Complementary and alternative medicine therapies for the anesthesiologist and pain practitioner: a narrative review.
This narrative review provides an overview of the complementary and alternative medicine (CAM) therapies that anesthesiologists and pain management practitioners commonly encounter along with recommendations for evaluation and implementation. A literature search of PubMed was performed using the comprehensive MeSH term, "Complementary Therapies OR Dietary Supplements", and a search was conducted of the various licensing organizations and books published on the topics of CAM and integrative medicine. In North America, the most commonly encountered CAM therapies include 1) manipulation and procedural therapies; 2) herbs, nutritional supplements (nutraceuticals), and dietary therapies; and 3) mind-body and energy therapies. Controversy exists regarding many of these therapies, particularly those with a higher risk of harm, such as chiropractic manipulation, acupuncture, and nutraceutical use. Several well-conducted studies were analyzed to show how research in CAM can control for placebo responses. Practical considerations are provided for patients and practitioners interested in pursuing or already employing CAM in perioperative and chronic pain management settings. Complementary and alternative medicine therapies in general may provide a useful adjunct in the management of chronic pain. Nevertheless, many patients are not aware of the risks and benefits of individual therapies. In the perioperative setting, the most concerning CAM therapy is the use of herbs and other supplements that may produce physiologic and metabolic derangements and may interact with prescription medications. Resources exist to aid pain specialists, anesthesiologists, and patients in the evidence-based utilization of CAM therapies.


Midterm outcomes for 605 patients receiving Endologix AFX or AFX2 Endovascular AAA Systems in an integrated healthcare system.
Endologix issued important safety updates for the AFX Endovascular AAA System in 2016 and 2018 owing to the risk of type III endoleaks. Outcomes with these devices are limited to small case series with short-term follow-up. We describe the midterm outcomes for a large cohort of patients who received an Endologix AFX or AFX2 device. Data from an integrated healthcare system's implant registry, which prospectively monitors all patients after endovascular aortic repair, was used for this descriptive study. Patients undergoing endovascular aortic repair with three AFX System variations (Strata [AFX-S], Duraply [AFX-D], and AFX2 with Duraply [AFX2]) were identified (2011-2017). Crude cumulative event probabilities for endoleak (types I and III), major reintervention, conversion to open, rupture, and mortality (aneurysm related and all cause) were estimated. Among 605 patients, 375 received AFX-S, 197 received AFX-D, and 33 received AFX2. Median follow-up for the cohort was 3.9 (interquartile range, 2.5-5.1) years. The crude 2-year incidence of overall endoleak, any subsequent reintervention or conversion, and mortality was 8.8% (95% confidence interval [CI], 6.3-12.3), 12.0% (95% CI, 9.1-15.9), and 8.8% (95% CI, 6.3-12.2) for AFX-S. Respective estimates for AFX-D were 7.9% (95% CI, 4.8-13.0), 10.6% (95% CI, 6.9-16.1), and 9.7% (95% CI, 6.3-14.7); for AFX2, they were 14.1% (95% CI, 4.7-38.2), 16.2% (95% CI, 6.4-37.7), and 21.2% (95% CI, 10.7-39.4). The midterm outcomes of a large U.S. patient cohort with an Endologix AFX or AFX2 System demonstrate a concerning rate of adverse postoperative events. Patients with these devices should receive close clinical surveillance to prevent device-related adverse events.


[Concentration of myoglobin in serum in patients with heart transplantation].
The studies were carried out, the aim of which was the answer to question what are the changes of myoglobin concentration in patients after heart transplantation. For this purpose, 31 healthy persons being the control group (C) and 15 patients after heart transplantation (HTP) were studied. In both groups myoglobin concentration was determined by the RIA method, finding no statistically significant differences in changes of this parameter between the two studied groups. However, the nephrotoxic effect was confirmed of cyclosporin A which was continuously taken by the patients after heart transplantation, expressed as the decrease of creatinine clearance.


Association Between Psychosocial Disorders and Gastroesophageal Reflux Disease: A Systematic Review and Meta-analysis.
The incidence of gastroesophageal reflux disease (GERD) is increasing annually. Studies have suggested that psychosocial disorders may be linked to the development of GERD. However, studies evaluating the association between psychosocial disorders and GERD have been inconsistent. Thus, we conducted a systematic review and meta-analysis of observational studies that evaluated the association between psychosocial disorders and GERD. We systematically searched the PubMed, Embase, Cochrane, and Web of Science databases until October 17, 2020. Pooled OR with 95% CI and subgroup analyses were calculated using a random-effects model. Subgroup analyses were performed to identify the sources of heterogeneity. Sensitivity analysis by one-study removal was used to test the robustness of our results. This meta-analysis included 1 485 268 participants from 9 studies. Studies using psychosocial disorders as the outcome showed that patients with GERD had a higher incidence of psychosocial disorders compared to that in patients without GERD (OR, 2.57; 95% CI, 1.87-3.54; I2 = 93.8%; P < 0.001). Studies using GERD as an outcome showed an association between psychosocial disorders and an increased risk of GERD (OR, 2.23; 95% CI, 1.42-3.51; I2 = 97.1%; P < 0.001). The results of the subgroup analysis showed that the non-erosive reflux disease group had a higher increased risk of anxiety than erosive reflux disease group (OR, 9.45; 95% CI, 5.54- 16.13; I2 = 12.6%; P = 0.285). Results of our meta-analysis showed that psychosocial disorders are associated with GERD; there is an interaction between the two.


Fenoterol inhibits superoxide anion generation by human polymorphonuclear leukocytes via beta-adrenoceptor-dependent and -independent mechanisms.
Beta2-adrenoceptor agonists, used widely as bronchodilator in treating bronchial asthma, may have anti-inflammatory activity. We examined whether various widely prescribed beta2-adrenoceptor agonists differ in anti-inflammatory mechanisms. We investigated effects of these drugs on superoxide anion generation by stimulated human polymorphonuclear leukocytes in vitro using chemiluminescence. At high concentrations, fenoterol significantly inhibited both N-formylmethionyl-leucyl-phenylalanine- and phorbol myristate acetate-induced superoxide generation by neutrophils. In contrast, salbutamol or procaterol partially inhibited generation with the former stimulus but not the latter. Inhibition by salbutamol or procaterol was completely reversed by either propranolol, a nonselective beta-adrenoceptor antagonist, or ICI-118551, a beta2-adrenoceptor-selective antagonist. In contrast, the effect of fenoterol at concentrations exceeding 10(-6) M against superoxide generation with the former stimulus was only partially reversed by antagonists, and the effect of high concentrations of fenoterol against generation with the latter stimulus was not reversed. No drugs scavenged superoxide at the highest concentration used (10(-5) M). Fenoterol at high concentrations has an inhibitory effect on superoxide generation that includes a component not mediated via beta2-adrenoceptors. Direct inhibition at or downstream from protein kinase C may be involved.


Epistemic causality and evidence-based medicine.
Causal claims in biomedical contexts are ubiquitous albeit they are not always made explicit. This paper addresses the question of what causal claims mean in the context of disease. It is argued that in medical contexts causality ought to be interpreted according to the epistemic theory. The epistemic theory offers an alternative to traditional accounts that cash out causation either in terms of "difference-making" relations or in terms of mechanisms. According to the epistemic approach, causal claims tell us about which inferences (e.g., diagnoses and prognoses) are appropriate, rather than about the presence of some physical causal relation analogous to distance or gravitational attraction. It is shown that the epistemic theory has important consequences for medical practice, in particular with regard to evidence-based causal assessment.


Multitype violence exposures and adolescent antiretroviral nonadherence in South Africa.
HIV-positive adolescents have low-ART adherence, with consequent increased risks of mortality, morbidity, and viral resistance. Despite high rates of violence against children in the Africa region, no known studies have tested impacts on HIV-positive adolescents. We examine associations of ART adherence with adolescent violence victimization by caregivers, teachers, peers, community members, and healthcare providers. HIV-positive adolescents were interviewed (n = 1060), and clinic biomarker data collected. We sampled all 10-19-year olds ever ART-initiated within 53 clinics in 180 South African communities (90.1% reached). Analyses examined associations between nonadherence and nine violence types using sequential multivariate logistic regressions. Interactive and additive effects were tested with regression and marginal effects. Past-week self-reported ART nonadherence was 36%. Nonadherence correlated strongly with virologic failure (OR 2.3, CI 1.4-3.8) and symptomatic pulmonary tuberculosis (OR 1.49, CI 1.18-2.05). Four violence types were independently associated with nonadherence: physical abuse by caregivers (OR 1.5, CI 1.1-2.1); witnessing domestic violence (OR 1.8, CI 1.22-2.66); teacher violence (OR 1.51, CI 1.16-1.96,) and verbal victimization by healthcare staff (OR 2.15, CI 1.59-2.93). Past-week nonadherence rose from 25% with no violence to 73.5% with four types of violence exposure. Violence exposures at home, school, and clinic are major and cumulating risks for adolescent antiretroviral nonadherence. Prevention, mitigation, and protection services may be essential for the health and survival of HIV-positive adolescents.


Pharmacotherapy for borderline personality disorder--current evidence and recent trends.
Drug treatment of patients with borderline personality disorder (BPD) is common but mostly not supported by evidence from high-quality research. This review summarises the current evidence up to August 2014 and also aims to identify research trends in terms of ongoing randomised controlled trials (RCTs) as well as research gaps. There is some evidence for beneficial effects by second-generation antipsychotics, mood stabilisers and omega-3 fatty acids, while the overall evidence base is still unsatisfying. The dominating role SSRI antidepressants usually play within the medical treatment of BPD patients is neither reflected nor supported by corresponding evidence. Any drug treatment of BPD patients should be planned and regularly evaluated against this background of evidence. Research trends indicate increasing attention to alternative treatments such as dietary supplementation by omega-3 fatty acids or oxytocin.


Intravitreal dexamethasone versus bevacizumab in Aboriginal and Torres Strait Islander patients with diabetic macular oedema: The OASIS study (a randomised control trial).
Frequent intravitreal anti-VEGF injections are impractical for many Aboriginal patients with diabetic macular oedema (DMO). The longer acting intravitreal dexamethasone implant (DEX-implant) is approved for DMO but has not been assessed in an Aboriginal population. This was a prospective, multicentre, randomised, single-masked, non-inferiority clinical trial. Aboriginal adults from Western Australia with DMO were randomised to receive 3-monthly DEX-implant, or monthly intravitreal bevacizumab. The primary outcome was the change in best corrected visual acuity (BCVA) at 12 months. The final endpoint was analysed for 24 DEX-implant and 28 bevacizumab injection eyes. Mean BCVA improved by 4.0 letters (-0.08 LogMAR) in the DEX-implant group and worsened by 5.5 letters (0.11 LogMAR) in the bevacizumab group. Before adjusting for cataract surgery, the upper bound of the two-sided 90% CI for the DEX-implant was 3.5 letters (0.07 LogMAR), which met non-inferiority criteria. The BCVA of remote participants who received the DEX-implant improved by 5.5 letters (0.11 LogMAR), compared to an 18.5 letter (0.37 LogMAR) decline for bevacizumab (p = 0.04). The incidence of steroid-induced ocular hypertension for the DEX-implant was 33.3%. Before adjusting for the effect of cataract surgery, the DEX-implant was non-inferior to bevacizumab for treating DMO in Aboriginal participants. In remote participants, the DEX-implant surpassed non-inferiority to achieve superior outcomes to bevacizumab. The incidence of steroid-induced hypertension was comparable to that reported in non-Aboriginal populations. We provide guidelines for the judicious use of DEX-implant among Aboriginal people, and a framework for performing ophthalmic clinical trials in Aboriginal communities.


Observation of resonance soliton trapping due to a photoinduced gap in wave number.
We investigate the nonlinear propagation of two forward propagating modes coupled by a resonant traveling-wave grating, which is photoinduced by illuminating an optical fiber with a beat signal. This interaction, representative of systems whose dispersion relation K=K(Omega) exhibits a gap in momentum K, shows evidence of localization mediated by resonance solitons. The signature of a still (in the grating frame) soliton is grating-induced cancellation of modal group-velocity mismatch.


Use of antidepressants among community-dwelling persons with Alzheimer's disease: a nationwide register-based study.
Antidepressants are used to treat depression and behavioral symptoms in Alzheimer's disease (AD), although their effectiveness has been questioned and evidence about the risks is accumulating. The objective of this study was to compare antidepressant use among persons with and without AD in Finland. The Social Insurance Institution of Finland (SII) identified all persons with a verified diagnosis of AD in Finland on December 31, 2005. For each person with AD a comparison person matched for age, sex and region of residence was also identified. Data on reimbursed drug purchases in 2005 were extracted from the Finnish National Prescription Register (FNPR). Conditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for antidepressant use. The study sample comprised of 28,089 matched pairs of persons with and without AD (mean age 80.0 SD 6.8, 32.2% men).The prevalence of antidepressant use was higher among persons with AD than without AD (29.4% vs. 10.7%, OR = 3.54; 95% CI: 3.38, 3.70). Among the persons with AD, the prevalence of antidepressant use increased with time since AD diagnosis but not with age. Overall, 90.4% of antidepressant users with AD were co-dispensed anti-dementia drugs. The antidepressant use was three times more prevalent among persons with AD compared to those without. Though the antidepressant selection was largely consistent with clinical practice guidelines, the high prevalence of use warrants further investigation given the uncertain effectiveness and adverse events related to these drugs.


Changes in the Sexual Relationship and Relationship Adjustment Precede Extradyadic Sexual Involvement.
Extradyadic sexual involvement (ESI) is associated with negative consequences for individuals and threatens couple stability. Research on ESI in unmarried samples has been marked by methodological limitations, such as examining only mean levels of sexual satisfaction or frequency to predict later ESI as opposed to changes in various aspects of the sexual relationship over time. The current study compared linear trajectories of four aspects of the sexual relationship-sexual satisfaction, frequency of sex, comfort communicating about sex, and sexual closeness-between individuals in opposite-sex, unmarried relationships who subsequently engaged in ESI (ESI group; n = 183) compared to individuals who did not engage in ESI (non-ESI group; n = 603). Trajectories of relationship adjustment were also evaluated leading up to ESI as well as controlled for in models evaluating the sexual relationship. Results indicated that relationship adjustment declined for individuals preceding ESI, but did not change for the non-ESI group. When controlling for relationship adjustment, comfort communicating about sex decreased for ESI women but increased for ESI men. Some results became nonsignificant after controlling for relationship adjustment, including that sexual satisfaction declined more steeply in the ESI group compared to the non-ESI group, and ESI women significantly decreased in sexual closeness while ESI men demonstrated no significant change. Some mean level differences were also discovered directly before ESI. Conclusions include that changes in a couple's sexual relationship and relationship adjustment are associated with ESI behaviors, providing novel information regarding normative and risk trajectories.


MgtE From Rhizobium leguminosarum Is a Mg²⁺ Channel Essential for Growth at Low pH and N2 Fixation on Specific Plants.
MgtE is predicted to be a Rhizobium leguminosarum channel and is essential for growth when both Mg²⁺ is limiting and the pH is low. N₂was only fixed at 8% of the rate of wild type when the crop legume Pisum sativum was inoculated with an mgtE mutant of R. leguminosarum and, although bacteroids were present, they were few in number and not fully developed. R. leguminosarum MgtE was also essential for N₂fixation on the native legume Vicia hirsuta but not when in symbiosis with Vicia faba. The importance of MgtE and the relevance of the contrasting phenotypes is discussed.


Helix-forming propensity of aliphatic urea oligomers incorporating noncanonical residue substitution patterns.
Aliphatic N,N'-linked oligoureas are peptidomimetic foldamers that adopt a well-defined helical secondary structure stabilized by a collection of remote three-center H-bonds closing 12- and 14-membered pseudorings. Delineating the rules that govern helix formation depending on the nature of constituent units is of practical utility if one aims to utilize this helical fold to place side chains in a given arrangement and elaborate functional helices. In this work, we tested whether the helix geometry is compatible with alternative substitution patterns. The central -NH-CH(R)-CH2-NH-CO- residue in a model oligourea pentamer sequence was replaced by guest units bearing various substitution patterns [e.g., -NH-CH2-CH2-NH-CO-, -NH-CH2-CH(R)-NH-CO-, and -NH-CH(R(1))-CH(R(2))-NH-CO-], levels of preorganization (cyclic vs acyclic residues), and stereochemistries, and the helix formation was systematically assessed. The extent of helix perturbation or stabilization was primarily monitored in solution by Fourier transform IR, NMR, and electronic circular dichroism spectroscopies. Our results indicate that although three new substitution patterns were accommodated in the 2.5-helix, the helical urea backbone in short oligomers is particularly sensitive to variations in the residue substitution pattern (position and stereochemistry). For example, the trans-1,2-diaminocyclohexane unit was experimentally found to break the helix nucleation, but the corresponding cis unit did not. Theoretical calculations helped to rationalize these results. The conformational preferences in this series of oligoureas were also studied at high resolution by X-ray structure analyses of a representative set of modified oligomers.


Ancestral Variation in Orbital Rim Shape: A Three-Dimensional Pilot Study.
Traditional nonmetric methods of ancestry assessment posit orbital rim shape varies among ancestral groups. This pilot study uses morphometric analysis of 3D orbital variation to test discrimination among individuals of primarily European, African, and Asian ancestry. Although the size and nature of the sample analyzed limit inferences for other samples, principal components analysis suggests ancestry has a significant effect on rim shape (p = 2.93e-04). European orbits display more marked folding of the orbit in the sagittal plane than either African or Asian orbits, while the lateral margin of African orbits lies further posterior relative to the medial margin when compared to Asian orbits. The findings suggest curviplanar relationships are the most ancestrally informative aspect of orbital rim shape; these relationships may be distorted by perspective based on orientation of the skull relative to the viewer in traditional nonmetric analyses. Additional studies on geometric morphometric approaches to ancestry assessment are therefore warranted.


Morphological characterization of a plant-made virus-like particle vaccine bearing influenza virus hemagglutinins by electron microscopy.
Plant-made virus-like particle (VLP) vaccines that display wild-type influenza hemagglutinin (HA) are rapidly advancing through clinical trials. Produced by transient transfection of Nicotiana benthamiana, these novel vaccines are unusually immunogenic, eliciting both humoral and cellular responses. Here, we directly visualized VLPs bearing either HA trimers derived from strains A/California/7/2009 or A/Indonesia/5/05 using cryo-electron microscopy and determined the 3D organization of the VLPs using cryo-electron tomography. More than 99.9% of the HA trimers in the vaccine preparations were found on discoid and ovoid-shaped particles. The discoid-shaped VLPs presented HA trimers on their outer diameter. The ovoid-shaped VLPs contained HA trimers evenly distributed at their surface. The VLPs were stable for 12 months at 4 °C. Early interactions of the VLPs with mouse dendritic and human monocytoid (U-937) cells were visualized by electron microscopy after resin-embedding and sectioning. The VLP particles were observed bound to plasma membranes as well as inside vesicles. Mouse dendritic cells exposed to VLPs displayed classic morphological changes associated with activation including the extensive formation of dendrites. Our findings demonstrate that plant-made VLPs bearing influenza HA trimers are morphologically stable over time and raise the possibility that these VLPs may interact with and activate antigen-presenting cells in a manner similar to the intact virus.


Prospective evaluation of samarium-153-EDTMP radionuclide treatment for bone metastases in patients with hormone-refractory prostate cancer.
Bone is a common site of metastatic disease and the most frequent site of metastatic spread in patients with prostate cancer. Most patients with bone metastases complain of bone pains. This pain may be alleviated or eliminated by administration of radiotherapy at the site of metastases. Currently, two forms of radiotherapy administration exist: external-beam irradiation or intravenous administration of bone-seeking therapeutic radiopharmacon such as samarium-153-ethylene-diamino-tetramethylene-phosphonate (EDTMP). This radiopharmacon produces beta-particles and concentrates in the areas of enhanced osteoblastic activity. The aim of this study was to assess the efficacy of (153)Sm-EDTMP therapy. 32 men (aged 50-83, mean 70 years) with bone disseminated hormone-refractory prostate cancer and bone pain received (153)Sm-EDTMP. Mean applied dosage was 40 MBq/kg of the patient's body weight. Karnofsky performance status, pain score (numerical rating scale), analgesic score (WHO) and blood count were evaluated before, and 1 and 3 months after the treatment. Significant pain relief was observed in 44 and 38% of patients, mild relief in 31 and 34% and no effect in 25 and 28% of patients, 1 and 3 months after administration, respectively. Pain palliation was accompanied by an improvement in mobility and a decrease in necessary dosage of analgesics. Mild and transient bone marrow suppression was observed as a side effect of (153)Sm-EDTMP treatment. None of the patients showed hematological toxicity grade 4, and only 2 showed grade 3 (NCI CTC). The majority of the patients had hematological toxicity grade 1 or 2. After (153)Sm-EDTMP administration, bone pain palliation was observed in 72% of patients for 3 months. Hematological toxicity after (153)Sm-EDTMP treatment was mild and transient.


[miR-590-5p inhibits A375 cell invasion and migration in malignant melanoma by directly inhibiting YAP1 expression].
Objective To detect the expression of miR-590-5p in malignant melanoma A375 cells, its effect on the invasion and migration of A375 cells, and underlying mechanism. Methods Real-time PCR was performed to detect the expression of miR-590-5p in A375 cells and human normal melanocyte (HM) cells; TranswellTM assay and wound healing assay were used to observe the effect of miR-590-5p on the invasion and migration of A375 cells; Luciferase assay was done to determine whether YAP1 was the direct target of miR-590-5p; quantitative real-time PCR and Western blotting were performed to investigate the effect of miR-590-5p on YAP1 expression. Results Compared with HM cells, miR-590-5p was significantly down-regulated in A375 cells. Compared with A375 cells transfected with miR-590-5p-NC, cell invasion and migration were significantly inhibited in A375 cells transfected with miR-590-5p mimics. Luciferase assay indicated that YAP1 was the direct target of miR-590-5p. Compared with A375 cells transfected with miR-590-5p-NC, mRNA and protein levels of YAP1 were significantly inhibited in A375 cells transfected with miR-590-5p mimics. Conclusion miR-590-5p is downregulated in A375 cells, and inhibits the invasion and migration of A375 cells by directly regulating the expression of YAP1.


Effect of different bleaching protocols on whitening efficiency and enamel superficial microhardness.
Tooth bleaching is a popular aesthetic treatment to modify the color of teeth. Despite the extensive literature concerning the subject, there is still no consensus regarding the application mode of the different bleaching agents and their effect on enamel. Therefore, this study evaluated the influence of different bleaching protocols on whitening efficiency and enamel superficial hardness. Bovine enamel fragments were embedded in acrylic resin and wet-sanded to obtain a flat buccal surface. The specimens were then randomly divided into 6 groups (n=10), based on the bleaching material [HP Maxx 35% (35% hydrogen peroxide), HP Blue 35% (35% hydrogen peroxide + Ca) and Whiteness Perfect 10% (10% carbamide peroxide)] and application mode (3 applications of 15 min, 1 application of 45 min, 1 application of 1h30 or 1 application of 3h30). The color and superficial hardness were assessed before and after bleaching. The color was assessed by means of a digital spectrophotometer, using CIELab parameters. Vickers hardness was determined using a load of 200g for 10s. Data were statistically analyzed by one-way ANOVA with repeated measures and Tukey's test (α = 0.05). Concerning the color alteration, the groups were similar to each other, except for at-home bleaching protocols, which were statistically different from each other. Similarly, there was a reduction in hardness values comparing the initial and final periods, with lowest final hardness for the at-home bleaching protocol group applied for 3h30. It can be concluded that the bleaching protocols influenced the final color and enamel surface hardness, evidencing that lower gel concentrations applied for longer periods promoted greater variation in color and lower final hardness. Key words:Tooth bleaching, roughness, microhardness, in-office, at-home bleaching.


Differential response of cultured mammalian cells to cytochalasin B in multinucleation.
Cytochalasin B (CB) was applied to 13 kinds of non-tumorigenic or tumorigenic cells in vitro to investigate whether the drug would be applicable as an indicator to identify the transformation of cells. Normal cell strains suffered from more deteriorative changes in morphology than cell lines, showing arborization of their cytoplasm at 5 mug/ml. CB at 2.5 mug/ml consistently prevented cytoplasmic cleavage without interfering with nuclear division. Multinucleation of the cells exposed to CB was not related to their generation time. The correlation between multinucleation and tumorigenicity of the cells was found with some exceptions. It appears, however, that multinucleation induced by CB would not be a reliable parameter for identifying malignant transformation of cells in vitro.


HepaCAM inhibits cell proliferation and invasion in prostate cancer by suppressing nuclear translocation of the androgen receptor via its cytoplasmic domain.
Hepatocyte cell adhesion molecule (HepaCAM) is a tumour suppressor. However, the mechanism of HepaCAM function in prostate cancer (PCa) remains unknown. In the present study, HepaCAM, androgen receptor (AR) and Ran were analysed in 46 PCa tissue samples using immunohistochemistry. Subsequently, the influence of HepaCAM and its cytoplasmic domain on cell proliferation, migration, and invasion, and associated proteins was examined using MTT, wound healing, Transwell and western blotting assays, respectively. Furthermore, nuclear translocation of AR and Ran was analysed using immunofluorescence and Western blot assays. The results demonstrated that HepaCAM expression was reduced in PCa, and there was an association between downregulation of HepaCAM and changes in the distribution of AR and Ran. Furthermore, HepaCAM, specifically the cytoplasmic domain, was involved in cell proliferation, migration and invasion. Nuclear translocation of AR was dependent on HepaCAM and its cytoplasmic domain. Additionally, HepaCAM suppression of the nuclear translocation of AR occurred via Ran. The results suggest that HepaCAM and its cytoplasmic domain suppress the nuclear translocation of AR via Ran in PCa. The cytoplasmic domain of HepaCAM may serve as a novel target for therapy in PCa.


Impact of body mass index and gender on wound complications after lower extremity arterial surgery.
Wound complications (WCs) after lower extremity arterial surgery (LEAS) are common, resulting in readmissions and reinterventions. Whereas diabetes and obesity are known risk factors for WCs, gender-specific variability in body fat distribution (android vs gynoid) may drive differential risks of WCs after LEAS. We analyzed the independent and synergistic effects of gender and body mass index (BMI) on WCs. We performed a retrospective review of prospectively collected data from a published, randomized, multicenter trial assessing the incidence of WCs (dehiscence, surgical site infections, seroma, and hematoma) after LEAS. Postoperative outcomes were compared between genders. A multivariable regression model assessed the impact of gender and BMI on WCs. Subanalysis focused on the synergy of gender and body habitus, groin-only incisions, and clinical outcomes. There were 502 patients who underwent LEAS between October 2010 and September 2013. The cohort was elderly (67.6 ± 10.5 years), mostly male (72%), and overweight (BMI, 27.6 ± 5.7); 225 (45%) patients had a groin-only incision. In 171 patients (37.9%), a WC developed within 30 days, 85% of which were infectious in etiology. On multivariable regression, obesity (odds ratio [OR], 2.10; 95% confidence interval [CI], 1.17-3.77), morbid obesity (OR, 2.87; 95% CI, 1.32-6.23), and female gender (OR, 1.17; 95% CI, 1.06-2.75) were independent predictors of infectious WCs at 30 days. When stratified by groin-only incision, BMI was no longer significant, but female gender (OR, 2.70; 95% CI, 1.24-5.87) was predictive of infectious WCs at 30 days. There was no synergistic effect of BMI and gender on WCs. WCs are common after LEAS. BMI is an independent risk factor for the development of any WC. Female gender, a potential surrogate for high hip to waist ratio body habitus, is also an independent predictor of groin WCs, suggesting the clinical importance of gynoid vs android fat distribution.


The Treatment of Dysmenorrhea.
Menstrual disorders and abnormal uterine bleeding are common concerns of young women. Complaints include menses that are: too painful (dysmenorrhea), absent or occur irregularly (amenorrhea or oligoamenorrhea), or prolonged and heavy (menorrhagia, or excessive uterine bleeding). In providing optimal reproductive care, the medical provider must be able to distinguish between normal developmental patterns or symptoms requiring education and reassurance from pathologic conditions requiring prompt assessment and treatment. This article discusses the normal menstrual patterns seen in adolescent females and provides an evaluation and management approach to primary and secondary dysmenorrhea.


The genetics revolution in rheumatology: large scale genomic arrays and genetic mapping.
Susceptibility to rheumatic diseases, such as osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, systemic lupus erythematosus, juvenile idiopathic arthritis and psoriatic arthritis, includes a large genetic component. Understanding how an individual's genetic background influences disease onset and outcome can lead to a better understanding of disease biology, improved diagnosis and treatment, and, ultimately, to disease prevention or cure. The past decade has seen great progress in the identification of genetic variants that influence the risk of rheumatic diseases. The challenging task of unravelling the function of these variants is ongoing. In this Review, the major insights from genetic studies, gained from advances in technology, bioinformatics and study design, are discussed in the context of rheumatic disease. In addition, pivotal genetic studies in the main rheumatic diseases are highlighted, with insights into how these studies have changed the way we view these conditions in terms of disease overlap, pathways of disease and potential new therapeutic targets. Finally, the limitations of genetic studies, gaps in our knowledge and ways in which current genetic knowledge can be fully translated into clinical benefit are examined.


Evaluation of human embryonic stem cell-derived hepatocyte-like cells for detection of CYP1A inducers.
There is a great deal of interest in differentiation of human embryonic stem cells (hESCs) into hepatocyte-like cells for application in pharmaceutical screening. Cytochrome P450 (CYP) 1A is involved in the metabolic activation of procarcinogenic compounds as well as in detoxification of drugs. We differentiated hESCs into hepatocyte-like cells (hESC-derived hepatocyte-like cells) and examined whether CYP1A was induced in these cells by typical inducers of CYP1A. hESC-derived hepatocyte-like cells expressed albumin, α-fetoprotein, CYP3A4, CYP3A7, CYP1A1, CYP1A2, and UDP-glucuronyl transferase (UGT) 1A1 mRNA. The levels of CYP1A1, CYP1A2, and UGT1A1 mRNA expression were increased by omeprazole and 3-methylcholanthrene. Furthermore, the enzyme activity of CYP1A was also increased by these compounds. In conclusion, hESC-derived hepatocyte-like cells are available for the detection of CYP1A inducers.


Ten-year incidence and progression of age-related maculopathy: the blue Mountains Eye Study.
To assess the 10-year incidence of age-related maculopathy (ARM) in an older Australian cohort. Population-based cohort study. Three thousand six hundred fifty-four Blue Mountains Eye Study participants > or =49 years old were examined during 1992 through 1994; 2335 (75% of survivors) were reexamined after 5 years (1997-1999) and 1952 (76% of survivors) after 10 years (2002-2004). The same graders performed retinal photographic grading in all examinations, using the Wisconsin Age-Related Maculopathy Grading System. Photographs of participants with ARM lesions at any of the examinations were subsequently regraded using a side-by-side comparison method. The diagnosis of incident late ARM was given if neovascular ARM or geographic atrophy was detected at either follow-up examination in persons free of these lesions at baseline. Incident early ARM was diagnosed if early ARM (soft indistinct or reticular drusen or combined soft distinct drusen and retinal pigment abnormality) was present in persons free of early and late ARM at baseline. Age-related maculopathy incidence was calculated using Kaplan-Meier methods to incorporate information from both 5- and 10-year examinations. Discrete logistic models were used to assess the risk of incident late ARM according to various baseline factors, including early ARM lesion characteristics. After excluding 72 late ARM cases present at baseline, 2395 of 3582 subjects at risk of late ARM (67%) were reexamined at either follow-up time point or both follow-up time points. Over the 10-year period, 72 of 2395 subjects (3.7%) developed late ARM and 266 of 2255 subjects (14.1%) developed early ARM. After age standardization to the Beaver Dam Eye Study population, our 10-year incidences of late and early ARM were 2.8% and 10.8%, respectively. Baseline age and early ARM lesion characteristics and severity were strong predictors of late ARM incidence. Long-term follow-up of this older population confirms that the risk of ARM progression is related strongly to the severity of early-stage lesions. The study provides evidence-based criteria for identifying persons at high risk of developing late ARM.


Socioeconomic impact of the COVID-19 crisis and early perceptions of COVID-19 vaccines among immigrant and nonimmigrant people living with HIV followed up in public hospitals in Seine-Saint-Denis, France.
The burden of the first year of the coronavirus disease 2019 (COVID-19) pandemic was greater for vulnerable populations, such as immigrants, people living in disadvantaged urban areas, and people with chronic illnesses whose usual follow-up may have been disrupted. Immigrants receiving care for HIV in Seine-Saint-Denis' hospitals have a combination of such vulnerabilities, while nonimmigrant people living with HIV (PLWHIV) have more heterogeneous vulnerability profiles. The ICOVIH study aimed to compare the socioeconomic effects of the COVID-19 crisis as well as attitudes toward COVID-19 vaccination among immigrant and nonimmigrant PLWHIV. A questionnaire assessed vulnerabilities prior to the COVID-19 epidemic and the impact of the early epidemic on administrative, residential, professional, and financial fields. We surveyed 296 adults living with HIV at four hospitals in Seine-Saint-Denis, the poorest metropolitan French department, between January and May 2021. Administrative barriers affected 9% of French-born versus 26.3% of immigrant participants. Immigrants experienced financial insecurity and hunger more often than nonimmigrant participants (21.8% versus 7.1% and 6.6% versus 3%, respectively). Spontaneous acceptance of vaccination was higher among nonimmigrant than among immigrant participants (56.7% versus 32.1%), while immigrants were more likely to wait for their doctor's recommendation or for their doctor to convince them than their French-born counterparts (34.2% versus 19.6%). The trust-based doctor‒patient relationship established through HIV follow-up appeared to be a determining factor in the high acceptance of the COVID-19 vaccine among immigrant participants.


[Disturbances in the regulation of phospholipid metabolism of the whole liver, mitochondria and microsomes in acute thioacetamide poisoning and the influcence of silymarin].
In the whole liver of rats, pretreated with 4% polyvinylpyrrolidone solution, 24 h after i.p. application of 300 mg thioacetamide/kg body weight, an increase of total lipids, triglycerides and phospholipids is observed, in the mitochondrial fraction phospholipid concentrations are decreased. At the same time, phosphatidylcholine/phosphatidyl-ethanolamine ratio is diminished in mitochondrial and microsomal fraction. After administration of [l-14C]-palmitate, in comparison with non-intoxicated animals, a statistically significant reduction of specific radioactivity of phosphatidylethanolamine could be observed in microsomal and mitochondrial fraction; specific radioactivities of total lipids, total phospholipids and phosphatidyl choline trend to diminution in the whole liver and in subcellular fractions. By prophylactic i.p. application of silymarin-N-methylglucamine salt (400 mg/kg body weight), dissolved in 4% polyvinylpyrrolidone solution, there is a normalization of altered microsomal phosphatidylcholine/phosphatidylethanolamine ratio as well as an enhancement of diminished mitochondrial phosphatidylcholine concentration, while the reduction of specific radioactivities of phosphatidylethanolamine is partially abolished in the mitochondrial fraction.


How do clinicians prepare family members for the role of surrogate decision-maker?
Although surrogate decision-making (SDM) is prevalent in intensive care units (ICUs) and concerns with decision quality are well documented, little is known about how clinicians help family members understand the surrogate role. We investigated whether and how clinicians provide normative guidance to families regarding how to function as a surrogate. We audiorecorded and transcribed 73 ICU family conferences in which clinicians anticipated discussing goals of care for incapacitated patients at high risk of death. We developed and applied a coding framework to identify normative statements by clinicians regarding what considerations should guide surrogates' decisions, including whether clinicians explained one or more of Buchanan and Brock's three standard principles of SDM to family members. Clinicians made at least one statement about how to perform the surrogate role in 24 (34%) conferences (mean of 0.83 statements per conference (1.77; range 0-9)). We observed three general types of normative guidance provided to surrogates, with some conferences containing more than one type of guidance: counselling about one or more standard principles of SDM (24% of conferences); counselling surrogates to make decisions centred on the patient as a person, without specifying how to accomplish that (14% of conferences); and counselling surrogates to make decisions based on the family's values (8% of conferences). Clinicians did not provide normative guidance about the surrogate role in two-thirds of family conferences for incapacitated patients at high risk for death. When they did, clinicians' guidance was often incomplete and sometimes conflicted with standard principles of SDM. Future work is needed to understand whether providing explicit guidance on how to perform the surrogate role improves decision-making or mitigates surrogates' psychological distress.


[Comparative analysis of risk factors for preterm and small-for-gestational-age births].
To compare the risk factors between preterm and small-for-gestational-age (SGA) births. A total of 1 270 newborns who had no obstetric risk factors or maternal diseases were enrolled in this study. Their mothers' stature, body weight, passive smoking, and history of abnormal pregnancy were investigated using the self-designed questionnaire. The infants were divided into four groups: preterm, appropriate-for-gestational-age (AGA), SGA, and term infants. Multivariate logistic regression analysis was performed to compare the risk factors between preterm and SGA births. A weight gain less than 9 kg during pregnancy increased the risks of preterm (OR=1.63, 95% CI: 1.12-2.07) and SGA (OR=1.92, 95% CI: 1.56-2.58). The histories of abortion (OR=1.46, 95% CI: 1.09-1.93) and preterm birth (OR=2.63, 95% CI: 1.81-3.92) were independent risk factors for preterm births, while low pre-pregnancy body mass index (<18.5) (OR=2.16, 95% CI: 1.53-3.16), short stature (<1.55 m) (OR=2.46, 95% CI: 1.78-3.48), and passive smoking (OR=2.24, 95% CI: 1.65-2.98) were independent risk factors for SGA births. Due to different risk factors between preterm and SGA births, specific preventive measures should be taken pertinently to reduce the incidence of the two bad pregnancy outcomes.


Angiotensin-converting enzyme inhibition in mild to moderate congestive heart failure: an evolving approach.
As a result of the understanding of the factors governing myocardial performance achieved in the physiology laboratory, vasodilator therapy was introduced for patients with refractory heart failure nearly two decades ago. Ten years later, investigations began with the first orally active angiotensin-converting enzyme inhibitor (ACEI), captopril, in patients with severe congestive heart failure (CHF). Subsequent studies have definitively demonstrated that ACEIs produce symptomatic and exercise tolerance improvement in patients with moderate and severe CHF. This favorable experience led to the investigation of captopril in patients with milder symptoms in whom the goals of treatment must be defined more rigorously. An optimal agent for this patient group would not only reduce symptoms, but improve prognosis and have demonstrable advantages over existing treatments. A growing body of investigational data and clinical experience indicates that the ACEIs achieve these goals. As a result, they are being used with increasing frequency in patients with milder grades of heart failure.


Suramin inhibits binding of the V3 region of HIV-1 envelope glycoprotein gp120 to galactosylceramide, the receptor for HIV-1 gp120 on human colon epithelial cells.
The infection of human colonic epithelial cells HT-29 by human immunodeficiency virus type 1 (HIV-1) occurs independently of CD4, the main HIV-1 receptor expressed on lymphocytes and macrophages. Recent studies from our group have shown that HT-29 cells express the glycosphingolipid galactosylceramide (GalCer), a potential alternative receptor for the HIV-1 envelope glycoprotein gp120. The binding of recombinant gp120 to GalCer was blocked by monoclonal antibodies directed against the third variable region (V3) of gp120, suggesting that the V3 domain was implicated in GalCer recognition. In the present report, we show that suramin, a polysulfonyl naphtylurea known to inhibit retroviral reverse transcriptases in vitro, blocks HIV-1 infection in HT-29 cells. The effect is dose dependent, with a half-maximal inhibition (IC50) achieved for a suramin concentration of 54 micrograms/ml. Since [3H]suramin was not significantly internalized into HT-29 cells during our infection assay (i.e. 2 h), we have considered the possibility that the drug could act at an extracellular step of the HIV-1 cycle. Using a high performance thin layer chromatography binding assay, we show that suramin inhibits binding of HIV-1 gp120 to purified GalCer with an IC50 of 25 micrograms/ml. Suramin does not bind to GalCer, since preincubation of GalCer with suramin did not prevent the subsequent attachment of gp120. Using a solid-phase assay, we show that [3H]suramin specifically binds to recombinant gp120 and that this binding could be blocked by a monoclonal antibody specific for the conserved GPGRAF motif of the V3 domain of gp120. We also demonstrate that [3H]suramin binds to multibranched synthetic GPGRAF peptides that block HIV-1 infection in HT-29 cells. Binding of [3H]suramin to V3 peptides is specific and inhibited by unlabeled suramin (IC50 of 28 micrograms/ml). In contrast, the suramin derivative NF036, that is unable to block HIV-1 infection in HT-29 cells, does not inhibit the binding of [3H]suramin to V3 peptides. Taken together, these results suggest that suramin blocks HIV-1 infection in HT-29 cells because it binds to the V3 domain of gp120 and hence prevents the interaction between gp120 and the GalCer receptor.


Reproductive switch and aging: the case of leptin change in dietary restriction.
We have proposed that normal food intake is geared toward optimizing the internal milieu for reproduction, despite some components of this milieu being detrimental to health. In dietary restriction, the animal is prevented from eating enough to attain or maintain reproductive capacity and this particular milieu does not materialize. Life extension occurs as a by-product. This idea provides a framework for exploring biomolecular changes in dietary restriction and their relevance to aging. Leptin is a case in point: here, a decrease in leptin level in dietary restriction is explored in the light of leptin's role in the complex signaling system of reproductive switch.


Sodium valproate enhances urethane tumorigenicity in lungs of male but not female mice.
In the study, the possible effect of sodium valproate (NaVP) on urethane-induced lung tumors in mice has been evaluated. BALB/c mice (n = 120; 4-6 weeks old, both sexes) were used in the following groups: 1) urethane-treated, 2) urethane-NaVP-treated, 3) only NaVP-treated, 4) control. In the same groups, castrated male mice (n = 48) were investigated. Urethane was given by intraperitoneal injections 10 mg/mouse, twice a week, the total dose 50 mg/mouse. In NaVP-treated mice, the 0.4 % NaVP aqueous solution was offered to mice ad libitum. The duration of the experiment was 6 months. The number of tumors per mouse in urethane-NaVP-treated males was significantly higher than in those treated with urethane only (13.82 ± 1.12 vs 6.77 ± 0.43, p < 0.0001). No significant difference in the number of tumors per mouse was revealed while comparing the female urethane- and urethane-NaVP-treated groups (6.50 ± 0.79 vs 8.15 ± 0.55, p = 0.105). No difference in the number of tumors per mouse was found in urethane-NaVP-treated castrated males as compared with urethane-treated castrated males. However, in the urethane-NaVP-treated castrated males the number of tumors per mouse was significantly lower than in analogous non-castrated males (7.8 ± 1.67 vs 13.82 ± 1.12, p < 0.01). NaVP combined with urethane potentiates urethane tumorigenicity in BALB/c non-castrated but not in female and castrated male mice. These data indicate an important role of testosterone in the urethane-NaVP induced lung tumorigenesis.


Prediction of the biologically active sites in eclosion hormone from the silkworm, Bombyx mori.
The structure-activity relationship of eclosion hormone from the silkworm, Bombyx mori, was analyzed. First, the probable active residues in silkworm eclosion hormone and also tobacco hornworm eclosion hormone were predicted by the average distance map method. To examine the contributions of those residues to the activity of silkworm eclosion hormone, Gly-substituted mutants for those predicted residues were produced by site-directed mutagenesis and their activities were evaluated by a bioassay. Finally, Glu12, Met24 and Phe25 were estimated to be the crucial residues for the eclosion hormone activity. The possibility of the development of a blocker of an eclosion hormone receptor on the basis of the present work is also discussed.


The endoplasmic reticulum: A hub of protein quality control in health and disease.
One third of the eukaryotic proteome is synthesized at the endoplasmic reticulum (ER), whose unique properties provide a folding environment substantially different from the cytosol. A healthy, balanced proteome in the ER is maintained by a network of factors referred to as the ER quality control (ERQC) machinery. This network consists of various protein folding chaperones and modifying enzymes, and is regulated by stress response pathways that prevent the build-up as well as the secretion of potentially toxic and aggregation-prone misfolded protein species. Here, we describe the components of the ERQC machinery, investigate their response to different forms of stress, and discuss the consequences of ERQC break-down.


Immunomodulatory Biomaterials for Tissue Repair.
All implanted biomaterials are targets of the host's immune system. While the host inflammatory response was once considered a detrimental force to be blunted or avoided, in recent years, it has become a powerful force to be leveraged to augment biomaterial-tissue integration and tissue repair. In this review, we will discuss the major immune cells that mediate the inflammatory response to biomaterials, with a focus on how biomaterials can be designed to modulate immune cell behavior to promote biomaterial-tissue integration. In particular, the intentional activation of monocytes and macrophages with controlled timing, and modulation of their interactions with other cell types involved in wound healing, have emerged as key strategies to improve biomaterial efficacy. To this end, careful design of biomaterial structure and controlled release of immunomodulators can be employed to manipulate macrophage phenotype for the maximization of the wound healing response with enhanced tissue integration and repair, as opposed to a typical foreign body response characterized by fibrous encapsulation and implant isolation. We discuss current challenges in the clinical translation of immunomodulatory biomaterials, such as limitations in the use of in vitro studies and animal models to model the human immune response. Finally, we describe future directions and opportunities for understanding and controlling the biomaterial-immune system interface, including the application of new imaging tools, new animal models, the discovery of new cellular targets, and novel techniques for in situ immune cell reprogramming.


Direct numerical simulations for non-Newtonian rheology of concentrated particle dispersions.
The non-Newtonian behavior of a monodisperse concentrated dispersion of spherical particles was investigated using a direct numerical simulation method, which takes into account hydrodynamic interactions and thermal fluctuations accurately. Simulations were performed under steady shear flow with periodic boundary conditions in the three directions. The apparent shear viscosity of the dispersions was calculated at volume fractions ranging from 0.31 to 0.56. Shear-thinning behavior was clearly observed at high volume fractions. The low- and high-limiting viscosities were then estimated from the apparent viscosity by fitting these data into a semiempirical formula. Furthermore, the short-time motions were examined for Brownian particles fluctuating in concentrated dispersions, for which the fluid inertia plays an important role. The mean square displacement was monitored in the vorticity direction at several different Peclet numbers and volume fractions so that the particle diffusion coefficient is determined from the long-time behavior of the mean square displacement. Finally, the relationship between the non-Newtonian viscosity of the dispersions and the structural relaxation of the dispersed Brownian particles is examined.


Liposomal encapsulation of vancomycin improves killing of methicillin-resistant Staphylococcus aureus in a murine infection model.
Methicillin-resistant Staphylococcus aureus (MRSA) poses a major problem to public health worldwide. MRSA strains with increased resistance to vancomycin cause infections that are associated with greater morbidity and threaten the use of this once gold-standard antistaphylococcal drug. We investigated whether encapsulation of vancomycin within liposomes could improve its antistaphylococcal activity. Two liposomal formulations of vancomycin were prepared using a rehydration-dehydration method. MICs and MBCs of the liposomal vancomycin for strains of MRSA were determined. The efficacy of one of the liposomal vancomycin formulations was also investigated in a time-kill assay in vitro and in a murine systemic infection model. Encapsulation in either liposome preparation decreased the vancomycin MICs and MBCs for MRSA strains by approximately 2-fold. Liposomal vancomycin increased killing of MRSA in vitro in a kinetic study. In a systemic murine infection model, treatment with a 50 mg/kg intraperitoneal injection of liposomal vancomycin improved kidney clearance of a USA300 strain by 1 log compared with an injection of 50 mg/kg of free vancomycin. Our findings suggest that entrapment within liposomes could improve the antistaphylococcal efficacy of vancomycin.


The endosymbiotic bacterium Wolbachia induces resistance to dengue virus in Aedes aegypti.
Genetic strategies that reduce or block pathogen transmission by mosquitoes have been proposed as a means of augmenting current control measures to reduce the growing burden of vector-borne diseases. The endosymbiotic bacterium Wolbachia has long been promoted as a potential vehicle for introducing disease-resistance genes into mosquitoes, thereby making them refractory to the human pathogens they transmit. Given the large overlap in tissue distribution and intracellular localization between Wolbachia and dengue virus in mosquitoes, we conducted experiments to characterize their interactions. Our results show that Wolbachia inhibits viral replication and dissemination in the main dengue vector, Aedes aegypti. Moreover, the virus transmission potential of Wolbachia-infected Ae. aegypti was significantly diminished when compared to wild-type mosquitoes that did not harbor Wolbachia. At 14 days post-infection, Wolbachia completely blocked dengue transmission in at least 37.5% of Ae. aegypti mosquitoes. We also observed that this Wolbachia-mediated viral interference was associated with an elevated basal immunity and increased longevity in the mosquitoes. These results underscore the potential usefulness of Wolbachia-based control strategies for population replacement.


Plasticity of a holobiont: desiccation induces fasting-like metabolism within the lichen microbiota.
The role of host-associated microbiota in enduring dehydration and drought is largely unknown. We have used lichens to study this increasingly important problem because they are the organisms that are optimally adapted to reoccurring hydration/dehydration cycles, and they host a defined and persistent bacterial community. The analysis of metatranscriptomic datasets from bacterial communities of the lung lichen (Lobaria pulmonaria (L.) Hoffm.), sampled under representative hydration stages, revealed significant structural shifts and functional specialization to host conditions. The hydrated samples showed upregulated transcription of transport systems, tRNA modification and various porins (Omp2b by Rhizobiales), whereas the desiccated samples showed different functions related to stress adaption prominently. Carbohydrate metabolism was activated under both conditions. Under dry conditions, upregulation of a specialized ketone metabolism indicated a switch to lipid-based nutrition. Several bacterial lineages were involved in a functional transition that was reminiscent of a 'fasting metaorganism'. Similar functional adaptions were assigned to taxonomically unrelated groups, indicating hydration-related specialization of the microbiota. We were able to show that host-associated bacterial communities are well adapted to dehydration by stress protection and changes of the metabolism. Moreover, our results indicate an intense interplay in holobiont functioning under drought stress.


Climatic changes and their role in emergence and re-emergence of diseases.
Global warming and the associated climate changes are predictable. They are enhanced by burning of fossil fuels and the emission of huge amounts of CO2 gas which resulted in greenhouse effect. It is expected that the average global temperature will increase with 2-5 °C in the next decades. As a result, the earth will exhibit marked climatic changes characterized by extremer weather events in the coming decades, such as the increase in temperature, rainfall, summertime, droughts, more frequent and stronger tornadoes and hurricanes. Epidemiological disease cycle includes host, pathogen and in certain cases intermediate host/vector. A complex mixture of various environmental conditions (e.g. temperature and humidity) determines the suitable habitat/ecological niche for every vector host. The availability of suitable vectors is a precondition for the emergence of vector-borne pathogens. Climate changes and global warming will have catastrophic effects on human, animal and environmental ecosystems. Pathogens, especially neglected tropical disease agents, are expected to emerge and re-emerge in several countries including Europe and North America. The lives of millions of people especially in developing countries will be at risk in direct and indirect ways. In the present review, the role of climate changes in the spread of infectious agents and their vectors is discussed. Examples of the major emerging viral, bacterial and parasitic diseases are also summarized.


Adenomyomatous hyperplasia of distal common bile duct: a case report and review of the literature.
Adenomyomatous hyperplasia (AH) is commonly found in the gallbladder and is considered a tumor-like inflammatory lesion arising from Rokitansky-Aschoff sinus. It is extremely rare in the extrahepatic bile duct and only 15 cases have been reported to date. We describe a 63-year-old male patient who presented with cholangitis, underwent an extensive diagnostic workup, and ultimately had a Whipple procedure. Final pathology showed a 2.0 × 1.5 × 0.5 cm3 granular lesion in the distal common bile duct. There was prominent biliary epithelial proliferation with tubular-papillary architecture and minimal nuclear atypia in association with chronic inflammation, stroma reaction and smooth muscle proliferation. AH of the extrahepatic bile duct is a benign process but often requires a major operation to definitively diagnose.


Characterization of Potential Probiotic Activity of Lactic Acid Bacteria Isolated from Camel Colostrum by Biochemical and Molecular Methods.
A total of 60 isolates of lactic acid bacteria (LAB) were isolated from Jordanian camel colostrum using biochemical and molecular methods. Two dominant species were identified, and they were Lactobacillus salivarius and Enterococcus faecium. The entire 60 isolated LAB were tested for their acidity and bile tolerance, antimicrobial activity, and antibiotic sensitivity to test their potential probiotic activity. All 60 isolates were tolerant to different pH concentrations (2, 3, 4, 5, 6, 7, 8, 9, and 10) with different survival rates (%). The entire isolates were also tolerant to different bile salt concentrations (0.2, 0.4, 0.6, 0.8, 1, 2, and 3) with different bile resistance (%). All isolates have a different range of antimicrobial activity against Staphylococcus aureus, E. coli, and Salmonella typhimurium. The 60 isolates were almost sensitive to ampicillin, amoxicillin, and clarithromycin when different concentrations were used except some isolates of intermediate resistance. Only 6% of the isolates were resistant to clarithromycin at a concentration of 15 µg per disc.


Implications of an impact origin for the martian hemispheric dichotomy.
The observation that one hemisphere of Mars is lower and has a thinner crust than the other (the 'martian hemispheric dichotomy') has been a puzzle for 30 years. The dichotomy may have arisen as a result of internal mechanisms such as convection. Alternatively, it may have been caused by one or several giant impacts, but quantitative tests of the impact hypothesis have not been published. Here we use a high-resolution, two-dimensional, axially symmetric hydrocode to model vertical impacts over a range of parameters appropriate to early Mars. We propose that the impact model, in addition to excavating a crustal cavity of the correct size, explains two other observations. First, crustal disruption at the impact antipode is probably responsible for the observed antipodal decline in magnetic field strength. Second, the impact-generated melt forming the northern lowlands crust is predicted to derive from a deep, depleted mantle source. This prediction is consistent with characteristics of martian shergottite meteorites and suggests a dichotomy formation time approximately 100 Myr after martian accretion, comparable to that of the Moon-forming impact on Earth.


Noninvasive surface damage assessment of bovine articular cartilage explants by reflected polarized light microscopy.
Articular surface damage is a hallmark of cartilage degeneration. Noninvasive assessment of cartilage microstructural alterations has potential clinical value. In this study, we use bovine patellofemoral articular cartilage explants treated with mechanical scraping and collagenase to create cartilage surface disruption, and use polarized reflectance microscopy to quantify alterations to surface and sub-surface microstructure. Reflected polarized signal was sensitive to mild damage to the cartilage surface, and highlighted disruptive alterations. The results indicate the efficacy of reflected polarized light microscopy in assessing the microstructural status of superficial articular cartilage.


Deposition of fibrinogen on the surface of in vitro thrombi prevents platelet adhesion.
The initial accumulation of platelets after vessel injury is followed by thrombin-mediated generation of fibrin which is deposited around the plug. While numerous in vitro studies have shown that fibrin is highly adhesive for platelets, the surface of experimental thrombi in vivo contains very few platelets suggesting the existence of natural anti-adhesive mechanisms protecting stabilized thrombi from platelet accumulation and continuous thrombus propagation. We previously showed that adsorption of fibrinogen on pure fibrin clots results in the formation of a nonadhesive matrix, highlighting a possible role of this process in surface-mediated control of thrombus growth. However, the deposition of fibrinogen on the surface of blood clots has not been examined. In this study, we investigated the presence of intact fibrinogen on the surface of fibrin-rich thrombi generated from flowing blood and determined whether deposited fibrinogen is nonadhesive for platelets. Stabilized fibrin-rich thrombi were generated using a flow chamber and the time that platelets spend on the surface of thrombi was determined by video recording. The presence of fibrinogen and fibrin on the surface of thrombi was analyzed by confocal microscopy using specific antibodies. Examination of the spatial distribution of two proteins revealed the presence of intact fibrinogen on the surface of stabilized thrombi. By manipulating the surface of thrombi to display either fibrin or intact fibrinogen, we found that platelets adhere to fibrin- but not to fibrinogen-coated thrombi. These results indicate that the fibrinogen matrix assembled on the outer layer of stabilized in vitro thrombi protects them from platelet adhesion.


A myosin chaperone, UNC-45A, is a novel regulator of intestinal epithelial barrier integrity and repair.
The actomyosin cytoskeleton serves as a key regulator of the integrity and remodeling of epithelial barriers by controlling assembly and functions of intercellular junctions and cell-matrix adhesions. Although biochemical mechanisms that regulate the activity of non-muscle myosin II (NM-II) in epithelial cells have been extensively investigated, little is known about assembly of the contractile myosin structures at the epithelial adhesion sites. UNC-45A is a cytoskeletal chaperone that is essential for proper folding of NM-II heavy chains and myofilament assembly. We found abundant expression of UNC-45A in human intestinal epithelial cell (IEC) lines and in the epithelial layer of the normal human colon. Interestingly, protein level of UNC-45A was decreased in colonic epithelium of patients with ulcerative colitis. CRISPR/Cas9-mediated knock-out of UNC-45A in HT-29cf8 and SK-CO15 IEC disrupted epithelial barrier integrity, impaired assembly of epithelial adherence and tight junctions and attenuated cell migration. Consistently, decreased UNC-45 expression increased permeability of the Drosophila gut in vivo. The mechanisms underlying barrier disruptive and anti-migratory effects of UNC-45A depletion involved disorganization of the actomyosin bundles at epithelial junctions and the migrating cell edge. Loss of UNC-45A also decreased contractile forces at apical junctions and matrix adhesions. Expression of deletion mutants revealed roles for the myosin binding domain of UNC-45A in controlling IEC junctions and motility. Our findings uncover a novel mechanism that regulates integrity and restitution of the intestinal epithelial barrier, which may be impaired during mucosal inflammation.


Oral zinc supplementation in persistent diarrhoea in infants.
A controlled randomized trial was conducted in 40 infants (6-18 months old) with persistent diarrhoea (greater than 2 weeks' duration) to evaluate the effect of oral zinc supplementation. After completion of rehydration, 20 infants in group A received oral zinc sulphate (20 mg elemental zinc twice daily) and an equal number in group B were given a placebo (glucose). Each child was given oral nalidixic acid and a similar milk-free feeding schedule. Both the groups were comparable with respect to various initial characteristics including nutrition, diarrhoeal disease, serum alkaline phosphatase and serum and rectal mucosal zinc content. During therapy, all the assessed parameters of zinc status (serum alkaline phosphatase and serum and rectal zinc) recorded significant elevation and reduction in groups A and B, respectively. At recovery, the zinc status of group A was significantly higher than that of group B. The diarrhoeal duration and frequency in the zinc-supplemented group were lower but the differences were not statistically significant (p = 0.078 and p = 0.076, respectively). Weight gain in both groups was comparable. It is concluded that in persistent diarrhoea there is depletion of zinc with the progression of disease and oral zinc administration can improve the zinc status. The possible anti-diarrhoeal effect of zinc, however, merits further study.


Dose-dependent pharmacokinetics of antipyrine in the rat.
In rats given a single intravenous dose, the disposition of antipyrine was dose-dependent and followed apparent first-order kinetics only at the lowest (20 mg/kg) dose administered. The initial rate of disposition decreased with increasing dose, indicating apparent saturation of antipyrine metabolism. The observed nonlinearity was unusual in that the terminal elimination rate increased significantly with increasing dose, suggesting that autoinduction of metabolism may occur after a single exposure to antipyrine. The potential implications of dose-dependent antipyrine pharmacokinetics for the use of antipyrine as a model substrate in the estimation of hepatic microsomal oxidative enzyme activity are discussed.


Self-serving interpretations of flattery: why ingratiation works.
Persons who are flattered are more likely to assign credibility to and like the flatterer than observers, presumably because they are motivated by vanity. In existing studies, however, the difference between targets and observers has been confounded with other variables. The present experiments demonstrate that the target-observer difference in judgments of an ingratiator is not affected by these confounding variables, such as cognitive resources, the motive to like one's interaction partner, or to form an accurate impression, or mood. Results further suggest that, whereas cognitive responses to ingratiation are different among participants with high versus low self-esteem, affective responses and judgments of the ingratiator are not qualified by any personality variables.


Fiber-optic cavity sensing of hydrogen diffusion.
A novel type of fiber-optic cavity sensor for hydrogen diffusion into and out of fibers is presented. The sensor is an implementation of a cavity ringdown scheme in a silica-based single-mode fiber that has been exposed to gaseous hydrogen at normal pressure. The measured ringdown times during the H2 diffusion show good agreement with a theoretical diffusion model. This model allows the determination of the diffusion coefficient of hydrogen in silica, resulting in D = (3.02 +/- 0.07) x 10(-15) m2/s at 30 degrees C.


[Keratinization of the senile epidermis (author's transl)].
The ultrastructural study of the senile epidermis without an apparent lesion, in the phase of cicatrization of a traumatic lesion and in a state of hyperkeratosic transformation in comparison with those performed in the normal epidermis, reveals decrease in the number of clear keratinocytes (only compensated in the process of cicatrization) it is in concord with the most recent theory of the aging of cells of Gelfant and Smith. The increase of clear suprabasal cells in the epidermis degenerative process with a constant of the percentage of clear and dark basal cells suggest a liberation of bloqued cells, which constituted probably the direct source of neoplasic differentiation.


Improving Computer-Aided Detection Using Convolutional Neural Networks and Random View Aggregation.
Automated computer-aided detection (CADe) has been an important tool in clinical practice and research. State-of-the-art methods often show high sensitivities at the cost of high false-positives (FP) per patient rates. We design a two-tiered coarse-to-fine cascade framework that first operates a candidate generation system at sensitivities ∼ 100% of but at high FP levels. By leveraging existing CADe systems, coordinates of regions or volumes of interest (ROI or VOI) are generated and function as input for a second tier, which is our focus in this study. In this second stage, we generate 2D (two-dimensional) or 2.5D views via sampling through scale transformations, random translations and rotations. These random views are used to train deep convolutional neural network (ConvNet) classifiers. In testing, the ConvNets assign class (e.g., lesion, pathology) probabilities for a new set of random views that are then averaged to compute a final per-candidate classification probability. This second tier behaves as a highly selective process to reject difficult false positives while preserving high sensitivities. The methods are evaluated on three data sets: 59 patients for sclerotic metastasis detection, 176 patients for lymph node detection, and 1,186 patients for colonic polyp detection. Experimental results show the ability of ConvNets to generalize well to different medical imaging CADe applications and scale elegantly to various data sets. Our proposed methods improve performance markedly in all cases. Sensitivities improved from 57% to 70%, 43% to 77%, and 58% to 75% at 3 FPs per patient for sclerotic metastases, lymph nodes and colonic polyps, respectively.


Evaluation of Autoimmune Bullous Diseases in Elderly Patients in Iran: A 10-Year Retrospective Study.
Autoimmune bullous diseases (ABDs) are uncommon but significant skin disorders with relatively high morbidity and mortality. Some surveys have been carried out to describe the spectrum of ABDs in a region, but this is the first that has focused on ABDs in elderly patients. This study was conducted to determine the clinicoepidemiologic features of ABDs in elderly patients. Medical records of all ABD patients with disease onset after the age of 60 years who presented to the Autoimmune Bullous Diseases Research Center, Tehran, Iran between April 2003 and March 2013 were reviewed. Patients with dermatitis herpetiformis were not included. During the 10-year period studied, 296 patients with ABD and disease onset after 60 years of age were diagnosed. Bullous pemphigoid (BP) was observed to be the most common ABD (48.3%), followed by pemphigus vulgaris (45.3%), pemphigus foliaceus (3.7%), mucous membrane pemphigoid (1.4%), paraneoplastic pemphigus (0.7%), epidermolysis bullosa acquisita (0.3%), and linear IgA bullous disease (0.3%). A predominance in women was observed for total ABDs, BP, and pemphigus vulgaris. Although Iran is known to have a high prevalence of pemphigus, BP is the most frequent ABD among elderly patients in Iran, highlighting the importance of the clinical diagnosis of BP in elderly patients.


Review of non-invasive blood pressure measurement in animals: Part 2 - Evaluation of the performance of non-invasive devices.
Arterial blood pressure is a common parameter evaluated in conscious and anesthetized veterinary patients for a variety of reasons. Non-invasive blood pressure measurement techniques, such as Doppler ultrasound and oscillometry, are attractive in certain veterinary patients due to their availability and ease of use. The greatest limitation to non-invasive blood pressure monitoring can be its inaccuracy, particularly in hypotensive or hypertensive patients and in certain species. Part 1 of this 2-part review summarized the current techniques available to non-invasively measure arterial blood pressure in veterinary species and discussed validation of non-invasive devices. Part 2 summarizes the veterinary literature that evaluates the use of non-invasive blood pressure measurement techniques in conscious and anesthetized species and develops general conclusions for proper use and interpretation of non-invasive blood pressure devices.


Age- and CGG repeat-related slowing of manual movement in fragile X carriers: A prodrome of fragile X-associated tremor ataxia syndrome?
Fragile X premutation carriers are at increased risk for fragile X-associated tremor ataxia syndrome (FXTAS), but to date we know little about prediction of onset and rate of progression and even less about treatment of this neurodegenerative disease. Thus, the longitudinal study of carriers, and the identification of potential biomarkers and prodromal states, is essential. Here we present results of baseline assessments from an ongoing longitudinal project. The cohort consisted of 73 men, 48 with the fragile X mental retardation 1 (FMR1) premutation (55-200 cytosine-cytosine-guanine or CGG repeats) and 25 well-matched controls (< 40 repeats) aged between 40 and 75 years. At enrollment, none met criteria for FXTAS or had any clinically significant tremor or ataxia by blinded neurological examination. The battery consisted of measures of visual memory, spatial working memory, response inhibition, motor speed and control, planning and problem solving, sustained attention, and a standardized movement disorder evaluation. Contrary to expectations, there were no significant differences between premutation carriers and controls on any measure of executive function. However, the premutation carriers had significantly longer manual movement and reaction times than controls, and the significant interaction between CGG repeat and age revealed the slowest movement times among older carriers with higher CGG repeat alleles. A subset of premutation carriers had marginally lower scores on the ataxia evaluation, and they performed no differently from controls on the parkinsonism assessment. Early-developing cerebellar or fronto-motor tract white matter changes, previously documented in MRI studies, may underlie motor slowing that occurs before clinically observable neurological symptoms associated with FXTAS. © 2018 International Parkinson and Movement Disorder Society.


Radiomic Feature-Based Nomogram: A Novel Technique to Predict EGFR-Activating Mutations for EGFR Tyrosin Kinase Inhibitor Therapy.
To develop and validate a radiomic feature-based nomogram for preoperative discriminating the epidermal growth factor receptor (EGFR) activating mutation from wild-type EGFR in non-small cell lung cancer (NSCLC) patients. A group of 301 NSCLC patients were retrospectively reviewed. The EGFR mutation status was determined by ARMS PCR analysis. All patients underwent nonenhanced CT before surgery. Radiomic features were extracted (GE healthcare). The maximum relevance minimum redundancy (mRMR) and LASSO, were used to select features. We incorporated the independent clinical features into the radiomic feature model and formed a joint model (i.e., the radiomic feature-based nomogram). The performance of the joint model was compared with that of the other two models. In total, 396 radiomic features were extracted. A radiomic signature model comprising 9 selected features was established for discriminating patients with EGFR-activating mutations from wild-type EGFR. The radiomic score (Radscore) in the two groups was significantly different between patients with wild-type EGFR and EGFR-activating mutations (training cohort: P<0.0001; validation cohort: P=0.0061). Five clinical features were retained and contributed as the clinical feature model. Compared to the radiomic feature model alone, the nomogram incorporating the clinical features and Radscore exhibited improved sensitivity and discrimination for predicting EGFR-activating mutations (sensitivity: training cohort: 0.84, validation cohort: 0.76; AUC: training cohort: 0.81, validation cohort: 0.75). Decision curve analysis demonstrated that the nomogram was clinically useful and surpassed traditional clinical and radiomic features. The joint model showed favorable performance in the individualized, noninvasive prediction of EGFR-activating mutations in NSCLC patients.


Sharing of Clinically Important Antimicrobial Resistance Genes by Companion Animals and Their Human Household Members.
The aims of this study were to implement a rapid easy methodology, to characterize the antimicrobial resistance gene (AMR) gut content associated with Enterobacteriales and staphylococci; and to evaluate statistical association between AMRs present in fecal samples from healthy companion animals and their human household members. Fecal samples were collected from 27 humans and 29 companion animals living in close contact in 20 households. Nineteen healthy humans without daily contact with companion animals were the control group. After DNA extraction, β-lactamase families and 10 genes of other antimicrobial classes were screened by PCR. Furthermore, third-generation cephalosporin-resistant, carbapenem-resistant, and colistin-resistant Enterobacteriales and methicillin-resistant staphylococci were screened by bacteriological methods. The blaTEM-1B gene with a P3 promotor was the most frequent β-lactam-resistant gene detected in humans and companion animals from households (33.3%, and 17.2%, respectively). The sul2 was the most frequently shared gene by humans and animals from the same household. In 50% of households at least one AMR was detected simultaneously in companion animal/owner pairs. Healthy humans and companion animals carried several AMRs of clinical importance. To the best our knowledge, this study reports the first detection of the blaSHV-27 gene in fecal samples from healthy humans in Portugal and in Europe.


Role of arginine-163 and the 163REEK166 motif in the oligomerization of truncated alpha A-crystallins.
To gain insight into the mechanism by which Arg-163 influences oligomerization of alphaA-crystallin, we prepared a series of truncated alphaA-crystallins with or without mutation of the Arg-163 residue. Expression of the proteins was achieved in Escherichia coli BL21 (DE3) pLysS cells, and alphaA-crystallin was purified by size-exclusion chromatography. Molecular mass was determined by molecular sieve HPLC, chaperone activity was assayed with alcohol dehydrogenase as the target protein, and structural changes were ascertained by circular dichroism (CD) measurements. With an increasing number of residues deleted, there was about a 3% decrease in oligomeric size per residue, until 10 residues were deleted. When 11 residues, including Arg-163, were deleted, the oligomeric size decreased 85%. Mutation of Arg-163 to Gly (R163G) did not affect the molecular mass in the full-length alphaA-crystallin. However, R163G mutants of all the truncated alphaA-crystallins showed a decrease in oligomeric size, those lacking 8, 9, and 10 residues showing 60-80% decrease and those lacking 5, 6, and 7 residues showing only a 7-14% decrease as compared to the corresponding truncated alphaA-crystallin. These data suggest that R163, E164, E165, and K166 in the REEK motif are also relevant to alphaA-crystallin oligomerization. The molecular masses of alphaA1-163 and alphaA1-163 (R163K) were nearly the same, which suggests that the role of Arg-163 is to provide a positive charge for intersubunit electrostatic interactions in the C-terminal domain. In alphaA1-162 (S162R), recovery of the molecular mass to the level in alphaA1-163 has not occurred; this shows that the actual position of R163 is important.


Regulatory accepted but out of domain: In vitro skin irritation tests for agrochemical formulations.
Several in vitro methods have gained regulatory acceptance for the prediction of skin irritation and corrosion. However, the test guidelines for the majority of in vitro methods do not state whether they are applicable to agrochemical formulations. Hence, we would like to share the results from our routine skin corrosion and irritation testing of agrochemical formulations in which both in vitro (according to OECD TG 431 and OECD TG 439) and in vivo (according to OECD TG 404) tests were conducted as regulatory requirements. The in vitro skin irritation test did not correlate well with the CLP classification by in vivo results (44% sensitivity, 60% specificity, and 54% accuracy, based on 65 data pairs). This indicates a lack of applicability of the current protocol of the in vitro skin irritation test for agrochemical formulations. The data set did not contain formulations which were skin corrosive in vivo and hence its applicability could not be assessed. The correlation of in vitro skin corrosion testing to formulations which were not corrosive in vivo was, however, high (95% specificity based on 81 data pairs).


Avian uterine fluid proteome: Exosomes and biological processes potentially involved in sperm survival.
Uterine fluid is an aqueous milieu to which sperm are exposed during their storage and ascent. In this study, a bottom-up proteomic strategy and bioinformatic analysis of hen uterine fluid was performed to improve the understanding of this fluid and its potential role in sperm survival mechanisms. The proteomic data were submitted to ProteomeXchange. Among the 913 proteins identified, 160 are known to be secreted and 640 are referenced in exosomes databases. We isolated exosomes from the avian uterine fluid, analyzed them using electron microscopy, and targeted several exosomes markers (ANXA1/2/4/5, VCP, HSP90A, HSPA8, PARK7, and MDH1) using immunoblotting. Electron microscopy and immunohistochemistry were also used to analyze uterovaginal junctions for the exosomal proteins ANXA4, VCP, and PARK7. Exosomes were observed both at the surface epithelium and inside sperm storage tubules. Our data were compared with two previously published studies on proteomic of hen uterine fluid, and with one study describing the proteomic content of rooster seminal plasma and sperm. In conclusion, we demonstrated for the first time that avian uterine fluid contains exosomes. These may play a key role in preserving sperm functions within the female genital tract. Their presence in the sperm storage tubules may represent an important mechanism regarding interaction between the female genital tract and sperm.


Duodenal obstruction by self-expanding biliary stents in patients with pancreatic cancer.
Self-expanding biliary drains seem to allow long-term patency and prevent stent migration in peri-ampullary neoplastic lesions. We report two cases of duodenal occlusions due to the stent advancing towards the intestinal lumen in patients with tumours of the pancreatic head. The stents had been percutaneously positioned after an endoscopic papillotomy or palliative choledocho-jejunostomy and were impacted by alimentary debris, blocking the passage of food. Dislodgement of the metallic mesh, in conjunction with duodenal wall stiffness and reduced absorption ability due to the pancreatic cancer, can give rise to progressive intestinal occlusion.


Biological characteristics and whole-genome analysis of the Enterococcus faecalis phage PEf771.
Enterococcus faecalis is a common pathogen causing refractory periapical periodontitis and secondary intraradicular infections. In this study, E. faecalis YN771 isolated from a re-treated root canal at a stomatology department was used as the host bacterium and was co-cultured with wastewater from the same department and patient samples to isolate a phage that lyses E. faecalis. We studied the biological and genomic characteristics of this phage. Transmission electron microscopy showed that this phage's head is icosahedral in structure, with a head diameter of around 98.4 nm, and a contractile tail of around 228.5 nm in length and a diameter of 17.3 nm. The phage was identified as a member of the Myoviridae family and named PEf771. It is sensitive to proteinase K but resistant to chloroform and Triton X-100. Its lytic cycle is 45 min, burst size is 78, optimal multiplicity of infection is 0.1, lysis spectrum is narrow, and host strain specificity is strong. Its optimal growth temperature is 37 °C, most suitable pH is 6.0, and is sensitive to ultraviolet radiation. Whole-genome sequencing of PEf771 indicated it has a genome size of 151 052 bp, with a GC content of 36.97%, and encodes 197 proteins plus 26 tRNAs. PEf771 is most closely related to E. faecalis phage EFDG1. Phage PEf771 has strong host specificity and lytic ability, so it is important to further characterize this phage and its interaction with E. faecalis.


Effect of fenofibrate on lipoprotein(a) in hypertriglyceridemic patients: impact of change in triglyceride level and liver function.
We investigated the effect of fenofibrate on lipoprotein(a)levels in hypertriglyceridemic patients and the parameters relating to its effect. Patients with a triglyceride level >/=300 mg/dL or with a triglyceride level >/=200 mg/dL and a high density lipoprotein cholesterol level </=40 mg/dL were treated either with 200 mg of fenofibrate(Fenofibrate group, n = 56) or with general measures (Control group,n = 56). Lipid and lipoprotein levels were measured at baseline and 2 months. Baseline lipoprotein(a) levels were negatively correlated with triglyceride (r = 20.30, P = 0.001) and alanine aminotransferase levels (r = 20.24, P = 0.012). Fenofibrate therapy increased lipoprotein(a) level from 9.4 6 10.6 to 15.6 6 17.5 mg/dL (P = 0.000). The more triglyceride levels decreased, the more lipoprotein(a) levels increased in all subjects (r = 20.46, P = 0.000) and in Control (r =20.35, P = 0.008) and Fenofibrate groups (r = 20.35, P = 0.008). Fenofibrate elevated lipoprotein(a) level greater in patients with a normal liver function. When Fenofibrate group was divided into two subgroups according to the degree of percentage change in lipoprotein(a) level, change in triglyceride level and alanine aminotransferase level were independent predictors by forward logistic regression analysis. In summary, fenofibrate therapy increases lipoprotein(a) level,and this elevation is associated with change in triglyceride level and liver function.


Epidemiological Characteristics and Spatial-Temporal Clusters of Hand, Foot, and Mouth Disease in Zhejiang Province, China, 2008-2012.
Hand, foot and mouth disease (HFMD) is one of the major public health concerns in China. Being the province with high incidence rates of HFMD, the epidemiological features and the spatial-temporal patterns of Zhejiang Province were still unknown. The objective of this study was to investigate the epidemiological characteristics and the high-incidence clusters, as well as explore some potential risk factors. The surveillance data of HFMD during 2008-2012 were collected from the communicable disease surveillance network system of Zhejiang Provincial Center for Disease Control and Prevention. The distributions of age, gender, occupation, season, region, pathogen's serotype and disease severity were analyzed to describe the epidemiological features of HFMD in Zhejiang Province. Seroprevalence survey for human enterovirus 71 (EV71) in 549 healthy children of Zhejiang Province was also performed, as well as 27 seroprevalence publications between 1997 and 2015 were summarized. The spatial-temporal methods were performed to explore the clusters at county level. Furthermore, pathogens' serotypes such as EV71 and coxsackievirus A16 (Cox A16) and meteorological factors were analyzed to explore the potential factors associated with the clusters. A total of 454,339 HFMD cases were reported in Zhejiang Province during 2008-2012, including 1688 (0.37%) severe cases. The annual average incidence rate was 172.98 per 100,000 (ranged from 72.61 to 270.04). The male-to-female ratio for mild cases was around 1.64:1, and up to 1.87:1 for severe cases. Of the total cases, children aged under three years old and under five years old accounted for almost 60% and 90%, respectively. Among all enteroviruses, the predominant serotype was EV71 (49.70%), followed by Cox A16 (26.05%) and other enteroviruses (24.24%) for mild cases. In severe cases, EV71 (82.85%) was the major causative agent. EV71 seroprevalence survey in healthy children confirmed that occult infection was common in children. Furthermore, literature summary for 26 seroprevalence studies during 1997-2015 confirmed that 0-5 years group showed lowest level of EV71 seroprevalence (29.1% on average) compared to the elder children (6-10 years group: 54.6%; 11-20 years group: 61.8%). Global positive spatial autocorrelation patterns (Moran's Is>0.25, P<0.05) were discovered not only for mild cases but also for severe cases, and local positive spatial autocorrelation patterns were revealed for counties from the eastern coastal and southern regions. The retrospective space-time cluster analysis also confirmed these patterns. Risk factors analyses implied that more EV71 and less sunshine were associated with the clusters of HFMD in Zhejiang Province. Our study confirmed that Zhejiang Province was one of the highly epidemic provinces in China and that the epidemiological characteristics of HFMD were similar to other provinces. Occult infection in elder children and adults was one of the important reasons why most HFMD cases were children aged under-five. Combining the results of spatial autocorrelation analysis and the space-time cluster analysis, the major spatial-temporal clusters were from the eastern coastal and southern regions. The distribution of pathogens' serotypes and the level of sunshine could be risk factors for, and serve as an early warning of, the outbreak of HFMD in Zhejiang Province.


The diagnostic value of cranial MRI findings in idiopathic intracranial hypertension: evaluating radiological parameters associated with intracranial pressure.
Idiopathic intracranial hypertension (IIH) is a disease that can result in blindness if there is a delay in diagnosis. Although it is stated that cranial imaging should be normal among the diagnostic criteria, we know that some radiological parameters can be used for the pre-diagnosis of IIH. To determine the predictive value of radiological parameters for the diagnosis of IIH with cranial magnetic resonance imaging (MRI). The study included a group of 19 patients with IIH ("IIH Group"), a group of 34 patients with hyperintensity around the optic nerve in cranial MRI ("Radiological Increased Intracranial Pressure Group"), and a "Control Group" consisting of 45 healthy individuals. All patients were evaluated using cranial MRI with respect to the presence/absence of empty sella, flattening of the posterior globe, hyperintensity around the optic nerve, optic nerve tortuosity, and optic nerve protrusion. In addition, optic nerve sheath diameter measurement was performed in all patients using cranial axial T2 sequence. It was found that optic nerve tortuosity (P = 0.002), flattening of the posterior globe (P = 0.013), and optic nerve protrusion (P = 0.033) were the best parameters to distinguish patients with IIH and those with optic nerve subarachnoid space enlargement. A scoring system was developed according to these data. In the presence of hyperintensity around the optic nerve, it may be possible to evaluate optic nerve tortuosity, flattening of the posterior globe, and optic nerve protrusion using cranial MRI in order to come upon a preliminary diagnosis of IIH.


The impact of noninvasive follicular thyroid neoplasm with papillary-like nuclear features on the performance of the Afirma gene expression classifier.
A recent revision in thyroid tumor nomenclature has resulted in a change from a malignant diagnosis (noninvasive follicular variant of papillary thyroid carcinoma) to one that is nonmalignant (noninvasive follicular thyroid neoplasm with papillary-like nuclear features [NIFTP]). The objective of the current study was to evaluate the impact of this change on the performance of the Afirma gene expression classifier (GEC). The authors retrospectively analyzed consecutive thyroid fine-needle aspiration specimens with indeterminate diagnoses on which GEC was performed. Surgical pathology material was reviewed with the reclassification of nodules into NIFTP. GEC testing was performed on 384 fine-needle aspiration specimens diagnosed as atypia of undetermined significance (AUS) (304 cases) and suspicious for a follicular neoplasm (SFN) (80 cases) and yielded a suspicious result in 152 of the AUS cases (50%) and 50 of the SFN cases (63%). Thyroidectomy was performed on 177 patients. After reclassifying NIFTP, the positive predictive value of GEC decreased from 42% (95% confidence interval [95% CI], 39%-45%) to 24% (95% CI, 22%-26%) in the AUS group and from 23% (95% CI, 19%-27%) to 13% (95% CI, 9%-18%) in the SFN group. Total thyroidectomy was performed more frequently than a partial thyroidectomy in patients with AUS with a suspicious GEC result compared with pre-GEC controls (68% vs 49%; P = .037). Reclassification of NIFTP significantly decreases the positive predictive value of GEC in indeterminate thyroid nodules. Nevertheless, the majority of patients with indeterminate thyroid nodules with a suspicious GEC result in the study institution have undergone total thyroidectomy. This finding raises concerns over reliance on a suspicious GEC result by clinicians to justify total thyroidectomy. Cancer Cytopathol 2017;125:683-91. © 2017 American Cancer Society.