomes containing HSP60. A mechanism for linking neuron and astrocyte inflammation will provide new therapeutic approaches to modulate neuroinflammation and therefore potentially ameliorate the cognitive impairment in diabetic brains associated with vascular dementia.


Falling Cardiovascular Mortality in Heart Failure With Reduced Ejection Fraction and Implications for Clinical Trials.
This study examined the trends in the relative contributions of cardiovascular and noncardiovascular mortality to total mortality according to use of beta-blockers in clinical trials of patients with heart failure with reduced ejection fraction (HF-REF). With the increasingly widespread use of disease-modifying therapies, particularly beta-blockers, in HF-REF, the proportion of patients dying from cardiovascular causes is likely to be decreasing. In a systematic review, 2 investigators independently searched online databases to identify clinical trials including >400 patients with chronic heart failure published between 1986 and 2014 and that adjudicated cause of death. Trials were divided into 3 groups on the basis of the proportion of patients treated with a beta-blocker (<33% [low], 33% to 66% [medium], and >66% [high]). Percentages of total deaths adjudicated as cardiovascular or noncardiovascular were calculated by weighted means and weighted standard deviations. Weighted Student t tests were used to compare results between groups. Sixty-six trials met the inclusion criteria with a total of 136,182 patients and 32,140 deaths. There was a sequential increase in the percentage of noncardiovascular deaths with increasing beta-blocker use from 11.4% of all deaths in trials with low beta-blocker use to 19.1% in those with high beta-blocker use (p < 0.001). In trials of patients with HF-REF, the proportion of deaths adjudicated as cardiovascular has decreased. Cardiovascular mortality, and not all-cause mortality, should be used as an endpoint for trials of new treatments for HF-REF.


Antibody responses to lytic and latent human herpesvirus 8 antigens among HIV-infected patients in central China.
Human herpesvirus 8 (HHV8) is an important opportunistic infection of HIV/AIDS. However, very little is known about antibody seropositivities to HHV8 lytic and latent antigens among HIV-infected patients in China. Therefore, a cross-sectional study was conducted to explore HHV8 serostatus among 316 HIV-infected patients in a rural area of central China. The antibody seropositivity to HHV8 ORF65 (lytic) and LANA (latent) antigens was 12.7% and 10.4%, respectively. Patients who were naïve to antiretroviral therapy (ART) were more likely to be seropositive for antibodies to ORF65 (OR: 3.79; 95% CI: 1.71-8.42) and LANA (OR: 3.77; 95% CI: 1.55-9.14) than patients receiving ART. Patients having CD4+ cell counts less than 200 cells/mm3 were more likely to be seropositive for LANA antibody (OR: 3.53; 95% CI: 1.44-8.64) and to have lower LANA antibody titer (p = 0.007). They were also more likely to be seropositive for ORF65 antibody (OR: 2.12; 95% CI: 0.94-4.78) and to have a lower ORF65 antibody titer (p = 0.065), though the difference was marginally significant. No associations between other viral coinfections studied and antibody seropositivity to either latent or lytic HHV8 antigens were identified. Study findings suggest that antibody responses to both lytic and latent HHV8 antigens among HIV patients in China were fairly high and were associated with immunodeficiency status and ART.


LIMPRINT in Specialist Lymphedema Services in United Kingdom, France, Italy, and Turkey.
Background: There is no standardized international model for specialist lymphedema services, which covers the types of lymphedema treated and the treatments provided. The aim of this study was to provide a profile of patients attending specialist lymphedema services in different countries to explore similarities and differences. Methods and Results: The LIMPRINT core tool was used in specialist lymphedema services in the United Kingdom, France, Italy, and Turkey. Services in Turkey saw a slightly younger age group, with a higher proportion of female patients reflecting a particular focus on breast cancer-related lymphedema. There were higher levels of obesity and restricted mobility in patients in the United Kingdom compared with other countries. Italy and France saw the highest percentage of patients with primary lymphedema. Diabetes was a common comorbidity in the United Kingdom and Turkey. The United Kingdom saw the largest number of patients with lower limb lymphedema. Conclusions: The results show a wide range of complexity of patients treated in specialist lymphedema services. Some of the differences between countries may reflect different stages in the evolution of specialist lymphedema services, rather than a true difference in prevalence, with those with "younger" services treating a high proportion of patients with cancer and those with more established services treating a wider range of different types of lymphedema, including more elderly people with multiple comorbidities.


Inter-leg systolic blood pressure difference predicts cardiovascular events and mortality in incident hemodialysis patients.
High inter-arm blood pressure difference, a marker of vascular disease, may be difficult to assess in hemodialysis patients with arm arteriovenous fistulae. We investigated if high inter-leg systolic blood pressure difference associates with cardiovascular events and increased mortality in hemodialysis patients. Among 118 incident Japanese dialysis patients, bilateral leg blood pressure, arm blood pressure, brachial-ankle pulse wave velocity, and ankle-brachial index were measured, and the relative risk associated with inter-leg systolic blood pressure difference and other indices of vascular status was analyzed. During follow-up (median, 46 months), 18 deaths and 75 cardiovascular events occurred in 38 patients. Kaplan-Meier curves showed that higher inter-leg systolic blood pressure difference was associated with overall (log-rank 9.35, p = 0.002) and cardiovascular (log-rank 5.81, p = 0.02) mortality. The period from the start of dialysis therapy to the first cardiovascular event was shorter as inter-leg systolic blood pressure difference increased (log-rank 23.7, p < 0.0001). In Cox hazard models, inter-leg systolic blood pressure difference greater than median independently predicted deaths (relative risk, 3.8; 95% confidence interval, 1.3-13.9) and cardiovascular events (relative risk, 3.9; 95% confidence interval, 1.9-9.21) after adjustments for age, sex, nutritional status, and diabetes, whereas other indices were not related to the risks. For well-nourished, moderately malnourished, and severely malnourished patients, the cumulative number of cardiovascular events in the high-inter-leg systolic blood pressure difference patients were 4.96, 31.44, and 55.18 events per 100 patient-years. Higher inter-leg systolic blood pressure difference associated with increased risk of mortality and cardiovascular events suggesting that wider application of inter-leg systolic blood pressure difference measurements may be warranted in hemodialysis patients.


Adenovirus infection in pediatric small bowel transplantation recipients.
The purpose of this study was to determine the prevalence of adenoviral infection in pediatric small bowel transplantation (SBT) recipients, examine risk factors for progression to histologic disease, and examine the impact of adenovirus on outcome. Beginning in July 2000, all SBT recipients had viral cultures for adenovirus, cytomegalovirus (CMV), and herpes simplex virus (HSV) obtained routinely during graft biopsies. The medical records were retrospectively reviewed for frequency and site of viral culture, types and doses of immunosuppressive drugs, episodes of rejection, histology of allograft biopsies, and other infections. Adenoviral isolates were typed by polymerase chain reaction and type-specific neutralization assays. All 14 SBT recipients who met enrollment criteria had evidence of adenoviral infection (intestinal graft, 13; liver graft, 1). Eight of 14 developed histologic disease with identifiable adenoviral intranuclear inclusions. In contrast, CMV enteritis was identified in only one patient, who subsequently also developed adenoviral disease. No other viruses were detected. Adenoviral cultures were first positive within 30 days of transplant in nine. Patients with histologic disease were more likely than those without to have received intensive corticosteroid therapy (P<0.007), had virus isolated from more than one site (P=0.03), and had persistent positive cultures (P<0.01). Adenovirus was commonly isolated from children undergoing intestinal transplantation. Progression to disease may be associated with more intensive immunosuppressive therapy and inability to clear virus.


Carboxydothermus pertinax sp. nov., a thermophilic, hydrogenogenic, Fe(III)-reducing, sulfur-reducing carboxydotrophic bacterium from an acidic hot spring.
A novel anaerobic, Fe(III)-reducing, hydrogenogenic, carboxydotrophic bacterium, designated strain Ug1(T), was isolated from a volcanic acidic hot spring in southern Kyushu Island, Japan. Cells of the isolate were rod-shaped (1.0-3.0 µm long) and motile due to peritrichous flagella. Strain Ug1(T) grew chemolithoautotrophically on CO (100% in the gas phase) with reduction of ferric citrate, amorphous iron (III) oxide, 9,10-anthraquinone 2,6-disulfonate, thiosulfate or elemental sulfur. No carboxydotrophic growth occurred with sulfate, sulfite, nitrate or fumarate as electron acceptor. During growth on CO, H(2) and CO(2) were produced. Growth occurred on molecular hydrogen as an energy source and carbon dioxide as a sole carbon source. Growth was observed on various organic compounds under an N(2) atmosphere with the reduction of ferric iron. The temperature range for carboxydotrophic growth was 50-70 °C, with an optimum at 65 °C. The pH(25 °C) range for growth was 4.6-8.6, with an optimum between 6.0 and 6.5. The doubling time under optimum conditions using CO with ferric citrate was 1.5 h. The DNA G+C content was 42.2 mol%. Analysis of 16S rRNA gene sequences demonstrated that this strain belongs to the thermophilic carboxydotrophic bacterial genus Carboxydothermus, with sequence similarities of 94.1-96.6% to members of this genus. The isolate can be distinguished from other members of the genus Carboxydothermus by its ability to grow with elemental sulfur or thiosulfate coupled to CO oxidation. On the basis of phylogenetic analysis and unique physiological features, the isolate represents a novel species of the genus Carboxydothermus for which the name Carboxydothermus pertinax sp. nov. is proposed; the type strain of the novel species is Ug1(T) (=DSM 23698(T)=NBRC 107576(T)).


Computational design of water-soluble α-helical barrels.
The design of protein sequences that fold into prescribed de novo structures is challenging. General solutions to this problem require geometric descriptions of protein folds and methods to fit sequences to these. The α-helical coiled coils present a promising class of protein for this and offer considerable scope for exploring hitherto unseen structures. For α-helical barrels, which have more than four helices and accessible central channels, many of the possible structures remain unobserved. Here, we combine geometrical considerations, knowledge-based scoring, and atomistic modeling to facilitate the design of new channel-containing α-helical barrels. X-ray crystal structures of the resulting designs match predicted in silico models. Furthermore, the observed channels are chemically defined and have diameters related to oligomer state, which present routes to design protein function.


Family aggression in a social lizard.
The evolution of family living is underpinned by conflict and cooperation between family members. While family groups can be maintained by reducing conflict between parents and offspring, interactions between siblings may play an equally important role. Here, we compared the level of aggressive interactions between siblings to that between parents and their offspring in the family living skink Liopholis whitii. Aggressive interactions occurred much more frequently between siblings and between fathers and offspring than between mothers and their offspring. These results suggest that ecological and social conditions that reduce conflict between siblings and between males and offspring will be fundamental in the evolutionary maintenance and diversification of family living in these lizards.


A cost-effective IoT strategy for remote deployment of soft sensors - a case study on implementing a soft sensor in a multistage MBBR plant.
Model-based soft sensors can enhance online monitoring in wastewater treatment processes. These soft sensor scripts are executed either locally on a programmable logic controller (PLC) or remotely on a system with data-access over the internet. This work presents a cost-effective, flexible, open source IoT solution for remote deployment of a soft sensing algorithm. The system uses low-priced hardware and open-source programming language to set up the communication and remote-access system. Advantages of the new IoT architecture are demonstrated through a case study for remote deployment of an Extended Kalman Filter (EKF) to estimate additional water quality parameters in a multistage moving bed biofilm reactor (MBBR) plant. The soft-sensor results are successfully validated against standardised laboratory measurements to prove their ability to provide real-time estimations.


Can Caries-Affected Dentin be Completely Remineralized by Guided Tissue Remineralization?
INTRODUCTION: To date, there is no evidence that conventional remineralization techniques using calcium and phosphate ion- containing media will completely remineralize carious lesions in regions where remnant apatite seed crystallites are absent. Conversely, guided tissue remineralization using biomimetic analogs of dentin matrix proteins is successful in remineralizing thin layers of completely demineralized dentin. THE HYPOTHESIS: Conventional remineralization strategy depends on epitaxial growth over existing apatite crystallites. If there are no or few crystallites, there will be no remineralization. Guided tissue remineralization uses biomimetic analogs of dentin matrix proteins to introduce sequestered amorphous calcium phosphate nanoprecursors into the internal water compartments of collagen fibrils. Attachment of templating analogs of matrix phosphoproteins to the collagen fibrils further guided the nucleation and growth of apatite crystallites within the fibril. Such a strategy is independent of apatite seed crystallites. Our hypothesis is that 250-300 microns thick artificial carious lesions can be completely remineralized in vitro by guide tissue remineralization but not by conventional remineralization techniques. EVALUATION OF THE HYPOTHESIS: Validation of the hypothesis will address the critical barrier to progress in remineralization of caries- affected dentin and shift existing paradigms by providing a novel method of remineralization based on a nanotechnology-based bottom-up approach. This will also generate important information to support the translation of the proof-of-concept biomimetic strategy into a clinically-relevant delivery system for remineralizing caries-affected dentin created by micro-organisms in the oral cavity.


Comprehensive Analysis of Applied Machine Learning in Indoor Positioning Based on Wi-Fi: An Extended Systematic Review.
Nowadays, there are a multitude of solutions for indoor positioning, as opposed to standards for outdoor positioning such as GPS. Among the different existing studies on indoor positioning, the use of Wi-Fi signals together with Machine Learning algorithms is one of the most important, as it takes advantage of the current deployment of Wi-Fi networks and the increase in the computing power of computers. Thanks to this, the number of articles published in recent years has been increasing. This fact makes a review necessary in order to understand the current state of this field and to classify different parameters that are very useful for future studies. What are the most widely used machine learning techniques? In what situations have they been tested? How accurate are they? Have datasets been properly used? What type of Wi-Fi signals have been used? These and other questions are answered in this analysis, in which 119 papers are analyzed in depth following PRISMA guidelines.


Mig-6 suppresses endometrial cancer associated with Pten deficiency and ERK activation.
PTEN mutations are the most common genetic alterations in endometrial cancer. Loss of PTEN and subsequent AKT activation stimulate estrogen receptor α-dependent pathways that play an important role in endometrial tumorigenesis. The major pathologic phenomenon of endometrial cancer is the loss of ovarian steroid hormone control over uterine epithelial cell proliferation and apoptosis. However, the precise mechanism of PTEN/AKT signaling in endometrial cancer remains poorly understood. The progesterone signaling mediator MIG-6 suppresses estrogen signaling and it has been implicated previously as a tumor suppressor in endometrial cancer. In this study, we show that MIG-6 also acts as a tumor suppressor in endometrial cancers associated with PTEN deficiency. Transgenic mice, where Mig-6 was overexpressed in progesterone receptor-expressing cells, exhibited a relative reduction in uterine tumorigenesis caused by Pten deficiency. ERK1/2 was phosphorylated in uterine tumors and administration of an ERK1/2 inhibitor suppressed cancer progression in PR(cre/+)Pten(f/f) mice. In clinical specimens of endometrial cancer, MIG-6 expression correlated inversely with ERK1/2 phosphorylation during progression. Taken together, our findings suggest that Mig-6 regulates ERK1/2 phosphorylation and that it is crucial for progression of PTEN-mutant endometrial cancers, providing a mechanistic rationale for the evaluation of ERK1/2 inhibitors as a therapeutic treatment in human endometrial cancer.


Personality disorder: a new global perspective.
Personality disorder is now being accepted as an important condition in mainstream psychiatry across the world. Although it often remains unrecognized in ordinary practice, research studies have shown it is common, creates considerable morbidity, is associated with high costs to services and to society, and interferes, usually negatively, with progress in the treatment of other mental disorders. We now have evidence that personality disorder, as currently classified, affects around 6% of the world population, and the differences between countries show no consistent variation. We are also getting increasing evidence that some treatments, mainly psychological, are of value in this group of disorders. What is now needed is a new classification that is of greater value to clinicians, and the WPA Section on Personality Disorders is currently undertaking this task.


The Zika Virus Individual Participant Data Consortium: A Global Initiative to Estimate the Effects of Exposure to Zika Virus during Pregnancy on Adverse Fetal, Infant, and Child Health Outcomes.
This commentary describes the creation of the Zika Virus Individual Participant Data Consortium, a global collaboration to address outstanding questions in Zika virus (ZIKV) epidemiology through conducting an individual participant data meta-analysis (IPD-MA). The aims of the IPD-MA are to (1) estimate the absolute and relative risks of miscarriage, fetal loss, and short- and long-term sequelae of fetal exposure; (2) identify and quantify the relative importance of different sources of heterogeneity (e.g., immune profiles, concurrent flavivirus infection) for the risk of adverse fetal, infant, and child outcomes among infants exposed to ZIKV in utero; and (3) develop and validate a prognostic model for the early identification of high-risk pregnancies and inform communication between health care providers and their patients and public health interventions (e.g., vector control strategies, antenatal care, and family planning programs). By leveraging data from a diversity of populations across the world, the IPD-MA will provide a more precise estimate of the risk of adverse ZIKV-related outcomes within clinically relevant subgroups and a quantitative assessment of the generalizability of these estimates across populations and settings. The ZIKV IPD Consortium effort is indicative of the growing recognition that data sharing is a central component of global health security and outbreak response.


Detection of nerve gases using surface-enhanced Raman scattering substrates with high droplet adhesion.
Threats from chemical warfare agents, commonly known as nerve gases, constitute a serious security issue of increasing global concern because of surging terrorist activity worldwide. However, nerve gases are difficult to detect using current analytical tools and outside dedicated laboratories. Here we demonstrate that surface-enhanced Raman scattering (SERS) can be used for sensitive detection of femtomol quantities of two nerve gases, VX and Tabun, using a handheld Raman device and SERS substrates consisting of flexible gold-covered Si nanopillars. The substrate surface exhibits high droplet adhesion and nanopillar clustering due to elasto-capillary forces, resulting in enrichment of target molecules in plasmonic hot-spots with high Raman enhancement. The results may pave the way for strategic life-saving SERS detection of chemical warfare agents in the field.


Drosophila amyloid precursor protein-like is required for long-term memory.
The amyloid precursor protein (APP) plays an important role in Alzheimer's disease (AD), a progressive neurodegenerative pathology that first manifests as a decline of memory. While the main hypothesis for AD pathology centers on the proteolytic processing of APP, very little is known about the physiological function of the APP protein in the adult brain. Likewise, whether APP loss of function contributes to AD remains unclear. Drosophila has been used extensively as a model organism to study neuronal function and pathology. In addition, many of the molecular mechanisms underlying memory are thought to be conserved from flies to mammals, prompting us to study the function of APPL, the fly APP ortholog, during associative memory. It was previously shown that APPL expression is highly enriched in the mushroom bodies (MBs), a specialized brain structure involved in olfactory memory. We analyzed memory in flies in which APPL expression has been silenced specifically and transiently in the adult MBs. Our results show that in adult flies, APPL is not required for learning but is specifically involved in long-term memory, a long lasting memory whose formation requires de novo protein synthesis and is thought to require synaptic structural plasticity. These data support the hypothesis that disruption of normal APP function may contribute to early AD cognitive impairment.


Re-irradiation with stereotactic body radiation therapy as a novel treatment option for isolated local recurrence of pancreatic cancer after multimodality therapy: experience from two institutions.
Limited treatment options exist for isolated local recurrence of pancreatic ductal adenocarcinoma (PDA) following surgical resection accompanied by neoadjuvant or adjuvant chemoradiation therapy (CRT). While select patients are eligible for re-resection, recurrent lesions are often unresectable. Stereotactic body radiation therapy (SBRT) represents a possible minimally invasive treatment option for these patients, although published data in this setting are currently lacking. This study examines the safety, efficacy, and palliative capacity of re-irradiation with SBRT for isolated local PDA recurrence. All patients undergoing SBRT at two academic centers from 2008-2012 were retrospectively reviewed to identify those who received re-irradiation with SBRT for isolated local recurrence or progression of PDA after previous conventionally fractionated CRT. Information regarding demographics, clinicopathologic characteristics, therapies received, survival, symptom palliation, and toxicity was obtained from patient charts. Kaplan-Meier statistics were used to analyze survival and the log-rank test was used to compare survival among patient subgroups. Eighteen patients were identified. Fifteen had previously undergone resection with neoadjuvant or adjuvant CRT, while 3 received definitive CRT for locally advanced disease. Median CRT dose was 50.4 Gy [interquartile range (IQR), 45.0-50.4 Gy] in 28 fractions. All patients subsequently received gemcitabine-based maintenance chemotherapy, but developed isolated local disease recurrence or progression without evidence of distant metastasis. Locally recurrent or progressive disease was treated with SBRT to a median dose of 25.0 Gy (range, 20.0-27.0 Gy) in 5 fractions. Median survival from SBRT was 8.8 months (95% CI, 1.2-16.4 months). Despite having similar clinicopathologic disease characteristics, patients who experienced local progression greater than vs. less than 9 months after surgery/definitive CRT demonstrated superior median survival (11.3 vs. 3.4 months; P=0.019) and progression-free survival (10.6 vs. 3.2 months; P=0.030) after SBRT. Rates of freedom from local progression at 6 and 12 months after SBRT were 78% (14 of 18 patients) and 62% (5 of 8 patients), respectively. Effective symptom palliation was achieved in 4 of 7 patients (57%) who reported symptoms of abdominal or back pain prior to SBRT. Five patients (28%) experienced grade 2 acute toxicity; none experienced grade ≥3 acute toxicity. One patient (6%) experienced grade 3 late toxicity in the form of small bowel obstruction. In conclusion, re-irradiation with hypofractionated SBRT in this salvage scenario appears to be a safe and reasonable option for palliation of isolated local PDA recurrence or progression following previous conventional CRT. Patients with a progression-free interval of greater than 9 months prior to isolated local recurrence or progression may be most suitable for re-irradiation with SBRT, as they appear to have a better prognosis with survival that is long enough for local control to be of potential benefit.


Stable early maternal report of behavioral inhibition predicts lifetime social anxiety disorder in adolescence.
Behavioral inhibition (BI), a temperamental style identifiable in early childhood, is considered a risk factor for the development of anxiety disorders, particularly social anxiety disorder (SAD). However, few studies examining this question have evaluated the stability of BI across multiple developmental time points and followed participants into adolescence-the developmental period during which risk for SAD onset is at its peak. The current study used a prospective longitudinal design to determine whether stable early BI predicted the presence of psychiatric disorders and continuous levels of social anxiety in adolescents. It was hypothesized that stable BI would predict the presence of adolescent psychiatric diagnoses, specifically SAD. Participants included 126 adolescents aged 14 to 16 years who were first recruited at 4 months of age from hospital birth records. Temperament was measured at multiple time points between the ages of 14 months and 7 years. In adolescence, diagnostic interviews were conducted with parents and adolescents, and continuous measures of adolescent- and parent-reported social anxiety were collected. Stable maternal-reported early BI was associated with 3.79 times increased odds of a lifetime SAD diagnosis, but not other diagnoses, during adolescence (95% confidence interval 1.18-12.12). Stable maternal-reported early BI also predicted independent adolescent and parent ratings of ongoing social anxiety symptoms. Findings suggesting that stable maternal-reported early BI predicts lifetime SAD have important implications for the early identification and prevention of SAD.


Income, Poverty, and Material Hardship Among Older Americans.
Using data from the 2008 and 2010 waves of the Health and Retirement Study to analyze the determinants of material hardship among individuals ages sixty-five and older, I look at five self-reported hardships: food insecurity, skipped meals, medication cutbacks, difficulty paying bills, and dissatisfaction with one's financial situation. One-fifth of the elderly report one or more of these hardships. Although hardship is more likely for those with low incomes, most older Americans experiencing hardship are not poor. I analyze whether alternative measures of resources do a better job of predicting hardship than does income relative to the federal poverty threshold. I find that spending relative to the poverty threshold does a worse job predicting hardship than does income relative to poverty. Subtracting out-of-pocket medical spending from income yields a measure that is an even better predictor of hardship. In multivariate models, I find that self-reported health, activity limitations, and disability are significant predictors of hardship. Having reliable children (as assessed by the respondent) or an able-bodied spouse reduces the likelihood of hardship. Poor health increases hardship through three channels: by lowering income, by increasing out-of-pocket medical spending, and through its direct effect on hardship. The first two of these-lower income and higher medical spending-are much less quantitatively important than the third; in a nutshell, poor health makes it harder to get by with less.


Factors influencing serum neopterin and beta 2-microglobulin levels in a healthy diverse population.
Sera and questionnaire data from a population-based random sample of healthy adults was used to evaluate factors influencing neopterin and beta 2-microglobulin (beta 2m) values. Both neopterin and beta 2m levels increased with age and were higher among white than blacks (mean values for whites and blacks: neopterin, 5.06 vs 4.49 nmol/L; beta 2m, 1.36 vs 1.28 mg/L). Gender differences were noted for beta 2m but not neopterin values (beta 2m males vs females: 1.37 vs 1.29 mg/L). Neopterin values were lower among current smokers than among nonsmokers (4.32 vs 5.16 nmol/L) and were higher among users of antihistamines (5.46 among users vs 4.65 nmol/L among nonusers). Neopterin and beta 2m were correlated in this healthy adult population (adjusted r = 0.53, P = 0.001), yet no other interrelationships with numerous biologic markers except between beta 2m and serum-soluble interleukin-2 receptor levels (adjusted r = .41, P = 0.05) were observed. These findings provide important baseline information to consider before planning or evaluating studies utilizing neopterin or beta 2m levels.


Extended depth of field using a liquid crystal annular spatial light modulator.
A detailed investigation is presented on the tunable extended depth of field (EDOF) method, proposed recently by Klapp et al. [Opt. Lett.39, 1414 (2014)]. This method is based on temporal multiplexing of phase masks, using an annular liquid crystal spatial light modulator possessing a small number of rings. Examples of 3D simulations used to determine the phase profiles in the pupil plane are presented, as well as more detailed experimental results. Both the experimental and numerical results include comprehensive analysis of contrast dependence on both the spatial spectrum of the object and the amount of defocus. In addition, for the first time, we present the EDOF order inversion in the experimental and simulated data. The results show a profound performance of the proposed system and method.


Health literacy and shared decision making for prostate cancer patients with low socioeconomic status.
Quality of life (QOL) considerations are important in the treatment decision making process for prostate cancer patients. Although patient involvement in the treatment decision process has been encouraged, low health literacy can limit patient understanding of the complex information about treatments and their probable QOL outcomes and is a barrier to patient participation in the decision-making process. The objectives of the study were to evaluate (i) knowledge, level of satisfaction, and treatment preferences and intentions of men newly diagnosed with prostate cancer after participation in a CD-ROM shared decision making program; and (ii) the relationship between prostate cancer knowledge and health literacy. Thirty newly diagnosed prostate cancer patients from two Veteran's Administration (VA) hospitals in Chicago completed a demographic questionnaire and participated in an interactive CD-ROM shared decision making program. Subsequently, knowledge of prostate cancer, satisfaction with the information in the computer CD-ROM program, treatment preferences, and likelihood of following treatment preferences were assessed using interviewer-administered questionnaires. Health literacy was assessed using the Rapid Estimate of Adult Literacy in Medicine (REALM). The Pearson correlation test was used to assess the relationship between health literacy and prostate cancer knowledge. The chi2 test and the Fischer exact test were used to evaluate relationships between patient demographics and other variables. More than three-quarters of the patients rated the information in the CD-ROM as "very satisfactory" (highest possible rating). Two-thirds of the patients (21 of 30) selected a treatment after participation in the CD-ROM program and 90.5% of these patients stated that they were very or somewhat likely to adhere to their selection. However, prostate cancer knowledge was variable, with one-third of the patients scoring 69.9% or lower. Participants' health literacy was equivalent to a 7th-8th grade reading level (mean = 57.1+/-10.9), and more than one-third of participants (36.7%) had lower than 9th grade literacy levels. Participants' prostate cancer knowledge was correlated with health literacy (Pearson correlation rhor = 0.65, rhop = 0.0001). Patients were satisfied with the interactive shared decision making CD-ROM program, and two-thirds of patients were able to select a preferred treatment based on the information presented in the program that they intended to follow. However, prostate cancer knowledge scores varied among participants after participation in the CD-ROM program, raising doubts that patients were adequately informed to make appropriate choices regarding their treatment. Lower prostate cancer knowledge scores corresponded to lower literacy scores, indicating that low literacy may have hindered patient understanding of the shared decision making program. The development of shared decision making tools should include collaborative efforts with the target population to improve the success of shared decision making programs among patients with low health literacy.


Manipulation of the recipient retinal environment by ectopic expression of neurotrophic growth factors can improve transplanted photoreceptor integration and survival.
Degeneration of the neural retina is the leading cause of untreatable blindness in the developed world. Stem cell replacement therapy offers a novel strategy for retinal repair. Postmitotic photoreceptor precursors derived from the early postnatal (P) retina are able to migrate and integrate into the adult mouse retina following transplantation into the subretinal space, but it is likely that a large number of these cells would be required to restore vision. The adult recipient retina presents a very different environment to that from which photoreceptor precursor donor cells isolated from the developing postnatal retina are derived. Here we considered the possibility that modulation of the recipient environment by ectopic expression of developmentally regulated growth factors, normally present during photoreceptor development, might enhance the migration and integration of transplanted cells into the adult neural retina. Adeno-associated viral (AAV) vectors were used to introduce three growth factors previously reported to play a role in photoreceptor development, IGF1, FGF2, and CNTF, into the adult retina, prior to transplantation of P4 cells derived from the Nrl.GFP(+ve) neural retina. At 3 weeks posttransplantation the number of integrated, differentiated photoreceptor cells present in AAV-mediated neurotrophic factor-treated eyes was assessed and compared to control treated contralateral eyes. We show, firstly, that it is possible to manipulate the recipient retinal microenvironment via rAAV-mediated gene transfer with respect to these developmentally relevant growth factors. Moreover, when combined with cell transplantation, AAV-mediated expression of IGF1 led to significantly increased levels of cell integration, while overexpression of FGF2 had no significant effect on integrated cell number. Conversely, expression of CNTF led to a significant decrease in cell integration and an exacerbated glial response that led to glial scarring. Together, these findings demonstrate the importance of the extrinsic environment of the recipient retina for photoreceptor cell transplantation and show for the first time that it is possible to manipulate this environment using viral vectors to influence photoreceptor transplantation efficiency.


Vertical-coupling optical interface for on-chip optical interconnection.
We present a vertical-coupling optical interface with a grating coupler for transmitting and receiving optical signals between single-mode optical fibers and microphotonic waveguides with a view to realize on-chip optical interconnection. The optical interface consisting of a simple grating structure with a reflective mirror and an optical power combiner exhibits high optical coupling efficiency and wide tolerance range for the misalignment of optical fibers. The optical interface exhibits high coupling efficiency even if the optical input is almost vertical to the chip surface.


Impediments for the uptake of the Botswana government's male circumcision initiative for HIV prevention.
Botswana remains one of the countries with high prevalence of HIV infection with a population prevalence rate of 17.6 in 2008. In 2009, the Ministry of Health launched male circumcision as an additional strategy to the already existing HIV preventive efforts. The purpose of this paper is to share what the participants of a survey to evaluate a short-term male circumcision communication strategy in seven health districts of Botswana reported as impediments for the program's uptake. Qualitative data were obtained from 32 key informants and 36 focus group discussions in 2011. Content analysis method was used to analyze data and to derive themes and subthemes. Although male circumcision was generally acceptable to communities in Botswana, the uptake of the program was slow, and participants attributed that to a number of challenges or impediments that were frustrating the initiative. The impediments were organized into sociocultural factors, knowledge/informational factors, and infrastructural and system factors.


Bone marrow NK1.1(-) and NK1.1(+) T cells reciprocally regulate acute graft versus host disease.
Sorted CD4(+) and CD8(+) T cells from the peripheral blood or bone marrow of donor C57BL/6 (H-2(b)) mice were tested for their capacity to induce graft-versus-host disease (GVHD) by injecting the cells, along with stringently T cell-depleted donor marrow cells, into lethally irradiated BALB/c (H-2(d)) host mice. The peripheral blood T cells were at least 30 times more potent than the marrow T cells in inducing lethal GVHD. As NK1.1(+) T cells represented <1% of all T cells in the blood and approximately 30% of T cells in the marrow, the capacity of sorted marrow NK1.1(-) CD4(+) and CD8(+) T cells to induce GVHD was tested. The latter cells had markedly increased potency, and adding back marrow NK1.1(+) T cells suppressed GVHD. The marrow NK1.1(+) T cells secreted high levels of both interferon gamma (IFN-gamma) and interleukin 4 (IL-4), and the NK1.1(-) T cells secreted high levels of IFN-gamma with little IL-4. Marrow NK1.1(+) T cells obtained from IL-4(-/-) rather than wild-type C57BL/6 donors not only failed to prevent GVHD but actually increased its severity. Together, these results demonstrate that GVHD is reciprocally regulated by the NK1.1(-) and NK1.1(+) T cell subsets via their differential production of cytokines.


Comparing sound localization deficits in bilateral cochlear-implant users and vocoder simulations with normal-hearing listeners.
Bilateral cochlear-implant (BiCI) users are less accurate at localizing free-field (FF) sound sources than normal-hearing (NH) listeners. This performance gap is not well understood but is likely due to a combination of compromises in acoustic signal representation by the two independent speech processors and neural degradation of auditory pathways associated with a patient's hearing loss. To exclusively investigate the effect of CI speech encoding on horizontal-plane sound localization, the present study measured sound localization performance in NH subjects listening to vocoder processed and nonvocoded virtual acoustic space (VAS) stimuli. Various aspects of BiCI stimulation such as independently functioning devices, variable across-ear channel selection, and pulsatile stimulation were simulated using uncorrelated noise (Nu), correlated noise (N0), or Gaussian-enveloped tone (GET) carriers during vocoder processing. Additionally, FF sound localization in BiCI users was measured in the same testing environment for comparison. Distinct response patterns across azimuthal locations were evident for both listener groups and were analyzed using a multilevel regression analysis. Simulated implant speech encoding, regardless of carrier, was detrimental to NH localization and the GET vocoder best simulated BiCI FF performance in NH listeners. Overall, the detrimental effect of vocoder processing on NH performance suggests that sound localization deficits may persist even for BiCI patients who have minimal neural degradation associated with their hearing loss and indicates that CI speech encoding plays a significant role in the sound localization deficits experienced by BiCI users.


Regulation of the rate of asexual growth and commitment to sexual development by diffusible factors from in vitro cultures of Plasmodium falciparum.
The mechanism of switching to sexual differentiation (gametocytogenesis) of Plasmodium falciparum appears to be controlled by stochastic mechanisms that are sensitive to environmental conditions. In any given conditions, only a proportion of genetically identical parasites will become committed to sexual development. We used an experimental co-culture system to detect the presence of diffusible molecules from asexually replicating bloodstream stages of P. falciparum that were capable of influencing the growth and differentiation of the parasite. We cultured two populations of P. falciparum in a shared environment separated by a membrane that allowed free diffusion of molecules. The data presented show that P. falciparum parasites in culture stimulate their own growth and replication, and constitutively inhibit sexual conversion via diffusible molecules. These observations support the model that for P. falciparum, the sexual pathway of development is the default, and that constitutive repression of the sexual pathway permits asexual multiplication to occur in the bloodstream of the human host.


The effect of detergents on the basement membrane complex of a biologic scaffold material.
The basement membrane complex (BMC) is a critical component of the extracellular matrix (ECM) that supports and facilitates the growth of cells. This study investigates four detergents commonly used in the process of tissue decellularization and their effect upon the BMC. The BMC of porcine urinary bladder was subjected to 3% Triton-X 100, 8mM 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate (CHAPS), 4% sodium deoxycholate or 1% sodium dodecyl sulfate (SDS) for 24h. The BMC structure for each treatment group was assessed by immunolabeling, scanning electron microscopy (SEM) and second harmonic generation (SHG) imaging of the fiber network. The composition was assessed by quantification of dsDNA, glycosaminoglycans (GAG) and collagen content. The results showed that collagen fibers within samples treated with 1% SDS and 8mM CHAPS were denatured, and the ECM contained fewer GAG compared with samples treated with 3% Triton X-100 or 4% sodium deoxycholate. Human microvascular endothelial cells (HMEC) were seeded onto each BMC and cultured for 7 days. Cell-ECM interactions were investigated by immunolabeling for integrin β-1, SEM imaging and semi-quantitative assessment of cellular infiltration, phenotype and confluence. HMEC cultured on a BMC treated with 3% Triton X-100 were more confluent and had a normal phenotype compared with HMEC cultured on a BMC treated with 4% sodium deoxycholate, 8mM CHAPS and 1% SDS. Both 8mM CHAPS and 1% SDS damaged the BMC to the extent that seeded HMEC were able to infiltrate the damaged sub-basement membrane tissue, showed decreased confluence and an atypical phenotype. The choice of detergents used for tissue decellularization can have a marked effect upon the integrity of the BMC of the resultant bioscaffold.


The detection of THC, CBD and CBN in the oral fluid of Sativex® patients using two on-site screening tests and LC-MS/MS.
Sativex(®) is an oromucosal spray used to treat spasticity in multiple sclerosis sufferers in some European countries, the United Kingdom, Canada and New Zealand. The drug has also recently been registered by the Therapeutic Goods Administration (TGA) in Australia for treatment of multiple sclerosis. Sativex(®) contains high concentrations of Δ(9)-tetrahydrocannabinol (THC) and cannabidiol (CBD), with the former being the subject of random roadside drug tests across Australia to detect cannabis use. This pilot study aims to determine whether or not patients taking Sativex(®) will test positive to THC using these roadside screening tests. Detectable levels of THC, CBD and cannabinol (CBN) in their oral fluid were also confirmed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The study was a double-blind, placebo controlled design. Oral fluid was tested prior to and immediately after dosing with either Sativex(®) or placebo at intervals up to 2h after the dose. Two Sativex(®) doses were studied. The low dose contained 5.4mg THC, the high dose 21.6mg THC. Results indicate that the primary screening test used in Australian roadside drug testing, the DrugWipe(®) II Twin, often gave a false negative response for THC, even with high concentrations present. However, secondary screening test, Cozart(®) DDS (used by police after a DrugWipe test gives a positive result), gave true positive results in all cases where patients were being treated with Sativex(®). Confirmatory testing showed high concentrations of THC and CBD (>5356ng/mL THC and >3826ng/mL CBD) in the oral fluid shortly after dosing and also elevated concentrations of CBN. Levels dropped quickly but remained at detectable concentrations (>67.6ng/mL) two hours after drug administration. The average concentration ratio of THC/CBD across all positive samples was 1.10 (%RSD 19.9) reflecting the composition of the Sativex(®) spray. In conclusion, Sativex(®) users may test positive for THC by roadside drug testing within 2-3h of use. Confirmatory analysis can identify Sativex(®) treatment through use of THC/CBD ratios, however, these ratios would unlikely be sufficient to differentiate non-medicinal cannabis use from Sativex(®) use if both are taken concurrently.


High-level resistance to moxifloxacin and gatifloxacin associated with a novel mutation in gyrB in toxin-A-negative, toxin-B-positive Clostridium difficile.
To determine the mechanism of high-level resistance to fluoroquinolone antimicrobials in toxin-A-negative, toxin-B-positive (A- B+) Clostridium difficile isolates. Following culture 16-23S PCR ribotyping was used to determine genomic relationships between A- B+ C. difficile isolates. Antimicrobial susceptibilities were determined using Etests in the presence and absence of the efflux pump inhibitors reserpine (20 microg/mL), L-phenylalanine-L-arginine-beta-naphthylamide (PAbetaN; 20 microg/mL) and verapamil (100 microg/mL). Genomic regions including the quinolone-resistance-determining-region (QRDR) of gyrA and gyrB were amplified and characterized. PCR ribotyping profiles identified one major cluster of A- B+ C. difficile, universally resistant to the fluoroquinolones tested (ofloxacin, ciprofloxacin, levofloxacin, moxifloxacin and gatifloxacin; MICs > 32 mg/L). All isolates with high-level resistance had a transversion mutation (A-->T) resulting in the amino acid substitution Asp-426-->Val in gyrB. Non-clonal isolates were susceptible to moxifloxacin and gatifloxacin (MICs 0.3 and 0.4 mg/L, respectively) with reduced susceptibility to levofloxacin (MIC 3 mg/L) consistent with the wild-type genotype. The MICs for resistant isolates were not significantly affected by the addition of any of the efflux pump inhibitors. No amino acid substitutions were identified in the QRDR of gyrA. High-level resistance to fluoroquinolones in A- B+ C. difficile is associated with a novel transversion mutation in gyrB. The emergence of universal resistance in different C. difficile strain types may be a factor promoting outbreaks in hospitals.


Drug interactions of natural supplements in dermatology: a review.
Limited information is available on the drug-drug interactions of natural supplements in dermatology. Many natural supplements are available over the counter, but drug-drug interactions can occur. This study reviews the clinical use and drug interactions of six natural supplements commonly recommended in dermatology: nicotinic acid (nicotinamide), polypodium leucotomos (heliocare), turmeric, horse chestnut seed extract, zinc, and N-acetylcysteine. We reviewed the drug-drug interactions of each supplement using the PubMed database and IBM Micromedex. For nicotinic acid, zinc, horse chestnut, and N-acetylcysteine, IBM Micromedex generated 11, 23, one, and two results, respectively. Further review of literature from PubMed identified two drug interactions with polypodium leucotomos, two with turmeric, and two more with zinc. Notable interactions included an increased risk of myopathy and rhabdomyolysis when nicotinic acid is taken by patients using statins, an increased risk of bleeding associated with horse chestnut seed, especially when used in combination with warfarin, and reduced plasma concentration in many drugs when taken with zinc. Furthermore, N-acetylcysteine may interfere with concentrations of other medications used in the psychiatric setting, and polypodium leucotomos and turmeric may interfere with the CYP metabolic pathway, which may affect drugs metabolized by this pathway. Prior to recommending a treatment, dermatologists should foster awareness of these interactions. In order to advance the practice as a whole, research should continue to evaluate the drug interactions of these natural supplements.


Evaluation of detector material and radiation source position on Compton camera's ability for multitracer imaging.
We present a study on the effects of detector material, radionuclide source and source position on the Compton camera aimed at realistic characterization of the camera's performance in multitracer imaging as it relates to brain imaging. The GEANT4 Monte Carlo simulation software was used to model the physics of radiation transport and interactions with matter. Silicon (Si) and germanium (Ge) detectors were evaluated for the scatterer, and cadmium zinc telluride (CZT) and cerium-doped lanthanum bromide (LaBr(3):Ce) were considered for the absorber. Image quality analyses suggest that the use of Si as the scatterer and CZT as the absorber would be preferred. Nevertheless, two simulated Compton camera models (Si/CZT and Si/LaBr(3):Ce Compton cameras) that are considered in this study demonstrated good capabilities for multitracer imaging in that four radiotracers within the nuclear medicine energy range are clearly visualized by the cameras. It is found however that beyond a range difference of about 2 cm for (113m)In and (18)F radiotracers in a brain phantom, there may be a need to rotate the Compton camera for efficient brain imaging.


Combination Therapy with Renin-Angiotensin System Blockers and Vitamin D Receptor Activators for Predialysis Patients Is Associated with the Incidence of Cardiovascular Events after Dialysis Initiation: A Multicenter Nonrandomized Prospective Cohort Study.
Several human studies reported that the combined use of renin-angiotensin system blockers (RASBs) and vitamin D receptor activators (VDRAs) resulted in decreased urinary protein excretion. However, it is unknown whether this combination therapy influences the incidence of cardiovascular (CV) events in dialysis patients. The study was a multicenter nonrandomized prospective cohort analysis including 1,518 patients. Patients were classified into 4 groups based on medications prescribed before dialysis initiation: those who did not receive RASBs or oral VDRAs (N group), those receiving only RASBs, those receiving only VDRAs, and those receiving a combination of RASBs and VDRAs (RD group). CV events after dialysis initiation were compared using the log-rank test. Factors contributing to the incidence of CV events were examined using multivariate Cox proportional hazard regression analysis. Significant differences were observed in the incidence of CV events and all-cause mortality between the 4 groups (p = 0.021 and p = 0.001, respectively). Cox proportional hazard analysis revealed that the incidence of CV events was significantly lower in the RD group than in the N group (hazard ratio [HR] = 0.65, 95% confidence interval [CI]: 0.50-0.86, p = 0.002). Multivariate analysis revealed that the incidence of CV events was significantly lower in the RD group than in the N group (HR = 0.66, 95% CI: 0.47-0.93, p = 0.016). Combination therapy with RASBs and VDRAs in patients before dialysis initiation was associated with a reduction in CV events during maintenance dialysis.


Mitochondria, PPARs, and Cancer: Is Receptor-Independent Action of PPAR Agonists a Key?
Before the discovery of peroxisome proliferator activated receptors (PPARs), it was well known that certain drugs considered as classical PPAR-alpha agonists induced hepatocarcinoma or peroxisome proliferation in rodents. These drugs were derivatives of fibric acid, and they included clofibrate, bezafibrate, and fenofibrate. However, such toxicity has never been observed in human patients treated with these hypolipidemic drugs. Thiazolidinediones are a new class of PPAR activators showing greater specificity for the gamma isoform of PPARs. These drugs are used as insulin sensitizers in the treatment of type II diabetes. In addition, they have been shown to induce cell differentiation or apoptosis in various experimental models of cancer. PPAR-alpha ligands have also been shown to induce cancer cell differentiation and, paradoxically, PPAR-gamma drug activators have been reported to act as carcinogens. The confusing picture that emerges from these data is further complicated by the series of intriguing side effects observed following administration of pharmacological PPAR ligands (rhabdomyolysis, liver and heart toxicity, anemia, leucopenia). These side effects cannot be easily explained by simple interactions between the drug and nuclear receptors. Rather, these side effects seem to indicate that the ligands have biological activity independent of the nuclear receptors. Considering the emerging role of mitochondria in cancer and the potential metabolic connections between this organelle and PPAR physiology, characterization of the reciprocal influences is fundamental not only for a better understanding of cancer biology, but also for more defined pharmacotoxicological profiles of drugs that modulate PPARs.


Efficacy of Crocus sativus (saffron) in treatment of major depressive disorder associated with post-menopausal hot flashes: a double-blind, randomized, placebo-controlled trial.
Due to concerns regarding the side effects of hormone therapy, many studies have focused on the development of non-hormonal agents for treatment of hot flashes. The aim of this study was to evaluate the efficacy and safety of saffron (stigma of Crocus sativus) in treatment of major depressive disorder associated with post-menopausal hot flashes. Sixty women with post-menopausal hot flashes participated in this study. The patients randomly received either saffron (30 mg/day, 15 mg twice per day) or placebo for 6 weeks. The patients were assessed using the Hot Flash-Related Daily Interference Scale (HFRDIS), Hamilton Depression Rating Scale (HDRS) and the adverse event checklist at baseline and also at the second, fourth, and sixth weeks of the study. Fifty-six patients completed the trial. Baseline characteristics of the participants did not differ significantly between the two groups. General linear model repeated measures demonstrated significant effect for time × treatment interaction on the HFRDIS score [F (3, 162) = 10.41, p = 0.0001] and HDRS score [F (3, 162) = 5.48, p = 0.001]. Frequency of adverse events was not significantly different between the two groups. Results from this study revealed that saffron is a safe and effective treatment in improving hot flashes and depressive symptoms in post-menopausal healthy women. On the other hand, saffron, with fewer side effects, may provide a non-hormonal and alternative herbal medicine option in treatment of women with hot flashes.


Predictors of cardiac hepatopathy in patients with right heart failure.
Some patients with right heart failure develop cardiac hepatopathy (CH). The pathophysiology of CH is thought to be secondary to hepatic venous congestion and arterial ischemia. We sought to define the clinical and hemodynamic characteristics associated with CH. A retrospective cross sectional analysis was performed in which subjects were identified from our institutional cardiology database if echocardiography showed either right ventricular (RV) hypokinesis or dilatation, and was performed within 30 days of right heart catheterization. A chart review was then performed to identify patient clinical characteristics and to determine if the patients had underlying liver disease. Subjects with non-cardiac causes for hepatopathy were excluded. In 188 included subjects, etiology for right heart dysfunction included left heart failure (LHF), shunt, pulmonary hypertension, mitral- tricuspid- and pulmonic valvular disease. On multivariate analysis, higher RV diastolic pressure and etiology for RV dysfunction other than LHF were both associated with CH. Low cardiac output was associated with CH only amongst those without LHF. CH is most often seen in subjects with elevated RV diastolic pressure suggesting a congestive cause in most cases. CH associated with low cardiac output in patients without LHF suggests that low flow may be contributing to the patophysiology in some cases.


Identifying suicidal subtypes and dynamic indicators of increasing and decreasing suicide risk in active duty military personnel: Study protocol.
Several recent studies have demonstrated that posttraumatic stress disorder (PTSD) and insomnia treatments are associated with significant reductions in suicidal ideation (SI) among service members. However, few investigations have evaluated the manner in which suicide risk changes over time among military personnel receiving PTSD or insomnia treatments. This paper describes the study protocol for a project with these aims: (1) explore potential genetic, clinical, and demographic subtypes of suicide risk in a large cohort of deployed service members; (2) explore subtype change in SI as a result of evidence-based psychotherapies for PTSD and insomnia; (3) evaluate the speed of change in suicide risk; and (4) identify predictors of higher- and lower-risk for suicide. Active duty military personnel were recruited for four clinical trials (three for PTSD treatment and one for insomnia treatment) and a large prospective epidemiological study of deployed service members, all conducted through the South Texas Research Organizational Network Guiding Studies on Trauma and Resilience (STRONG STAR Consortium). Participants completed similar measures of demographic and clinical characteristics and subsets provided blood samples for genetic testing. The primary measures that we will analyze are the Beck Scale for Suicide Ideation, Beck Depression Inventory, and the PTSD Checklist for DSM-IV. Results from this study will offer new insights into the presence of discrete subtypes of suicide risk among active duty personnel, changes in risk over time among those subtypes, and predictors of subtypes. Findings will inform treatment development for military service members at risk for suicide.


Diagnosis of Streptococcus canis periprosthetic joint infection: the utility of next-generation sequencing.
A 62-year-old man who had undergone a primary knee arthroplasty 3 years earlier, presented to the emergency department with an infected prosthesis. He underwent prosthesis resection. All cultures failed to identify the infecting organism. Analysis of the intraoperative samples by next-generation sequencing revealed Streptococcus canis (an organism that resides in the oral cavity of dogs). It was later discovered that the patient had sustained a dog scratch injury several days earlier. The patient reports that his dog had licked the scratch. Treatment was delivered based on the sensitivity of S. canis, and the patient has since undergone reimplantation arthroplasty.


Dislocation rate after hip hemiarthroplasty in patients with tumor-related conditions.
Hemiarthroplasty is frequently used to treat femoral neck insufficiency resulting from neoplastic disease in the proximal part of the femur. The authors of a recent study analyzed the dislocation rates following hemiarthroplasty but excluded patients with tumor involvement of the site of the surgery as they hypothesized that the dislocation rates would be markedly higher in such patients. The current study was performed to compare the dislocation rate following hemiarthroplasties performed in patients without tumor involvement with the rate following hemiarthroplasties in patients with tumor involvement of the surgical site. Patients who had undergone hemiarthroplasty following resection of a tumor involving the proximal part of the femur were identified in a total joint registry, and the patients' charts were reviewed retrospectively to determine dislocation rates, preoperative conditions, and postoperative outcomes and treatments. Between 1974 and 2001, 1812 patients were treated with hemiarthroplasty for reasons other than tumor involvement and 320 hemiarthroplasties were performed because of tumor-related conditions. The patients who were treated for a tumor-related condition were younger, and a higher proportion of them were men. The ten-year dislocation rate after the hemiarthroplasties performed for tumor-related conditions (10.9%) was higher than that following the hemiarthroplasties performed for non-tumor-related conditions (2.1%) (p = 0.002). The median time to dislocation in the patients with a tumor-related condition (twenty-four days) was shorter than that for the patients without tumor involvement (thirty-seven days). Preservation of the greater trochanter in patients with tumor involvement did not have a significant influence on the dislocation rate, but it showed a favorable trend toward decreasing that rate (hazard ratio = 3.5, p = 0.06). The short-term and long-term dislocation rates associated with hemiarthroplasties performed for a tumor-related condition at the site of the surgery were significantly higher than those associated with hemiarthroplasties performed for reasons other than tumor involvement. Preservation of the greater trochanter showed a trend toward decreasing the likelihood of dislocation following the hemiarthroplasty, and it was more influential than the level of resection and the extent of soft-tissue compromise. We think that preservation of the greater trochanter should be attempted when it is justifiable according to the principles of oncologic surgery.


Bohmian dynamics on subspaces using linearized quantum force.
In the de Broglie-Bohm formulation of quantum mechanics the time-dependent Schrodinger equation is solved in terms of quantum trajectories evolving under the influence of quantum and classical potentials. For a practical implementation that scales favorably with system size and is accurate for semiclassical systems, we use approximate quantum potentials. Recently, we have shown that optimization of the nonclassical component of the momentum operator in terms of fitting functions leads to the energy-conserving approximate quantum potential. In particular, linear fitting functions give the exact time evolution of a Gaussian wave packet in a locally quadratic potential and can describe the dominant quantum-mechanical effects in the semiclassical scattering problems of nuclear dynamics. In this paper we formulate the Bohmian dynamics on subspaces and define the energy-conserving approximate quantum potential in terms of optimized nonclassical momentum, extended to include the domain boundary functions. This generalization allows a better description of the non-Gaussian wave packets and general potentials in terms of simple fitting functions. The optimization is performed independently for each domain and each dimension. For linear fitting functions optimal parameters are expressed in terms of the first and second moments of the trajectory distribution. Examples are given for one-dimensional anharmonic systems and for the collinear hydrogen exchange reaction.


A genetic screen for increased loss of heterozygosity in Saccharomyces cerevisiae.
Loss of heterozygosity (LOH) can be a driving force in the evolution of mitotic/somatic diploid cells, and cellular changes that increase the rate of LOH have been proposed to facilitate this process. In the yeast Saccharomyces cerevisiae, spontaneous LOH occurs by a number of mechanisms including chromosome loss and reciprocal and nonreciprocal recombination. We performed a screen in diploid yeast to identify mutants with increased rates of LOH using the collection of homozygous deletion alleles of nonessential genes. Increased LOH was quantified at three loci (MET15, SAM2, and MAT) on three different chromosomes, and the LOH events were analyzed as to whether they were reciprocal or nonreciprocal in nature. Nonreciprocal LOH was further characterized as chromosome loss or truncation, a local mutational event (gene conversion or point mutation), or break-induced replication (BIR). The 61 mutants identified could be divided into several groups, including ones that had locus-specific effects. Mutations in genes involved in DNA replication and chromatin assembly led to LOH predominantly via reciprocal recombination. In contrast, nonreciprocal LOH events with increased chromosome loss largely resulted from mutations in genes implicated in kinetochore function, sister chromatid cohesion, or relatively late steps of DNA recombination. Mutants of genes normally involved in early steps of DNA damage repair and signaling produced nonreciprocal LOH without an increased proportion of chromosome loss. Altogether, this study defines a genetic landscape for the basis of increased LOH and the processes by which it occurs.


Nitrogen metabolism in Sinorhizobium meliloti-alfalfa symbiosis: dissecting the role of GlnD and PII proteins.
To contribute nitrogen for plant growth and establish an effective symbiosis with alfalfa, Sinorhizobium meliloti Rm1021 needs normal operation of the GlnD protein, a bifunctional uridylyltransferase/uridylyl-cleavage enzyme that measures cellular nitrogen status and initiates a nitrogen stress response (NSR). However, the only two known targets of GlnD modification in Rm1021, the PII proteins GlnB and GlnK, are not necessary for effectiveness. We introduced a Tyr→Phe variant of GlnB, which cannot be uridylylated, into a glnBglnK background to approximate the expected state in a glnD-sm2 mutant, and this strain was effective. These results suggested that unmodified PII does not inhibit effectiveness. We also generated a glnBglnK-glnD triple mutant and used this and other mutants to dissect the role of these proteins in regulating the free-living NSR and nitrogen metabolism in symbiosis. The glnD-sm2 mutation was dominant to the glnBglnK mutations in symbiosis but recessive in some free-living phenotypes. The data show that the GlnD protein has a role in free-living growth and in symbiotic nitrogen exchange that does not depend on the PII proteins, suggesting that S. meliloti GlnD can communicate with the cell by alternate mechanisms.


Hyperreactive platelet phenotypes: relationship to altered serotonin transporter number, transport kinetics and intrinsic response to adrenergic co-stimulation.
The mechanism underlying a hyperreactive platelet phenotype remains unknown. Since serotonin has been shown to influence platelet biology and atherothrombosis, we sought to investigate the association of platelet serotonin transporter number, binding affinity, and uptake kinetics with platelet aggregation. A total of 542 healthy volunteers had light transmittance platelet aggregometry measured in response to varying concentrations of epinephrine, serotonin, epinephrine plus serotonin, ADP and collagen. Transporter-dependent serotonin uptake rate was determined (Vmax), as were serotonin transporter number (Bmax) and binding affinity (Kd) using 3H paroxetine binding in a homologous displacement assay, nonlinear regression and validated algorithms for kinetic modelling. Stimulation with submaximal (2μM) epinephrine concentration elicited a distinct, bimodal pattern of platelet aggregation in this population. In contrast, subjects exhibited minimal aggregation in response to serotonin alone. Co-stimulation with submaximal epinephrine and serotonin induced platelet aggregation to a level beyond that observed with either agonist alone and maintained a bimodal response distribution. Subjects with heightened (>60%) platelet aggregation to both epinephrine alone and epinephrine plus serotonin exhibited increased platelet serotonin uptake, and transporter number and affinity. In a population of healthy subjects, co-stimulation with submaximal concentrations of epinephrine and serotonin identifies a subset of individuals with a hyperreactive platelet aggregation profile that is associated with changes in platelet serotonin function.


The risk factors for hospital re-admission in medical patients in Singapore.
Unplanned hospital re-admissions are common, expensive and often unpreventable in the community. The study aimed to identify risk factors associated with unplanned hospital re-admission in Singapore. In a cross-sectional survey, 1509 patients admitted to the medical wards of a large acute hospital in Singapore during 2010 were recruited (78.8% response rate), data being collected using a structured questionnaire based on the Andersen behavioural model underlying healthcare use. The dependent variable was re-admission within 28 days, with independent variables in the four areas of predisposing characteristics, needs, enabling resources and health behaviour. Hierarchical logistic regression was used to evaluate the risk factors associated with unplanned hospital re-admission. There were 222 inpatients re-admitted (14.7%) within 28 days and the final model showed that patients who were unemployed (OR = 1.5; 95% CI = 1.1-2.1) and had chronic obstructive pulmonary disease (OR = 2.0; 95% CI = 1.1-3.7) with abnormal respiratory patterns (OR = 1.6; 95% CI = 1.1-2.2) were more likely to be re-admitted. Less likely to be re-admitted were patients doing regular daily activities (OR = 0.7; 95% CI = 0.5-0.9), those assisted by a social worker (OR = 0.3; 95% CI = 0.2-0.6), those referred to other health professionals when sick (OR = 0.6; 95% CI = 0.4-0.7) and those who had received health education programmes before discharge in the previous admission (OR = 0.7; 95% CI = 0.4-0.9). Unplanned re-admissions are a concern to healthcare providers because this suggests that patients are discharged with unresolved problems that reflect ineffective care in hospital. This study provides evidence to prompt more effective discharge educational care programmes that incorporate patients' enabling and need outcomes, thereby reducing re-admission rates. Community-based healthcare should play an important role in reducing patients' re-admission rates.


Impregnation of cotton fabric with silver nanoparticles synthesized by dextran isolated from bacterial species Leuconostoc mesenteroides T3.
This study was aimed to highlight the possibility of cotton fabric impregnation with silver nanoparticles synthesized by dextran isolated from Leuconostoc mesenteroides T3 in order to obtain antimicrobial properties. The fabrication of dextran was proved by FTIR spectroscopy. Particle sizes of synthesized dextran and silver nanoparticles were measured by dynamic light scattering method. The presence of silver nanoparticles on the surface of cotton fabric was confirmed by scanning electron microscopy, X-ray diffraction measurements and reflectance spectrophotometry. Antimicrobial activity of cotton fabric impregnated with silver nanoparticles was tested against bacteria Escherichia coli and Staphylococcus aureus, and fungus Candida albicans. The results indicated that synthesized silver nanoparticles can provide satisfactory antimicrobial activity. However, maximum reduction (99.9%) of all tested microorganisms can be obtained only when 1.0mmolL(-1) colloid consisting of silver nanoparticles is applied.


Dietary Cholesterol and the Lack of Evidence in Cardiovascular Disease.
Cardiovascular disease (CVD) is the leading cause of death in the United States. For years, dietary cholesterol was implicated in increasing blood cholesterol levels leading to the elevated risk of CVD. To date, extensive research did not show evidence to support a role of dietary cholesterol in the development of CVD. As a result, the 2015⁻2020 Dietary Guidelines for Americans removed the recommendations of restricting dietary cholesterol to 300 mg/day. This review summarizes the current literature regarding dietary cholesterol intake and CVD. It is worth noting that most foods that are rich in cholesterol are also high in saturated fatty acids and thus may increase the risk of CVD due to the saturated fatty acid content. The exceptions are eggs and shrimp. Considering that eggs are affordable and nutrient-dense food items, containing high-quality protein with minimal saturated fatty acids (1.56 gm/egg) and are rich in several micronutrients including vitamins and minerals, it would be worthwhile to include eggs in moderation as a part of a healthy eating pattern. This recommendation is particularly relevant when individual's intakes of nutrients are suboptimal, or with limited income and food access, and to help ensure dietary intake of sufficient nutrients in growing children and older adults.


Analysis of some commercial preparations for migraine treatment using ion-pair high-performance liquid chromatography with addition of salts to the mobile phase.
When appropriate salts are added to the mobile phase in ion-pair high-performance liquid chromatography (HPLC) it is possible to arrive at an isocratic solvent with which complex mixtures of nitrogenous compounds of different pKa values and lipophilic characteristics may be separated. Selectivity in the manipulation of solute retention depends on the salt type, its concentration, the percentage of organic modifier in the mobile solvent and the solute itself. In addition to a dramatic reduction in analysis time, the use of salts can also improve the resolution of closely eluted peaks. With judicious control of the pH of the mobile solvent, the addition of salts to the mobile phase can cause the retention of compounds of different pKa values to alter in a contrasting manner. Under typical ion-pair HPLC conditions, an increase in salt concentration in the mobile solvent enhances the retention of neutral compounds and reduces the retention of ionized compounds. An inverse log-log relationship between the capacity factor of a solute and the salt concentration in the mobile phase was found. Examples are given of the use of salts in mobile solvents for ion-pair HPLC of a number of pharmaceutical preparations employed for the treatment of migraine.


High-resolution structures of mutants of residues that affect access to the ligand-binding cavity of human lipocalin-type prostaglandin D synthase.
Lipocalin-type prostaglandin D synthase (L-PGDS) catalyzes the isomerization of the 9,11-endoperoxide group of PGH2 (prostaglandin H2) to produce PGD2 (prostaglandin D2) with 9-hydroxy and 11-keto groups. The product of the reaction, PGD2, is the precursor of several metabolites involved in many regulatory events. L-PGDS, the first member of the important lipocalin family to be recognized as an enzyme, is also able to bind and transport small hydrophobic molecules and was formerly known as β-trace protein, the second most abundant protein in human cerebrospinal fluid. Previous structural work on the mouse and human proteins has focused on the identification of the amino acids responsible and the proposal of a mechanism for catalysis. In this paper, the X-ray structures of the apo and holo forms (bound to PEG) of the C65A mutant of human L-PGDS at 1.40 Å resolution and of the double mutant C65A/K59A at 1.60 Å resolution are reported. The apo forms of the double mutants C65A/W54F and C65A/W112F and the triple mutant C65A/W54F/W112F have also been studied. Mutation of the lysine residue does not seem to affect the binding of PEG to the ligand-binding cavity, and mutation of a single or both tryptophans appears to have the same effect on the position of these two aromatic residues at the entrance to the cavity. A solvent molecule has also been identified in an invariant position in the cavity of virtually all of the molecules present in the nine asymmetric units of the crystals that have been examined. Taken together, these observations indicate that the residues that have been mutated indeed appear to play a role in the entrance-exit process of the substrate and/or other ligands into/out of the binding cavity of the lipocalin.