Family history of psychiatric disorders as a risk factor for maternal postpartum depression: a systematic review protocol.
Postpartum depression (PPD) is the most common postpartum psychiatric disorder, affecting 11-15% of new mothers, and initiatives towards early identification and treatment are essential due to detrimental consequences. Family history of psychiatric disorders is a risk factor for developing psychiatric episodes outside the postpartum period, but evidence of the association between familial risk and PPD is not clear. Hence, the objective of this systematic review is to summarize the current literature on the association between family history of psychiatric disorders and PPD. This protocol has been developed and reported according to the PRISMA-P guidelines for systematic reviews. A comprehensive literature search will be conducted in PubMed, Embase, and PsycINFO from inception of the databases, supplemented with citation tracking and reference screening of the included studies. Two independent authors will examine all retrieved articles for inclusion in two steps: title/abstract screening and full-text screening. Eligible studies are case-control and cohort studies reporting a risk estimate for the association between family history of psychiatric disorders and PPD. Studies will be assessed for risk of bias using the Newcastle-Ottawa Scale. The association between family psychiatry and PPD will be combined in a meta-analysis using a restricted maximum likelihood method (REML). Heterogeneity will be quantified using I2 and investigated through meta-regression, subgroup and sensitivity analyses, and publication bias will be evaluated via visual inspection of a funnel plot. The overall strength and quality of the findings will be evaluated using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach. If meta-analysis is not possible, data will be synthesized narratively in text and tables. This systematic review will be the first to summarize current knowledge and present an overall estimate for the association between family history of psychiatric disorders and PPD. Evaluation of psychiatric family history as a PPD risk factor is essential to assist early identification of women at high risk of PPD in routine perinatal care. PROSPERO ID: 277998 (registered 10th of September 2021).


Family physicians' experience and understanding of evidence-based practice and guideline implementation in primary care practice, Cape Town, South Africa.
In primary care, patients present with multimorbidity and a wide spectrum of undifferentiated illnesses, which makes the application of evidence-based practice (EBP) principles more challenging than in other practice contexts. The goal of this study was to explore the experiences and understanding of family physicians (FP) in primary care with regard to EBP and the implementation of evidence-based guidelines. The study was conducted in Cape Town primary care facilities and South African university departments of Family Medicine. For this phenomenological, qualitative study, 27 purposefully selected FPs from three groups were interviewed: senior academic FPs; local FPs in public-sector practice; and local FPs in private-sector practice. Data were analysed using the framework method with the assistance of ATLAS.ti, version 6.1. Guideline development should be a more inclusive process that incorporates more evidence from primary care. Contextualisation should happen at an organisational level and may include adaptation as well as the development of practical or integrated tools. Organisations should ensure synergy between corporate and clinical governance activities. Dissemination should ensure that all practitioners are aware of and know how to access guidelines. Implementation should include training that is interactive and recognises individual practitioners' readiness to change, as well as local barriers. Quality improvement cycles may reinforce implementation and provide feedback on the process. Evidence-based practice is currently limited in its capacity to inform primary care. The conceptual framework provided illustrates the key steps in guideline development, contextualisation, dissemination, implementation and evaluation, as well as the interconnections between steps and barriers or enablers to progress. The framework may be useful for policymakers, health care managers and practitioners in similar settings.


Lignin-Retaining Transparent Wood.
Optically transparent wood, combining optical and mechanical performance, is an emerging new material for light-transmitting structures in buildings with the aim of reducing energy consumption. One of the main obstacles for transparent wood fabrication is delignification, where around 30 wt % of wood tissue is removed to reduce light absorption and refractive index mismatch. This step is time consuming and not environmentally benign. Moreover, lignin removal weakens the wood structure, limiting the fabrication of large structures. A green and industrially feasible method has now been developed to prepare transparent wood. Up to 80 wt % of lignin is preserved, leading to a stronger wood template compared to the delignified alternative. After polymer infiltration, a high-lignin-content transparent wood with transmittance of 83 %, haze of 75 %, thermal conductivity of 0.23 W mK-1 , and work-tofracture of 1.2 MJ m-3 (a magnitude higher than glass) was obtained. This transparent wood preparation method is efficient and applicable to various wood species. The transparent wood obtained shows potential for application in energy-saving buildings.


Procalcitonin usefulness for the initiation of antibiotic treatment in intensive care unit patients.
To test the usefulness of procalcitonin serum level for the reduction of antibiotic consumption in intensive care unit patients. Single-center, prospective, randomized controlled study. Five intensive care units from a tertiary teaching hospital. All consecutive adult patients hospitalized for >48 hrs in the intensive care unit during a 9-month period. Procalcitonin serum level was obtained for all consecutive patients suspected of developing infection either on admission or during intensive care unit stay. The use of antibiotics was more or less strongly discouraged or recommended according to the Muller classification. Patients were randomized into two groups: one using the procalcitonin results (procalcitonin group) and one being blinded to the procalcitonin results (control group). The primary end point was the reduction of antibiotic use expressed as a proportion of treatment days and of daily defined dose per 100 intensive care unit days using a procalcitonin-guided approach. Secondary end points included: a posteriori assessment of the accuracy of the infectious diagnosis when using procalcitonin in the intensive care unit and of the diagnostic concordance between the intensive care unit physician and the infectious-disease specialist. There were 258 patients in the procalcitonin group and 251 patients in the control group. A significantly higher amount of withheld treatment was observed in the procalcitonin group of patients classified by the intensive care unit clinicians as having possible infection. This, however, did not result in a reduction of antibiotic consumption. The treatment days represented 62.6±34.4% and 57.7±34.4% of the intensive care unit stays in the procalcitonin and control groups, respectively (p=.11). According to the infectious-disease specialist, 33.8% of the cases in which no infection was confirmed, had a procalcitonin value>1µg/L and 14.9% of the cases with confirmed infection had procalcitonin levels<0.25 µg/L. The ability of procalcitonin to differentiate between certain or probable infection and possible or no infection, upon initiation of antibiotic treatment was low, as confirmed by the receiving operating curve analysis (area under the curve=0.69). Finally, procalcitonin did not help improve concordance between the diagnostic confidence of the infectious-disease specialist and the ICU physician. Procalcitonin measuring for the initiation of antimicrobials did not appear to be helpful in a strategy aiming at decreasing the antibiotic consumption in intensive care unit patients.


[Limitation of oxidative stress as the main factor of the universal protective properties of melatonin].
Natural hormone melatonin, which is produced by pineal gland and apudocytes of peripheral tissues, has unique and universal protective features against various cerebral and somatic diseases. Melatonin effects may be based on many factors. On the cellular level, the main role in the therapeutic properties of melatonin is played by the antioxidant activity. Much evidence for this hypothesis is presented and reviewed.


Bloodmeal sources of Aedes triseriatus and Aedes vexans in a southern Wisconsin forest endemic for La Crosse encephalitis virus.
The micro enzyme-linked immunosorbent assay (ELISA) was used to specifically identify bloodmeal sources of Aedes triseriatus Say and Aedes vexans Meigen collected at a site endemic for La Crosse (LAC) encephalitis virus. Deer were the source of 65% of Ae. triseriatus and 94% of Aedes vexans bloodmeals, respectively. Chipmunks and tree squirrels, which are considered to be the major vertebrate amplifying hosts of LAC virus, were the sources of 8% and 16%, respectively, of the bloodmeals of Ae. triseriatus, the vector of LAC virus. The relatively small proportion of vector bloodmeals taken from the amplifying hosts raises further doubts as to the significance of vertebrate amplification in perpetutation of La Crosse virus in nature, i.e. whether vertebrate amplification alone is sufficient to make up for the shortfall of virus infection that occurs during vertical transmission.


Body iron stores in relation to risk of type 2 diabetes in apparently healthy women.
Type 2 diabetes is a common manifestation of hemochromatosis, a disease of iron overload. However, it is not clear whether higher iron stores predict the development of type 2 diabetes in a healthy population. To examine plasma ferritin concentration and the ratio of the concentrations of transferrin receptors to ferritin in relation to risk of type 2 diabetes. Prospective nested case-control study within the Nurses' Health Study cohort. Of the 32 826 women who provided blood samples during 1989-1990 and were free of diagnosed diabetes, cardiovascular disease, and cancer, 698 developed diabetes during 10 years of follow-up. The controls (n = 716) were matched to cases on age, race, and fasting status; and on body mass index (BMI) for cases in the top BMI decile. Incident cases of type 2 diabetes. Among cases, the mean (SD) concentration of ferritin was significantly higher (109 [105] vs 71.5 [68.7] ng/mL for controls; P<.001 for difference) and the mean (SD) ratio of transferrin receptors to ferritin was significantly lower (102 [205] vs 141 [340], respectively; P =.01). In conditional logistic regression stratified on the matching factors and controlled for BMI and other diabetes risk factors, the multivariate relative risks [RRs] of incident type 2 diabetes across increasing quintiles of ferritin were 1.00, 1.09 (95% confidence interval [CI], 0.70-1.70), 1.26 (95% CI, 0.82-1.95), 1.30 (95% CI, 0.83-2.04), and 2.68 (95% CI, 1.75-4.11) (P<.001 for trend). The RRs across increasing quintiles of transferrin receptors to ferritin ratio were 2.44 (95% CI, 1.61-3.71), 1.00 (95% CI, 0.64-1.56), 1.13 (95% CI, 0.73-1.74), 0.99 (95% CI, 0.64-1.53), and 1.00 (P =.01 for trend). Further adjustment for an inflammatory marker (C-reactive protein) did not change the results appreciably. The associations persisted within strata defined by levels of BMI, menopausal status, alcohol consumption, and C-reactive protein. Higher iron stores (reflected by an elevated ferritin concentration and a lower ratio of transferrin receptors to ferritin) are associated with an increased risk of type 2 diabetes in healthy women independent of known diabetes risk factors.


Psychosocial predictors of an interest in cosmetic surgery among young Norwegian women: a population-based study.
The present study investigated psychosocial factors expected to predict an interest in cosmetic surgery. It was hypothesized that body dysmorphic disorder-like symptoms, personality, interpersonal attachment insecurity, low self-esteem, poor body image, dissatisfaction with sexual life, distorted eating behavior, emotional distress, low education, poor relationship with parents and friends, teasing history, social acceptance of cosmetic surgery, and low level of physical activity would relate to an interest in cosmetic surgery. Questionnaire data were obtained from 1880 participants who responded to a survey distributed to a representative sample of 3500 Norwegian women between 18 and 35 years of age living in the two northernmost counties. Data were analyzed by univariate and multiple logistic regression analyses. Multiple regression analyses showed that an interest in cosmetic surgery was positively related to body dysmorphic disorder-like symptoms, body image orientation, having children, been teased for appearance, knowing someone who has had cosmetic surgery, and being recommended cosmetic surgery. Agreeability, body image evaluation, education, and quality of relationship with parents were negatively related to an interest in cosmetic surgery. The study gives new insights into psychosocial factors predicting an interest in cosmetic surgery. In addition to previously known predictors, having been teased for appearance and having children were positive predictors, whereas education and quality of relationship with parents were negative predictors of an interest in cosmetic surgery. The results may contribute to a better understanding of the various factors that may motivate an individual to undergo cosmetic surgery.


Effect of entomopathogenic fungus Beauveria bassiana on the growth characteristics and metabolism of black soldier fly larvae.
Beauveria bassiana is an entomopathogenic fungus widely used in agriculture to reduce populations of various pests. However, when agricultural waste is utilized for organic recycling, B. bassiana has the potential to impact recycling performance, by affecting the survival, and body mass of decomposing organisms (such as insect's larvae). Additionally, in natural conditions where decayed organic matter contains a high load of different entomopathogenic organisms, larval growth may be affected when consumed or in contact. In a laboratory study, we aimed to comprehend the effects of B. bassiana on the growth characteristics and larval metabolism of the black soldier fly larvae, which is a known decomposing insect. The experiments used both feeding (mixing the spores with the diet, hereafter BF) and contact treatments (by dipping the larva in the spores solution, hereafter BD), and were compared to a water-treated control group. The BF treatment significantly reduced larval body weight, adult emergence, and adult weight compared to both the control and the BD treatment. Furthermore, an analysis of hemolymph metabolites, categorized by class, indicated a higher accumulation of metabolites belonging to the purine and purine derivative classes, as well as carboxylic acids and their derivatives, including peptides and oligopeptides, indicating potential disruption of protein synthesis or degradation caused by the BF treatment. Pathway enrichment analysis showed significant alterations in purine metabolism and D-Arginine and D-ornithine metabolism compared to the control. Taurine and hypotaurine metabolism were significantly altered in the BD treatment compared to the control but not significantly enriched in the BF treatment. Our results suggest that the BF treatment impairs protein synthesis or degradation, affecting larval growth characteristics. Future studies should explore innate immunity-related gene expression and antimicrobial peptide production in BSF larvae to understand their immunity to pathogens.


A maelstrom of migrating monocytes drives neurodegeneration.
Neurodegeneration is a devastating complication of Langerhans cell histiocytosis (LCH), but it is not clear how it develops. In this issue of Immunity, Wilk et al. demonstrate that circulating BRAFV600E+ myeloid cells damage the blood-brain barrier and infiltrate the brain. Dual inhibition of the MAPK and senescence pathways can block parenchymal injury, providing a potential therapeutic avenue for histiocytic neurodegeneration.


Engineered coiled-coil protein microfibers.
The fabrication of de novo proteins able to self-assemble on the nano- to meso-length scales is critical in the development of protein-based biomaterials in nanotechnology and medicine. Here we report the design and characterization of a protein engineered coiled-coil that not only assembles into microfibers, but also can bind hydrophobic small molecules. Under ambient conditions, the protein forms fibers with nanoscale structure possessing large aspect ratios formed by bundles of α-helical homopentameric assemblies, which further assemble into mesoscale fibers in the presence of curcumin through aggregation. Surprisingly, these biosynthesized fibers are able to form in conditions of remarkably low concentrations. Unlike previously designed coiled-coil fibers, these engineered protein microfibers can bind the small molecule curcumin throughout the assembly, serving as a depot for encapsulation and delivery of other chemical agents within protein-based 3D microenvironments.


Methodological quality checklist for studies based on observational methodology (MQCOM).
No existing instrument addresses the minimum number of items that guarantee methodological quality in studies based on observational methodology. Consequently, professionals who are not experts in observational methodology do not have a basic framework to guide their practice in this type of study. This study developed a checklist to measure the minimum number of items for methodological quality that studies based on observational methodology should consider and provided evidence of their validity based on test content and intercoder reliability. Fifty-four judges with at least 1 year of experience in observational methodology and research based on this methodology evaluated the items of the developed checklist in terms of relevance, usefulness, and feasibility. Items were selected if they obtained at least .5 in the Osterlind indexes of the three aspects evaluated. Two coders applied the selected items to a random selection of articles that used observational methodology to investigate soccer, and intercoder reliability was examined using Cohen's kappa (k) coefficients. The final checklist included 16 items grouped into 11 criteria/dimensions, with adequate reliability coefficients. This study developed a useful instrument for non-expert professionals to enhance the methodological quality of studies based on observational methodology.


Persistent Spillback of Bovine Tuberculosis From White-Tailed Deer to Cattle in Michigan, USA: Status, Strategies, and Needs.
Free-ranging white-tailed deer (Odocoileus virginianus) are believed to be a self-sustaining reservoir for bovine tuberculosis (bTB) in northeastern Lower Michigan, USA. Although a comprehensive control program is in place and on-farm mitigation strategies to curtail bTB transmission between cattle and deer have been implemented for over a decade, cattle and deer continue to become infected with the disease. Thus, renewed motivation to eradicate bTB is needed if that is truly the goal. Recurrent detection of bTB in cattle in the region is of mounting concern for state and federal agricultural agencies, producers, and wildlife managers. Current on-farm mitigation efforts include fencing and refined cattle feeding and watering practices. Liberal removal of antlerless deer through hunter harvest and disease control permits (DCPs) issued to cattle producers and agency sharp shooters have also been ongoing. Although these strategies have merit and efforts to reduce prevalence in deer and occurrence of positive farms are elevated, additional actions are needed. Heightened management actions to combat bTB in deer could include deer vaccination programs, strategic habitat manipulations to redistribute deer from farms, and precision removal of deer in proximity to high-risk farms. Foundational research to address development and delivery of vaccine to free-ranging deer is complete. Strategic management and habitat manipulation could reduce and disperse local concentrations of deer while better meeting wildlife, forestry, and agricultural goals. The responses of local deer populations to targeted removal of individuals are generally understood and there is potential to reduce deer activity around agricultural operations while allowing them to persist nearby on natural foods. We summarize the history and progress to date, discuss the realized merit of novel management strategies, and suggest options to rid deer and cattle in Michigan of bTB.


Spatial analysis of risk factors for childhood morbidity in Nigeria.
Recent Demographic and Health Surveys (DHS) from Sub-Saharan Africa (SSA) indicate a decline in childhood vaccination coverage but a high prevalence of childhood diarrhea, cough, and fever. We used Nigerian DHS data to investigate the impact of geographical factors and other important risk factors on diarrhea, cough, and fever using geoadditive Bayesian semiparametric models. A higher prevalence of childhood diarrhea, cough, and fever is observed in the northern and eastern states, while lower disease prevalence is observed in the western and southern states. In addition, children from mothers with higher levels of education and those from poor households had a significantly lower association with diarrhea; children delivered in hospitals, living in urban areas, or from mothers having received prenatal visits had a significantly lower association with fever. Our maps are a novel and relevant tool to help local governments to improve health-care interventions and achieve Millennium Development Goals (MDG4).


HMP16SData: Efficient Access to the Human Microbiome Project Through Bioconductor.
Phase 1 of the Human Microbiome Project (HMP) investigated 18 body subsites of 242 healthy American adults to produce the first comprehensive reference for the composition and variation of the "healthy" human microbiome. Publicly available data sets from amplicon sequencing of two 16S ribosomal RNA variable regions, with extensive controlled-access participant data, provide a reference for ongoing microbiome studies. However, utilization of these data sets can be hindered by the complex bioinformatic steps required to access, import, decrypt, and merge the various components in formats suitable for ecological and statistical analysis. The HMP16SData package provides count data for both 16S ribosomal RNA variable regions, integrated with phylogeny, taxonomy, public participant data, and controlled participant data for authorized researchers, using standard integrative Bioconductor data objects. By removing bioinformatic hurdles of data access and management, HMP16SData enables epidemiologists with only basic R skills to quickly analyze HMP data.


Evaluation of protein extraction protocols for 2DE in marine ecotoxicoproteomics.
In ecotoxicoproteomics, an accurate and reproducible extraction of proteins is a critical step for 2DE analysis and further protein identification using MS. The criteria for the assessment of protein extraction quality include protein yield, protein spots resolved in a 2DE gel, matched protein spots in replicate gels, reproducibility, and compatibility with MS. In this work, we evaluated three protein extraction systems, straightforward lysis buffer, trichloroacetic acid-acetone, and TRIzol reagent with some modifications, for the protein extraction from three animal species including mussel Mytilus galloprovincialis, flounder Paralichthys olivaceus, and polychaete Nereis diversicolor used in marine ecotoxicology. Our results indicated that these methods could extract significantly different protein profiles. The method using TRIzol reagent resulted in the most matched protein spots resolved in four replicate 2DE gels and highest reproducibilities for the gill of M. galloprovincialis and liver of P. olivaceus. However, a modified trichloroacetic acid-acetone solvent system was best for the whole soft tissue of N. diversicolor. This work provides the fundamental information of the extraction quality of protein extraction protocols from different marine animals, which may facilitate the selection of a suitable protein extraction protocol for ecotoxicoproteomics.


[Antibiotic consumption between 1996 and 2003: national survey and international comparison].
To describe the qualitative and quantitative changes of antibiotic consumption in Hungarian hospitals and in the primary care setting between 1996 and 2003. Sales data relating to community and hospital care antibiotic consumption were obtained for the 8 years period of 1996-2003. The 2003 version of the world health organisation (WHO) anatomical therapeutic chemical (ATC)/ defined daily dose (DDD) system was used for calculations and the 2005 version for classifications. The final expression units were DDD/100 bed-days and DDD/1000 inhabitants/day for hospital and community care utilization, respectively. Trend analysis was applied to assess the annual changes in antimicrobial consumption. The total antibiotic consumption in the community setting and in the hospitals remained relatively stable during the study period. The average antibiotic consumption in the community setting (20.20 +/- 1.42 DDD/1000 inhabitants/day was in line with the European average, while the national average hospital antibiotic consumption (24.81 +/- 1.69 DDD/ 100 bed-days) was very low in international benchmark. Changes in the pattern of antibiotic consumption was observed in both settings. Internationally outstanding consumption of penicillins plus beta-lactamase inhibitor combinations (J01CR) and sulphonamides and extremely low utilisation of beta lactamase resistant penicillins (J01CF) were detected. The hospital antibiotic consumption was characterized by extended use of sulphonamides, tetracyclines, and second generation cephalosporins. The low hospital consumption of antibiotics and the internationally extreme usage of certain antibiotic groups needs further pharmacoepidemiologic analysis.


Direct stereotactic MRI location in the globus pallidus for chronic stimulation in Parkinson's disease.
We evaluated the direct location in the globus pallidus (GP) under stereotactic MRI (sMRI) guidance in five parkinsonians treated with chronic deep brain stimulation (four bilaterally). The sMRI consisted of three orthogonal (horizontal, frontal, sagittal) sets of images obtained with a stereotactic frame and its localiser. The sMRI was coupled with ventriculography to compare the location with the classic indirect method based on commissural landmarks. The target was defined on T2-weighted slices in the anterior part of the medial GP, at the vertex of the nucleus. It was reached via one track with a semi-micro-electrode and step by step high frequency stimulation, then replaced by a quadripolar electrode once we located the site enabling the optimal clinical improvement. Stereotactic x-rays localised the final position of the electrode. A company software matched sMRI, ventriculography, and peroperative (perop) x-rays, with reference to the stereotactic location boxes. We analysed the effects of acute (perop) and chronic (six-month follow-up) stimulation of active plots (acplots), i.e. leading to optimal clinical improvement. Three distances with reference to the acplots were measured both on sMRI and ventriculography: the laterality from the median sagittal plane of the third ventricle; the anterior position from the midpoint of the intercommissural line (Icl), and the vertical position with regard to the Icl. We then compared the differences in measurements (n = 64) with the Bland and Altman method. The mean difference was 0.09 mm with 95% of the values between +/- 1 mm, but only the laterality had a statistically significant agreement (all the differences included between +/- two times the standard deviation of the mean). The acplots distances from the dorsal, ventral, and medial boundaries of GP (defined by manual surrounding on frontal and horizontal planes) were measured on sMRI. With one exception, the acplots were all included in the nucleus. The six-month acplots were located dorsally with reference to the perop ones. Clinical benefit at six-months follow-up showed results comparable to the literature. Direct location of GP target based on sMRI seems a simple and reliable method.


Visualization of Discontinuous Vector Field Topology.
This paper extends the concept and the visualization of vector field topology to vector fields with discontinuities. We address the non-uniqueness of flow in such fields by introduction of a time-reversible concept of equivalence. This concept generalizes streamlines to streamsets and thus vector field topology to discontinuous vector fields in terms of invariant streamsets. We identify respective novel critical structures as well as their manifolds, investigate their interplay with traditional vector field topology, and detail the application and interpretation of our approach using specifically designed synthetic cases and a simulated case from physics.


Cancer risk factors in Korean news media: a content analysis.
Little is known about the news coverage of cancer risk factors in Korea. This study aimed to examine how the news media encompasses a wide array of content regarding cancer risk factors and related cancer sites, and investigate whether news coverage of cancer risk factors is congruent with the actual prevalence of the disease. A content analysis was conducted on 1,138 news stories covered during a 5-year period between 2008 and 2012. The news stories were selected from nationally representative media in Korea. Information was collected about cancer risk factors and cancer sites. Of various cancer risk factors, occupational and environmental exposures appeared most frequently in the news. Breast cancer was mentioned the most in relation to cancer sites. Breast, cervical, prostate, and skin cancer were overrepresented in the media in comparison to incidence and mortality cases, whereas lung, thyroid, liver, and stomach cancer were underrepresented. To our knowledge, this research is the first investigation dealing with news coverage about cancer risk factors in Korea. The study findings show occupational and environmental exposures are emphasized more than personal lifestyle factors; further, more prevalent cancers in developed countries have greater media coverage, not reflecting the realities of the disease. The findings may help health journalists and other health storytellers to develop effective ways to communicate cancer risk factors.


The correlation between the clinical laboratory data and the telomere length in peripheral blood leukocytes of Japanese female patients with hypertension.
This study investigated the correlation between the chronological age, telomere length in peripheral blood leukocytes and blood laboratory data of female patients with mild hypertension to identify laboratory data that reflect the biological aging of individuals. Cross-sectional population-based study. Outpatient clinic of the Department of Cardiovascular, Respiratory, and Geriatric Medicine Kyushu University Hospital at Beppu in Japan. Outpatients with mild hypertension treated with a low dose of amlodipine. The laboratory data of female patients were collected and the telomere length parameters in their peripheral blood leukocytes were determined by Southern blotting. Any correlations between the laboratory data and the telomere length parameters were assessed. The patients showed a positive correlation between the telomere length and the high density lipoprotein, albumin, creatinine, hemoglobin levels, red blood cell counts, and a negative correlation with the globulin level. The extent of subtelomeric methylation of long telomeres tended to correlate negatively with the telomeric attrition. Only the creatinine level correlated with subtelomeric methylation, but not with telomeric length. HDL and the albumin/globulin ratio were potential indicators for individual somatic genomic aging. Creatinine may therefore be a useful indicator for a predisposition for telomeric attrition.


Expression of J1/tenascin in the crypt-villus unit of adult mouse small intestine: implications for its role in epithelial cell shedding.
The localization of the extracellular matrix recognition molecule J1/tenascin was investigated in the crypt-villus unit of the adult mouse ileum by immunoelectron microscopic techniques. In the villus region, J1/tenascin was detected strongly in the extracellular matrix (ECM) between fibroblasts of the lamina propria. It was generally absent in the ECM at the interface between subepithelial fibroblasts and intestinal epithelium, except for some restricted areas along the epithelial basal lamina of villi, but not of crypts. These restricted areas corresponded approximately to the basal part of one epithelial cell. In J1/tenascin-positive areas, epithelial cells contacted the basal lamina with numerous microvillus-like processes, whereas in J1/tenascin-negative areas the basal surface membranes of epithelial cells contacted their basal lamina in a smooth and continuous apposition. In order to characterize the functional role of J1/tenascin in the interaction between epithelial cells and ECM, the intestinal epithelial cell line HT-29 was tested for its ability to adhere to different ECM components. Cells adhered to substratum-immobilized fibronectin, laminin and collagen types I to IV, but not to J1/tenascin. When laminin or collagen types I to IV were mixed with J1/tenascin, cell adhesion was as effective as without J1/tenascin. However, adhesion was completely abolished when cells were offered a mixture of fibronectin and J1/tenascin as substratum. The ability of J1/tenascin to reduce the adhesion of intestinal epithelial cells to their fibronectin-containing basal lamina suggests that J1/tenascin may be involved in the process of physiological cell shedding from the villus.


Effect of contact angle, zeta potential and particles size on the in vitro studies of Al2O3 and SiO2 nanoparticles.
Currently, nanometal oxides find their role in different biological applications such as tissue engineering, implant and bone replacement materials. Owing to the increased use of nanoparticles, it is necessary to understand their release and toxicity in the biological system. In this regard, three independent studies such as in vitro cytotoxicity, antioxidant activity and biocompatibility of nano- and micrometal oxide particles such as alumina (Al2O3) and silica (SiO2) are evaluated. It is evident from cell viability study that nanoAl2O3 and SiO2 particles are less toxic when compared with microAl2O3 and SiO2 to NIH 3T3 cell lines up to 200 µg/ml. Antioxidant properties of micro- and nanoAl2O3 in terms of radical scavenging percentage for micro- and nanoAl2O3 are 59.1% and 72.1%, respectively, at 100 mg. Similarly, the radical scavenging percentage of nano- and bulk SiO2 are 81.0% and 67.2%, respectively. The present study reveals that the cellular behaviour, interaction and biocompatibility of metal oxides differ with dose, particle size, contact angle and zeta potential. The present study opens up a new strategy to analyse in vitro nanotoxicity.


Whole-transcriptome analysis reveals mechanisms underlying antibacterial activity and biofilm inhibition by a malic acid combination (MAC) in Pseudomonas aeruginosa.
Pseudomonas aeruginosa is a highly prevalent bacterial species known for its ability to cause various infections and its remarkable adaptability and biofilm-forming capabilities. In earlier work, we conducted research involving the screening of 33 metabolites obtained from a commercial source against two prevalent bacterial strains, Escherichia coli and Staphylococcus aureus. Through screening assays, we discovered a novel malic acid combination (MAC) consisting of malic acid, citric acid, glycine, and hippuric acid, which displayed significant inhibitory effects. However, the precise underlying mechanism and the potential impact of the MAC on bacterial biofilm formation remain unknown and warrant further investigation. To determine the antibacterial effectiveness of the MAC against Pseudomonas aeruginosa, we conducted minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) assays. Transmission electron microscopy (TEM) and scanning electron microscopy (SEM) techniques were employed to observe bacterial morphology and biofilm formation. We further performed a biofilm inhibition assay to assess the effect of the MAC on biofilm formation. Whole-transcriptome sequencing and bioinformatics analysis were employed to elucidate the antibacterial mechanism of the MAC. Additionally, the expression levels of differentially expressed genes were validated using the real-time PCR approach. Our findings demonstrated the antibacterial activity of the MAC against P. aeruginosa. SEM analysis revealed that the MAC can induce morphological changes in bacterial cells. The biofilm assay showed that the MAC could reduce biofilm formation. Whole-transcriptome analysis revealed 1093 differentially expressed genes consisting of 659 upregulated genes and 434 downregulated genes, in response to the MAC treatment. Mechanistically, the MAC inhibited P. aeruginosa growth by targeting metabolic processes, secretion system, signal transduction, and cell membrane functions, thereby potentially compromising the survival of this human pathogen. This study provides valuable insights into the antibacterial and antibiofilm activities of the MAC, a synergistic and cost-effective malic acid combination, which holds promise as a potential therapeutic drug cocktail for treating human infectious diseases in the future.


Involvement of presynaptic alpha 2-adrenoreceptors in the depressor response produced by repeated administration of dextro-methamphetamine.
The mechanism for the depressor response produced by the repeated administration of dextro-methamphetamine was studied in rats and rabbits. In the urethane anaesthetized and atropinized rat, the methamphetamine-induced depressor response was markedly inhibited by alpha-adrenoreceptor antagonists or by chronic reserpinization in combination with alpha-methyl-p-tyrosine, while it was not affected by propranolol. Yohimbine reversed the methamphetamine-induced depressor response to a pressor one when it was administered during the course of the depressor phase whilst prazosin or phentolamine caused only a further depressor response. In the pithed rat with electrical stimulation of the spinal cord, the first administration of methamphetamine elicited a marked pressor response whereas, following treatment with cocaine, the first administration of methamphetamine produced only a depressor response which was abolished by yohimbine. In the rabbit isolated aorta prelabeled with 3H-noradrenaline, methamphetamine enhanced the stimulation-evoked 3H-overflow and caused an enhanced contraction. However, in the presence of cocaine, methamphetamine reduced both stimulation-evoked 3H-overflow and neurogenic contractions. These findings suggest that the methamphetamine-induced depressor response results from the inhibition of catecholamine release from noradrenergic nerve terminals probably mediated by the activation of peripheral presynaptic alpha 2-adrenoreceptors.


Identification of coupling direction: application to cardiorespiratory interaction.
We consider the problem of experimental detection of directionality of weak coupling between two self-sustained oscillators from bivariate data. We further develop the method introduced by Rosenblum and Pikovsky [Phys. Rev. E 64, 045202 (2001)], suggesting an alternative approach. Next, we consider another framework for identification of directionality, based on the idea of mutual predictability. Our algorithms provide directionality index that shows whether the coupling between the oscillators is unidirectional or bidirectional, and quantifies the asymmetry of bidirectional coupling. We demonstrate the efficiency of three different algorithms in determination of directionality index from short and noisy data. These techniques are then applied to analysis of cardiorespiratory interaction in healthy infants. The results reveal that the direction of coupling between cardiovascular and respiratory systems varies with the age within the first 6 months of life. We find a tendency to change from nearly symmetric bidirectional interaction to nearly unidirectional one (from respiration to the cardiovascular system).


[Type-II dyserythropoietic anemia. A partial form of the glycoprotein degradation syndrome?].
The authors present a case of a boy, aged 8 years and 11 months, yellow race, with dyserythropoietic anemia type II, diagnosed at two months of age. Screening for partial form of carbohydrate deficient glycoprotein syndrome was normal. This result did not confirm the publication by Fukuda in 1990.


A Sampling of Alternative Payment Models.
Understanding the current selection of CMS-approved alternative payment models is critical for providers in the current healthcare policy climate who wish to pursue alternatives to traditional reimbursement schemes. This has become a topic of increasing interest with the recent passage of the Medicare Access and CHIP Reauthorization Act of 2015, as traditional fee-for-service payments will be altered-either positively or negatively-by criteria defined under the Merit-Based Incentive Payment System (MIPS). This article offers a framework for current and proposed models being implemented or investigated by the CMS. Further exploration of the topic can be carried out through supplementary or primary sources to determine best fits for specific practice environments.


Dehydroepiandrosterone supplementation improves ovarian reserve and pregnancy rates in poor responders.
We investigated whether DHEA supplementation had an impact on ovarian reserve parameters and pregnancy rates in patients with poor ovarian response (POR) and primary ovarian insufficiency (POI). A total of 34 people, 6 patients with POI and 28 patients with POR, were included in the study. The patients in the POR group consisted of two different groups: diminished ovarian reserve (DOR) and premature ovarian failure (PMOF). Patients in the POI and POR group were given 50 mg DHEA supplementation daily for 5 months. The primary outcome was to determine spontaneous clinical pregnancy rates. The monthly changes in the serum hormone levels and AFC were recorded for five months. AMH levels were also measured before and after treatment. The total follow-up time was 152 cycles. The number of pregnancies during the follow-up period was 9. The ratio of pregnancies to the number of patients was 26.5% and the rate per cycle was 5.9%. While 8 of 9 pregnancies resulted in a live birth, one resulted in a miscarriage. The rate of abortion was 11.1%. The mean AFC was 0 to 5 before treatment. Following DHEA administration, a significant increase was detected in 30.8% of the patients. There was an increase in AMH levels after DHEA, but this was not significant. The live birth rate and pregnancy rate per cycle were significantly higher in POR patients than those in POF. Patients with POF had no pregnancy. Although the PMOF patients were younger than the DOR patients, the rate of pregnancy (36% vs. 29%), and pregnancy rates per cycle (8.5% vs. 6.35%) were higher in the DOR group. The rates of live birth were the same in the PMOF and DOR groups (29% vs. 29%). Oral DHEA supplementation improves both ovarian reserve and pregnancy rates in women with POR.


Type I and type II corticosteroid receptor gene expression in the rat: effect of adrenalectomy and dexamethasone administration.
We have used 32P-labeled cRNA probes directed against Type I (mineralocorticoid, high affinity glucocorticoid) and Type II (classical glucocorticoid) receptor mRNA to screen various tissues, and have investigated the effect of adrenalectomy (ADX) and dexamethasone (DM) administration on their levels in hippocampus. Both Northern blot and S1 nuclease analysis showed Type I mRNA to be high in hippocampus, colon, and heart; low in liver; and undetectable in thymus. Type II mRNA was high in liver, thymus, and brain; and low in testis and parotid. A transient increase in both hippocampal Type I and Type II mRNA was noted at 1-3 days post ADX. DM similarly elicited a rise in hippocampal Type I mRNA at 2-4 days after ADX, but prevented the ADX-induced increment in Type II mRNA. In contrast to the transient increase in Type I receptor mRNA levels, hippocampal levels of Type I receptors measured by [3H]aldosterone binding were constant 1-16 days post ADX. DM administration caused a doubling in Type I receptor levels over 4 days, with plateau levels at 4-16 days; previously, DM has been shown to lower Type II receptor levels in the hippocampus.(ABSTRACT TRUNCATED AT 250 WORDS)


Optimal cone size to predict positive surgical margins after cold knife conization (CKC) and the risk factors for residual disease.
To determine the optimal cone size to achieve a reliable sensitivity and specificity for clear surgical margins after cold knife conization (CKC). The medical reports of patients who had high-grade cervical intraepithelial lesions, carcinoma in situ, or stage 1A1 microinvasive carcinoma in their CKC specimens between June 2008 and January 2015 were reviewed retrospectively. In total, 315 women fulfilled the inclusion criteria. The mean age of the patients was 40.7 years. The conization results were microinvasive carcinoma and high-grade squamous lesion (HSIL) for 8 and 307 patients, respectively. Ninety-nine patients had positive surgical margins. Eighty-one patients with positive cone margins underwent the repeat excisional procedure and 35 of them showed residual disease. In the univariate analyses, the patient age, menopausal status, and mean cone height parameters showed statistically significant differences between the patients with positive and negative margins. Also, residual disease was associated with the menopausal status and age of the patients. There is no optimal cone depth that is applicable for all patients. The most important predictors for positive margins are the menopausal status of the patient and that more than two quadrants are involved. However, the menopausal status and age of the patients were still predictors for residual disease.


Use of shape correspondence analysis to quantify skeletal changes associated with bone-anchored Class III correction.
To evaluate the three-dimensional (3D) skeletal changes in the mandibles of Class III patients treated with bone-anchored maxillary protraction using shape correspondence analysis. Twenty-five consecutive patients with skeletal Class III who were between the ages of 9 and 13 years (mean age, 11.10 ± 1.1 years) were treated using Class III intermaxillary elastics and bilateral miniplates (two in the infrazygomatic crests of the maxilla and two in the anterior mandible). Cone-beam computed tomography (CBCT) was performed for each patient before initial loading (T1) and at 1 year out (T2). From the CBCT scans, 3D models were generated, registered on the anterior cranial base, and analyzed using 3D linear distances and vectors between corresponding point-based surfaces. Bone-anchored traction produced anteroposterior and vertical skeletal changes in the mandible. The novel application of Shape correspondence analysis showed vectors of mean (± standard deviation) distal displacement of the posterior ramus of 3.6 ± 1.4 mm, while the chin displaced backward by 0.5 ± 3.92 mm. The lower border of the mandible at the menton region was displaced downward by 2.6 ± 1.2 mm, and the lower border at the gonial region moved downward by 3.6 ± 1.4 mm. There was a downward and backward displacement around the gonial region with a mean closure of the gonial angle by 2.1°. The condyles were displaced distally by a mean of 2.6 ± 1.5 mm, and there were three distinct patterns for displacement: 44% backward, 40% backward and downward, and 16% backward and upward. This treatment approach induces favorable control of the mandibular growth pattern and can be used to treat patients with components of mandibular prognathism.


Is Serial Electroneuronography Indicated Following Temporal Bone Trauma?
Contemporary guidelines advise facial nerve (FN) decompression within 2 weeks of temporal bone trauma if a single electroneuronography (ENoG) demonstrates more than 90% degeneration of the FN. We report a case series demonstrating the potential of serial ENoG to guide FN management more than 2 weeks following injury. Adults with traumatic temporal bone fractures and resultant ipsilateral FN paresis. Serial ENoG followed by observation or decompression of the FN. House-Brackmann (HB) graded FN function. Nine cases of blunt temporal bone trauma resulting in ispilateral FN paralysis were identified and reviewed. Two patients were women, and average age at the time of trauma was 30 years (range, 17-52). Immediate paralysis occurred in four cases, while five were delayed. A single ENoG was performed in seven patients and was predictive of final function in six, while one patient had an initially reassuring ENoG but did not obtain full recovery of FN function (HB 4). Two patients underwent serial ENoG on a weekly basis which, while initially reassuring, demonstrated declining FN function on subsequent testing. Decompression was performed in both patients with excellent recovery of FN function (HB1 and HB2). The majority of ENoGs performed within 2 weeks of temporal bone trauma provide sufficient prognostic data for treatment decisions; however, in selected cases, a single ENoG may not adequately predict long-term FN outcomes. For patients failing to improve with observation alone, serial ENoG may capture declining FN function, identifying patients that may benefit from late decompression.


Critical amino acid residues determine the binding affinity and the Ca2+ release efficacy of maurocalcine in skeletal muscle cells.
Maurocalcine (MCa) is a 33 amino acid residue peptide toxin isolated from the scorpion Scorpio maurus palmatus. MCa and mutated analogues were chemically synthesized, and their interaction with the skeletal muscle ryanodine receptor (RyR1) was studied on purified RyR1, sarcoplasmic reticulum (SR) vesicles, and cultured myotubes. MCa strongly potentiates [3H]ryanodine binding on SR vesicles (7-fold at pCa 5) with an apparent EC50 of 12 nm. MCa decreases the sensitivity of [3H]ryanodine binding to inhibitory high Ca2+ concentrations and increases it to the stimulatory low Ca2+ concentrations. In the presence of MCa, purified RyR1 channels show long-lasting openings characterized by a conductance equivalent to 60% of the full conductance. This effect correlates with a global increase in Ca2+ efflux as demonstrated by MCa effects on Ca2+ release from SR vesicles. In addition, we show for the first time that external application of MCa to cultured myotubes produces a cytosolic Ca2+ increase due to Ca2+ release from 4-chloro-m-cresol-sensitive intracellular stores. Using various MCa mutants, we identified a critical role of Arg24 for MCa binding onto RyR1. All of the other MCa mutants are still able to modify [3H]ryanodine binding although with a decreased EC50 and a lower stimulation efficacy. All of the active mutants produce both the appearance of a subconductance state and Ca2+ release from SR vesicles. Overall, these data identify some amino acid residues of MCa that support the effect of this toxin on ryanodine binding, RyR1 biophysical properties, and Ca2+ release from SR.


White Blood Cell Count and C-Reactive Protein Variations After Posterior Surgery With Intraoperative Radiotherapy for Spinal Metastasis.
Retrospective case series. To evaluate the feasibility of blood test parameters [white blood cell (WBC) count and C-reactive protein (CRP)] for predicting and diagnosing postoperative infection after posterior surgery with intraoperative radiotherapy (IORT) for spinal metastasis. Posterior surgery with IORT is effective for treating spinal metastasis, as we previously reported. However, the procedure requires that the patient be transferred from the operating room to the irradiation room. In addition, the patient's general status is often poor, and the risk of postoperative infection is high. A total of 279 patients who underwent IORT for the treatment of spinal metastasis between August 2004 and June 2013 were included in this study. The WBC count (/10 μL) and CRP level (mg/dL) were recorded in all patients preoperatively and on alternative days for up to 7 days after surgery. We assessed the development of surgical-site infection (SSI) for up to 1 month after surgery. SSI occurred in 41 patients (14.7%). The preoperative WBC count and CRP level did not differ between the infected and noninfected patients. The WBC counts on postoperative day (POD) 1 and POD 7 and the CRP levels on POD 7 were significantly higher in the infected patients (8.8 vs. 10.0, P=0.04; 6.1 vs. 8.8, P=0.002; 3.89 vs. 9.50, P<0.001). A receiver-operating characteristic curve analysis of the WBC count and CRP level for detecting SSI showed cutoff values of 9.6 (WBC count, POD 1), 6.5 (WBC count, POD 7), and 5.0 (CRP level, POD 7). A high WBC count and CRP level on POD 7 may be used to predict or detect SSI. In particular, a CRP level of 5.0 mg/dL on POD 7 strongly suggests the future development of SSI (sensitivity: 78%, specificity: 74%).


Human-macaque comparisons illuminate variation in neutral substitution rates.
The evolutionary distance between human and macaque is particularly attractive for investigating local variation in neutral substitution rates, because substitutions can be inferred more reliably than in comparisons with rodents and are less influenced by the effects of current and ancient diversity than in comparisons with closer primates. Here we investigate the human-macaque neutral substitution rate as a function of a number of genomic parameters. Using regression analyses we find that male mutation bias, male (but not female) recombination rate, distance to telomeres and substitution rates computed from orthologous regions in mouse-rat and dog-cow comparisons are prominent predictors of the neutral rate. Additionally, we demonstrate that the previously observed biphasic relationship between neutral rate and GC content can be accounted for by properly combining rates at CpG and non-CpG sites. Finally, we find the neutral rate to be negatively correlated with the densities of several classes of computationally predicted functional elements, and less so with the densities of certain classes of experimentally verified functional elements. Our results suggest that while female recombination may be mainly responsible for driving evolution in GC content, male recombination may be mutagenic, and that other mutagenic mechanisms acting near telomeres, and mechanisms whose effects are shared across mammalian genomes, play significant roles. We also have evidence that the nonlinear increase in rates at high GC levels may be largely due to hyper-mutability of CpG dinucleotides. Finally, our results suggest that the performance of conservation-based prediction methods can be improved by accounting for neutral rates.


Dietary patterns, dietary nutrients and cardiovascular disease.
A healthy dietary pattern can benefit multiple cardiovascular disease (CVD) risk factors. In conjunction with current standard-of-care pharmaceutical interventions it can provide an effective strategy for the prevention of CVD. Previous dietary recommendations have focused on targeting macronutrients. However, most of the recent international dietary guidelines now recommend a whole food, dietary pattern approach, whilst avoiding quantitative nutrient advice. The guidelines recommend: (1) increased intake of plant-based foods including complex, fibre-rich carbohydrates such as wholegrains, fruits and vegetables, but restricting the intake of refined starches; (2) substituting saturated fats with polyunsaturated and monounsaturated oils; (3) reducing salt intake; (4) increased fish consumption (or fish oils where applicable); (5) reducing sugar-sweetened drinks and added sugars; (6) avoiding butter and cream particularly in individuals at increased risk of CVD, but encouraging fermented products such as yoghurt; there is no specific advice on cheese and milk; (7) allowing consumption of lean meat in moderation but restricting processed meats; and (8) reducing cholesterol intake and foods rich in cholesterol (e.g., eggs and crustaceans) for those with diabetes and at increased CVD risk. The dietary guidelines should be adhered to in conjunction with low-to-moderate alcohol consumption, regular physical activity, avoiding tobacco and maintaining a healthy weight. This review summarises recently published research, international guidelines and position statements for minimizing CVD risk.


Derivation of clones close to met by preparative field inversion gel electrophoresis.
The molecular analysis of genes identified by mutations is a major problem in mammalian genetics. As a step toward this goal, preparative field inversion gel electrophoresis (FIGE) was used to selectively isolate clones from the environment of genetically linked markers, and to select a subset of these clones containing sequences next to specific restriction sites rare in mammalian DNA. This approach has been used to generate a library highly enriched in sequences closely linked to the cystic fibrosis marker met. One clone derived from the end of a Not I restriction fragment containing the met sequence was analyzed in detail and localized within a long range map to a position 300 kilobase pairs 5' of the metD sequence.


PPARγ is critical for Mycobacterium tuberculosis induction of Mcl-1 and limitation of human macrophage apoptosis.
Peroxisome proliferator-activated receptor (PPAR)γ is a global transcriptional regulator associated with anti-inflammatory actions. It is highly expressed in alveolar macrophages (AMs), which are unable to clear the intracellular pathogen Mycobacterium tuberculosis (M.tb). Although M.tb infection induces PPARγ in human macrophages, which contributes to M.tb growth, the mechanisms underlying this are largely unknown. We undertook NanoString gene expression analysis to identify novel PPARγ effectors that condition macrophages to be more susceptible to M.tb infection. This revealed several genes that are differentially regulated in response to PPARγ silencing during M.tb infection, including the Bcl-2 family members Bax (pro-apoptotic) and Mcl-1 (pro-survival). Apoptosis is an important defense mechanism that prevents the growth of intracellular microbes, including M.tb, but is limited by virulent M.tb. This suggested that M.tb differentially regulates Mcl-1 and Bax expression through PPARγ to limit apoptosis. In support of this, gene and protein expression analysis revealed that Mcl-1 expression is driven by PPARγ during M.tb infection in human macrophages. Further, 15-lipoxygenase (15-LOX) is critical for PPARγ activity and Mcl-1 expression. We also determined that PPARγ and 15-LOX regulate macrophage apoptosis during M.tb infection, and that pre-clinical therapeutics that inhibit Mcl-1 activity significantly limit M.tb intracellular growth in both human macrophages and an in vitro TB granuloma model. In conclusion, identification of the novel PPARγ effector Mcl-1 has determined PPARγ and 15-LOX are critical regulators of apoptosis during M.tb infection and new potential targets for host-directed therapy for M.tb.


Usage of FT-ICR-MS Metabolomics for Characterizing the Chemical Signatures of Barrel-Aged Whisky.
Whisky can be described as a complex matrix integrating the chemical history from the fermented cereals, the wooden barrels, the specific distillery processes, aging, and environmental factors. In this study, using Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR-MS) and liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS), we analyzed 150 whisky samples from 49 different distilleries, 7 countries, and ranging from 1 day new make spirit to 43 years of maturation with different types of barrel. Chemometrics revealed the unexpected impact of the wood history on the distillate's composition during barrel aging, regardless of the whisky origin. Flavonols, oligolignols, and fatty acids are examples of important chemical signatures for Bourbon casks, whereas a high number of polyphenol glycosides, including for instance quercetin-glucuronide or myricetin-glucoside as potential candidates, and carbohydrates would discriminate Sherry casks. However, the comparison of barrel aged rums and whiskies revealed specific signatures, highlighting the importance of the initial composition of the distillate and the distillery processes.


A modular computational framework for medical digital twins.
This paper presents a modular software design for the construction of computational modeling technology that will help implement precision medicine. In analogy to a common industrial strategy used for preventive maintenance of engineered products, medical digital twins are computational models of disease processes calibrated to individual patients using multiple heterogeneous data streams. They have the potential to help improve diagnosis, prognosis, and personalized treatment for a wide range of medical conditions. Their large-scale development relies on both mechanistic and data-driven techniques and requires the integration and ongoing update of multiple component models developed across many different laboratories. Distributed model building and integration requires an open-source modular software platform for the integration and simulation of models that is scalable and supports a decentralized, community-based model building process. This paper presents such a platform, including a case study in an animal model of a respiratory fungal infection.


In vitro and in vivo activities of AM-1155, a new fluoroquinolone, against Chlamydia spp.
The in vitro and in vivo activities of AM-1155, a new quinolone, against Chlamydia spp. were investigated. The MIC of AM-1155 for 10 standard strains of different Chlamydia spp. and 25 wild-type strains of Chlamydia pneumoniae isolated in Japan, which were morphologically different from clinical isolates from the United States, ranged from 0.063 to 0.125 microg/ml. Its activity was almost the same as those of sparfloxacin and tosufloxacin and was 4 and 16 times superior to those of levofloxacin and ciprofloxacin, respectively, but lower than those of clarithromycin and minocycline (range for each, 0.016 to 0.031 microg/ml). The minimal chlamydiacidal concentration of AM-1155 ranged from 0.063 to 0.125 microg/ml, while those of clarithromycin and minocycline ranged from 0.016 to 0.031 microg/ml and 0.016 to 0.063 microg/ml, respectively. The therapeutic effect of a 7-day course of AM-1155 at doses of 5 and 10 mg/kg of body weight administered orally twice daily to mice with experimental Chlamydia psittaci pneumonia was excellent, with a 100% survival rate at 21 days after infection. The efficacy was equal to those of clarithromycin and minocycline and higher than those of ciprofloxacin and ofloxacin.


Vaccines are not associated with metabolic events in children with urea cycle disorders.
Despite the success of childhood immunizations in prevention of infectious diseases, questions remain about the safety of vaccines in medically fragile children with inborn errors of metabolism such as urea cycle disorders (UCDs). Patients with UCDs are subject to hyperammonemic episodes (HAEs) after infection, fever, or other stressors. We sought to assess the risk of HAEs that required urgent care or hospitalization after routine vaccinations in pediatric patients with underlying UCDs. This was a retrospective investigation of vaccine safety in children with UCDs within the longitudinal Rare Diseases Clinical Research Consortium for UCD. Postvaccination exposure periods were defined as 7 or 21 days after any immunization. The association of vaccines and HAEs was modeled by using conditional Poisson regression, adjusting for age, and using a self-controlled case series method including all patients with ≥1 HAE and with any vaccine exposure. The study enrolled 169 children younger than 18 years. Of these children, 74 had records of at least 1 HAE and at least 1 vaccination. With adjustment for age, there was no increase in relative incidence of HAEs in either the 7-day (1.31 [95% confidence interval (CI): 0.80-2.13]) or 21-day (1.05 [95% CI: 0.74-1.47]) exposure period after vaccination compared with HAEs outside of the vaccination periods. No vaccine type was associated with significantly more HAEs. We found no statistically significant association between childhood immunizations and HAEs in children with UCDs. The results support the safety of immunization in this medically vulnerable population.


Methodological Approach to Improve Surgical Outcomes of a Pig Subretinal Implantation Model.
To improve outcomes for subretinal implantation surgery in pigs. Analysis of variables affecting the success of subretinal implantation surgery was performed on videos of 37 surgeries. Ex vivo experiments were conducted to measure intraocular pressure (IOP) and test various prototyped implanters for effectiveness at maintaining IOP. A video analysis revealed a prolonged sclerotomy open time owing to a combination of uncontrolled bleeding and excessive fluid outflow often resulting in retinal prolapse. Precauterization of the choroid before full-thickness sclerotomy (n = 10) resulted in a reduced incidence of uncontrolled bleeding from 39.1% (9/23) versus 0% (0/10) (P = 0.005) and improved implantation success from 73% to 90%. An ex vivo analysis of the IOP revealed a mean decrease in the IOP from 30.2 ± 3.0 mm Hg to 5.0 ± 2.1 mm Hg after a fully penetrating sclerotomy. To address this situation, we produced a series of plugs that integrated with a custom implant insertion device to seal the sclerotomy during implantation. The use of the plugs was cumbersome, however, and so we opted instead to increase the width of the inserter tip to fill the open sclerotomy. This improved device restored and maintained IOP during implantation (27.1 ± 1.9 mm Hg). Combined with precauterization the improved inserter resulted in 100% successful implantation (n = 4). For subretinal implantation in pigs, a modified procedure to precauterize the choroid before sclerotomy combined with an instrument that better fills the scleral opening decreases bleeding, hypotony, and open sclerotomy time, improving the success rate. Better management of IOP and bleeding from a sclerotomy will improve implant-based therapies.


Reproductive factors, intima media thickness and carotid plaques in a cross-sectional study of postmenopausal women enrolled in the population-based KORA F4 study.
Reproductive events may affect the onset of chronic diseases. We examined the possible association between reproductive parameters and intima media thickness (IMT) or carotid plaques in the common carotid artery in a population-based sample. This cross-sectional study analysed data of 800 postmenopausal women aged 50 to 81 years of the population-based KORA F4 study, conducted between 2006 and 2008 in Southern Germany. Reproductive parameters were obtained by standardised interviews. Age at menarche below 12 years compared to 12-15 years was significantly associated with carotid plaques (age-adjusted OR 2.23, 95% CI 1.13-4.43, p-value 0.018, multivariable adjusted 2.11, 1.05-4.26, 0.037), but not with IMT. Ever use of hormone replacement therapy was inversely associated with carotid plaques (age-adjusted 0.60, 0.44-0.81, p = 0.001, multivariable-adjusted 0.62, 0.45-0.86, 0.003) and IMT in the age-adjusted model (mean 0.89, 95% CI 0.88-0.90, p = 0.033) but not in the multivariable-adjusted model (mean 0.89, 95% CI 0.88-0.90, p = 0.075). Parity, age at menopause, time since menopause, duration of fertile period, current use of hormone replacement therapy, ever use of oral contraceptives, hysterectomy, bilateral oophorectomy, hot flashes and depressive mood in relation to the menopausal transition were not associated with carotid plaques or IMT. Our study showed, that there may be an independent association between the reproductive parameters age at menarche and ever use of hormone replacement therapy with carotid plaques in the common carotid artery, but not with IMT. Further research, especially in studies with prospective population-based study design, is necessary to assess in detail what events in women's life lead to increased IMT or CP.


Amino acid substitutions in membrane-spanning domains of Hol1, a member of the major facilitator superfamily of transporters, confer nonselective cation uptake in Saccharomyces cerevisiae.
Selection for the ability of Saccharomyces cerevisiae cells to take up histidinol, the biosynthetic precursor to histidine, results in dominant mutations at HOL1. The DNA sequence of HOL1 was determined, and it predicts a 65-kDa protein related to the major facilitator family (drug resistance subfamily) of putative transport proteins. Two classes of mutations were obtained: (i) those that altered the coding region of HOL1, conferring the ability to take up histidinol; and (ii) cis-acting mutations (selected in a mutant HOL1-1 background) that increased expression of the Hol1 protein. The ability to transport histidinol and other cations was conferred by single amino acid substitutions at any of three sites located within putative membrane-spanning domains of the transporter. These mutations resulted in the conversion of a small hydrophobic amino acid codon to a phenylalanine codon. Selection for spontaneous mutations that increase histidinol uptake by such HOL1 mutants resulted in mutations that abolish the putative start codon of a six-codon open reading frame located approximately 171 nucleotides downstream of the transcription initiation site and 213 nucleotides upstream of the coding region of HOL1. This single small upstream open reading frame (uORF) confers translational repression upon HOL1; genetic disruption of the putative start codon of the uORF results in a 5- to 10-fold increase in steady-state amounts of Hol1 protein without significantly affecting the level of HOL1 mRNA expression.


Correlation between metabolic syndrome and knee osteoarthritis: data from the Korean National Health and Nutrition Examination Survey (KNHANES).
This study was designed to investigate the correlations of knee osteoarthritis (OA) with metabolic syndrome (MetS) and MetS parameters in Korean subjects. This study included data from 270 subjects with knee OA and 1964 control subjects with a mean age of 54.56 (SD 11.53) years taken from the Korean National Health and Nutritional Examination Survey (KNHANES) 2008. Multivariate logistic regression analysis was conducted to examine possible associations for knee OA with MetS and MetS parameters. MetS was shown to be associated with an increased risk of knee OA in female subjects in unadjusted analysis (OR 1.798, 95% CI 1.392, 2.322), but this significance disappeared when adjusted for confounding factors (OR 1.117, 95% CI 0.805, 1.550). No significant association between MetS and knee OA was found in male subjects. Among parameters of MetS, only high waist circumference (WC) in female subjects was significantly associated with an increased prevalence of knee OA, even after adjusting for confounding factors, while no other significant associations were found in both male and female subjects. We found that WC was associated with knee OA in female subjects, but neither MetS nor any parameters thereof were shown to be associated with knee OA in the Korean subjects of this study. Although we found no relationship between a pre-inflammatory state of MetS and knee OA, we believe further investigation of this relationship in various aspects is warranted, as MetS may also be a risk factor for complications in knee OA related procedures.


Structure and dynamics of the hydration shells of the Zn(2+) ion from ab initio molecular dynamics and combined ab initio and classical molecular dynamics simulations.
Results of ab initio molecular dynamics (AIMD) simulations (density functional theory+PBE96) of the dynamics of waters in the hydration shells surrounding the Zn(2+) ion (T approximately 300 K, rho approximately 1 gm/cm(3)) are compared to simulations using a combined quantum and classical molecular dynamics [AIMD/molecular mechanical (MM)] approach. Both classes of simulations were performed with 64 solvating water molecules ( approximately 15 ps) and used the same methods in the electronic structure calculation (plane-wave basis set, time steps, effective mass, etc.). In the AIMD/MM calculation, only six waters of hydration were included in the quantum mechanical (QM) region. The remaining 58 waters were treated with a published flexible water-water interaction potential. No reparametrization of the water-water potential was attempted. Additional AIMD/MM simulations were performed with 256 water molecules. The hydration structures predicted from the AIMD and AIMD/MM simulations are found to agree in detail with each other and with the structural results from x-ray data despite the very limited QM region in the AIMD/MM simulation. To further evaluate the agreement of these parameter-free simulations, predicted extended x-ray absorption fine structure (EXAFS) spectra were compared directly to the recently obtained EXAFS data and they agree in remarkable detail with the experimental observations. The first hydration shell contains six water molecules in a highly symmetric octahedral structure is (maximally located at 2.13-2.15 A versus 2.072 A EXAFS experiment). The widths of the peak of the simulated EXAFS spectra agree well with the data (8.4 A(2) versus 8.9 A(2) in experiment). Analysis of the H-bond structure of the hydration region shows that the second hydration shell is trigonally bound to the first shell water with a high degree of agreement between the AIMD and AIMD/MM calculations. Beyond the second shell, the bonding pattern returns to the tetrahedral structure of bulk water. The AIMD/MM results emphasize the importance of a quantum description of the first hydration shell to correctly describe the hydration region. In these calculations the full d(10) electronic structure of the valence shell of the Zn(2+) ion is retained. The simulations show substantial and complex charge relocation on both the Zn(2+) ion and the first hydration shell. The dipole moment of the waters in the first hydration shell is 3.4 D (3.3 D AIMD/MM) versus 2.73 D bulk. Little polarization is found for the waters in the second hydration shell (2.8 D). No exchanges were seen between the first and the second hydrations shells; however, many water transfers between the second hydration shell and the bulk were observed. For 64 waters, the AIMD and AIMD/MM simulations give nearly identical results for exchange dynamics. However, in the larger particle simulations (256 waters) there is a significant reduction in the second shell to bulk exchanges.


Psychogenic movement disorders in children.
Psychogenic movement disorders (PMDs) are well characterized in adults, but childhood-onset PMDs have not been extensively studied. We reviewed the medical records of children who were diagnosed in our clinic with PMDs since 1988 and identified 54 patients with PMDs, representing 3.1% of our pediatric movement disorder population and 5.7% of all PMD cases. The mean age at symptom onset was 14.2 years (+/-2.11, range 7.6-17.7). Similar to published data in adults, two-thirds of children exhibited multiple PMD phenotypes, the most common being tremor followed by dystonia and myoclonus. Most PMDs were abrupt in onset, paroxysmal and triggered by identifiable physical or psychological trauma. As in adults, childhood PMDs were more likely to affect females, but there was no female predominance in children less than 13 years old. Although prior studies suggest that medically unexplained symptoms beginning in childhood often follow a benign course, this cohort of children experienced marked disability and morbidity related to PMDs, including prolonged school absences and unnecessary surgical procedures in more than one-fifth of patients.


Factors associated with increased academic productivity among US academic radiation oncology faculty.
Publication productivity metrics can help evaluate academic faculty for hiring, promotion, grants, and awards; however, limited benchmarking data exist, which makes intra- and interdepartmental comparisons difficult. Therefore, we sought to evaluate the scholarly activity of physician faculty at academic radiation oncology (RO) departments and establish factors associated with increased academic productivity. Citation database searches were performed for all physician-faculty in US residency-affiliated academic RO departments. Demographics, National Institutes of Health (NIH) funding, and bibliometrics (number of publications, Hirsch-[h]-index, and m-index [Hirsch index divided by the number of years since first publication]) were collected and stratified by academic rank. Senior academic rank was defined as full professor, professor, and/or chair. Junior academic rank was defined as all others. Logistic regression was performed to determine the association of academic rank and other factors with h- and m-indices. A total of 1191 academic RO physician faculty from 75 institutions were included in the analysis. The mean (standard deviation) number of publications and h- and m-indices were 48.2 (71.2), 14.5 (15), and 0.86 (0.83), respectively. The median (interquartile range) number of publications and h- and m-indices were 20 (6-61), 9 (4-20), and 0.69 (0.38-1.10), respectively. Recursive partitioning analysis revealed a statistically significant numeric h-index threshold of 21 between junior and senior faculty (LogWorth 114; receiver operating characteristic, 0.828). Senior faculty status, receipt of NIH funding, and a larger department size were associated with increased h- and m-indices. Current academic RO departments have relatively high objective metrics of scholastic productivity compared with prior benchmarking analyses of RO departments and compared with published metrics from other academic medicine subspecialties. An h-index of 21 or greater was associated with senior faculty status. Additionally, receipt of NIH funding and greater departmental size were associated with a higher h-index. These data may be of interest to faculty preparing for promotion or award applications as well as institutional leadership evaluating their departments.


Impact of a Behavioral Intervention on Diet, Eating Patterns, Self-Efficacy, and Social Support.
To examine the effectiveness of a structured multimodal behavioral intervention to change dietary behaviors, as well as self-efficacy and social support for engaging in healthier diets. A quasi-experimental design was used to assign sites into intervention and comparison groups. Data were collected at baseline, 3 months, and 6 months. The intervention group participated in Texercise Select, a 12-week lifestyle enhancement program. Multiple mixed-effects models were used to examine nutrition-related changes over time. For the intervention group, significant improvements were observed for fast food consumption (P = .011), fruit/vegetable consumption (P = .008), water consumption (P = .009), and social support (P < .001) from baseline to 3 months. The magnitude of these improvements was significantly greater than changes in the comparison group. Findings suggest the intervention's ability to improve diet-related outcomes among older adults; however, additional efforts are needed to maintain changes over longer periods.


Molecular characterization and expression of interleukin-10 and interleukin-22 in golden pompano (Trachinotus ovatus) in response to Streptococcus agalactiae stimulus.
In the present study, members of the interleukin (IL)-10 family of cytokines, including IL-10 (TOIL-10) and IL-22 (TOIL-22) of golden pompano (Trachinotus ovatus), were cloned for the first time, and their expression patterns and 3D structures analyzed. The full-length cDNA sequences of TOIL-10 and TOIL-22 contained open reading frames of 564 and 567 bp, respectively. TOIL-10 and TOIL-22 shared higher homology (78%-89%) with the corresponding genes from various fish relative to other species (25%-34%) and contained the IL-10 family signature and four cysteine residues that are well conserved in other vertebrate IL-10 members. Phylogenetic tree analysis of our sequences alongside other IL-10 family proteins revealed that TOIL-10 and TOIL-22 cluster together with other teleost IL-10 and IL-22 molecules. Expression of TOIL-10 and TOIL-22 genes was ubiquitous in all tissues examined. The TOIL-10 gene was also highly expressed in skin, heart, gill, spleen, kidney, brain and liver, and lower levels were detected in intestine and muscle. High expression of the TOIL-22 gene was observed in gill, intestine, kidney, spleen, with the lowest levels in liver. TOIL-10 and TOIL-22 were rapidly activated after SAΔphoB immunization and significantly increased to peak levels at 12 h and 4 d in golden pompano kidney and spleen respectively following challenge. Expression in the brain reached peak levels at 4 d and 3 d respectively after post-immunization. Our results collectively indicate that TOIL-10 and TOIL-22 participate in the host immune response to bacterial infection. Moreover, TOIL-22 plays a potentially important role in mucosal immunity.


TCF7L2 genetic defect and type 2 diabetes.
After two decades of limited success, the genetic architecture of type 2 diabetes (T2D) is finally being revealed. Within only 2 years, an avalanche of studies identified several genes expressed in pancreatic beta cells and involved in the control of insulin secretion, such as transcription factor 7-like 2 (TCF7L2), a key element of the Wnt signaling pathway. In Europeans, genome-wide association scans showed that TCF7L2 has been the most important locus predisposing to T2D so far. For the first time, a gene is consistently involved in T2D susceptibility in all major ethnic groups. At the individual level, carrying the TCF7L2 risk allele increases T2D risk 50%. However, at the population level, the attributable risk is lower than 25% and varies with the allele frequency. The presence of the TCF7L2 rs7903146 risk allele increases TCF7L2 gene expression in beta cells, possibly impairing glucagon-like peptide-1-induced insulin secretion and/or the production of new mature beta cells. The tremendous association of TCF7L2 polymorphisms with T2D provides new insights into future genetic predisposition tests but remains the tip of the T2D genetic iceberg.


Use of Suture Button in the Treatment of Syndesmosis Injuries.
A suture button device provides fixation of syndesmosis injuries of the ankle with or without concomitant malleolar fracture. The suture button device consists of a fiber thread attached between 2 small metal buttons. The buttons are placed on the cortical bone on the medial and lateral sides of the ankle, and the fiber thread is tightened to stabilize the syndesmosis. The suture button device offers stable yet dynamic fixation of the injured syndesmosis. The major steps of the procedure are (1) lateral skin incision straight to the bone; (2) open reduction and plate fixation of the fibular fracture if one is present; (3) reduction of the syndesmosis and temporary stabilization with a pin or clamp; (4) use of an appropriate burr to make a hole through 4 cortices at the level of the inferior tibiofibular joint, approximately 1.5 cm proximal to the ankle joint line and at a 20° to 30° lateral-to-anteromedial angle; (5) pulling the needle attached to the suture button device through the drill-hole from lateral to medial and flipping the small plate on the cortical bone of the medial cortex of the medial malleolus; (6) tightening the device by pulling the 2 threads on the lateral side with care taken to remove all of the slack from the system; and (7) checking placement and fixation with fluoroscopy, cutting the threads, and skin closure. Use of a walker boot or cast is decided on the basis of the fracture fixation. Partial weight-bearing is allowed for the first 6 weeks, after which full weight-bearing is permitted as pain allows. Routine removal of the suture button device is not required.


Unilateral and bilateral breast cancer in women surviving pediatric Hodgkin's disease.
To define demographic and therapeutic associations with the risk of breast cancer in children treated for Hodgkin's disease (HD), particularly the frequency and interval to the development of contralateral breast cancer. All 398 female patients (<19 years) treated for HD in five institutions during the accrual period were evaluated. Mean follow-up was 16.9 years. The standardized incidence ratio (SIR) was calculated as the ratio of the observed number of cases to the expected number of cases, estimated using age-matched controls from the Surveillance, Epidemiology, and End Results database. A total of 29 women developed breast cancer (25 invasive, 4 ductal carcinoma in situ; SIR, 37.25; 95% confidence interval, 24.96-53.64). Time to diagnosis was 9.4 to 36.1 years. Cumulative incidence was 24% at 30 years. Ten patients (34%) had bilateral disease (9 metachronous, 1 synchronous). The interval to contralateral breast cancer was 12 to 34 months. On univariate analysis, significant variables included stage of HD, mantle radiation dose, pelvic radiation (protective), and follow-up time. On multivariate analysis, early stage and older age at diagnosis of HD (<or=12 vs. >12 years) were significant predictors of secondary breast cancer. Women surviving pediatric HD were found to have a 37-fold increase in the risk of breast cancer and a high likelihood of rapidly developing bilateral disease. Early-stage HD and age greater than 12 years at diagnosis of HD were independent risk factors. Higher radiation doses may augment risk, and pelvic radiation may be protective. Breast cancer screening methodology and frequency, plus the role of prophylaxis in patients with unilateral disease, require definition.


Automated light-induced synthesis of 89Zr-radiolabeled antibodies for immuno-positron emission tomography.
Clinical production of 89Zr-radiolabeled antibodies (89Zr-mAbs) for positron emission tomography imaging relies on the pre-conjugation of desferrioxamine B (DFO) to the purified protein, followed by isolation and characterization of the functionalized intermediate, and then manual radiosynthesis. Although highly successful, this route exposes radiochemists to a potentially large radiation dose and entails several technological and economic hurdles that limit access of 89Zr-mAbs to just a specialist few Nuclear Medicine facilities worldwide. Here, we introduce a fully automated synthesis box that can produce individual doses of 89Zr-mAbs formulated in sterile solution in < 25 min starting from [89Zr(C2O4)4]4- (89Zr-oxalate), our good laboratory practice-compliant photoactivatable desferrioxamine-based chelate (DFO-PEG3-ArN3), and clinical-grade antibodies without the need for pre-purification of protein. The automated steps include neutralization of the 89Zr-oxalate stock, chelate radiolabeling, and light-induced protein conjugation, followed by 89Zr-mAb purification, formulation, and sterile filtration. As proof-of-principle, 89ZrDFO-PEG3-azepin-trastuzumab was synthesized directly from Herceptin in < 25 min with an overall decay-corrected radiochemical yield of 20.1 ± 2.4% (n = 3), a radiochemical purity > 99%, and chemical purity > 99%. The synthesis unit can also produce 89Zr-mAbs via the conventional radiolabeling routes from pre-functionalized DFO-mAbs that are currently used in the clinic. This automated method will improve access to state-of-the-art 89Zr-mAbs at the many Nuclear Medicine and research institutions that require automated devices for radiotracer production.


Pathogenicity and virulence of Francisella tularensis.
Tularaemia is a zoonotic disease caused by the Gram-negative bacterium, Francisella tularensis. Depending on its entry route into the organism, F. tularensis causes different diseases, ranging from life-threatening pneumonia to less severe ulceroglandular tularaemia. Various strains with different geographical distributions exhibit different levels of virulence. F. tularensis is an intracellular bacterium that replicates primarily in the cytosol of the phagocytes. The main virulence attribute of F. tularensis is the type 6 secretion system (T6SS) and its effectors that promote escape from the phagosome. In addition, F. tularensis has evolved a peculiar envelope that allows it to escape detection by the immune system. In this review, we cover tularaemia, different Francisella strains, and their pathogenicity. We particularly emphasize the intracellular life cycle, associated virulence factors, and metabolic adaptations. Finally, we present how F. tularensis largely escapes immune detection to be one of the most infectious and lethal bacterial pathogens.


Performance of N95 FFRs Against Combustion and NaCl Aerosols in Dry and Moderately Humid Air: Manikin-based Study.
The first objective of this study was to evaluate the penetration of particles generated from combustion of plastic through National Institute for Occupational Safety and Health (NIOSH)-certified N95 filtering facepiece respirators (FFRs) using a manikin-based protocol and compare the data to the penetration of NaCl particles. The second objective was to investigate the effect of relative humidity (RH) on the filtration performance of N95 FFRs. Two NIOSH-certified N95 FFRs (A and B) were fully sealed on a manikin headform and challenged with particles generated by combustion of plastic and NaCl particles. The tests were performed using two cyclic flows [with mean inspiratory flow (MIF) rates = 30 and 85 l min(-1), representing human breathing under low and moderate workload conditions] and two RH levels (≈20 and ≈80%, representing dry and moderately humid air). The total and size-specific particle concentrations inside (C in) and outside (C out) of the respirators were measured with a condensation particle counter and an aerosol size spectrometer. The penetration values (C in/C out) were calculated after each test. The challenge aerosol, RH, MIF rate, and respirator type had significant (P < 0.05) effects on the performance of the manikin-sealed FFR. Its efficiency significantly decreased when the FFR was tested with plastic combustion particles compared to NaCl aerosols. For example, at RH ≈80% and MIF = 85 l min(-1), as much as 7.03 and 8.61% of combustion particles penetrated N95 respirators A and B, respectively. The plastic combustion particles and gaseous compounds generated by combustion likely degraded the electric charges on fibers, which increased the particle penetration. Increasing breathing flow rate or humidity increased the penetration (reduced the respirator efficiency) for all tested aerosols. The effect of particle size on the penetration varied depending on the challenge aerosol and respirator type. It was observed that the peak of the size distribution of combustion particles almost coincided with their most penetrating particle size, which was not the case for NaCl particles. This finding was utilized for the data interpretation. N95 FFRs have lower filter efficiency when challenged with contaminant particles generated by combustion, particularly when used under high humidity conditions compared to NaCl particles.


Rapid screening procedure for pesticides and polychlorinated biphenyls in fish: collaborative study.
A simplified rapid method is presented to determine organochlorine pesticides and polychlorinated biphenyls in fish. Samples are mixed with sodium sulfate and blended with petroleum ether. A portion of the blend is placed on a miniaturized Florisil column and compounds are eluted with mixtures containing 6 and 15% ethyl ether in petroleum ether. Gas-liquid chromatography with electron capture detection comparable to the official methods (29.018) is used for determination of residues. Each of 7 collaborators reported results in duplicate for 10 samples containing one or more of the following compounds: p,p'-DDD, p,p'-DDE, p,p'-DDT, dieldrin, heptachlor epoxide, Aroclor 1254, and Aroclor 1260. Recoveries ranged from 79.3 to 100.7%. The coefficients of variation between laboratories ranged from 6.3 to 20.6%. This method allows up to 80% reduction in reagents and up to 50% reduction in analytical time, and requires less laboratory space than current official methods. The method has been adopted official first action.


Colchicine in Patients With Chronic Coronary Disease in Relation to Prior Acute Coronary Syndrome.
Colchicine reduces risk of cardiovascular events in patients post-myocardial infarction and in patients with chronic coronary disease. It remains unclear whether this effect is related to the time of onset of treatment following an acute coronary syndrome (ACS). This study investigates risk for major adverse cardiovascular events in relation to history and timing of prior ACS, to determine whether the benefits of colchicine are consistent independent of prior ACS status. The LoDoCo2 (Low-Dose Colchicine 2) trial randomly allocated patients with chronic coronary disease to colchicine 0.5 mg once daily or placebo. The rate of the composite of cardiovascular death, spontaneous myocardial infarction, ischemic stroke, or ischemia-driven coronary revascularization was compared between patients with no prior, recent (6-24 months), remote (2-7 years), or very remote (>7 years) ACS; interaction between ACS status and colchicine treatment effect was assessed. In 5,522 randomized patients, risk of the primary endpoint was independent of prior ACS status. Colchicine consistently reduced the primary endpoint in patients with no prior ACS (incidence: 2.8 vs 3.4 events per 100 person-years; hazard ratio [HR]: 0.81; 95% confidence interval [CI]: 0.52-1.27), recent ACS (incidence: 2.4 vs 3.3 events per 100 person-years; HR: 0.75; 95% CI: 0.51-1.10), remote ACS (incidence: 1.8 vs 3.2 events per 100 person-years, HR: 0.55; 95% CI: 0.37-0.82), and very remote ACS (incidence: 3.0 vs 4.3 events per 100 person-years, HR: 0.70; 95% CI: 0.51-0.96) (P for interaction = 0.59). The benefits of colchicine are consistent irrespective of history and timing of prior ACS. (The LoDoCo2 Trial: Low Dose Colchicine for secondary prevention of cardiovascular disease [LoDoCo2] ACTRN12614000093684).


Clinico-demographic and Outcome Predictors in Solid Tumor Patients with Unplanned Intensive Care Unit Admissions: An Observational Study.
Critically ill solid organ malignancy patients admitted to intensive care unit (ICU) as unplanned medical admissions behave differently from other subsets of cancer patients (hematolymphoid malignancies and cancer patients admitted for postoperative care). These patients if appropriately selected may benefit from the ICU care. There is paucity of data on critically ill unplanned admissions of solid organ malignancies from South Asia. We analyzed data of patients with solid tumors with unplanned admissions to the ICU to determine the clinical, epidemiological characteristics, and predictors of hospital mortality in an Indian ICU. This prospective, observational study was done in our 14-bedded mixed medical-surgical ICU from July 2014 to November 2015. We included all consecutive adult unplanned admissions with solid organ malignancies having ICU stay of >24 hours. Surgical admissions, hematolymphoid malignancies, advanced malignancy with no treatment options, and those cured of cancer >5 years were excluded. Two hundred and thirty-five consecutive patients were included in this cohort. ICU and hospital mortalities were 36.6 and 40%, respectively. On multivariate analysis, cancer status [odds ratio (OR): 3.204; 95% confidence interval (CI): 1.271-8.078], invasive mechanical ventilation (OR: 5.940; 95% CI: 2.632-13.408), and sequential organ failure assessment (SOFA) score on the day of ICU admission (OR: 1.199; 95% CI: 1.042-1.379) were independent predictors of hospital mortality. Acute respiratory failure and septic shock are the common reasons of unplanned ICU admission for patients with solid organ malignancies. With good patient selection, more than half of such patients are likely to be discharged alive from the hospital. Siddiqui SS, Narkhede AM, Chaudhari HK, Ravisankar NP, Dhundi U, Sarode S, et al. Clinico-demographic and Outcome Predictors in Solid Tumor Patients with Unplanned Intensive Care Unit Admissions: An Observational Study. Indian J Crit Care Med 2021;25(12):1421-1426.


Investigating Principal Working Memory Features in Generalized, Panic, and Social Anxiety Spectrum Disorders.
Anxiety spectrum disorders are characterized by excessive and uncontrollable worrying about potential negative events in the short- and long-term future. Various reports linked anxiety spectrum disorders with working memory (WM) deficits despite conflicting results stemming from different study approaches. It remains unclear, however, how different anxiety spectrum disorders such as generalized anxiety disorder (GAD), social anxiety disorder (SAD), and panic disorder (PD), differ in WM function. In this study, we utilized verbal, numerical, and sequential evaluations of WM to cover most possible facets of the WM data space. We used principal component analysis to extract the uncorrelated/whitened components of WM based on these measures. We evaluated medication-free patients with GAD, SAD, and PD patients as well as matched healthy individuals using a battery that measures WM duration and load. We found that patients with GAD and SAD, but not PD, exhibited poor performance only in the WM principal component that represents maintenance. There were no other significant differences between the four groups. Further, different WM components significantly predicted the severity of anxiety symptoms in the groups. We explored the clinical utility of WM components for differentiating patients with anxiety spectrum disorders from healthy individuals. By only using the WM components that represent maintenance and encoding, we managed to differentiate patients from controls in 84% of cases. For the first time, we present multiple novel approaches to examine cognitive function and design cognitive screening, and potentially diagnostics, for psychiatric disorders.