Health issues in the Arab American community. A review: depression and smoking.
The association between depression and smoking has been well-documented in multiple countries and age groups. This review examines recent publications that address the magnitude of the association and its causal patterns (ie, due to lowered success of quitting in people with depression, depression causing smoking, smoking causing depression or third factor related to both smoking and depression). We conclude that the association may be multi-factorial with each of the causal directions possibly contributing to the observed association. Also, the association extends beyond depression to other mental disorders, including consumption of illegal drugs and non-medical use of prescription medications. Although the studies emphasize cigarette smoking, it is plausible to generalize the findings to other tobacco delivery systems involving deep inhalation, such as a hookah, due to the pharmacodynamics of nicotine. Although this review did not examine any studies specific to Arab Americans, the findings should generalize if smoking is stigmatized or, alternatively, as stigmatization increases. The good news is that even with the robust association between depression and smoking, people with depression can quit smoking and continue to be smoke-free. Because 44.3% of cigarettes in the United States are consumed by individuals with mental illnesses, mental illness deserves a prominent focus to allow our public health goal of reducing the prevalence of smoking to be reached.


Isolation and characterization of hemorrhagic toxin g from the venom of Crotalus atrox (western diamondback rattlesnake).
Hemorrhagic toxin g (HT-g) was isolated from Crotalus atrox (western diamondback rattlesnake) venom using a five-step purification procedure to obtain approximately equal to 5.9 mg of purified HT-g from 2.0 g of crude venom. The purified toxin was homogeneous by disc electrophoresis on polyacrylamide gel at pH 8.3 and 4.3, and by isoelectric focusing. HT-g possessed lethal, hemorrhagic and proteolytic activities. These activities of toxin were inhibited by ethylenediamine-tetraacetic acid (EDTA), 1,10-phenanthroline or ethyleneglycol (beta-amino-ethyl) N,N,N',N'-tetracetic acid (EGTA), but not by cysteine or soybean trypsin inhibitor (SBTI). Its molecular weight was approximately 60,000 and the isoelectric point was 6.8. The toxin contains 516 amino acid residues. HT-g did not coagulate fibrinogen to fibrin; however, the toxin hydrolysed the A alpha-chain or B beta-chain of fibrinogen without cleaving the gamma-chain. HT-g produced only local hemorrhage in internal organs such as the intestine, heart and liver.


Automated EEG inter-burst interval detection in neonates with mild to moderate postasphyxial encephalopathy.
EEG inter-burst interval (IBI) and its evolution is a robust parameter for grading hypoxic encephalopathy and prognostication in newborns with perinatal asphyxia. We present a reliable algorithm for the automatic detection of IBIs. This automated approach is based on adaptive segmentation of EEG, classification of segments and use of temporal profiles to describe the global distribution of EEG activity. A pediatric neurologist has blindly scored data from 8 newborns with perinatal postasphyxial encephalopathy varying from mild to severe. 15 minutes of EEG have been scored per patient, thus totaling 2 hours of EEG that was used for validation. The algorithm shows good detection accuracy and provides insight into challenging cases that are difficult to detect.


Digital Interventions to Enhance PrEP Uptake and Adherence Through Stigma Reduction.
Although pre-exposure prophylaxis (PrEP) is effective for reducing risk of HIV transmission, stigma persists as a barrier to HIV prevention. Digital technologies present opportunities to access hard-to-reach populations and increase the efficiency of established interventions. This review examines current digital interventions addressing stigma to improve PrEP-related outcomes. Digital technologies are increasingly used for HIV prevention and include a wide range of formats. Recent interventions focused on stigma and PrEP tend to engage mobile phone-related technology and focus on younger populations with particular attention to men who have sex with men and transgender women. Digital interventions that address stigma are promising for improving PrEP-related outcomes. No single technology currently demonstrates consistent superiority. Limited access to PrEP and heightened stigma in under-resourced countries present challenges for interventions supporting diverse communities. Further research should examine how digital interventions can reduce stigma beyond the individual level to enhance PrEP use and explore opportunities to improve and integrate approaches to stigma measurement.


Activation of the C-Type Lectin MGL by Terminal GalNAc Ligands Reduces the Glycolytic Activity of Human Dendritic Cells.
Many tumors display alterations in the biosynthetic pathways of glycosylation, resulting in increased expression of specific tumor-associated glycan structures. Expression of these altered glycan structures is associated with metastasis and poor prognosis. Antigen presenting cells can recognize tumor-associated glycan structures, including the truncated O-glycan Tn antigen, via specific glycan receptors. Tn antigen-mediated activation of the C-type lectin MGL on dendritic cells induces regulatory T cells via the enhanced secretion of IL-10. Although these findings indicate that MGL engagement by glycan ligands can modulate immune responses, the impact of MGL ligation on dendritic cells is still not completely understood. Therefore, we employed RNA sequencing, GO term enrichment and pathway analysis on human monocyte-derived dendritic cells stimulated with two different MGL glycan ligands. Our analyses revealed a reduced expression of genes coding for key enzymes involved in the glycolysis pathway, TCA cycle, and oxidative phosphorylation. In concordance with this, extracellular flux analysis confirmed the decrease in glycolytic activity upon MGL triggering in human dendritic cells. To our knowledge, we are the first to report a diminished glycolytic activity of human dendritic cells upon C-type lectin stimulation. Overall, our findings highlight the impact of tumor-associated glycans on dendritic cell biology and metabolism and will increase our understanding on how glycans can shape immunity.


Pharmacy access to electronic patient records.
Electronic medical record keeping may prove to be a boon to the managed care industry, enabling efficient administration of health delivery and better access to a particular patient's long-term medical history. It is hoped that better quality care will result. The availability of electronic medical records to pharmacists has tremendous implications on pharmacy's ability to deliver on the promise of pharmaceutical care.


A Prospective Treatment Option for Lysosomal Storage Diseases: CRISPR/Cas9 Gene Editing Technology for Mutation Correction in Induced Pluripotent Stem Cells.
Ease of design, relatively low cost and a multitude of gene-altering capabilities have all led to the adoption of the sophisticated and yet simple gene editing system: clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9). The CRISPR/Cas9 system holds promise for the correction of deleterious mutations by taking advantage of the homology directed repair pathway and by supplying a correction template to the affected patient's cells. Currently, this technique is being applied in vitro in human-induced pluripotent stem cells (iPSCs) to correct a variety of severe genetic diseases, but has not as of yet been used in iPSCs derived from patients affected with a lysosomal storage disease (LSD). If adopted into clinical practice, corrected iPSCs derived from cells that originate from the patient themselves could be used for therapeutic amelioration of LSD symptoms without the risks associated with allogeneic stem cell transplantation. CRISPR/Cas9 editing in a patient's cells would overcome the costly, lifelong process associated with currently available treatment methods, including enzyme replacement and substrate reduction therapies. In this review, the overall utility of the CRISPR/Cas9 gene editing technique for treatment of genetic diseases, the potential for the treatment of LSDs and methods currently employed to increase the efficiency of this re-engineered biological system will be discussed.


Variation in soil aluminium tolerance genes is associated with local adaptation to soils at the Park Grass Experiment.
Studies of the wild grass Anthoxanthum odoratum at the long-term Park Grass Experiment (PGE, Harpenden, UK) document a well-known example of rapid plant evolution in response to environmental change. Repeated fertilizer applications have acidified the soil in some experimental plots over the past 150+ years, and Anthoxanthum subpopulations have quickly become locally adapted. Early reciprocal transplants showed subpopulation differentiation specifically in response to soil aluminium (Al) toxicity across the experiment, even at small (30 m) spatial scales. Almost 40 years after its original measurement, we reassessed the degree of local adaptation to soil Al at the PGE using updated phenotyping methods and identified genes with variation linked to the tolerance trait. Root growth assays show that plants are locally adapted to soil Al at both the seedling and adult growth stages, but to a smaller extent than previously inferred. Among a large suite of candidate loci that were previously shown to have Al-sensitive expression differences between sensitive and tolerant plants, three loci contained SNPs that are associated with both Al tolerance and soil acidity: an Al-sensitive malate transporter (ALMT), a tonoplast intrinsic protein (TIP) and the putative homolog of the rice cell-wall modification gene STAR1. Natural genetic variation at these loci is likely to have contributed to the recent rapid evolution at PGE. Continued study of Al tolerance variants in Anthoxanthum will allow us to test hypotheses about the nature and source of genetic variation that enables some species to adapt to soil acidification and other types of rapid environmental change.


[Intravenous propofol as a supplement in epidural anesthesia].
Under study were thirty patients of ASA class I-II scheduled for lower abdominal and lower extremities surgery. Premedication included intramuscular injection of pethidine, atropine and prochlorperazine. Epidural anesthesia was accomplished with 12-15 ml 2% lidocaine with epinephrine (1:80,000). Thirty minutes later, when blood pressure returned to control value, patients were put to sleep by 2 mg/kg propofol and the sleep was maintained with continuous infusion of propofol at a rate of 6 mg/kg/h. Infusion rate was adjusted when necessary. Patients breathed room air spontaneously through the whole course of anesthesia. The results showed that all patients fell to sleep within 28.3 +/- 2.7 s after intravenous injection of propofol 2 mg/kg. Sleeping dose was satisfactorily achieved using a mean infusion rate of 6.1 +/- 1.7 mg/kg/h. The mean time from the end of the infusion of propofol to opening of the eyes on command and telling the correct date of birth were 7.9 +/- 2.8 min and 9.9 +/- 3.8 min respectively. Two minutes after injection, there were significant decrease in systolic pressure, diastolic pressure, cardiac output, and stroke volume with a mean of 17.9 +/- 3.8%, 18.8 +/- 3.3%, 7.6 +/- 0.5% and 11.1 +/- 1.9% respectively. Two patients (7%) developed apnea after 2 mg/kg propofol which was considered to be the most serious side effect. Propofol infusion had to be stopped in 13% patients due to a 30% fall of arterial blood pressure during maintenance. In the recovery stage, no other complications were noted except one patient who felt dizziness. Propofol, used as the supplementary sedative, provides satisfactory result for surgery under epidural anesthesia.(ABSTRACT TRUNCATED AT 250 WORDS)


Use of streptokinase or urokinase in recurrent CAPD peritonitis.
In patients undergoing CAPD treatment, removal of peritoneal catheters has become a standard practice after two or more episodes of recurrent peritonitis which are refractory to antibiotic treatment. Immediate replacement of peritoneal catheters is not always safe in the presence of active peritonitis. Temporary institution of hemodialysis treatment in some of these patients may also be impossible because of unstable hemodynamic states or loss of vascular access sites. Successful continuation of CAPD treatment in some of these patients has been reported by using intraperitoneal (IP) administration of fibrinolytic agents such as streptokinase or urokinase as an adjunctive therapy to antibiotic treatment and as an outpatient procedure. Although numbers of cases reported are few in the literature and controlled studies in large numbers of patients are lacking, these reports emphasize the safety of IP use of these agents without any major systemic adverse effects. The reports are reviewed here to provide some practical guidelines for safe use of these agents in selected patients with recurrent CAPD-associated peritonitis.


Interplay between alcohol, smoking and HLA genes in RA aetiology.
The relationship between alcohol consumption and risk for rheumatoid arthritis (RA) is incompletely understood. We aimed to determine the influence of alcohol on anticitrullinated protein antibody (ACPA) positive and ACPA-negative RA and investigate potential interactions between alcohol consumption, smoking and the presence of human leucocyte antigen (HLA)-DRB1-shared epitope (SE). A Swedish population-based case-control study with incident cases of RA was used (3353 cases, 2836 matched controls). Subjects with different HLA-DRB1-SE status, smoking and alcohol consumption were compared regarding risk of ACPA-positive and ACPA-negative RA, by calculating OR with 95% CI employing logistic regression. Interaction on the additive scale between alcohol, HLA-DRB1-SE and smoking was estimated by calculating the attributable proportion (AP) due to interaction. Compared with non-drinking, low and moderate alcohol consumption was dose dependently associated with a reduced risk of ACPA-positive and ACPA-negative RA. Independent of smoking habits, non-drinking and the presence of HLA-DRB1-SE interacted to increase the risk of ACPA-positive RA. Among HLA-DRB1-SE positive subjects, there was also a significant interaction between non-drinking and smoking with regard to risk for ACPA-positive RA. A three-way interaction was observed between alcohol, smoking and HLA-DRB1-SE with regard to risk for ACPA-positive RA (AP 0.7, 95% CI 0.6 to 0.8) that remained significant when the influence from the two-way interactions was removed (AP 0.4, 95% CI 0.2 to 0.6). Our findings emphasize the need to investigate complex interactions between several environmental and genetic factors in order to better understand the etiology of RA. Whereas of great interest in an aetiological perspective, the finding of a protective role of alcohol on risk for RA must, however, be interpreted with caution in a clinical and public health perspective.


Susceptibility of bacteria isolated from dental unit waterlines to disinfecting chemical agents.
Susceptibility testing of bacteria to disinfecting chemical agents isolated from dental unit waterlines (DUWL) is necessary for the development of effective disinfectant products. However, until now, susceptibility tests for chemical agents, which are components of DUWL disinfectant products, have not been conducted on bacteria isolated from DUWL water. The aim of this study was to evaluate and compare the susceptibilities of DUWL isolates in planktonic and biofilm states to cetylpyridinium chloride, as well as to the four chemical agents currently used for DUWL management. A total of 56 isolates, including 12 genera, were identified by 16S rDNA sequencing, and one strain of each genus was selected for susceptibility testing. A total of 12 isolates were used for the susceptibility tests. We determined the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) for the planktonic state and the minimum biofilm inhibitory concentration (MBIC) and minimum biofilm eradication concentration (MBEC) for the biofilm state using microtiter plates. MIC, MBC, MBIC, and MBEC of the 12 isolates for ethanol were the highest, followed by sodium hypochlorite, hydrogen peroxide, and chlorhexidine. Similar to chlorhexidine, the lowest MIC, MBC, MBIC, and MBEC were found in cetylpyridinium chloride. The susceptibilities of the isolates for sodium hypochlorite and ethanol were similar in the planktonic and biofilm states. For hydrogen peroxide and chlorhexidine, the MBIC and MIC were similar, but MBEC was 256 times higher than MBC. The MBIC and MBEC of isolates for cetylpyridinium chloride were 128 and 256 times higher than the MIC and MBC, respectively. As far as we know, this was the first study reporting the susceptibility of DUWL isolates to cetylpyridinium chloride and chemical agents used for disinfecting DUWLs. Cetylpyridinium chloride, for which the DUWL isolates showed the highest susceptibility, could be used for disinfecting DUWLs.


The 1-kb-repeat-encoded DNA-binding protein as repressor of an alpha-glucosidase operon flanking the amplifiable sequence AUD1 of Streptomyces lividans.
High-copy-number amplification of the AUD1 element is frequently associated with the large chromosomal deletions responsible for genetic instability in Streptomyces lividans TK64. Five ORFs were found in a 7 kb region directly adjacent to AUD1. The putative products of ORF1, ORF2 and ORF3 showed similarities to ATP-binding cassette (ABC) sugar transporters, the deduced protein sequence of ORF4 displayed similarities to alpha-glucosidases whilst no homology to proteins with known functions was found for ORF5. ORF4 (renamed aglA) was expressed in Escherichia coli and the protein purified and characterized. An alpha-glucosidase activity was detected using the synthetic alpha-glucoside p-nitrophenyl alpha-D-glucopyranoside. Of the many oligosaccharides tested, only sucrose was hydrolysed at a measurable rate [specific activity 32.4 units (mg protein)(-1)] but no growth of S. lividans TK64 on sucrose was observed. A strain in which aglA was disrupted showed the same low alpha-glucosidase activity as strain TK64 and in both strains no stimulation of activity was seen by sucrose, trehalose or maltose; dextrin increased alpha-glucosidase activity about 10-fold. This probably resulted from induction of a second alpha-glucosidase-encoding gene. The AUD1 element contains three 1 kb repeats which encode DNA-binding proteins necessary for high-frequency amplification. In strains with a unique 1 kb repeat, disruption of the repeat led to a significant increase in the alpha-glucosidase activity. These results strongly suggest that the 1-kb-repeat-encoded proteins of AUD1 have a dual function: they are the repressors of the agl genes and they promote amplification of AUD1.


[Recording cardiorespiratory arrest by the Utstein method].
The author introduces a "Case History Form to Serve to Follow the Process of Cardiorespiratory Arrest" drawn up by means of the recommended guidelines for uniform data communication in cases of cardiorespiratory arrest outside the hospital, following the Utstein method. At the same time, given that there still are no set guidelines in the hospital milieu, the author includes a form on which to record the subsequent actions carried out during cardiorespiratory arrest. This case history form was presented orally at a Congress on Resuscitation in Seville.


Cardiovascular effects of positive pressure ventilation in humans.
Pulsus paradoxus is the pathological exaggeration of the normal transient decrease in arterial blood pressure that occurs during spontaneous inspiration. The transient increase in arterial pressure associated with positive pressure inspiration is termed reversed pulsus paradoxus (RPP). Cardiorespiratory interactions and the mechanism of these effects have been studied extensively in animals, and to a lesser extent, in humans. In this clinical investigation pulsus paradoxus and RPP were studied in 10 postoperative cardiac patients with invasive monitoring and mediastinal pressure catheters placed intraoperatively. From end-expiration to end-inspiration, RPP was accompanied by decreased transmural pressures in the right atrium, left atrium, and aorta. Left ventricular end-systolic volume measured by radionuclide studies diminished during a positive pressure inspiration, without a significant change in end-diastolic volume. These results are consistent with decreased left ventricular afterload as the major mechanism of RPP. During spontaneous breathing, inspiration was associated with converse effects, a fall in arterial pressure and an increase in transmural right atrial, left atrial, and aortic pressures from end-expiration to end-inspiration. End-systolic volume was significantly larger at end-expiration than end-inspiration, with no change in end-diastolic volume. These findings suggest that an increase in left ventricular afterload during inspiration is responsible for the observed pulsus paradoxus.


Systematic Review and Meta-Analysis of Incidence and Prevalence of Endometriosis.
There is still much controversy regarding the epidemiology of endometriosis. The objective of this work is to conduct a systematic review, and if possible, proceed with a meta-analysis of studies that have analyzed the incidence and prevalence of this condition among women in the general population. The inclusion criteria were papers published after 1997 that had reported data of the incidence or prevalence of endometriosis. The PubMed search engine was used to identify papers meeting the inclusion criteria from 1997 to 2019, with an additional manual search for the identification of potentially eligible studies. The search was limited to papers published in English. The risk of bias was assessed according to the Joanna Briggs Institute Critical Appraisal Checklist. As a result, 27 papers, which included a total of 28,660,652 women, were classified according to the type of design and sources of information in five subgroups. Pooled estimates of prevalence for studies with self-reported data were 0.05 (95% CI: 0.03; 0.06), 0.01 for population-based integrated information systems (95% CI: 0.01; 0.02), and 0.04 (95% CI 0.04; 0.05) in studies using other designs. The pooled incidence rate of endometriosis was: 1.36 per 1000 person-years (PY) (95% CI: 1.09; 1.63) for studies based on hospital discharges, 3.53 per 1000 PY (95% CI: 2.06; 4.99) for cohort studies, and 1.89 per 1000 PY (95% CI: 1.42; 2.37) for population-based integrated information systems. Meta-analysis indicated high heterogeneity based on I-squared statistics. This significant variability may not only be due to methodological issues and the specific limitations of the different designs and data analyzed, including case definitions and subject selection strategies, but also to the inherent heterogeneity of endometriosis. Epidemiological studies with appropriate study designs remain necessary to provide a valid estimation of the population burden of endometriosis.


Lifestyle modifications result in alterations in the gut microbiota in obese children.
The association between the gut microbiota and pediatric obesity was analyzed in a cross-sectional study. A prospective study of obese children was conducted to assess the gut microbial alterations after a weight change. We collected fecal samples from obese children before and after a 2-month weight reduction program that consisted of individual counseling for nutritional education and physical activity, and we performed 16S rRNA gene amplicon sequencing using an Illumina MiSeq platform. Thirty-six participants, aged 7 to 18 years, were classified into the fat loss (n = 17) and the fat gain (n = 19) groups according to the change in total body fat (%) after the intervention. The baseline analysis of the gut microbiota in the preintervention stages showed dysbiotic features of both groups compared with those of normal-weight children. In the fat loss group, significantly decreased proportions of Bacteroidetes phylum, Bacteroidia class, Bacteroidales order, Bacteroidaceae family, and Bacteroides genus, along with increased proportions of Firmicutes phylum, Clostridia class, and Clostridiales order, were observed after intervention. The microbial richness was significantly reduced, without a change in beta diversity in the fat loss group. The fat gain group showed significantly deceased proportions of Firmicutes phylum, Clostridia class, Clostridiales order, Lachnospiraceae family, and Eubacterium hallii group genus, without a change in diversity after the intervention. According to the functional metabolic analysis by the Phylogenetic Investigation of Communities by Reconstruction of Unobserved States 2, the "Nitrate Reduction VI" and "Aspartate Superpathway" pathways were predicted to increase significantly in the fat loss group. The cooccurring networks of genera were constructed and showed the different microbes that drove the changes between the pre- and postintervention stages in the fat loss and fat gain groups. This study demonstrated that lifestyle modifications can impact the composition, richness, and predicted functional profiles of the gut microbiota in obese children after weight changes. ClinicalTrials.gov NCT03812497 , registration date January 23, 2019, retrospectively registered.


The control of body size in insects.
Control mechanisms that regulate body size and tissue size have been sought at both the cellular and organismal level. Cell-level studies have revealed much about the control of cell growth and cell division, and how these processes are regulated by nutrition. Insulin signaling is the key mediator between nutrition and the growth of internal organs, such as imaginal disks, and is required for the normal proportional growth of the body and its various parts. The insulin-related peptides of insects do not appear to control growth by themselves, but act in conjunction with other hormones and signaling molecules, such as ecdysone and IDGFs. Size regulation cannot be understood solely on the basis of the mechanisms that control cell size and cell number. Size regulation requires mechanisms that gather information on a scale appropriate to the tissue or organ being regulated. A new model mechanism, using autocrine signaling, is outlined by which tissue and organ size regulation can be achieved. Body size regulation likewise requires a mechanism that integrates information at an appropriate scale. In insects, this mechanism operates by controlling the secretion of ecdysone, which is the signal that terminates the growth phase of development. The mechanisms for size assessment and the pathways by which they trigger ecdysone secretion are diverse and can be complex. The ways in which these higher-level regulatory mechanisms interact with cell- and molecular- level mechanisms are beginning to be elucidated.


Does Obesity Modify the Ability of Prebiopsy Prostate Specific Antigen to Detect Prostate Cancer on Repeat Biopsy? Results from the REDUCE Study.
Higher body mass index is linked to lower prostate specific antigen. This has given rise to concerns that prostate specific antigen may be less reliable for predicting prostate cancer among obese men. We tested the accuracy of prebiopsy prostate specific antigen for predicting prostate cancer across body mass index categories. We used the REDUCE study, which tested dutasteride for prostate cancer risk reduction in men with a prostate specific antigen of 2.5 to 10.0 ng/ml and a negative pre-study biopsy. All men were required to have a biopsy at 2 and 4 years independent of prostate specific antigen. We assessed the performance of prebiopsy prostate specific antigen to predict overall and high grade prostate cancer (Gleason sum 7 or greater) in each body mass index group using AUC. Of 6,103 men who had a 2-year biopsy 1,646 (27%) were normal weight, 3,209 (53%) were overweight and 1,248 (20%) were obese. Mean adjusted prostate specific antigen for normal weight, overweight and obese subjects on placebo was 7.73, 7.17 and 6.79 ng/ml (p-trend=0.192), and on dutasteride 3.16, 2.93 and 2.62 ng/ml (p=0.008). AUC analysis using raw prostate specific antigen data for predicting prostate cancer ranged from 0.60 to 0.64 in the placebo arm and 0.58 to 0.66 in the dutasteride arm with no difference across body mass index categories (p-interactions ≥0.212). Similar results were found for high grade prostate cancer with AUC ranging from 0.69 to 0.70 in the placebo arm and 0.65 to 0.75 in the dutasteride arm but no differences across body mass index categories (p-interactions ≥0.157). Among men with a previous negative biopsy the accuracy of prebiopsy prostate specific antigen to predict overall and high grade prostate cancer was independent of body mass index.


Interplay Between Cytosolic Free Zn2+ and Mitochondrion Morphological Changes in Rat Ventricular Cardiomyocytes.
The Zn2+ in cardiomyocytes is buffered by structures near T-tubulus and/or sarcoplasmic/endoplasmic reticulum (S(E)R) while playing roles as either an antioxidant or a toxic agent, depending on the concentration. Therefore, we aimed first to examine a direct effect of ZnPO4 (extracellular exposure) or Zn2+ pyrithione (ZnPT) (intracellular exposure) application on the structure of the mitochondrion in ventricular cardiomyocytes by using histological investigations. The light microscopy data demonstrated that Zn2+ exposure induced marked increases on cellular surface area, an indication of hypertrophy, in a concentration-dependent manner. Furthermore, a whole-cell patch-clamp measurement of cell capacitance also supported the hypertrophy in the cells. We observed marked increases in mitochondrial matrix/cristae area and matrix volume together with increased lysosome numbers in ZnPO4- or ZnPT-incubated cells by using transmission electron microscopy, again in a concentration-dependent manner. Furthermore, we observed notable clustering and vacuolated mitochondrion, markedly disrupted and damaged myofibrils, and electron-dense small granules in Zn2+-exposed cells together with some implications of fission-fusion defects in the mitochondria. Moreover, we observed marked depolarization in mitochondrial membrane potential during 1-μM ZnPT minute applications by using confocal microscopy. We also showed that 1-μM ZnPT incubation induced significant increases in the phosphorylation levels of GSK3β (Ser21 and Ser9), Akt (Ser473), and NFκB (Ser276 and Thr254) together with increased expression levels in ER stress proteins such as GRP78 and calregulin. Furthermore, a new key player at ER-mitochondria sites, promyelocytic leukemia protein (PML) level, was markedly increased in ZnPT-incubated cells. As a summary, our present data suggest that increased cytosolic free Zn2+ can induce marked alterations in mitochondrion morphology as well as depolarization in mitochondrion membrane potential and changes in some cytosolic signaling proteins as well as a defect in ER-mitochondria cross talk.


Venous thromboembolism prophylaxis and multiple myeloma patients in real-life: Results of a large survey and clinical guidance recommendations from the IFM group.
Venous thromboembolism (VTE) remains a critical issue in the management of patients with multiple myeloma (MM), particularly when immunomodulatory drugs (IMiDs) combined with dexamethasone therapy are being prescribed as first-line and relapse therapy. One possible explanation for the persistent high rates of VTE, is the use of inappropriate thromboprophylaxis strategies for patients starting antimyeloma treatment. To tackle the issue, the Intergroupe francophone du myélome (IFM) offered convenient guidance for VTE thromboprophylaxis in MM patients initiating systemic therapy. This guidance is mainly supported by the results of a large survey on the clinical habits regarding VTE of physicians who are substantially involved in daily care of MM patients. VTE prophylaxis should be considered for all patients treated with IMiDs in combination with dexamethasone, in the absence of significant comorbidities, such as renal failure or bleeding risk. Anticoagulant should be preferred to antiplatelet agents for thromboprophylaxis. Despite the absence of large randomized controlled trials comparing those attitudes/options, available data on direct oral anticoagulants, which are already used in daily management of MM patients, are consistent with their potential usefulness for VTE prophylaxis in such patients. However, in order to implement a personalized continuous improvement strategy, clinicians must to be organized to collect all the data regarding this management. In other situations, thromboprophylaxis should be evaluated by using risk models and after careful evaluation of the risk/benefit ratio.


Antioxidant N-acetylcysteine removing ROS: an antifouling strategy inspired by mussels.
Marine biofouling is a thorny issue that causes serious economic losses and adverse ecological impacts on marine ecosystems. Effective and promising antifouling strategies such as surface hydration, flow shear force, and lubricant injection have been developed to address this challenge. However, for the complex marine environment, they still appear inadequate. Mussels are a common fouling organism with strong surface adhesion ability. However, when hypoxia and the oxidative cross-linking reaction of 3,4-dihydroxy phenyl-L-alanine (DOPA) in the structure of adhesion proteins are disrupted, their adhesion ability will be greatly reduced. Inspired by this, we developed an effective antifouling strategy based on reactive oxygen species (ROS) scavenging using N-acetylcysteine (NAC) and evaluated its performance. As a ROS scavenger interfered with the oxidative cross-linking reaction of DOPA in an aqueous solution, the adhesion of DOPA was also affected on the surface of NAC functionalized polyvinyl chloride (PVC) (PVC-NAC). In addition, the colonization level of mussels and the adhesion rate of marine bacteria and benthic diatoms on PVC-NAC were low. The antifouling strategy proposed in this paper was eco-friendly and broad-spectrum, and may provide a new idea for solving marine biofouling and reducing the environmental and economic impacts of fouling organisms.


Quantitative bias analysis of a reported association between perfluoroalkyl substances (PFAS) and endometriosis: The influence of oral contraceptive use.
An association between serum levels of perfluoroalkyl substances (PFAS) and endometriosis has recently been reported in an epidemiologic study. Oral contraceptive use to treat dysmenorrhea (pelvic pain associated with endometriosis) could potentially influence this association by reducing menstrual fluid loss, a route of excretion for PFAS. In this study, we aimed to evaluate the influence of differential oral contraceptive use on the association between PFAS and endometriosis. We used a published life-stage physiologically based pharmacokinetic (PBPK) model to simulate plasma levels of perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) from birth to age at study participation (range 18-44years). In the simulated population, PFAS level distributions matched those for controls in the epidemiologic study. Prevalence and geometric mean duration (standard deviation [SD]) of oral contraceptive use in the simulated women were based on data from the National Health and Nutrition Examination Survey; among the women with endometriosis the values were, respectively, 29% and 6.8 (3.1) years; among those without endometriosis these values were 18% and 5.3 (2.8) years. In simulations, menstrual fluid loss (ml/cycle) in women taking oral contraceptives was assumed to be 56% of loss in non-users. We evaluated the association between simulated plasma PFAS concentration and endometriosis in the simulated population using logistic regression. Based on the simulations, the association between PFAS levels and endometriosis attributable to differential contraceptive use had an odds ratio (95% CI) of 1.05 (1.02, 1.07) for a loge unit increase in PFOA and 1.03 (1.02, 1.05) for PFOS. In comparison, the epidemiologic study reported odds ratios of 1.62 (0.99, 2.66) for PFOA and 1.25 (0.87, 1.80) for PFOS. Our results suggest that the influence of oral contraceptive use on the association between PFAS levels and endometriosis is relatively small.


Streptococcus anginosus adheres to vascular endothelium basement membrane and purified extracellular matrix proteins.
The mechanisms of bacterial adherence in the initial stages of native valve endocarditis are unclear, especially in patients without valve disease or the presence of a platelet-fibrin thrombus. Extracellular matrix may act as a ligand in areas of exposed basement membrane on the endothelial monolayer. In this study, adherence of 55 clinical blood and 21 oral viridans streptococcal isolates was examined using purified extracellular matrix compounds. The majority of blood and oral isolates exhibited adherence to purified laminin, fibronectin, and fibrinogen, with lesser adherence to type I and IV collagens. Adherence to laminin and fibronectin was concentration dependent, saturable, and competitively inhibited with soluble ligand. A Streptococcus anginosus isolate and other viridans strains exhibiting a strong laminin adherence phenotype bound extensively to the endothelial aspect of human and porcine valve tissue sections and were inhibited by soluble laminin and anti-laminin antibody fragments. Using a novel native porcine valve explant adherence model, we localized binding to areas of exposed basement membrane by confocal and scanning electron microscopy. These studies support the hypothesis that bacterial adherence to exposed basement membrane plays a role in the initial phase of native valve endocarditis.


Membrane fluidity and enzyme activities in brush border and basolateral membranes of the dog kidney.
The physical state of membrane lipids and relationships with the activity of Na+-K+-ATPase and alkaline phosphatase were studied in basolateral and brush border membranes of the dog kidney. Fluorescence polarization and electron spin resonance experiments demonstrate that basolateral membranes are much more fluid than brush border membranes. This can be accounted for by a difference in fluidity of the lipid part of the membranes. Broad (43-17 degrees C) thermotropic transitions are observed in liposomes made from total lipid extracts of brush border and basolateral membranes. Fluorescence data strongly suggest that thermotropic transitions also occur in intact membranes and that a change in membrane physical state may take place around the physiological temperature. A nonlinear Arrhenius plot for the Na+-K+-ATPase activity in basolateral membranes (breakpoint 21 degrees C) provides additional support for the existence of a lipid liquid leads to gel transition in antiluminal plasma membranes. A break in the Arrhenius plot of alkaline phosphatase activity is also observed but at a temperature significantly higher (26 degrees C) than that of the end of the thermotropic transition. "Room temperature" appears as a critical zone for lipid physical state and activities of both enzymes.


Treatment and posttreatment effects of a facial mask combined with a bite-block appliance in Class III malocclusion.
In this cephalometric investigation, we analyzed the treatment and posttreatment effects of an orthopedic protocol for Class III malocclusion consisting of a facial mask combined with a removable bite-block appliance. The treated sample consisted of 22 Class III patients treated with the facial mask and bite-block protocol before the pubertal growth spurt (mean age, 8.9 +/- 1.5 years). Treated subjects were evaluated after facial mask and bite-block therapy and at a posttreatment observation in absence of retention. The treated group was compared with a matched control group of 12 untreated Class III subjects. All treated and control subjects were postpubertal at the final observation. Significant differences between the treated and control groups were assessed with the Mann-Whitney U test (P <0.05). Both angular and linear sagittal measurements of the maxilla showed significant improvements during active treatment. Significant improvements of SNA angle, ANB angle, overjet, and molar relationship remained stable during the posttreatment period. No significant effect was found in the mandibular skeletal measures. No significant protraction of the maxillary incisors or retraction of the mandibular incisors was observed. A bite-block appliance in the mandibular arch with a facial mask enabled effective control of mandibular rotation with progressive closure of the gonial angle. This added to the favorable maxillary outcomes of the treatment protocol.


Long Non-Coding RNA CASC19 Sponges microRNA-532 and Promotes Oncogenicity of Clear Cell Renal Cell Carcinoma by Increasing ETS1 Expression.
The long non-coding RNA cancer susceptibility 19 (CASC19) is recognized as an important regulator in gastric cancer, colorectal cancer, and non-small cell lung cancer. Nevertheless, to the best of our knowledge, the expression status and detailed roles of CASC19 in clear cell renal cell carcinoma (ccRCC) have not been elucidated. Hence, we aimed to determine CASC19 expression in ccRCC and investigate its roles in ccRCC oncogenicity. The molecular mechanisms underlying CASC19 functions in ccRCC were also determined. CASC19 expression was measured by using reverse transcription-quantitative polymerase chain reaction. The effects of CASC19 on ccRCC cell proliferation, colony formation, migration, and invasiveness in vitro, as well as on tumor growth in vivo, were examined by the MTT assay, colony formation assay, cell migration and invasiveness assays, and tumor xenograft in nude nice, respectively. CASC19 was overexpressed in ccRCC tissues and cell lines. High expression of CASC19 was closely associated with unfavorable clinicopathological parameters and predicted negative clinical outcomes in patients with ccRCC. Knockdown of CASC19 decreased ccRCC cell proliferation, colony formation, migration, and invasiveness, as well as attenuated tumor growth in vivo. Mechanistically, CASC19 functioned as a competing endogenous RNA and upregulated the expression of ETS proto-oncogene 1 (ETS1) through sponging microRNA-532 (miR-532). Furthermore, rescue assays revealed that inhibiting miR-532 or restoring ETS1 expression partially abolished the impacts of CASC19 knockdown on ccRCC cells. The CASC19/miR-532/ETS1 regulatory pathway is crucial for the malignant manifestations of ccRCC, which makes it an attractive target for potential treatments of ccRCC.


Vaccine development: Current trends and technologies.
Despite the effectiveness of vaccination in reducing or eradicating diseases caused by pathogens, there remain certain diseases and emerging infections for which developing effective vaccines is inherently challenging. Additionally, developing vaccines for individuals with compromised immune systems or underlying medical conditions presents significant difficulties. As well as traditional vaccine different methods such as inactivated or live attenuated vaccines, viral vector vaccines, and subunit vaccines, emerging non-viral vaccine technologies, including viral-like particle and nanoparticle vaccines, DNA/RNA vaccines, and rational vaccine design, offer new strategies to address the existing challenges in vaccine development. These advancements have also greatly enhanced our understanding of vaccine immunology, which will guide future vaccine development for a broad range of diseases, including rapidly emerging infectious diseases like COVID-19 and diseases that have historically proven resistant to vaccination. This review provides a comprehensive assessment of emerging non-viral vaccine production methods and their application in addressing the fundamental and current challenges in vaccine development.


P-glycoprotein substrate models using support vector machines based on a comprehensive data set.
P-glycoprotein (P-gp) is one of the major ABC transporters and involved in many essential processes such as lipid and steroid transport across cell membranes but also in the uptake of drugs such as HIV protease and reverse transcriptase inhibitors. Despite its importance, reliable models predicting substrates of P-gp are scarce. In this study, we have built several computational models to predict whether or not a compound is a P-gp substrate, based on the largest data set yet published, employing 332 distinct structures. Each molecule is represented by ADRIANA.Code, MOE, and ECFP_4 fingerprint descriptors. The models are computed using a support vector machine based on a training set which includes 131 substrates and 81 nonsubstrates that were evaluated by 5-, 10-fold, and leave-one-out (LOO) cross-validation. The best model gives a Matthews Correlation Coefficient of 0.73 and a prediction accuracy of 0.88 on the test set. Examination of the model based on ECFP_4 fingerprints revealed several substructures which could have significance in separating substrates and nonsubstrates of P-gp, such as the nitrile and sulfoxide functional groups which have a higher frequency in nonsubstrates than in substrates. In addition structural isomerism in sugars was found to result in remarkable differences regarding the likelihood of a compound to be a substrate for P-gp.


Computing H/D-exchange rates of single residues from data of proteolytic fragments.
Protein conformation and protein/protein interaction can be elucidated by solution-phase Hydrogen/Deuterium exchange (sHDX) coupled to high-resolution mass analysis of the digested protein or protein complex. In sHDX experiments mutant proteins are compared to wild-type proteins or a ligand is added to the protein and compared to the wild-type protein (or mutant). The number of deuteriums incorporated into the polypeptides generated from the protease digest of the protein is related to the solvent accessibility of amide protons within the original protein construct. In this work, sHDX data was collected on a 14.5 T FT-ICR MS. An algorithm was developed based on combinatorial optimization that predicts deuterium exchange with high spatial resolution based on the sHDX data of overlapping proteolytic fragments. Often the algorithm assigns deuterium exchange with single residue resolution. With our new method it is possible to automatically determine deuterium exchange with higher spatial resolution than the level of digested fragments.


Soy isoflavone genistein attenuates lipopolysaccharide-induced cognitive impairments in the rat via exerting anti-oxidative and anti-inflammatory effects.
Systemic inflammation during infectious disorders usually accompanies chronic complications including cognitive dysfunction. Neuroinflammation and cognitive deficit are also observed in some debilitating neurological disorders like Alzheimer's and Parkinson's diseases. Genistein is a soy isoflavone with multiple beneficial effects including anti-inflammatory, anti-oxidative, and protective properties. In this research study, the effect of genistein in prevention of lipopolysaccharide (LPS)-induced cognitive dysfunction was investigated. LPS was given i.p. (500 μg/kg/day) and genistein was orally given (10, 50, or 100 mg/kg) for one week. Findings showed that genistein could dose-dependently attenuate spatial recognition, discrimination, and memory deficits. Additionally, genistein treatment of LPS-challenged group lowered hippocampal level of malondialdehyde (MDA) and increased activity of superoxide dismutase (SOD) and catalase and glutathione (GSH) level. Furthermore, genistein ameliorated hippocampal acetylcholinesterase (AChE) activity in LPS-challenged rats. Furthermore, genistein administration to LPS-injected group lowered hippocampal level of interleukin 6 (IL-6), nuclear factor-kappaB (NF-κB) p65, toll-like receptor 4 (TLR4), tumor necrosis factor α (TNFα), cyclooxygenase-2 (COX2), inducible nitric oxide synthase (iNOS), glial fibrillary acidic protein (GFAP), and increased hippocampal level of antioxidant element nuclear factor (erythroid-derived 2)-like 2 (Nrf2). In conclusion, genistein alleviated LPS-induced cognitive dysfunctions and neural inflammation attenuation of oxidative stress and AChE activity and appropriate modulation of Nrf2/NF-κB/IL-6/TNFα/COX2/iNOS/TLR4/GFAP.


Clinical and histopathological differential diagnosis of eosinophilic pustular folliculitis.
Eosinophilic pustular folliculitis (EPF) is an inflammatory disease characterized by repeated pruritic follicular papules and pustules arranged in arcuate plaques, and folliculotropic infiltration of eosinophils. The diagnosis of EPF is occasionally difficult and problematic because EPF may share the clinical appearance and histological findings with other diseases. Moreover, EPF has several clinical subtypes, including the classical type, infantile type and immunosuppression-associated type. Because the therapies of EPF are relatively specific as compared to eczematous disorders, accurate diagnosis is essential for the management of EPF. Clinical differential diagnoses include tinea, acne, rosacea, eczematous dermatitis, granuloma faciale, autoimmune annular erythema, infestations and pustular dermatosis. Histologically, cutaneous diseases with eosinophilic infiltrates can be differentially diagnosed. Follicular mucinosis, mycosis fungoides and other cutaneous T-cell lymphomas are the most important differential diagnoses both clinically and histopathologically. It should be kept in mind particularly that the initial lesions of cutaneous T-cell lymphoma resemble EPF.


Dynamic stability during running gait termination: Predictors for successful control of forward momentum in children and adults.
Reported differences between children and adults with respect to COM horizontal and vertical position to maintain dynamic stability during running deceleration suggest that this relationship may not be as important in children. This study challenged the current dynamic stability paradigm by determining the features of whole body posture that predicted forward velocity and momentum of running gait termination in adults and children. Sixteen adults and 15 children ran as fast as possible and stopped at pre-determined location. Separate regression analyses determined whether COM posterior and vertical positions and functional limb length (distance between COM and stance foot) predicted velocity and momentum for adults and children. COM posterior position was the strongest predictor of forward velocity and momentum in both groups supporting the previously established relationship during slower tasks. COM vertical position also predicted momentum in children, not adults. Higher COM position in children was related to greater momentum; consistent with previously reported differences between children and adults in COM position across running deceleration. COM vertical position was related to momentum but not velocity in children suggesting that strategies used to terminate running may be driven by demands imposed not just by velocity, but also the mass being decelerated.


The ACA And The Courts: Litigation's Effects On The Law's Implementation And Beyond.
The Affordable Care Act's legacy extends beyond its provision of health insurance to millions of previously uninsured people and its improved consumer protections. It has also had a significant impact on the US legal system. Litigation over the law began on the day of its enactment and has been a constant in the decade since. Although the law has survived these challenges, its effectiveness has been hobbled. Litigation is now being used as a check on the efforts to undermine the Affordable Care Act by the administration of President Donald Trump. This article reviews the history of litigation over the Affordable Care Act, how the law generally has been shaped by this litigation, and what this experience might mean for the future of health reform efforts.


Patterns in Zika Virus Testing and Infection, by Report of Symptoms and Pregnancy Status - United States, January 3-March 5, 2016.
CDC recommends Zika virus testing for potentially exposed persons with signs or symptoms consistent with Zika virus disease, and recommends that health care providers offer testing to asymptomatic pregnant women within 12 weeks of exposure. During January 3-March 5, 2016, Zika virus testing was performed for 4,534 persons who traveled to or moved from areas with active Zika virus transmission; 3,335 (73.6%) were pregnant women. Among persons who received testing, 1,541 (34.0%) reported at least one Zika virus-associated sign or symptom (e.g., fever, rash, arthralgia, or conjunctivitis), 436 (9.6%) reported at least one other clinical sign or symptom only, and 2,557 (56.4%) reported no signs or symptoms. Among 1,541 persons with one or more Zika virus-associated symptoms who received testing, 182 (11.8%) had confirmed Zika virus infection. Among the 2,557 asymptomatic persons who received testing, 2,425 (94.8%) were pregnant women, seven (0.3%) of whom had confirmed Zika virus infection. Although risk for Zika virus infection might vary based on exposure-related factors (e.g., location and duration of travel), in the current setting in U.S. states, where there is no local transmission, most asymptomatic pregnant women who receive testing do not have Zika virus infection.


Reliability of intra-oral quantitative sensory testing (QST) in patients with atypical odontalgia and healthy controls - a multicentre study.
The reliability of comprehensive intra-oral quantitative sensory testing (QST) protocol has not been examined systematically in patients with chronic oro-facial pain. The aim of the present multicentre study was to examine test-retest and interexaminer reliability of intra-oral QST measures in terms of absolute values and z-scores as well as within-session coefficients of variation (CV) values in patients with atypical odontalgia (AO) and healthy pain-free controls. Forty-five patients with AO and 68 healthy controls were subjected to bilateral intra-oral gingival QST and unilateral extratrigeminal QST (thenar) on three occasions (twice on 1 day by two different examiners and once approximately 1 week later by one of the examiners). Intra-class correlation coefficients and kappa values for interexaminer and test-retest reliability were computed. Most of the standardised intra-oral QST measures showed fair to excellent interexaminer (9-12 of 13 measures) and test-retest (7-11 of 13 measures) reliability. Furthermore, no robust differences in reliability measures or within-session variability (CV) were detected between patients with AO and the healthy reference group. These reliability results in chronic orofacial pain patients support earlier suggestions based on data from healthy subjects that intra-oral QST is sufficiently reliable for use as a part of a comprehensive evaluation of patients with somatosensory disturbances or neuropathic pain in the trigeminal region.


Importance of endothelium-derived hyperpolarizing factor in human arteries.
The endothelium plays an important role in maintaining the vascular homeostasis by releasing vasodilator substances, including prostacyclin (PGI2), nitric oxide (NO), and endothelium-derived hyperpolarizing factor (EDHF). Although the former two substances have been investigated extensively, the importance of EDHF still remains unclear, especially in human arteries. Thus we tested our hypothesis that EDHF plays an important role in human arteries, particularly with reference to the effect of vessel size, its vasodilating mechanism, and the influences of risk factors for atherosclerosis. Isometric tension and membrane potentials were recorded in isolated human gastroepiploic arteries and distal microvessels (100-150 microm in diameter). The contribution of PGI2, NO, and EDHF to endothelium-dependent relaxations was analyzed by inhibitory effects of indomethacin, NG-nitro- L-arginine, and KCl, respectively. The nature of and hyperpolarizing mechanism by EDHF were examined by the inhibitory effects of inhibitors of cytochrome P450 pathway and of various K channels. The effects of atherosclerosis risk factors on EDHF-mediated relaxations were also analyzed. The results showed that (a) the contribution of EDHF to endothelium-dependent relaxations is significantly larger in microvessels than in large arteries; (b) the nature of EDHF may not be a product of cytochrome P450 pathway, while EDHF-induced hyperpolarization is partially mediated by calcium-activated K channels; and (c) aging and hypercholesterolemia significantly impair EDHF-mediated relaxations. These results demonstrate that EDHF also plays an important role in human arteries.


[Chemical constituents of rhizomes of Zingiber officinale].
To investigate the chemical constituents from the rhizomes of Zingiber officinale. Isolation and purification of the chemical constituents were carried out on the column chromatography of silica gel and Sephadex LH-20. The structures were elucidated on basis of physicochemical properties and spectral data. Ten compounds were isolated and identified as beta-sitosterol palmitate (1), isovanillin (2), glycol monopalmitate (3), hexacosanoic acid 2,3-dihydroxypropyl ester (4), maleimide-5-oxime (5), p-hydroxybenzaldehyde (6), adenine (7), 6-gingerol (8), 6-shogaol (9), and 1-(omega-ferulyloxyceratyl) glycerols (10a-10f). Compounds 1-7 and 10a-10e are obtained from Z. officinale for the first time, and compound 10f is a new compound.


Preventing and treating discitis: cephazolin penetration in ovine lumbar intervertebral disc.
Infection can occur after any spinal procedure that violates the disc and although it is not common, the potential consequences are serious. Treatment of discitis is not always successful and the key to management is prevention. Intradiscal prophylaxis with antibiotic is routinely used in spinal surgery, but there is a limited understanding of how well antibiotics can enter the avascular disc after intravenous injection. An in vivo ovine study to optimise prophylactic and parenteral treatment of discitis is described to assess the effectiveness of cephazolin in preventing and treating infection. The concentration of cephazolin was measured in disc tissue from normal and degenerate sheep discs to determine if cephazolin can enter the disc and if disc degeneration affects antibiotic uptake. Fourteen sheep were deliberately inoculated with bacteria to induce discitis. Eight sheep ("prophylaxis" group) were given either a 0, 1, 2 or 3 g dose of prophylactic cephazolin before inoculation while the remaining sheep ("treatment" group) were treated with cephazolin commencing 7 days after inoculation for 21 days at a dose of 50 mg/kg/day. Histopathology and radiography were used to assess the effect of the different treatments. Cephazolin was given 30 min prior to sacrifice and the intradiscal concentration was measured by biochemistry. In the "prophylaxis" group all doses of antibiotic provided some protection against infection, although it was not dose dependent. In the "treatment" group discitis was confirmed radiologically and histologically in all animals from 2 weeks onwards. Biochemical assay confirmed that antibiotic is distributed throughout the disc but was present in higher concentration in the anulus fibrosus than the nucleus pulposus. This study demonstrated that whilst the incidence of iatrogenic discitis can be reduced by antibiotic prophylaxis, it could not be abolished in all incidences with a broad-spectrum antibiotic such as cephazolin. Furthermore, antibiotics were ineffective at preventing endplate destruction once an intradiscal inoculum was established.


An analysis of the public perception of flood risk on the Belgian coast.
In recent years, perception of flood risks has become an important topic to policy makers concerned with risk management and safety issues. Knowledge of the public risk perception is considered a crucial aspect in modern flood risk management as it steers the development of effective and efficient flood mitigation strategies. This study aimed at gaining insight into the perception of flood risks along the Belgian coast. Given the importance of the tourism industry on the Belgian coast, the survey considered both inhabitants and residential tourists. Based on actual expert's risk assessments, a high and a low risk area were selected for the study. Risk perception was assessed on the basis of scaled items regarding storm surges and coastal flood risks. In addition, various personal and residence characteristics were measured. Using multiple regression analysis, risk perception was found to be primarily influenced by actual flood risk estimates, age, gender, and experience with previous flood hazards.


Intrafamilial variability in syndromic microphthalmia type 5 caused by a novel variation in OTX2.
Anophthalmia/microphthalmia/coloboma (MAC) spectrum encompasses the most severe malformations of the eye. Together, they have an incidence of 2 in 10,000 births and can be unilateral or bilateral. These disorders are genetically heterogeneous. We ascertained a large three-generation family with multiple members showing variable phenotypes of syndromic microphthalmia. Exome sequencing was performed for the proband and his affected maternal aunt. Targeted sequencing of OTX2 gene was performed for other family members. Variable clinical presentation in the form of unilateral microphthalmia and bilateral microphthalmia as well as nonpenetrance were noted. Exome sequencing revealed a novel heterozygous variant c.278G>T (p.W93L) in OTX2 in the proband. All affected members as well as the unaffected mother of the proband carried the same variant. Syndromic microphthalmia due to mutations in OTX2 can present with significant intrafamilial phenotypic variability.


HIV-associated neurocognitive disorders: antiretroviral regimen, central nervous system penetration effectiveness, and cognitive outcomes.
The human immunodeficiency virus (HIV) can give rise to a spectrum of neuropsychological impairments known collectively as HIV-associated neurocognitive disorders (HAND). Although antiretroviral therapy (ART) has reduced the incidence of HIV dementia, the prevalence of milder forms of HAND has increased. It has been postulated that incomplete central nervous system (CNS) viral suppression or potential drug toxicity, both of which could be related to the CNS penetration effectiveness (CPE) of ART regimens, may contribute to this phenomenon. This study compared cognitive outcomes in clade C-infected HIV patients in South Africa treated for 1 year with ART regimens with differing CPE scores. We assessed 111 HIV-positive patients with varying levels of cognitive function at baseline (pre-ART) and then a year later. A neuropsychological battery was administered at both visits to derive global deficit scores. ART regimen data were collected at the follow-up visit. Some participants remained ART-naïve during this period, thus providing a non-treatment control group. Significantly more ART recipients maintained or improved cognitive function compared with patients not on ART (p=0.017). There was no significant difference in cognitive outcomes between higher and lower CPE regimen groups (p=0.473). ART preserves or improves cognition in HIV-infected patients after 1 year, irrespective of the regimen's CPE. South Africa's current low CPE-scored first-line regimen performed as well as higher CPE-scored regimens. These findings are reassuring for South Africa, but larger, longer-term studies would be more definitive.


Identification of a DNA methylation signature in blood cells from persons with Down Syndrome.
Down Syndrome (DS) is characterized by a wide spectrum of clinical signs, which include segmental premature aging of central nervous and immune systems. Although it is well established that the causative defect of DS is the trisomy of chromosome 21, the molecular bases of its phenotype are still largely unknown. We used the Infinium HumanMethylation450 BeadChip to investigate DNA methylation patterns in whole blood from 29 DS persons, using their relatives (mothers and unaffected siblings) as controls. This family-based model allowed us to monitor possible confounding effects on DNA methylation patterns deriving from genetic and environmental factors. Although differentially methylated regions (DMRs) displayed a genome-wide distribution, they were enriched on chromosome 21. DMRs mapped in genes involved in developmental functions, including embryonic development (HOXA family) and haematological (RUNX1 and EBF4) and neuronal (NCAM1) development. Moreover, genes involved in the regulation of chromatin structure (PRMD8, KDM2B, TET1) showed altered methylation. The data also showed that several pathways are affected in DS, including PI3K-Akt signaling. In conclusion, we identified an epigenetic signature of DS that sustains a link between developmental defects and disease phenotype, including segmental premature aging.


Dietary restraint, body dissatisfaction, and psychological distress: a prospective analysis.
This study uses prospective data from a survey of 1,177 adolescent girls to examine whether emotional eating, binge eating, abnormal attitudes to eating and weight, low self-esteem, stress, and depression are associated with dietary restraint or body dissatisfaction. In analyses that included both restraint and body dissatisfaction as independent predictors, restraint was associated only with more negative attitudes to eating, whereas body dissatisfaction was significantly associated with all the adverse outcomes. These results cast doubt on the proposition that restrained eating is a primary cause of bulimic symptoms, emotional eating, and psychological distress seen in individuals who are trying to control their weight, and rather suggest that body dissatisfaction is the key factor.


Molecular simulations of zwitterlation-induced conformation and dynamics variation of glucagon-like peptide-1 and insulin.
Zwitterionic materials have shown their ability to improve the circulation time and stability of proteins. Zwitterionic peptides present unique potential because genetic technology can fuse them to any wild-type protein. One critical question is the effect of the fusing zwitterionic peptides on the conformation and dynamics of the original protein domain. To shed light on this question, we investigate the conformation and dynamics of six artificial proteins composed of two small therapeutic polypeptide and protein (glucan-like peptide-1 and insulin) and a zwitterionic (glutamic acid-lysine)10 peptide in an explicit solvent using molecular dynamics simulations. The zwitterionic peptide is fused to the N- and C-terminal of the glucan-like peptide-1 and the chain A and B of the insulin. We analyze the conformation and dynamics variation of the polypeptide and protein domain using root mean square deviation, root mean square fluctuation, solvent accessible surface area, and secondary structure distributions. The simulation results show that the zwitterlation induces substantial changes in the conformation of the glucan-like peptide-1 and a moderate change in the conformation of the insulin, while the two polypeptide and protein remain folded. The glucan-like peptide-1 presents a full α-helix conformation when zwitterlated at the C-terminal. The zwitterionic location also plays a role in the conformational change. These zwitterlation-induced conformation variations indicate a comprehensive relationship between zwitterlation and protein stability and activity.


Seizure secondary to cardiac arrythmias.
The relationship between seizure activity and arrhythmias is not well established. Sinus tachycardia is commonly seen post seizure. Bradyarrythmias leading to seizure activity is rarely reported in the literature thus far. A 62-year-old lady presented with nocturnal seizures and was subsequently started on oral anti-convulsant with no relief of her symptoms. Further investigations led to outpatient ambulatory ECGs which showed marked sinus bradycardia prior to seizure activity and post seizure atrial fibrillation with fast ventricular rate. The patient was commenced on oral anticoagulant and beta blocker for ventricular rate control in view of atrial fibrillation. A backup dual chamber permanent pacemaker was implanted to treat the bradycardia. The patient became seizure free since the implantation of permanent pacemaker. This case stresses the importance of investigating and treating cardiac arrhythmias underlying seizure activity.


Solamargine purified from Solanum incanum Chinese herb triggers gene expression of human TNFR I which may lead to cell apoptosis.
Solamargine possessed a potent cytotoxicity to human hepatocyte (Hep3B) and normal skin fibroblast. The inhibition curves of solamargine to the both cells were essentially overlapped, suggesting a parallel effect for the cell death. To define mechanism of cytotoxicity of solamargine, the changes of morphology and DNA content in cells were studied. A sub-G1 cell stage was drastically increased after 3-h incubation with solamargine. The results evidence that solamargine arises cell death by apoptosis. In addition, the gene expression of TNFR I were up-regulated within 30 min of solamargine treatment. Since TNF Receptor I has been involved in apoptosis, the overexpression of TNF receptor I may be related with the mechanism of cytotoxicity of solamargine. This communication is the first report that a component of Chinese herbs triggers gene expression of human TNFR I which may lead to cell apoptosis.


Distribution of squeezed states through an atmospheric channel.
Continuous variable quantum states of light are used in quantum information protocols and quantum metrology and known to degrade with loss and added noise. We were able to show the distribution of bright polarization squeezed quantum states of light through an urban free-space channel of 1.6 km length. To measure the squeezed states in this extreme environment, we utilize polarization encoding and a postselection protocol that is taking into account classical side information stemming from the distribution of transmission values. The successful distribution of continuous variable squeezed states is accentuated by a quantum state tomography, allowing for determining the purity of the state.


Diagnosis and Treatment in Neurosarcoidosis.
Sarcoidosis is an inflammatory multisystem disorder, affecting many systems such as lung, lymph nodes, skin and eye involvement. Nervous system involvement is often seen in 5-15% of patients with systemic sarcoidosis in the first two years. Preceding to systemic involvement the initial symptom as neurological complaints has been rarely reported. Lacking of any specific, clinical and / or radiological findings for neurosarcoidosis in these cases, it could be difficult to make an accurate diagnosis and histopathological evaluation may be required. Due to rarity and complexity diagnosis of the neurosarcoidosis, in this study, clinical, radiological and / or histopathological features, treatment modalities of the 7 neurosarcoidosis patients to be presented with detailed investigations of different neurological symptoms were evaluated.


Ethanol-induced Htr3a promoter methylation changes in mouse blood and brain.
Abnormal DNA methylation has been observed in promoter regions of a number of genes in human alcoholics. It is unclear whether DNA methylation changes in alcoholics result directly from alcohol consumption or predated the occurrence of alcohol abuse or dependence and whether altered DNA methylation influences gene expression. We investigated ethanol (EtOH)-induced DNA methylation changes in mouse serotonin receptor 3a gene (Htr3a). A 5-day drinking-in-the-dark paradigm was applied to 28 male outbred CD-1 mice (15 EtOH-drinking and 13 water-drinking). The Sequenom MassARRAY approach was used to quantify methylation levels of 8 CpGs around Htr3a transcription start site in trunk blood and 9 brain regions (dorsomedial prefrontal cortex [DMPFC], ventromedial prefrontal cortex, ventral tegmental area, dorsolateral striatum, dorsomedial striatum [DMSTR], ventral striatum, amygdala, hippocampus [HIPPO], and cerebellum). DNA methylation differences between the 2 groups of mice (EtOH- and water-drinking) were analyzed using multivariate analysis of covariance with consideration of EtOH consumption amount. Expression levels of Htr3a in the DMSTR were measured by real-time PCR in 14 EtOH-drinking and 14 water-drinking male CD-1 mice. EtOH drinking increased methylation levels of specific Htr3a promoter CpGs in mouse blood (CpG-27: p = 0.028; CpG+54: p = 0.044) and HIPPO (CpG+151: p = 0.012) but reduced methylation levels of specific Htr3a promoter CpGs in mouse DMSTR (CpG-96: p = 0.020; CpG-27: p = 0.035) and DMPFC (CpG+138: p = 0.011; CpG+151: p = 0.040). Nevertheless, methylation levels of Htr3a promoter CpGs in 6 other brain regions were not significantly altered by EtOH consumption. Additionally, the expression level of Htr3a in the DMSTR was 1.43-fold higher in alcohol-drinking mice than in water-drinking mice (p = 0.044). Our findings indicate that alcohol consumption may induce tissue-specific DNA methylation changes and further suggest that Htr3a promoter methylation levels may be reversely correlated with Htr3a expression levels in specific brain regions such as DMSTR.


Etanercept treatment in patients with refractory systemic onset juvenile rheumatoid arthritis.
. To assess the efficacy and safety of etanercept in a large cohort of children with refractory systemic onset juvenile rheumatoid arthritis (SOJRA). Standardized questionnaires were sent to US pediatric rheumatologists about patients with SOJRA treated with etanercept. Data were collected at baseline and at the last visit on etanercept. Response to treatment was assessed and compared to baseline as the mean percentage reduction in the following: acute phase reactants, prednisone dose, active joint count, and physician global assessment of disease activity. Response was defined as poor if the mean reduction was < 30%, fair if 30% to < 50%, good if 50% to < 70%, and excellent if > 70%. We analyzed data obtained by survey of 82 SOJRA patients treated with etanercept for a mean of 25 months. Poor response to treatment was observed in 45% of the children, fair response in 9%, good in 13%, and excellent in 33%. Baseline steroid therapy could be discontinued in 27/59 (46%) patients. One or more disease flares occurred in 45% of all patients. Twenty-nine patients (35%) discontinued therapy, mostly due to lack of response or flare. There were 32 adverse event reports, most not considered serious, except for 2 cases of macrophage activation syndrome. In this cohort of children with SOJRA, 46% had a good or excellent response, and most were able to reduce concomitant corticosteroid doses. The response to etanercept was fair or poor in more than half our study population, and disease flares were common. Due to the unique cytokine profile of SOJRA, tumor necrosis factor blockade may not be the optimal therapeutic approach for children with treatment-resistant SOJRA.


Structural Analysis of the Ancestral Haloalkane Dehalogenase AncLinB-DmbA.
Haloalkane dehalogenases (EC 126.96.36.199) play an important role in hydrolytic degradation of halogenated compounds, resulting in a halide ion, a proton, and an alcohol. They are used in biocatalysis, bioremediation, and biosensing of environmental pollutants and also for molecular tagging in cell biology. The method of ancestral sequence reconstruction leads to prediction of sequences of ancestral enzymes allowing their experimental characterization. Based on the sequences of modern haloalkane dehalogenases from the subfamily II, the most common ancestor of thoroughly characterized enzymes LinB from Sphingobium japonicum UT26 and DmbA from Mycobacterium bovis 5033/66 was in silico predicted, recombinantly produced and structurally characterized. The ancestral enzyme AncLinB-DmbA was crystallized using the sitting-drop vapor-diffusion method, yielding rod-like crystals that diffracted X-rays to 1.5 Å resolution. Structural comparison of AncLinB-DmbA with their closely related descendants LinB and DmbA revealed some differences in overall structure and tunnel architecture. Newly prepared AncLinB-DmbA has the highest active site cavity volume and the biggest entrance radius on the main tunnel in comparison to descendant enzymes. Ancestral sequence reconstruction is a powerful technique to study molecular evolution and design robust proteins for enzyme technologies.


Association of Prenatal Exposure to Early-Life Adversity With Neonatal Brain Volumes at Birth.
Exposure to early-life adversity alters the structural development of key brain regions underlying neurodevelopmental impairments. The association between prenatal exposure to adversity and brain structure at birth remains poorly understood. To examine whether prenatal exposure to maternal social disadvantage and psychosocial stress is associated with neonatal global and regional brain volumes and cortical folding. This prospective, longitudinal cohort study included 399 mother-infant dyads of sociodemographically diverse mothers recruited in the first or early second trimester of pregnancy and their infants, who underwent brain magnetic resonance imaging in the first weeks of life. Mothers were recruited from local obstetric clinics in St Louis, Missouri from September 1, 2017, to February 28, 2020. Maternal social disadvantage and psychosocial stress in pregnancy. Confirmatory factor analyses were used to create latent constructs of maternal social disadvantage (income-to-needs ratio, Area Deprivation Index, Healthy Eating Index, educational level, and insurance status) and psychosocial stress (Perceived Stress Scale, Edinburgh Postnatal Depression Scale, Everyday Discrimination Scale, and Stress and Adversity Inventory). Neonatal cortical and subcortical gray matter, white matter, cerebellum, hippocampus, and amygdala volumes were generated using semiautomated, age-specific, segmentation pipelines. A total of 280 mothers (mean [SD] age, 29.1 [5.3] years; 170 [60.7%] Black or African American, 100 [35.7%] White, and 10 [3.6%] other race or ethnicity) and their healthy, term-born infants (149 [53.2%] male; mean [SD] infant gestational age, 38.6 [1.0] weeks) were included in the analysis. After covariate adjustment and multiple comparisons correction, greater social disadvantage was associated with reduced cortical gray matter (unstandardized β = -2.0; 95% CI, -3.5 to -0.5; P = .01), subcortical gray matter (unstandardized β = -0.4; 95% CI, -0.7 to -0.2; P = .003), and white matter (unstandardized β = -5.5; 95% CI, -7.8 to -3.3; P < .001) volumes and cortical folding (unstandardized β = -0.03; 95% CI, -0.04 to -0.01; P < .001). Psychosocial stress showed no association with brain metrics. Although social disadvantage accounted for an additional 2.3% of the variance of the left hippocampus (unstandardized β = -0.03; 95% CI, -0.05 to -0.01), 2.3% of the right hippocampus (unstandardized β = -0.03; 95% CI, -0.05 to -0.01), 3.1% of the left amygdala (unstandardized β = -0.02; 95% CI, -0.03 to -0.01), and 2.9% of the right amygdala (unstandardized β = -0.02; 95% CI, -0.03 to -0.01), no regional effects were found after accounting for total brain volume. In this baseline assessment of an ongoing cohort study, prenatal social disadvantage was associated with global reductions in brain volumes and cortical folding at birth. No regional specificity for the hippocampus or amygdala was detected. Results highlight that associations between poverty and brain development begin in utero and are evident early in life. These findings emphasize that preventive interventions that support fetal brain development should address parental socioeconomic hardships.


Ethnic differences in the prognostic value of stress technetium-99m tetrofosmin gated single-photon emission computed tomography myocardial perfusion imaging.
This study was designed to evaluate the differential prognostic value of gated single-photon emission computed tomographic imaging (SPECT) imaging in an ethnically diverse multicenter registry. Ethnic minority patient populations have reportedly higher coronary heart disease mortality with greater comorbidity and a clustering of risk factors at a significantly younger age when compared with Caucasian, non-Hispanic patients. Despite our increasingly diverse population, the predictive accuracy of cardiac imaging in ethnic minority patients is ill-defined. A total of 7,849 patients were prospectively enrolled in a registry of patients undergoing exercise (44%) or pharmacologic stress (56%) technetium-99m tetrofosmin SPECT. Scans were scored using a 20-segment myocardial model with a 5-point severity index. Multivariable Cox proportional hazards models were employed to assess time to death or myocardial infarction. A total of 1,993 African-American, 464 Hispanic, and 5,258 Caucasian non-Hispanic patients underwent SPECT imaging. African-American and Hispanic patients more often had a history of stroke, peripheral arterial disease, angina, heart failure, diabetes, hypertension, and smoking at a younger age. Moderate or severely abnormal SPECT scans were noted in 21%, 17%, and 13% of African-American, Hispanic, and Caucasian non-Hispanic patients, respectively (p < 0.0001). Cardiovascular death rates were highest for ethnic minority patients (p < 0.0001). Annual rates of ischemic heart disease death ranged from 0.2% to 3.0% for Caucasian non-Hispanic and 0.8% to 6.5% for African-American patients with low-risk to severely abnormal SPECT scans (p < 0.0001). For post-stress ejection fraction <45%, annualized risk-adjusted death rates were 2.7% for Caucasian non-Hispanic patients versus 8.0% and 14.0% for African-American and Hispanic patients (p < 0.0001). The current results from a large observational registry reveal that exercise and pharmacologic stress SPECT effectively predicts major cardiovascular events in a large cohort of African-American and Hispanic patients evaluated for suspected myocardial ischemia. These results provide further evidence that ethnic minority patient populations have a worsening outcome related to cardiovascular disease.


Iterative most-likely point registration (IMLP): a robust algorithm for computing optimal shape alignment.
We present a probabilistic registration algorithm that robustly solves the problem of rigid-body alignment between two shapes with high accuracy, by aptly modeling measurement noise in each shape, whether isotropic or anisotropic. For point-cloud shapes, the probabilistic framework additionally enables modeling locally-linear surface regions in the vicinity of each point to further improve registration accuracy. The proposed Iterative Most-Likely Point (IMLP) algorithm is formed as a variant of the popular Iterative Closest Point (ICP) algorithm, which iterates between point-correspondence and point-registration steps. IMLP's probabilistic framework is used to incorporate a generalized noise model into both the correspondence and the registration phases of the algorithm, hence its name as a most-likely point method rather than a closest-point method. To efficiently compute the most-likely correspondences, we devise a novel search strategy based on a principal direction (PD)-tree search. We also propose a new approach to solve the generalized total-least-squares (GTLS) sub-problem of the registration phase, wherein the point correspondences are registered under a generalized noise model. Our GTLS approach has improved accuracy, efficiency, and stability compared to prior methods presented for this problem and offers a straightforward implementation using standard least squares. We evaluate the performance of IMLP relative to a large number of prior algorithms including ICP, a robust variant on ICP, Generalized ICP (GICP), and Coherent Point Drift (CPD), as well as drawing close comparison with the prior anisotropic registration methods of GTLS-ICP and A-ICP. The performance of IMLP is shown to be superior with respect to these algorithms over a wide range of noise conditions, outliers, and misalignments using both mesh and point-cloud representations of various shapes.


wzi Gene sequencing, a rapid method for determination of capsular type for Klebsiella strains.
Pathogens of the genus Klebsiella have been classified into distinct capsular (K) types for nearly a century. K typing of Klebsiella species still has important applications in epidemiology and clinical microbiology, but the serological method has strong practical limitations. Our objective was to evaluate the sequencing of wzi, a gene conserved in all capsular types of Klebsiella pneumoniae that codes for an outer membrane protein involved in capsule attachment to the cell surface, as a simple and rapid method for the prediction of K type. The sequencing of a 447-nucleotide region of wzi distinguished the K-type reference strains with only nine exceptions. A reference wzi sequence database was created by the inclusion of multiple strains representing K types associated with high virulence and multidrug resistance. A collection of 119 prospective clinical isolates of K. pneumoniae were then analyzed in parallel by wzi sequencing and classical K typing. Whereas K typing achieved typeability for 81% and discrimination for 94.4% of the isolates, these figures were 98.1% and 98.3%, respectively, for wzi sequencing. The prediction of K type once the wzi allele was known was 94%. wzi sequencing is a rapid and simple method for the determination of the K types of most K. pneumoniae clinical isolates.


The frequency of auditory neuropathy detected by universal newborn hearing screening program.
Auditory neuropathy/auditory dyssynchrony (AN/AD) has become a well-accepted clinical entity. The combined use of oto-acoustic emissions (OAEs) and auditory brainstem response (ABR) testing in the universal newborn hearing screening (UNHS) has led to the easy recognition of this disorder. Although, we are now able to diagnose AN/AD reliably, little is known about its epidemiology, etiology, and especially the frequency of its occurrence. The primary goal of this study was to determine the frequency of AN/AD in the Western Anatolian region of Turkey. The secondary goal was to compare the detection rate of AN/AD before and after the implementation of the UNHS in the audiology department of Dokuz Eylul University Hospital. Between 2005 and 2007, among the 23,786 newborns who were screened by automated click evoked oto-acoustic emissions (a-CEOAE) and automated auditory brainstem responses (a-ABRs), 2236 were referred to our department. All necessary audiological tests were performed for all the referred newborns. Among them, babies with deficient or abnormal ABR in combination with normal OAEs were considered as having AN/AD. These babies were evaluated with additional diagnostic audiological tests. Furthermore, comparison of the incidence of children diagnosed with AN/AD before and after the implementation of UNHS in our audiology department was also performed. Among the referred newborns, 65 had abnormal or deficient ABR test results. Ten of these 65 newborn babies (mean diagnostic age: 5.7 months) with hearing impairment showed electrophysiological test results that were consistent with AN/AD. The frequency of AN/AD in these 65 children with hearing loss was 15.38%. Moreover, the frequency of AN/AD within UNHS was found to be 0.044%. Seven of the 10 babies with AN/AD had hyperbilirubinemia as a risk factor, which is a high rate to be emphasized. On the other hand, the retrospective investigation of children diagnosed with AN/AD in the same audiology department between 1999 and 2005 (i.e. before the implementation of UNHS) revealed only 7 children, with an average diagnostic age of 34 months. After implementing the UNHS, the incidence of AN/AD in the audiology department increased from 1.16 to 4.13. Furthermore, the age of diagnosis of AN/AD decreased from 34 months to 5.7 months. This study shows that AN/AD, when screened, is a comparatively common disorder in the population of hearing-impaired infants. While newborn hearing screening provides early detection of babies with hearing loss, it also helps to differentiate AN/AD cases when the screening is performed with both a-ABR and automated oto-acoustic emission (a-OAE) tests. Thus, the routine combined use of a-ABR and a-OAE tests in UNHS programs, especially for the high-risk infants, can provide better detection of newborns with AN/AD. Furthermore, hyperbilirubinemia is merely an association and maybe etiologically linked.


SLIPS-LAB-A bioinspired bioanalysis system for metabolic evaluation of urinary stone disease.
Urinary stone disease is among the most common medical conditions. Standard evaluation of urinary stone disease involves a metabolic workup of stone formers based on measurement of minerals and solutes excreted in 24-hour urine samples. Nevertheless, 24-hour urine testing is slow, expensive, and inconvenient for patients, which has hindered widespread adoption in clinical practice. Here, we demonstrate SLIPS-LAB (Slippery Liquid-Infused Porous Surface Laboratory), a droplet-based bioanalysis system, for rapid measurement of urinary stone-associated analytes. The ultra-repellent and antifouling properties of SLIPS, which is a biologically inspired surface technology, allow autonomous liquid handling and manipulation of physiological samples without complicated sample preparation procedures and supporting equipment. We pilot a study that examines key urinary analytes in clinical samples from patients with urinary stone. The simplicity and speed of SLIPS-LAB hold the potential to provide actionable diagnostic information for patients with urinary stone disease and rapid feedback for responses to dietary and pharmacologic treatments.


Mutagenicity and safety evaluation of ethanolic extract of Prunus mume.
The ethanolic extract of Prunus mume (EPM) is a novel polyphenol preparation derived from branches (with leaves) of Prunus mume, which could be used as a functional ingredient for antioxidant and antiobesity therapy. The purpose of this study was to evaluate the safety of EPM. An EPM was prepared and evaluated for oral acute and subacute toxicity in Sprague-Dawley rats, while its mutagenic potential was assessed by a reverse mutation test using Salmonella typhimurium, by a bone marrow cell micronucleus test using ICR mice, and by a sperm abnormality test using ICR mice. The results showed no acute lethal effects at the maximal tested EPM dose of 20 g/kg bw in either rats or mice, suggesting that EPM can be regarded as virtually nontoxic. Administration at levels of 0.84, 1.67, and 3.33 g/kg bw to rats for 30 d did not induce any significant hematological, clinical, chemical, or histopathological changes. No mutagenicity evidence was detected in any of the 3 mutagenic tests. The level of "no observed adverse effect" (NOAEL) for EPM was above 3.33 g/kg bw for the subacute toxicity study.


A pilot study of Rhodiola rosea (Rhodax) for generalized anxiety disorder (GAD).
Rhodiola rosea is an herbal supplement that many in the general population in Russia and elsewhere in the world have used for decades to alleviate everyday anxiety, depression, and insomnia. Whether R. rosea is effective in reducing similar symptoms in clinical samples is unknown. The goal of this pilot study was to evaluate whether R. rosea is effective in reducing symptoms of generalized anxiety disorder (GAD). Ten (10) participants with a DSM-IV diagnosis of GAD, recruited from the UCLA Anxiety Disorders Program and between the ages of 34 and 55, were enrolled in this study from November 2005 to May 2006. Participants received a total daily dose of 340 mg of R. rosea extract for 10 weeks. Assessments included the Hamilton Anxiety Rating Scale (HARS), the Four-Dimensional Anxiety and Depression Scale, and the Clinical Global Impressions of Severity/Improvement Scale. Individuals treated with R. rosea showed significant decreases in mean HARS scores at endpoint (t=3.27, p=0.01). Adverse events were generally mild or moderate in severity, the most common being dizziness and dry mouth. Significant improvement in GAD symptoms was found with R. rosea, with a reduction in HARS scores similar to that found in clinical trials. These preliminary findings warrant further exploration of treatment with R. rosea in clinical samples.


Review of Integrated behavioral health in primary care: Step-by-step guidance for assessment and intervention (Second edition).
Reviews the book, Integrated Behavioral Health in Primary Care: Step-By-Step Guidance for Assessment and Intervention (Second Edition) by Anne C. Dobmeyer, Mark S. Oordt, Jeffrey L. Goodie, and Christopher L. Hunter (see record 2016-59132-000). This comprehensive book is well organized and covers many of the complex issues faced within the Primary Care Behavioral Health (PCBH) model and primary care setting: from uncontrolled type II diabetes to posttraumatic stress disorder. Primary care has changed since the initial release of this book, and the second edition covers many of these changes with up-to-date literature such as population health and the patient-centered medical home. The book is organized into three parts. The first three chapters describe the foundation of integrated behavioral consultation services. The next 12 chapters address common behavioral health issues that present in primary care. Last, the final two chapters focus on special topics such suicidal behavior and designing clinical pathways. This was an enjoyable read and worth the investment- especially if you are a trainee or a seasoned professional new to the practice of integrated behavioral health in primary care. (PsycINFO Database Record


The inhibin B response to testicular toxicants ethylene glycol monomethyl ether or dibromoacetic acid in male rats.
This study was conducted as part of an ILSI-HESIconsortium effort to assess the utility of circulating inhibin B as an early biomarker of testicular toxicity in rats. Two known testicular toxicants were selected for use in this study: ethylene glycol monomethyl ether (EGME) and dibromoacetic acid (DBAA). EGME (200 mg/kg/day), DBAA (250 mg/kg/day), or vehicle control (0.2% hydroxypropyl methylcellulose [HPMC]) was administered orally to male rats for 3, 6, or 14 consecutive days. On study days 4, 7, and 15, serum was collected for evaluation of inhibin B levels from all surviving animals and a subset of animals was necropsied from each of the control, EGME, and DBAAgroups. Administration of EGMEresulted in spermatocyte degeneration in late stage tubules and spermatocyte depletion to stage III on day 4, progressing to loss of spermatocytes and round spermatids to stage VI by day 7 and continued germ cell loss and degeneration of elongating spermatids by day 15. Inhibin B levels among EGME-treated animals progressively decreased relative to their respective controls at all time points. Administration of DBAA was associated with spermatid retention at all three time points and abnormal residual bodies at days 7 and 15. Inhibin B levels among DBAA-treated animals decreased progressively relative to their respective controls on days 7 and 15. Serum inhibin B levels in rats provided a signal of testicular toxicity for each of these known testicular toxicants administered at high levels; however, histopathology provided the earliest evidence of toxic effects.


Anhedonia and cognitive function in adults with MDD: results from the International Mood Disorders Collaborative Project.
Cognitive dysfunction is common in major depressive disorder (MDD) and a critical determinant of health outcome. Anhedonia is a criterion item toward the diagnosis of a major depressive episode (MDE) and a well-characterized domain in MDD. We sought to determine the extent to which variability in self-reported cognitive function correlates with anhedonia. A post hoc analysis was conducted using data from (N=369) participants with a Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM-IV-TR)-defined diagnosis of MDD who were enrolled in the International Mood Disorders Collaborative Project (IMDCP) between January 2008 and July 2013. The IMDCP is a collaborative research platform at the Mood Disorders Psychopharmacology Unit, University of Toronto, Toronto, Canada, and the Cleveland Clinic, Cleveland, Ohio. Measures of cognitive function, anhedonia, and depression severity were analyzed using linear regression equations. A total of 369 adults with DSM-IV-TR-defined MDD were included in this analysis. Self-rated cognitive impairment [ie, as measured by the Adult ADHD Self-Report Scale (ASRS)] was significantly correlated with a proxy measure of anhedonia (r=0.131, p=0.012). Moreover, total depression symptom severity, as measured by the total Montgomery-Åsberg Depression Rating Scale (MADRS) score, was also significantly correlated with self-rated measures of cognitive dysfunction (r=0.147, p=0.005). The association between anhedonia and self-rated cognitive dysfunction remained significant after adjusting for illness severity (r=0.162, p=0.007). These preliminary results provide empirical data for the testable hypothesis that anhedonia and self-reported cognitive function in MDD are correlated yet dissociable domains. The foregoing observation supports the hypothesis of overlapping yet discrete neurobiological substrates for these domains.


Natural Psychoplastogens As Antidepressant Agents.
Increasing prevalence and burden of major depressive disorder presents an unavoidable problem for psychiatry. Existing antidepressants exert their effect only after several weeks of continuous treatment. In addition, their serious side effects and ineffectiveness in one-third of patients call for urgent action. Recent advances have given rise to the concept of psychoplastogens. These compounds are capable of fast structural and functional rearrangement of neural networks by targeting mechanisms previously implicated in the development of depression. Furthermore, evidence shows that they exert a potent acute and long-term positive effects, reaching beyond the treatment of psychiatric diseases. Several of them are naturally occurring compounds, such as psilocybin, N,N-dimethyltryptamine, and 7,8-dihydroxyflavone. Their pharmacology and effects in animal and human studies were discussed in this article.