A microsphere immunoassay for detection of antibodies to avian influenza virus.
A microsphere immunoassay (MIA) was developed for the detection of serum antibodies to avian influenza virus. A recombinant influenza A nucleoprotein expressed in baculovirus was conjugated to microspheres and incubated with antibodies. High median fluorescent intensities (MFIs) were obtained with a monoclonal antibody and positive chicken sera. Chickens were inoculated with 10 strains of avian influenza virus representing different subtypes, including high and low pathogenic H5 and H7 subtypes. Three hundred and fifty-four samples from experimentally infected chickens and controls were tested with a competitive ELISA (cELISA) and the MIA. MFIs were converted to positive/negative (PN) ratios. The results of both tests, as percentage inhibition and PN ratio, showed a high correlation (R2 = 0.77). From the comparison data, a ratio of > or =4.5 was selected as the cut-off value for positivity in the MIA. Using this cut-off value, the sensitivity and specificity of the MIA relative to the cELISA when all discordant experimental samples were retested was 99.3 and 93.1%, respectively. The relative specificity increased to 94.7% when additional negative sera (n = 68) were tested. The MIA may be useful for surveillance testing and as a screening test for flocks infected with low pathogenic avian influenza virus and could be expanded for simultaneous detection of antibodies against other avian infectious disease agents.


Protective effect of plant compounds in pesticides toxicity.
The relationship between pesticide exposure and the occurrence of many chronic diseases, including cancer, is confirmed by literature data. In this review, through the analysis of more than 70 papers, we explore an increase in oxidative stress level caused by exposure to environmental pollutants and the protective effects of plant-origin antioxidants. One of the molecular mechanisms, by which pesticides affect living organisms is the induction of oxidative stress. However, recently many plant-based dietary ingredients with antioxidant properties have been considered as a chemopreventive substances due to their ability to remove free radicals. Such a food component must meet several conditions: eliminate free radicals, be easily absorbed and function at an appropriate physiological level. Its main function is to maintain the redox balance and minimize the cellular damage caused by ROS. Therefore, it should be active in aqueous solutions and membrane domains. These properties are characteristic for phenolic compounds and selected plant hormones. Phenolic compounds have proven antioxidant properties, while increasing number of compounds from the group of plant hormones with a very diverse chemical structure turn out to act as antioxidants, being potential food ingredients that can eliminate negative effects of pesticides.


The Clinical Phenotypes of Cutaneous Leishmaniasis in Central and Southwest Regions of Yemen.
Cutaneous leishmaniasis (CL) is endemic in Yemen. CL displays a spectrum of typical and atypical morphologies yet understudied in the central and southwest regions of Yemen. To identify the typical and atypical clinical phenotypes of CL in the central and southwest regions of Yemen. A survey of 145 patients who visited Prof. Al-Qubati Clinic in Taiz between 2010 and 2015, was conducted. Children and residents of the rural areas were at high risk of exposure to the insect vector. The typical phenotype was single (67%), facial (58%) and ulcerated nodule (35%). Other usual phenotypes were small ulcers (21.4%) and non-ulcerative papules and nodules (21%). Unusual phenotypes constituted 12% of the cohort and included psoriasiform, eczematous, erysipeloid, lupoid, verrucous, large ulcerative, leishmania recidivens, satellite, granulomatous infiltrative and hyperkeratotic plaques. Mucous membrane involvement was evident in 10.6% and was also polymorphic. CL has many morphologic patterns in central and southwest regions of Yemen, some are clinically deceptive.


[Pars plana vitrectomy in treatment of ocular toxocariasis complications--case report].
Ocular toxocariasis in adults may cause serious diagnostic and therapeutic problems. We describe a case of a 54-year-old farmer who developed peripheral granuloma with dense connective tissue strands joined to the disc. The diagnosis was confirmed by high ELISA titers in the serum and vitreous body. We performed pars plana vitrectomy with epiretinal membrane removal and laser photocoagulation of the inferior retina, obtaining improvement of visual acuity. After a few weeks the patient returned with central retinal detachment and macular hole. After the second vitrectomy with use of silicon oil we obtained reattachment of the retina but without functional improvement.


Prostacyclin modulation of contractions of the human pulmonary artery by cysteinyl-leukotrienes.
The contractile response to cysteinyl-leukotrienes was studied in isolated human pulmonary arterial rings. Concentration-response curves for leukotriene C(4) were significantly potentiated by the cyclooxygenase inhibitor indomethacin (1.7 microM) and after endothelial denudation. Measurements of 6-keto prostaglandin F(1alpha) showed that cysteinyl-leukotrienes stimulated the release of prostacyclin. A single concentration (1 microM) of either leukotriene C(4) or leukotriene D(4) resulted in both contraction and relaxation. Indomethacin abolished the relaxant phase and enhanced the amplitude of the contraction, supporting that cysteinyl-leukotriene-induced contractions of the human pulmonary artery may be functionally antagonised by the release of prostacyclin. The contractions induced by leukotriene C(4) were resistant to the two cysteinyl-leukotriene receptor antagonists MK 571 ((3-(-2(7-chloro-2-quinolinyl)ethenyl)phenyl)((3-(dimethylamino-3-oxo propyl)thio)methyl)thio propanoic acid, 1 microM) and BAY u9773 (6(R)-(4'-carboxyphenylthio)-5(S)-hydroxy-7(E),9(E), 11(Z)14(Z)-eicosatetrenoic acid, 3 microM), both in the absence and presence of indomethacin. These findings suggest a functional cysteinyl-leukotriene receptor in the human pulmonary artery with antagonist properties not previously described in human tissue.


Interendothelial junctional changes underlie the developmental 'tightening' of the blood-brain barrier.
The structural basis for the decline in non-specific permeability (tightening) of the blood-brain barrier (bbb) during development was investigated in fetal, newborn and weanling mice cerebral hemispheres. Permeability was assessed by measuring the peroxidase activity in the brain 4 h after i.p. injection of horseradish peroxidase--a commonly used vascular tracer that does not cross the intact bbb. Peroxidase activity in brain declined by about two-thirds between birth and weaning, despite increases in both circulating levels and vessel density. Morphometric analysis of the cerebral vessels showed that vesicular density was low (less than 4/micron 2 cytoplasm) at all ages examined , and therefore, is unlikely to be related to permeability changes. Interendothelial junctions changed in that the proportion of the junction composed of zonulae occludens increased, while junctional clefts decreased, and expanded junctional clefts virtually disappeared. We conclude, therefore, that junctional changes underlie the developmental tightening of the bbb. The observation that junctional changes also showed a strong inverse correlation with vessel density suggests that junctional leakiness, and therefore high non-specific permeability, may be a consequence of vessel proliferation in the developing brain.


Regional distribution of cardiac output at rest and during exercise in patients with exertional angina pectoris before and after nifedipine therapy.
The short-term effects of sublingual nifedipine (20 mg) on cardiac output and its distribution at rest and during exercise were evaluated by measurement of iliofemoral blood flow and cardiac output in 10 men with stable angina pectoris controlled by metoprolol. At rest, nifedipine significantly decreased iliofemoral vascular resistance from 294 +/- 36 to 165 +/- 29 dynes.s.cm-5.10(2) (p less than 0.01) and significantly increased iliofemoral blood flow from 0.34 +/- 0.04 to 0.57 +/- 0.11 liters/min (p less than 0.05). Systemic vascular resistance was reduced from 19 +/- 1 to 13 +/- 1 dynes.s.cm-5.10(2) (p less than 0.001) and cardiac output increased significantly from 4.7 +/- 0.3 to 5.8 +/- 0.5 liters/min (p less than 0.05). Mean arterial pressure decreased significantly and heart rate increased significantly. During maximal upright bicycle exercise during nifedipine therapy, iliofemoral vascular resistance and leg blood flow were unchanged compared with control (23 +/- 2 versus 21 +/- 3 dynes.s.cm-5.10(2) and 4.7 +/- 0.5 versus 4.4 +/- 0.6 liters/min), cardiac output remained significantly increased (12.8 +/- 0.8 to 15.2 +/- 1.2 liters/min, p less than 0.05) and systemic vascular resistance remained significantly reduced (8 +/- 1 to 5 +/- 1 dynes.s.cm-5.10(2); p less than 0.001). The proportion of cardiac output distributed to the working lower limbs was significantly reduced at all exercise levels. In summary, nifedipine caused a redistribution of cardiac output by vasodilating nonexercising vascular beds without altering the locally mediated vasodilation in exercising muscle. In patients with coronary artery disease given nifedipine therapy, an increase in exercise tolerance is due to relief of myocardial ischemia rather than to increased peripheral oxygen delivery.


Commentary: An open appeal to the EPA for Superfund ERA reform.
The ecological risk assessment guidance of virtually all federal and state agencies, private companies, and other interests can be traced to that of the essential design of the U.S. Environmental Protection Agency (EPA). The EPA ecological risk assessment paradigm has remained unchanged for all intents and purposes since its inception 30 years ago, this despite criticism expressed repeatedly by some, for many years. Despite the discipline's name, a core paradigm shortcoming is its inability to express risk, the probability of a receptor-of-concern at a contaminated site developing a toxicological endpoint (e.g., reproductive impairment). Further, common site context and biological realities (e.g., site sizes; home ranges of receptors-of concern) allow for the supported challenges that risk assessments aren't needed altogether, and instances of ecological damage at sites being unknown. This commentary is an open appeal to the EPA to replace the paradigm it has set forth, dispensing with failed processes (e.g., endeavoring to assess risk potential at 75 year-old sites; endeavoring to assess risk potential to wide-ranging species at one-acre properties). The commentary invites the EPA to respond, not with counter-arguments, but rather with explanations for the Agency's resistance to acknowledging problems with its guidance, followed by the Agency commitment to sorely needed ERA reform.


A Predictive Study Between Anxiety and Fear of COVID-19 With Psychological Behavior Response: The Mediation Role of Perceived Stress.
Despite the abundance of studies linking fear and anxiety to COVID-19, there are limited studies that examine how these elements impact psychological behavioral responses, especially in Iran. The aim of this study was to investigate the relationship between anxiety and fear of COVID-19 with psychological behavior response, whether this relationship is mediated by role of perceived stress among Iranian population during the COVID-19 pandemic. A predictive cross-sectional study was used to investigate the relationships between COVID-19 anxiety syndrome, fear of COVID-19 with psychological behavioral responses due to the pandemic, and the mediating role of the COVID-19 perceived stress in these relationships. The current study revealed that during the COVID-19 pandemic, fear and anxiety of COVID-19 can influence the psychological behavioral responses of individuals; however, this can be explained through perceived stress. As such, the current study points out that the individuals who perceived high stress due to COVID-19 were more likely to comply with guidelines, which has given new insight into this field. The current study findings are applicable for health policymakers in order to help them in understanding human behavior for developing health promotion programs and also for fostering resilience among the general population.


Health in exchange: teachers, doctors, and the strength of informal practices in Russia.
This article explores teachers' and doctors' informal medical exchange practices in the context of the transforming health care system in post-Soviet Russia. Despite the advent of a medical marketplace, most Russians have low incomes and cannot buy the goods and services the market offers. Instead, they bypass the formal market mechanisms (such as obtaining cheaper medicine through personal connections) and official procedures (such as obtaining free or cheaper health care services despite the emergence of paid services) by using their social networks. This paper uses a network perspective to investigate how doctors' and teachers' mutual relations are formed and what resources form the basis of these informal exchange practices. Drawing on structured diary data and qualitative interviews with 20 teachers, in addition to interviews with eight doctors in St. Petersburg, the study goes beyond mere statistics on health care and attempts to depict "from below" the implications health and illness have for survival in contemporary Russia.


Variations in Textbook Oncologic Outcomes After Curative-Intent Resection: Early Versus Intermediate Hepatocellular Carcinoma Based on Barcelona Clinic Liver Cancer Criteria and Child-Pugh Classification.
The impact of early versus intermediate hepatocellular carcinoma (HCC) on short-term "optimal" outcomes remains ill-defined. This study sought to define the incidence of textbook oncologic outcomes (TOO), as well as to identify factors associated with TOO among patients with early versus intermediate HCC. Patients who underwent curative-intent liver resection for HCC (1998-2020) were identified from a multi-institutional database. Textbook oncologic outcome (TOO) was defined as negative surgical margins, no return to the operating room, no extended hospital stay, no severe complications, and no 90-day mortality or readmission. Patients were stratified as early HCC (BCLC 0 or BCLC A/Child-Pugh A) or intermediate HCC (BCLC A/Child-Pugh B or BCLC B). Multivariate logistic regression analysis was used to assess factors associated with TOO. Among 1383 patients, the overall incidence of TOO was 69.0%. Patients with intermediate HCC were less likely to achieve a TOO (early [71.6 %] vs. intermediate [60.1%]; p < 0.001). On multivariate analysis, factors associated with decreased odds of a TOO were high tumor burden (odds ratio [OR], 0.57; 95% confidence interval [CI], 0.33-1.00), high aspartate transaminase-platelet ratio index (APRI) (OR, 0.46; 95% CI, 0.30-0.70), Charlson Comorbidity Index (CCI) greater than 3 (OR, 0.67; 95% CI, 0.49-0.91), major liver resection (OR, 0.68; 95% CI, 0.52-0.90), and intermediate HCC (OR, 0.68; 95% CI, 0.50-0.93) (all p < 0.05). Notably, although high APRI, CCI greater than 3, and major liver resection contributed to lower odds of a TOO in early HCC, the only factor that adversely impacted TOO in intermediate HCC was high tumor burden. Patients with intermediate HCC and early HCC patients with liver dysfunction, comorbidities, or an extensive resection were less likely to achieve an "optimal" postoperative outcome.


Progressive lymph node histology and its prognostic value in patients with acquired immunodeficiency syndrome and AIDS-related complex.
Seventy-four sequential lymph node biopsies from 30 acquired immunodeficiency syndrome (AIDS)/AIDS-related complex (ARC) patients showed temporal histologic progression from explosive follicular hyperplasia (EFH) to mixed follicular hyperplasia/involution (mixed) to follicular involution (FI) to lymphocyte depletion (LD). This histologic progression correlated with symptoms, development of opportunistic infections (OI), and mortality. At initial biopsy, only 50% of the AIDS/ARC patients with EFH/mixed compared to 100% with FI/LD were symptomatic with weight loss, night sweats, diarrhea, fever, or fatigue. 31% of ARC patients with EFH and 63% with FI developed an OI in a median of 69 months and 5 months, respectively; 86% with LD had a concurrent or previous OI. Ninety percent of ARC patients progressing to FI/LD died; 85% of those persisting with EFH/mixed remained alive 18 to 50 months after initial biopsy. AIDS patients with EFH lived twice as long as those with FI/LD. Progressive histology did not correlate with lymphoma. The number of ARC patients developing Kaposi's sarcoma was too small to draw definitive conclusions.


Glycosphingolipid composition of human semen.
Glycosphingolipids were extracted from human semen and purified. Based on the fluorometric assay of sphingosine, in spermatozoa a content of 4.4 +/- 0.9 nmol/10(8) cells of gangliosides and 22.1 +/- 1.7 nmol/10(8) cells of neutral glycosphingolipids was determined. Seminal plasma contained 4.1 +/- 0.6 nmol gangliosides and 29.3 +/- 1.5 nmol neutral glycosphingolipids per milliliter. The glycosphingolipid component patterns of human spermatozoa and seminal plasma were determined by thin-layer chromatography. Four neutral glycolipids were isolated and their carbohydrate moieties were characterized. All of these glycolipid components belonged to the globo-series. Gas chromatography, combined gas chromatography/mass fragmentography, and exoglycosidase treatments revealed the following structures for the glycosphingolipids of human semen: Glc1-Cer, Gal beta 1-4Glc1-Cer, Gal alpha 1-4Gal beta 1-4Glc1-Cer, and Gal-NAc beta 1-3Gal alpha 1-4Gal beta 1-4Glc1-Cer. In addition, the occurrence of trace amounts of lactoneotetraosyl- and lactoneohexaosylceramide was detected by immunostaining after thin-layer chromatographic separation. Human spermatozoa, as well as seminal plasma, contained the gangliosides Glac1,Glac2, a sialolactoneotetraosylceramide, and a sialolactoneohexaosylceramide. The gangliosides were identified on the basis of their running characteristics by high-performance thin-layer chromatography, exoglycosidase treatment, and immunostaining after thin-layer chromatography. The ceramide composition of the glycolipids in human spermatozoa, as well as in seminal plasma, was dominated by C22:0-behenic acid and the saturated sphingoid d18:0, sphinganine.


Cell surface engineering of Saccharomyces cerevisiae combined with membrane separation technology for xylitol production from rice straw hydrolysate.
Xylitol, a value-added polyol deriving from D-xylose, is widely used in both the food and pharmaceutical industries. Despite extensive studies aiming to streamline the production of xylitol, the manufacturing cost of this product remains high while demand is constantly growing worldwide. Biotechnological production of xylitol from lignocellulosic waste may constitute an advantageous and sustainable option to address this issue. However, to date, there have been few reports of biomass conversion to xylitol. In the present study, xylitol was directly produced from rice straw hydrolysate using a recombinant Saccharomyces cerevisiae YPH499 strain expressing cytosolic xylose reductase (XR), along with β-glucosidase (BGL), xylosidase (XYL), and xylanase (XYN) enzymes (co-)displayed on the cell surface; xylitol production by this strain did not require addition of any commercial enzymes. All of these enzymes contributed to the consolidated bioprocessing (CBP) of the lignocellulosic hydrolysate to xylitol to produce 5.8 g/L xylitol with 79.5 % of theoretical yield from xylose contained in the biomass. Furthermore, nanofiltration of the rice straw hydrolysate provided removal of fermentation inhibitors while simultaneously increasing sugar concentrations, facilitating high concentration xylitol production (37.9 g/L) in the CBP. This study is the first report (to our knowledge) of the combination of cell surface engineering approach and membrane separation technology for xylitol production, which could be extended to further industrial applications.


Galanin receptors in the rat gastrointestinal tract.
Galanin functions are mediated by three distinct G-protein-coupled receptors, galanin receptor 1 (GalR1), GalR2 and GalR3, which activate different intracellular signaling pathways. Here, we quantified mRNA levels of GalR1, GalR2 and GalR3 in the gastrointestinal tract using real time RT-PCR. GalR1 and GalR2 mRNAs were detected in all segments with the highest levels in the large intestine and stomach, respectively. GalR3 mRNA levels were quite low and mostly confined to the colon. We also investigated the effect of galanin 1-16, which has high affinity for GalR1 and GalR2 and low affinity for GalR3 on depolarization-evoked Ca2+ increases in rat cultured myenteric neurons using Ca2+-imaging. Intracellular Ca2+ changes in myenteric neurons were monitored using the Ca2+ sensitive dye, fluo-4, and confocal microscopy. Galanin 1-16 (1 microM) markedly inhibited the K+-evoked Ca2+ increases in myenteric neurons. In summary, the differential distribution of GalRs supports the hypothesis that the complex effects of galanin in the gastrointestinal tract result from the activation of multiple receptor subtypes. Furthermore, this study confirms the presence of functional GalRs and suggests that galanin modulates transmitter release from myenteric neurons through inhibition of voltage-dependent calcium channels involving a G(i/o)-coupled GalR.


High-Dose Neuromodulators: A Roundtable on Making Sense of the Data in Real-World Clinical Practice.
For aesthetic treatment with botulinum neurotoxin type A (BoNTA), interest in maximizing treatment duration and efficacy has prompted study of doses higher than those used in registration studies. As data emerge, it is important that physicians understand how to apply study findings to their own practice so that patient demand is satisfied. To bring together leading experts in neuromodulators for a roundtable discussion on the implications of high-dose BoNTA studies for patient care. The authors reviewed and discussed recent data from high-dose BoNTA studies for abobotulinum toxin A, incobotulinum toxin A, and Oonobotulinumtoxin A. Discussion focused on the challenges of data interpretation and extrapolation of study findings for real-world patient care. The authors participated in a candid discussion of whether the observed improvements in treatment duration and patient satisfaction warrant treatment with high-dose regimens delivered as high-concentration injections. Safety was also discussed, as well as economic considerations for both practices and patients. Of note, for BoNTA products, the registration dose, when administered in a smaller total volume, appears to give rise to more durable results than those observed in pivotal trials, implicating product concentration as an important consideration. Importantly, at higher doses, extended duration of effect does not appear to be at the expense of natural-looking results. While the authors provide considerations for the development of individual clinical practice, there is no one-size-fits-all recommendation. It may be that "high-dose" BoNTA is in reality the optimal dose; however, important economic considerations may prevent rapid uptake for all patients.


Electrically responsive photonic crystals with bistable states for low-power electrophoretic color displays.
Electrically responsive photonic crystals are promising materials for electrophoretic color displays with better brightness and color saturation. However, electric field must always be applied to maintain the specific colors, which brings concerns about the power consumption and signal stability and reversibility. Here, we show an electrically responsive photonic crystal with two stable states at 0 V, which are the colored state or the colorless state with ordered or disordered particle arrangement. The color state can be reversibly switched by applying a short-time electrical field, just like in the case of commercial electrophoretic ink. With optimized recipe and electric field, the photonic crystals encapsulated in the prototype display panel are proved to have potentials in high resolution, multi-color, and greyscale display, which lays down a firm basis for reflective displays with low power consumption and good visibility.


An overview of current and emerging devices for percutaneous left atrial appendage closure.
Atrial fibrillation (AF) is common and is a prominent risk factor for ischemic stroke. Oral anticoagulant (OAC) therapy has been the main strategy for stroke prevention in AF patients; however, OAC therapy carries a bleeding risk and is not tolerated by all patients. Left atrial appendage (LAA) closure offers a non-pharmacological alternative for stroke prevention in patients with non-valvular AF. In this update, an overview of current and emerging LAA occluders is given - with special attention to the key design features of every single device and, if available, preclinical or clinical data.


Measurement and interpretation of drinking behavior. I. On measuring patterns of alcohol consumption. II. Relationships between drinking behavior and social adjustment in a sample of problem drinkers.
Different systems for measuring drinking behavior were reviewed and compared. A revised system based on volume and pattern was devised, and its utility in predicting social adjustment was tested.


Capture and Identification of miRNA Targets by Biotin Pulldown and RNA-seq.
MicroRNAs (miRNAs) are small noncoding RNAs that regulate the stability and expression of target RNAs in a sequence-dependent manner. Identifying miRNA-regulated genes is key to understanding miRNA function. Here, we describe an unbiased biochemical pulldown method to identify with high-specificity miRNA targets. Regulated transcripts are enriched in streptavidin-captured mRNAs that bind to a transfected biotinylated miRNA mimic. The method is relatively simple, does not involve cross-linking and can be performed with only a million cells. Addition of an on-bead RNase digestion step also identifies miRNA recognition elements (MRE).


In vitro strain adaptation of CWD prions by serial protein misfolding cyclic amplification.
We used serial protein misfolding cyclic amplification (sPMCA) to amplify the D10 strain of CWD prions in a linear relationship over two logs of D10 dilutions. The resultant PMCA-amplified D10 induced terminal TSE disease in CWD-susceptible Tg(cerPrP)1536 mice with a survival time approximately 80 days shorter than the original D10 inoculum, similar to that produced by in vivo sub-passage of D10 in Tg(cerPrP)1536 mice. Both in vitro-amplified and mouse-passaged D10 produced brain lesion profiles, glycoform ratios and conformational stabilities significantly different than those produced by the original D10 inoculum in Tg(cerPrP)1536 mice. These findings demonstrate that sPMCA can amplify and adapt prion strains in vitro as effectively and much more quickly than in vivo strain adaptation by mouse passage. Thus sPMCA may represent a powerful tool to assess prion strain adaptation and species barriers in vitro.


Surface immobilization of biocompatible phospholipid polymer multilayered hydrogel on titanium alloy.
The aim of this study is to improve the biocompatibility of titanium alloy (Ti) implants by immobilization of multilayered phospholipid polymer hydrogel able to reduce protein adsorption and cell adhesion. We fabricated and characterized a multilayered hydrogel on Ti substrate via a layer-by-layer self-assembly deposition method using a phospholipid polymer bearing a phenylboronic acid moiety and poly(vinyl alcohol) (PVA). The water-soluble phospholipid polymer (PMBV) was synthesized from 2-methacrylocyloxyethyl phosphorylcholine, n-butyl methacrylate, and 4-vinylphenylboronic acid (VPBA). The PMBV reacted with PVA and formed a hydrogel due to covalent linkage between the VPBA units and hydroxyl groups of PVA. The hydrogel layer growth on the Ti surface was initialized by the deposition of one layer of photoreactive PVA bonded by UV irradiation to the Ti surface, which was modified with an alkylsilane compound. The multilayered hydrogel was built up by alternating the deposition of the PMBV and PVA; this was monitored by several methods: static contact angle measurement, X-ray photoelectron spectroscopy, and attenuated Fourier-transform infrared spectroscopy. The results revealed clearly the progressive construction of the multilayered hydrogel on the Ti substrate. The PMBV/PVA multilayer prepared on the Ti substrate reduced the adhesion of L929 cells compared with that on an untreated Ti substrate. Thus, we concluded that the formation of the multilayered hydrogel is effective to improve the biocompatibility on Ti-based medical devices.


Di-n-butyl-bis-(N-ethyl-N-phenyl-dithio-carbamato-κS)tin(IV).
The title compound, [Sn(C(4)H(9))(2)(C(9)H(10)NS(2))(2)], features a tetra-hedrally coordinated Sn(IV) atom; the dithio-carbamate ligands coordinate in a monodentate fashion, accompanied by two n-butyl chains. The non-coordinating thione S atoms are each proximate to the Sn(IV) atom [3.0136 (7) and 2.9865 (8) Å], giving rise to distortions from the ideal geometry as evident in the wide C-Sn-C bond angle of 139.06 (12) °. In the crystal, C-H⋯S inter-actions lead to the formation of a linear supra-molecular chain along the b axis. The chains are aligned into layers by C-H⋯π inter-actions, and the layers stack along [001]. One of the ethyl groups is statistically disordered over two sets of sites.


Pleomorphic liposarcoma of chest wall: a rare entity with challenging management.
Pleomorphic liposarcoma is the rarest subtype of liposarcoma, with a high recurrence rate and poor prognosis. We present the case of young man with a rapidly growing large anterior chest wall liposarcoma that was excised, but he suffered 3 local recurrences in one year, showing the aggressive nature of the disease. If not completely resected with a tumor-free margin, the patient may have to endure multiple extensive surgeries in quick succession, increasing the chances of metastasis and a fatal outcome. Pleomorphic liposarcoma should be radically excised along with radiotherapy and strict follow-up of such patients.


A new species of the genus Dendrolasiophilus Nomura, 2010 from the south of the Russian Far East (Coleoptera, Staphylinidae, Pselaphinae).
Dendrolasiophilus subitus sp. nov. from the Russian Far East is described and illustrated. Some nomenclatural notes on the genus Dendrolasiophilus Nomura, 2010 are given.


Ileus rate after abdominal wall reconstruction: a retrospective analysis of two clinical trials.
Postoperative ileus (POI) is the paralytic disruption of gastrointestinal motility, a common complication following abdominal wall reconstruction that often leads to increased patient morbidity and length of stay (LOS). We reviewed two randomized clinical trials to determine POI rates, predictive factors, LOS, and associated cost. Two randomized trials were performed from 2017-2019 with all patients receiving elective open abdominal wall reconstruction with retromuscular mesh. Using multivariate logistic regression, we performed a retrospective analysis including demographics and operative details from patients at a single site to determine predictive factors for POI. All medical costs encompassing surgery and the 30-day postoperative period were compared between ileus and non-ileus groups. Four hundred and seventy patients were reviewed with a POI rate of 13.0% (N = 61). There were no differences in age, body mass index (BMI), history of abdominal surgery, or comorbidities between patients with and without POI. Logistic regression showed no association with POI and age, BMI, hernia width, or operative time lasting longer than 4 h. Median LOS was 8 days for patients with POI compared to five for those without (p < 0.001). Relative median 30-day costs were 1.19 in patients with ileus and 1.0 in those without (p < 0.001). We identified a 13% rate of POI in patients undergoing open abdominal wall reconstruction with mesh with no clearly identified predisposing factors. This resulted in a 3 days increase in median LOS and 19% additional costs. Further efforts should be devoted to investigating interventions that may reduce postoperative ileus after abdominal wall reconstruction.


The relative role of soil, climate, and genotype in the variation of nutritional value of Annona senegalensis fruits and leaves.
Annona senegalensis Pers is a multipurpose tree species valued for food and medicinal uses in Africa. Although there have been attempts to document the proximate composition of fruits and leaves, little is known about the relative role of soil, climate, and genotype on the nutritional quality. The present study evaluated the variation of the proximate composition of fruits and leaves in populations from Benin and Mozambique. It further assessed the impact of soil, climate and genotype on the proximate composition. Data were collected from four populations genetically different and analyzed using descriptive statistics, analysis of variance (ANOVA), principal component analysis, redundancy analysis (RDA), and variance partitioning. Results revealed significant variation in the proximate composition of fruits and leaves among the studied populations. Ashes and fibers in fruits, and lipids in leaves were 4.8-fold, 2.5- fold, and 1.25-fold higher respectively, in populations from Mozambique. Fruits moisture and lipids content were rather 1.4-fold and 1.10-fold higher in populations from Benin. Moisture and lipids were respectively 6-fold and 1.27-fold higher in fruits than in leaves, while ashes, fibers and proteins were approximately twice higher in the leaves than in the fruits. Genetic groups, climate and soils were found to influence this variation. All three factors explained 74.4% of the variation of nutritional value of fruits and leaves, 31.9% of which was exclusively due to genetic variation, 2.8% to the interaction of climate and soils, 24.1% to the interaction of soil and genetic variation, and 15.5% to the interaction of all three factors. Our study shows that genetic variation and soil properties better than climate, explain the variation of nutritional value of A. senegalensis fruits and leaves and further provides essential information that could be harnessed in the domestication and breeding program of the species for its edible parts.


Microstructure evolution and texture tailoring of reduced graphene oxide reinforced Zn scaffold.
Zinc (Zn) possesses desirable degradability and favorable biocompatibility, thus being recognized as a promising bone implant material. Nevertheless, the insufficient mechanical performance limits its further clinical application. In this study, reduced graphene oxide (RGO) was used as reinforcement in Zn scaffold fabricated via laser additive manufacturing. Results showed that the homogeneously dispersed RGO simultaneously enhanced the strength and ductility of Zn scaffold. On one hand, the enhanced strength was ascribed to (i) the grain refinement caused by the pinning effect of RGO, (ii) the efficient load shift due to the huge specific surface area of RGO and the favorable interface bonding between RGO and Zn matrix, and (iii) the Orowan strengthening by the homogeneously distributed RGO. On the other hand, the improved ductility was owing to the RGO-induced random orientation of grain with texture index reducing from 20.5 to 7.3, which activated more slip systems and provided more space to accommodate dislocation. Furthermore, the cell test confirmed that RGO promoted cell growth and differentiation. This study demonstrated the great potential of RGO in tailoring the mechanical performance and cell behavior of Zn scaffold for bone repair.


Linoleic acid salt with ultrapure soft water as an antibacterial combination against dermato-pathogenic Staphylococcus spp.
Skin colonization of Staphylococcus spp. critically affects the severity of dermatitis in humans and animals. We examined different types of fatty acid salts for their antibacterial activity against Staphylococcus spp. when used in ultrapure soft water (UPSW). We also evaluated their therapeutic effect on a spontaneous canine model of dermatitis. UPSW, in which Ca(++) and Mg(++) were replaced with Na(+) , was generated using a water softener with cation-exchange resin. Staphylococcus aureus (Staph. aureus), Staphylococcus intermedius (Staph. intermedius), and Staphylococcus pseudintermedius (Staph. pseudintermedius) were incubated with various fatty acid salts in distilled water (DW) or UPSW and the number of bacteria was counted. Among the fatty acids, oleic acid salt and linoleic acid (LA) salt reduced the number of these bacteria. Also, UPSW enhanced the antibacterial effect of LA on Staph. spp. In spontaneously developed itchy dermatitis in companion dogs, shampoo treatment with liquid soap containing 10% LA in UPSW improved skin conditions. LA salt showed antibacterial activity against Staph. spp. Treatment with soap containing LA with UPSW reduced clinical conditions in dogs with dermatitis. Because colonization of Staph. spp. on the skin exacerbates dermatitis, the use of LA-containing soap in UPSW may reduce unpleasant clinical symptoms of the skin.


"It's a disease of families": Neurologists' insights on how to improve communication and quality of life for families of Parkinson's disease patients.
Parkinson's disease presents an evolving challenge for patients and families due to an unpredictable disease trajectory and symptoms that complicate social interactions. In this study, we explore neurologists' perspectives on the challenges Parkinson's disease presents for families and the strategies they use to improve communication and quality of life. We conducted hour-long semi-structured interviews with 16 neurologists at 4 care delivery institutions in the San Francisco Bay Area, focusing on techniques neurologists use to support families through the Parkinson's disease journey. Neurologists identified strategies for addressing caregiver-patient disagreements around symptom accuracy and negotiating driving safety. Family education is needed to contextualize patient symptoms and to identify psychosocial support resources. Unmet caregiver needs remain, particularly in the form of psychosocial support, respite care and support for unequal gender dynamics in the Parkinson's disease caregiving experience. Family members of Parkinson's disease patients face unique caregiving and interpersonal challenges due to the nature of the disease. Targeted education and structural support are needed to alleviate current burdens and allow for improved patient- and family-centered care.


Urologic manifestations of AIDS.
A retrospective analysis of 60 patients with Acquired Immune Deficiency Syndrome (AIDS) seen between 1981-1985 was performed to determine the genitourinary manifestations of this disease. Twenty-two per cent were found to have significant proteinuria, while 7 per cent had nephrotic syndrome which was associated with an extremely rapid demise. Renal insufficiency occurred in 27 per cent and renal biopsy results, when abnormal, revealed focal and segmental glomerulosclerosis. Pyuria was found in 52 per cent of patients, and urinary tract infections occurred in 20 per cent. Atypical pathogens including Candida, Salmonella, Acinetobacter calcoaticus, and cytomegalovirus were encountered.


Injury severity scoring: a comparison of early clinical versus discharge diagnosis.
The Abbreviated Injury Scale (AIS) and the Injury Severity Score (ISS) are objective means of assessing injury. Accepted methodology involves retrospective scoring of injury based on discharge diagnoses. Recently, early clinical scoring, supplemented by review at discharge, has been introduced. A prospective study was instituted to compare these methodologies. Four hundred sixty consecutive victims of blunt trauma were scored using both clinical and retrospective methodologies by independent, blinded observers. Of these, 333 patients had a change in ISS, 174 with a change of greater than four points. The population mean ISS remained unchanged; however, paired values were significantly different (p less than .03). We conclude that either methodology is applicable for studies of large populations of trauma victims. When accurate individual AIS or ISS scoring is required, the clinical method combined with discharge review is most appropriate.


Inhibition of tumor necrosis factor alpha secretion in rat Kupffer cells by siRNA: in vivo efficacy of siRNA-liposomes.
Tumor necrosis factor alpha (TNF-alpha), a pro-inflammatory cytokine, plays a key role in the pathogenesis of many inflammatory diseases, including alcoholic liver disease. In the liver, Kupffer cells are the primary source of the cytokine. Obliteration of Kupffer cells or neutralization of TNF-alpha by anti-TNF-alpha antibody or by an antisense oligonucleotide prevents ethanol-mediated liver damage. In this study, we report the identification of yet another highly efficacious gene-silencing molecule, the short interfering RNA (siRNA), SSL3, against TNF-alpha. The efficacies of various siRNA duplexes were tested against TNF-alpha mRNA in primary cultures of rat Kupffer cells. SSL3 (25 nM) inhibited lipopolysaccharide (LPS)-induced secretion of TNF-alpha by 55% (p<0.005) with a proportionate reduction in TNF-alpha mRNA; the inhibitory effect lasted for at least 96 h. Four nucleotide mismatches to SSL3 completely abolished the inhibitory effects of SSL3, suggesting the sequence specificity of the siRNA. Further, the in vivo efficacy of SSL3 was assessed following the i.v. administration of two doses (140 microg/kg body weight/day for 2 days) of liposome-encapsulated SSL3. The LPS-induced TNF-alpha secretion was inhibited by >60% (p<0.05) by SSL3 pre-treatment. These data demonstrate the identification of an siRNA against TNF-alpha, which, as a liposomal formulation, has therapeutic potential in the treatment of inflammatory diseases mediated by TNF-alpha.


Inverse association between altitude and obesity: A prevalence study among andean and low-altitude adult individuals of Peru.
To determine the association between altitude and obesity in a nationally representative sample of the Peruvian adult population. This is a cross-sectional analysis of publicly available data from the Food and Nutrition National Center (CENAN, Peru), period 2009-2010. The Prevalence ratio of obesity and abdominal obesity was determined as a measure of association. Obesity and abdominal obesity were diagnosed based on direct anthropometric measurements. The final data set consisted of 31,549 individuals ≥20 years old. The prevalence ratio of obesity was as follows: 1.00 between 0 and 499 m (reference category), 1.00 (95% confidence interval 0.87-1.16) between 500-1,499 m, 0.74 (0.63-0.86) between 1,500-2,999 m, and 0.54 (0.45-0.64) at ≥3,000 m, adjusting for age, sex, self-reported physical activity, out-migration rate, urbanization, poverty, education, and geographical latitude and longitude. In the same order, the adjusted prevalence ratio of abdominal obesity was 1.00, 1.01 (0.94-1.07), 0.93 (0.87-0.99), and 0.89 (0.82-0.95), respectively. We found an interaction between altitude and sex and between altitude and age (P < 0.001, for both interactions) on the association with obesity and abdominal obesity. Among Peruvian adult individuals, we found an inverse association between altitude and obesity, adjusting for multiple covariates. This adjusted association varied by sex and age.


Biochemical switching device: how to turn on (off) the switch.
We previously showed with computer simulations that cyclic enzyme systems have the reliability of ON-OFF types of operation (McCulloch-Pitts' neuronic equation) and the applicability for a switching circuit in a biocomputer. The switching time was inevitably determined in accordance with the difference in amount between two inputs of the system. This characteristic is, however, a disadvantage for practical use of a switching device; we need to improve the system in order for the switching time to optionally be changed. We shall present here how to turn on (off) the switch independently of the modes of two inputs. By introducing pulse perturbation, we could optionally set up the switching time of a cyclic enzyme system (biochemical switching device).


Psychological sense of community and motivation toward collective social change among community coalition members of color in the southwestern United States.
Drawing on McMillan and Chavis's psychological sense of community framework among southwestern community coalition members (N = 18), data were examined for narratives of how psychological sense of community and experiences of community manifest among coalition members. We were also interested in knowing how coalition members make meaning of social change. Findings illustrate that dimensions of psychological sense of community (e.g., membership, emotional connection, needs' fulfillment, and influence) are important in how members made meaning of community needs and their own participation in the coalition. Implications are put forward for theory and community programming.


Prosencephalic pathways related to the paleostriatum of the pigeon (Columba livia).
Afferent connections of the avian paleostriatal complex were traced by means of anterograde and retrograde transport of horseradish peroxidase (HRP). The paleostriatum augmentatum (PA), a cell field comparable to mammalian caudate nucleus and putamen, was found to receive projections from a distinct population of elencephalic neurons in the temporal-parietal-occipital (TPO) and lateral cortical (CDL) areas of the neostriatum. TPO neurons, in turn, were found to receive projections from the contralateral ventral archistriatum (Av) and from neurons in the ipsilateral frontal neostriatum adjacent to the rostral portion of the ectostriatum (e). the paleostriatum primitivum (PP), comparable to globus pallidus, receives projections from the small cells of PA, and from neutrons in the anterior nucleus of the ansa lenticularis (ALa). ALa appears similar to the mammalian subthalamic nucleus on the basis of its afferent and efferent connections. In addition, PA was also found to receive extensive projections from the nucleus tegmenti pedunculopontinus of the midbrain, a dopamine-containing cell group. Evidence of projections from the nucleus dorointermedius posterior (DIP), a cell group receiving both cerebellar and paleostriatal afferents, to the rostral telencephalon was also found.


The prevalence and perinatal repercussions of preeclampsia after the implementation of a prophylaxis protocol with aspirin.
To evaluate the prevalence and perinatal repercussions of preeclampsia (PE) after the implementation of a prophylaxis protocol with aspirin in singleton pregnancy at Maternity School of Federal University of Rio de Janeiro, Rio de Janeiro, Brazil (2015-2106). PE prevalence according to gestational age (GA) and the prevalence ratio (PR) between PE and prematurity, small for gestational age (SGA), and fetal death were calculated in patients assisted during 2015 and 2016. PE occurred in 373(10.75%) of 3468 investigated cases, where PE < 37 weeks was of 2.79% and PE greater than 37 weeks was of 7.95%. A total of 413 (11.9%) prematurity cases, 320 SGA (9.22%), and 50 fetal deaths (1.44%) occurred. In the PE group, 97 premature newborns (PR 0.90) and 51 SGA (PR 1.16) were born, and two fetal deaths occurred (PR 7.46). Concerning PE < 37 weeks, 27 SGA cases (PR 1.42) and two fetal deaths (PR 2.62) were observed. Regarding PE greater than 37 weeks, 24 SGA (PR 1.09) were born, and no fetal deaths were observed. Our findings were compared to previously published results. PE was significantly associated with SGA newborns, especially premature PE. Prescribing aspirin for PE prophylaxis based only on clinical risk factors in a real-life scenario does not appear to be effective but resulted in a PE screening and prophylaxis protocol review and update at ME/UFRJ.


Endothelial seeding of vascular prostheses: a technique of in situ enzymatic retrieval of endothelial cells without vein sacrifice.
The success of endothelial seeding of vascular prosthetic grafts is largely dependent on endothelial cell retrieval. An in situ cell harvesting technique using enzymatic dissolution in a temporarily excluded segment of the internal jugular vein is described. With this technique the cellular yield is adequate and the internal jugular vein remains patent. This technique allows for high-density seeding in a single stage. In two-stage seeding the excellent yield of cells reduces the duration of in vitro endothelial cell culture and allows for secondary massive and early seeding.


Osteoblastoma of the sternum.
Osteoblastoma has become a well defined bone tumor since its first description by Jaffe and Mayer in 1932. This tumor was considered to occur in almost any bone of the skeleton. Only one previous case of sternal osteoblastoma was described in the literature. Herein we report, as far as we know, the second reported case of osteoblastoma in the sternum, as an isolated tumor.


Clinical characteristics and prognostic implications of orthopedic ligament disorders in patients with wild-type transthyretin amyloidosis cardiomyopathy.
Wild-type transthyretin amyloidosis (ATTRwt) is associated with multiple ligament disorders (LD) such as carpal tunnel syndrome (CTS), lumbar spinal stenosis (LSS), and spontaneous tendon rupture (STR). No studies have investigated the prevalence of these LD in the same cohort of ATTRwt patients. Furthermore, the clinical characteristics and prognostic implications of such disorders have not been studied. From 2017 to 2022, 206 consecutive patients with ATTRwt were diagnosed and followed prospectively to the time of death or the censoring date of September 1st, 2022. Patients with and without LD were compared, and the presence of LD was used along with the baseline clinical, biochemical, and echocardiographic characteristics to predict hospitalization with worsening heart failure and death. CTS surgery was performed in 34 % of the patients, 8 % were treated for LSS, and 10 % had experienced an STR. The median follow-up time was 706 days (312-1067). Hospitalization with worsening heart failure occurred more frequently in patients with LD compared to patients without LD (p = 0.035). Presence of LD or surgery for CTS were found to be independent predictors of worsening heart failure with a hazard ratio of 2.0 (p = 0.01). The mortality was comparable between patients with and without LD (p = 0.10). Orthopedic disorders are prevalent in ATTRwt cardiomyopathy, and presence of LD was an independent predictor of hospitalization with worsening heart failure.


Nonlinear waves in dry and wet Hertzian granular chains.
A one-dimensional dry granular medium, a chain of beads which interact via the nonlinear Hertz potential, exhibits strongly nonlinear behaviors. When such an alignment further contains some fluid in the interstices between grains, it may exhibit new interesting features. We report some recent experiments, analysis and numerical simulations concerning nonlinear wave propagation in dry and wet chains of spheres. We consider first a monodisperse chain as a reference case. We then analyze how the pulse characteristics are modified in the presence of an interstitial viscous fluid. The fluid not only induces dissipation but also strongly affect the intergrain stiffness: in a wet chain, wave speed is enhanced and pulses are shorter. Simple experiments performed with a single sphere colliding a wall covered by a thin film of fluid confirm these observations. We demonstrate that even a very small amount of fluid can overcome the Hertzian potential and is responsible for a large increase of contact stiffness. Possible mechanisms for wet contact hardening are related to large fluid shear rate during fast elastohydrodynamic collision between grains.


Heinrich Müller (1820-1864) and the entoptic discovery of the site in the retina where vision is initiated.
Heinrich Müller was a nineteenth-century German retinal anatomist who, during his short career, was one of the discoverers of the rod photopigment rhodopsin and neuroglia in the retina, now known as Müller cells. He also described the ocular muscles and double foveae of some birds. An important, but largely neglected, insight by Müller was to combine careful psychophysical measurements and geometrical optics to find the location of the photosensitive layer of the retina in the living eye. Here, we provide translated passages from Müller's (1855) publication and compare his entoptic observations with retinal imaging using optical coherence tomography. Müller correctly deduced from his careful experiments that vision is initiated in the photoreceptors located in the back of the retina.


Mega-nano detection of foodborne pathogens and transgenes using molecular beacon and semiconductor quantum dot technologies.
Signature molecules derived from Listeria monocytogenes, Bacillus thuringiensis, and Salmonella Typhimurium were detected directly on food substrates (mega) by coupling molecular beacon technology utilizing fluorescent resonance energy transfer (FRET), luminescent nanoscale semiconductor quantum dots, and nanoscale quenchers. We designed target DNA sequences for detecting hlyA, Bt cry1Ac, and invA genes from L. monocytogenes, B. thuringiensis and Salmonella Typhimurium, respectively, and prepared molecular beacons for specific targets for use in real-time monitoring. We successfully detected increased fluorescence in the presence of signature molecules at molecular beacon (MB) concentrations from 1.17 nM to 40 nM, depending upon system tested in (water, milk or plant leaves), respective target (hlyA, Bt cry1Ac, or invA) and genomic DNA target concentration (50-800 ng). We were able to detect bacterial genomic DNA derived from L. monocytogenes and Salmonella sp. in a food system, 2% milk ( > 20% of total volume). Furthermore, we infiltrated the Bt cry1Ac beacon in the presence of genomic DNA extracted from B. thuringiensis into Arabidopsis thaliana leaves and observed increased fluorescence in the presence of the target, indicating the ability to use these beacons in a plant system.


Assessment of vaginal lactobacillary flora in wet mount and fresh or delayed gram's stain.
The assessment of the vaginal lactobacillary flora helps to direct further diagnostic microbiologic investigations in genital infectious disease and seems to represent a powerful tool in predicting infectious morbidity and preterm labor during pregnancy. In the absence of a "gold standard," we studied the variations in assessing lactobacillary morphotypes according to the method used. The lactobacillary flora from 183 pregnant women was classified according to 3 groups: normal, intermediate, and abnormal. This grading of lactobacilli was appled to vaginal and cervical specimens by means of 1) immediate wet-smear microscopy, 2) Gram's stain on a fresh, air-dried specimen, and 3)delayed Gram's stain after specimen transportation in Stuart's growth medium for 3-6 h. The assignment of intermediate or abnormal flora (grade II or grade III) showed high concordance rates among the different preparatory techniques, but the assignment of grade I (normal flora) did not. Fewer lactobacilli were found 2.6 times more often after Gram's stains of fresh specimens [Relative Risk (RR) 2.6, 95% confidence interval (CI) 1.7-4.1] and 6 times more often when the Gram%s stain was performed in a delayed examination after transport than in a fresh wet-mount specimen (RR 6.2, 95% CI 2.5-15.6). Disturbed lactobacillary grades were also found more frequently in specimens from the cervix than those from the vagina (RR 4.0, 95% CI, 1.5-10.4). There are discrepancies in the diagnosis of lactobacillary grades between gram-stained and fresh vaginal specimens. The evidence is ambiguous as to which of the 2 methods is responsible. If an evaluation is to be done on a gram-stained specimen, then the storage of the sample in Stuart transport medium before staining should be avoided.


Chemical sympathectomy favours vimentin expression in arterial smooth muscle cells of young rats.
The aim of the present study was to determine whether sympathectomy could influence the relative expression of two intermediate filament proteins, desmin and vimentin, two markers of differentiation, in arterial smooth muscle cells of the young rat. Newborn rats were treated with either repeated guanethidine or saline injections. Sections of the abdominal aorta, the femoral artery, the basilar and the middle cerebral arteries were processed simultaneously for immunofluorescence with monoclonal antibodies against desmin and vimentin and were then examined under either a conventional or a confocal laser-scanning microscope. In both cases, the mean optical density of the muscle layer staining was estimated by computerized image analysis. All artery sections from guanethidine-treated animals showed a significantly higher vimentin expression (108-119% of control values). Desmin expression was not significantly different except in the femoral artery after sympathectomy, where it was decreased by 6%. The relative increase of vimentin expression in sympathectomized blood vessels observed in the present study directly confirms previous morphometric and ultrastructural studies indicating that the sympathetic innervation of cerebral and peripheral blood vessels influences the phenotypic features of smooth muscle cells during post-natal development.


Metabolic and Non-Cognitive Manifestations of Alzheimer's Disease: The Hypothalamus as Both Culprit and Target of Pathology.
Alzheimer's disease (AD) is increasingly recognized as a complex neurodegenerative disease beginning decades prior to the cognitive decline. While cognitive deficits remain the cardinal manifestation of AD, metabolic and non-cognitive abnormalities, such as alterations in body weight and neuroendocrine functions, are also present, often preceding the cognitive decline. Furthermore, hypothalamic dysfunction can also be a driver of AD pathology. Here we offer a brief appraisal of hypothalamic dysfunction in AD and provide insight into an underappreciated dual role of the hypothalamus as both a culprit and target of AD pathology, as well as into new opportunities for therapeutic interventions and biomarker development.


Interprofessional collaboration in the mental health services in norway.
The aim of this study was to describe and interpret interprofessional collaboration between healthcare professionals (HCPs) working at the district psychiatric centre (DPC) and employed in community mental health care (CMHC) using a dialogue-oriented co-operative approach. Data were collected by means of multistage focus groups and qualitative content analysis was performed. The main theme "development of interprofessional collaboration by means of organisational strategies and interactional styles" encompassed the following categories: "improved communication skills," "developing structures for coordination and responsibility" and " increased professional insight into the values and conditions necessary for decision-making." In conclusion, more attention should be paid to leadership in terms of coordination and feedback. The HCPs must be acknowledged, understood and strengthened in their work to improve the quality of CMHC. Finally, we recommend that a range of organisational and administrative models of care be used in order to support improvement work.


Integrin-linked kinase (ILK) in pulmonary fibrosis.
Pulmonary fibrosis is a common feature of a large group of lung diseases. The molecular mechanisms underlying pulmonary fibrosis and the key macromolecules involved are not fully understood yet. In an effort to better understand aspects of pulmonary fibrosis, the established bleomycin injection model in mice was used and the focus of the present study was on integrin-linked kinase (ILK) expression. ILK is an intracellular protein involved in the regulation of integrin-mediated processes. In fibrosis, ILK has been examined in the kidney and in the liver where it mediates epithelial to mesenchymal transition (EMT) and hepatic stellate cell activation, respectively. However, information on ILK's involvement in lung fibrosis is missing. In order to examine ILK's role in pulmonary fibrosis, we used both an in vivo and an in vitro approach. In vivo, the bleomycin model was used in order to examine ILK's expression and localization in the fibrotic lung. In vitro, transforming growth factor-β1 was used to induce fibrotic characteristics and EMT in alveolar epithelial cells. ILK's role in alveolar EMT was studied by siRNA. Our results demonstrate that in the animal model used, ILK exhibits a decrease in expression at early stages of the fibrotic process and that a specific subset of fibroblasts is expressing ILK. The in vitro experiments suggested that ILK is not directly involved in E-cadherin downregulation and initiation of EMT (as is the case in renal fibrosis) but is involved in upregulation of vimentin. These results suggest that ILK is involved in lung fibrosis in a tissue-specific manner and raise the possibility to use it as a specific therapeutic target for lung fibrosis in the future.


Review: Structural Racism, Children's Mental Health Service Systems, and Recommendations for Policy and Practice Change.
Racism is a public health crisis that impacts on children's mental health, yet mental health service systems are insufficiently focused on addressing racism. Moreover, a focus on interpersonal racism and on individual coping with the impacts of racism has been prioritized over addressing structural racism at the level of the service system and associated institutions. In this paper, we examine strategies to address structural racism via policies affecting children's mental health services. First, we identify and analyze federal and state policies focused on racism and mental health equity. Second, we evaluate areas of focus in these policies and discuss the evidence base informing their implementation. Finally, we provide recommendations for what states, counties, cities, and mental health systems can do to promote antiracist evidence-based practices in children's mental health. Our analysis highlights gaps and opportunities in the evidence base for policy implementation strategies, including the following: mental health services for youth of color, interventions addressing interpersonal racism and bias in the mental health service system, interventions addressing structural racism, changes to provider licensure and license renewal, and development of the community health workforce. Recommendations are provided both within and across systems to catalyze broader systems transformation.


Invasive enterococcal infections in Poland: the current epidemiological situation.
The aim of this study was to investigate human invasive isolates of enterococci, obtained through prospective surveillance in Poland. The consecutive enterococcal isolates were collected in 30 hospitals between May 2010 and June 2011, and studied by species identification, antimicrobial susceptibility testing and, for Enterococcus faecium by detection of markers specific for the hospital meroclone, multilocus VNTR analysis (MLVA) and multilocus sequence typing (MLST). Additionally, the genomic difference regions (GDRs) characteristic for lineage 78 were searched by PCR. Among 259 isolates, a nearly equal number of Enterococcus faecalis (n = 140; 54.1 %) and E. faecium (n = 112; 43.2 %) was found. The observed 14-day mortality rate of infected patients reached 18.1 %. All isolates were susceptible to linezolid and daptomycin. High-level aminoglycoside resistance occurred in over 50 % of isolates. Vancomycin resistance mediated by vanA or vanB was detected in 7.1 % of E. faecium; 71.4 % of isolates were multidrug resistant. E. faecium isolates ubiquitously carried molecular markers of hospital-associated meroclone (IS16, esp(Efm), intA of ICEEfm1) and multilocus sequence typing showed the domination of representatives of lineages 78 and 17/18 (52.7 % and 46.4 %, respectively). Isolates of lineage 78 were significantly enriched in all the GDRs studied. The recent spread of E. faecium from this lineage contributed to the observed increase of E. faecium in enterococcal invasive infections in hospitals in Poland.


Tumours of the retrorectal space: management and outcome of a heterogeneous group of diseases.
Retrorectal tumours are a rare and complex entity in adults and children. They present a varied symptomatology and their treatment is very different according to their histology. We aimed to evaluate our experience of tumours of the retrorectal space. Forty patients with retrorectal tumours were divided into two groups according to age. The variables analysed were sex, signs and symptoms, complementary examinations, surgical approaches, adjuvant therapies, pathological analyses, recurrence and survival. Symptoms across the 30 adults varied--back pain (18) was the most common. Surgical intervention was performed on 20 patients; the rest were candidates for other treatments: five metastatic disease, two lymphomas and two Ewing tumour. The most common surgical approach was posterior, with 10 cases (50%). In all, 70% of adult tumours were malignant, with chordoma (30%) and metastases (20%) being the most common lesions. The most frequent benign lesion was hamartoma (10%). The 1- and 5-year mortality rates were 23.8% and 38.1%, respectively. In the paediatric group, three patients were diagnosed in utero. The symptoms among children varied and all were operated upon. The most frequent tumour was teratoma. Overall mortality was 20%. Given their complexity, these tumours should be addressed by experts and all treatment options must be contemplated. They continue to present a challenge, above all in malignant tumours where the tumour cannot be controlled at a locoregional level.


A PdMn bimetallene for low-energy electrocatalytic hydrogen generation coupled with formate oxidation.
In this communication, a PdMn bimetallene is synthesized using a template-free solvothermal method with the assistance of diamines. The PdMn bimetallene with rich defects and highly curved structures shows superior performance for the formate oxidation reaction (FOR) and the hydrogen evolution reaction (HER). For the two-electrode HER-FOR system, the PdMn bimetallene achieves a much lower voltage of 0.376 V at 10 mA cm-2, demonstrating an energy-effective path for hydrogen production.


Insomnia in the Military: Application and Effectiveness of Cognitive and Pharmacologic Therapies.
Insomnia is one of the most common complaints of US armed service members. Diagnosis and treatment of insomnia in active duty and veteran populations are often complicated by comorbid disorders experienced by military personnel, such as post-traumatic stress disorder (PTSD) and traumatic brain injury (TBI). Cognitive behavioral therapy for insomnia (CBTi), pharmacologic interventions, and alternative therapies are discussed as relevant to their applications within military populations. Future directions in research are suggested.


Structure of the pyrimidine-rich internal loop in the poliovirus 3'-UTR: the importance of maintaining pseudo-2-fold symmetry in RNA helices containing two adjacent non-canonical base-pairs.
Formation of non-canonical base-pairs in RNA often plays a very important functional role. In addition they frequently serve as factors in stabilizing the secondary structure elements that provide the frame of large compact RNA structures. Here we describe the structure of an internal loop containing a 5'CU3'/5'UU3' non-canonical tandem base-pair motif, which is conserved within the 3'-UTR of poliovirus-like enteroviruses. Structural details reveal striking regularities of the local helix geometry, resulting from alternating geometrical adjustments, which are important for understanding and predicting stabilities and configurations of tandem non-canonical base-pairs. The C-U and U-U base-pairs severely contract the minor groove of the sugar-phosphate backbone, which might be important for protein recognition or binding to other RNA elements.


Diagnosing depressive disorders in patients with alcohol and drug problems: a comparison of the SADS-L and the DIS.
The DIS and the SADS-L diagnostic procedures occupy an important position in psychiatric research. We compared these procedures for assessing depressive disorders in patients with substance abuse problems. The two instruments agreed poorly, and the SADS-L produced a considerably higher proportion of cases than the DIS. A number of factors were examined to determine their influence on the agreement obtained for Major Depression. These factors included (1) recency of the disorder, (2) the primary/secondary distinction, (3) clinical experience of the DIS interviewers, (4) numerous subject characteristics and (5) the DIS procedure for differentiating organic from non-organic affective symptomatology, which relies on subjects' attributions of the cause of symptoms. The first four factors did not influence agreement. However, removal of the influence of the fifth factor did increase agreement between the instruments appreciably. Validation evidence favored the SADS-L, although not definitively. Implications of the findings are discussed.


Calcium channel blockers in cardiac failure.
Congestive cardiac failure is an increasingly prevalent syndrome associated with a high morbidity and mortality. The role of calcium channel blockers in the treatment of heart failure is unclear. The potential benefits of these agents derive not only from their vasodilator properties, but also from anti-ischemic effects, beneficial effects on endothelial function and the development of atherosclerosis, and favorable effects on calcium cycling at a molecular level. Pitted against this array of potential benefits are direct negative inotropic effects and the potential for neuroendocrine activation. Treatment with short-acting dihydropyridine agents has not resulted in long-term clinical benefits in patients with cardiac failure. Diltiazem may be beneficial in patients with nonischemic heart failure, and verapamil has a neutral effect in cardiac failure, although it may have a role in combination with ace inhibition. To date, amlodipine has been associated with the most promising results, with evidence of a mortality benefit in nonischemic heart failure. Mibefradil is of no benefit in the management of heart failure, although the trend toward increased mortality in the treatment arm of the Mortality Assessment in Congestive Heart Failure (MACH)-1 trial may have been due to drug interactions. The potential role of calcium blockers in diastolic dysfunction and in combination with ace-inhibition requires further study.


[The influence of the chemo-mechanical removal of the smear-layer and the use of a dentin adhesive on microleakage of composite resin restorations].
We present an "in vitro" study of microfiltration in composite resin restorations with a perimetral seal placed totally in cement. We compare the sealing capability of a dentin adhesive (ScotchBond I) used in two ways: habitual, without conditioning dentin and conditioning it by means of the Caridex system. This produced no increasing of sealing capability under the study conditions.


Treatment of SARS-CoV-2 pneumonia with favipiravir: early results from the Ege University cohort, Turkey
The aim of this descriptive article is to share the experience in Ege University, Turkey with favipiravir in the treatment of severe SARS-CoV-2 pneumonia. This retrospective descriptive study included patients diagnosed with COVID-19 who presented with or developed severe pneumonia. Forty patients who completed a full course (at least 5 days) of favipiravir were included in the study. At baseline, 30 (75%) patients required treatment for respiratory distress. Thirty-three patients (82.5%) were discharged from the hospital with full recovery, 6 patients (15%) died and 1 case (2.5%) was still at the intensive care unit (ICU) when this paper was written. This study provides relevant information for the treatment of COVID-19, suggesting that favipiravir was associated with significant clinical and laboratory improvements in the majority of the patients, is a safe drug with no serious side effects and would merit further investigation.


Brazilian Maternal and Child Nutrition Consortium: establishment, data harmonization and basic characteristics.
Pooled data analysis in the field of maternal and child nutrition rarely incorporates data from low- and middle-income countries and existing studies lack a description of the methods used to harmonize the data and to assess heterogeneity. We describe the creation of the Brazilian Maternal and Child Nutrition Consortium dataset, from multiple pooled longitudinal studies, having gestational weight gain (GWG) as an example. Investigators of the eligible studies published from 1990 to 2018 were invited to participate. We conducted consistency analysis, identified outliers, and assessed heterogeneity for GWG. Outliers identification considered the longitudinal nature of the data. Heterogeneity was performed adjusting multilevel models. We identified 68 studies and invited 59 for this initiative. Data from 29 studies were received, 21 were retained for analysis, resulting in a final sample of 17,344 women with 72,616 weight measurements. Fewer than 1% of all weight measurements were flagged as outliers. Women with pre-pregnancy obesity had lower values for GWG throughout pregnancy. GWG, birth length and weight were similar across the studies and remarkably similar to a Brazilian nationwide study. Pooled data analyses can increase the potential of addressing important questions regarding maternal and child health, especially in countries where research investment is limited.


Optimizing fluorescent protein trios for 3-Way FRET imaging of protein interactions in living cells.
Powerful new methods have extended FRET microscopy to the imaging of three or more interacting proteins inside living cells. Here, we compared widely available fluorescent proteins to find the best trio for 3-Way FRET imaging. We focused on readily available cyan, yellow, and red proteins that have high quantum yields, large extinction coefficients and good photostability, which defined these candidate proteins: CyPet/mTFP1/mTurqoise2, mCitrine/YPet, and TagRFP/TagRFPt/mRuby2/mCherry. By taking advantage of the high structural similarity across the fluorescent proteins, we generated structurally similar, but photophysically distinct donor/acceptor and triple fluorophore fusion proteins and measured their FRET efficiencies inside living cells. Surprisingly, their published photophysical parameters and calculated Förster distances did not predict the best combinations of FPs. Using cycloheximide to inhibit protein synthesis, we found that the different FP maturation rates had a strong effect on the FRET efficiency. This effect was pronounced when comparing rapidly maturing yellow and slowly maturing red FPs. We found that red FPs with inferior photophysics gave superior FRET efficiencies because of faster maturation rates. Based on combined metrics for the FRET efficiency, fluorophore photophysics and fluorophore maturation we determined that Turqoise2, YPet and Cherry were the best available FPs for live cell 3-Way FRET measurements.


Computational Analysis of Hi-C Data.
The chromatin organization in the 3D nuclear space is essential for genome functionality. This spatial organization encompasses different topologies at diverse scale lengths with chromosomes occupying distinct volumes and individual chromosomes folding into compartments, inside which the chromatin fiber is packed in large domains (as the topologically associating domains, TADs) and forms short-range interactions (as enhancer-promoter loops). The widespread adoption of high-throughput techniques derived from chromosome conformation capture (3C) has been instrumental in investigating the nuclear organization of chromatin. In particular, Hi-C has the potential to achieve the most comprehensive characterization of chromatin 3D structures, as in principle it can detect any pair of restriction fragments connected as a result of ligation by proximity. However, the analysis of the enormous amount of genomic data produced by Hi-C techniques requires the application of complex, multistep computational procedures that may constitute a difficult task also for expert computational biologists. In this chapter, we describe the computational analysis of Hi-C data obtained from the lymphoblastoid cell line GM12878, detailing the processing of raw data, the generation and normalization of the Hi-C contact map, the detection of TADs and chromatin interactions, and their visualization and annotation.


Distribution of anionic sites on the basal lamina of Schwann cells.
Basal laminae (BL) were separated from Schwann cells of rat sciatic nerves by means of weak sonication, and the anionic sites of the BL were demonstrated by using cationized ferritin (CF) or ruthenium red (RR). CF particles were deposited in clusters at intervals of 100-150 nm on the interstitial side of the BL facing the connective tissue, while the cellular side facing the Schwann cell plasmalemma showed only an occasional deposition of CF particles. RR-positive sites were found only on the interstitial side with a pattern of distribution comparable to that of CF-binding sites. These results indicate that the patterns of anionic site distribution are different between the inner and outer surfaces of the Schwann cell BL.


Equine subchondral bone failure threshold under impact compression applied through articular cartilage.
Subchondral bone microdamage due to high-impact loading is a key factor leading to post-traumatic knee osteoarthritis. A quantified assessment of the mechanical characteristics of subchondral bone at the tissue-level is essential to study the mechanism of impact-induced microdamage. We combined mechanical impact testing of equine cartilage-bone with µCT image-based finite element models (μFEM) of each specimen to determine subchondral bone (including calcified cartilage: CCSB) elastic tissue modulus and local stresses and strains associated with micro-fractures within the CCSB tissue. The material properties of each specimen-specific μFEM were iteratively adjusted to match the FE-predicted stress-strain curves with experimental results. Isotropic homogeneous material properties for both uncalcified cartilage (UC) and CCSB were assumed. UC large-deformation was simulated using hyperelastic material properties. Final UC shear and CCSB tissue elastic modulus of G=38±20MPa and E(t)=3.3±0.7GPa were achieved after fit procedure. The results suggested that initial failure in CCSB occurred at local tensile and compressive stresses of 29.47±5.34 MPa and 64.3±21.3MPa, and tensile and compressive strains of 1.12±0.06% and 1.99±0.41%, respectively. Tissue-level material properties can be used in finite element modeling of diarthrodial joints under impact loading, and also in designing artificial cartilage-bone to replace the damaged tissue in the joint. Results can provide an estimate for the threshold of initial failure in subchondral bone tissue due to an impact compression transmitted through the overlying articular cartilage.


Intramuscular administration of PEGylated IGF-I improves skeletal muscle regeneration after myotoxic injury.
Musculoskeletal injuries represent a major public health problem and drugs that can improve muscle repair and restore function are needed for patients with these conditions and other related muscular pathologies. Increasing insulin-like growth factor-I (IGF-I) levels in skeletal muscle improves regeneration after myotoxic injury and while administration of IGF-I has a potential for accelerating healing after trauma, optimizing its method of delivery and obviating potential side-effects currently associated with recombinant human (rh) IGF-I, remain a hurdle. We compared the treatment efficacy of rhIGF-I with a polyethylene glycol modified IGF-I (PEG-IGF-I) analog to improve functional repair of mouse tibialis anterior muscles after myotoxic injury, testing the hypothesis that PEG-IGF-I would exert greater beneficial effects on regenerating skeletal muscles than rhIGF-I due to improved pharmacokinetic properties. We also examined the relative efficacy of systemic versus local delivery of these IGF-I variants for improving functional muscle regeneration. Local delivery of PEG-IGF-I, but not rhIGF-I, at 4 days post-injury significantly improved early functional recovery as evident by a 27% increase in normalized force compared with saline control (P<0.05), whereas systemic application of either IGF-I variant was not effective. The improved function with intramuscular PEG-IGF-I administration was attributed to a greater and prolonged residence within the regenerating muscles, resulting in increased Akt activation and a 13% larger fiber cross-sectional area compared with rhIGF-I (P<0.05). These data support the hypothesis that PEG-IGF-I is more efficacious than rhIGF-I in hastening early fiber regeneration and improving muscle function after injury, highlighting its therapeutic potential for muscular pathologies.


Extensive swelling reactions occurring after booster doses of diphtheria-tetanus-acellular pertussis vaccines.
Extensive local reactions are recognized to occur after administration of the fourth and fifth booster doses of diphtheria-tetanus-acellular pertussis (DTaP) vaccines. The incidence of these reactions is being delineated by prospective studies. Retrospective evaluations suggest that entire proximal limb swelling occurs in 2 to 6 percent of children given booster doses of DTaP vaccines. The reactions subside without sequelae, but they may be misdiagnosed as cellulitis and lead to unnecessary medical intervention. The pathogenesis of these reactions probably is multifactorial. Evidence suggests that both antigen content and prevaccination immunity have roles. Important, unanswered questions are the safety of revaccinating a child who previously has had an extensive local reaction and the safety of introducing further DTaP boosters into the adolescent and adult populations.


GLPG1205 for idiopathic pulmonary fibrosis: a phase 2 randomised placebo-controlled trial.
GLPG1205 is a selective functional antagonist of G-protein-coupled receptor 84, which plays an important role in fibrotic processes. This study assessed the efficacy, safety and tolerability of GLPG1205 for treatment of idiopathic pulmonary fibrosis (IPF). PINTA (ClinicalTrials.gov: NCT03725852) was a phase 2, randomised, double-blind, placebo-controlled, proof-of-concept trial. Patients with IPF were randomised 2:1 to once-daily oral GLPG1205 100 mg or placebo for 26 weeks and stratified to receive GLPG1205 alone or with local standard of care (nintedanib or pirfenidone). The primary end-point was change from baseline in forced vital capacity (FVC); other end-points were safety and tolerability, and lung volumes measured by imaging (high-resolution computed tomography). The study was not powered for statistical significance. In total, 68 patients received study medication. Least squares mean change from baseline in FVC at week 26 was -33.68 (95% CI -112.0-44.68) mL with GLPG1205 and -76.00 (95% CI -170.7-18.71) mL with placebo (least squares mean difference 42.33 (95% CI -81.84-166.5) mL; p=0.50). Lung volumes by imaging declined -58.30 versus -262.72 mL (whole lung) and -33.68 versus -135.48 mL (lower lobes) with GLPG1205 versus placebo, respectively. Treatment with GLPG1205 versus placebo resulted in higher proportions of serious and severe treatment-emergent adverse events and treatment-emergent discontinuations, most apparent with nintedanib. Treatment with GLPG1205 did not result in a significant difference in FVC decline versus placebo. GLPG1205 demonstrated a poorer safety and tolerability profile than placebo.


Longitudinal evaluation of the importance of homework assignment completion for the academic performance of middle school students with ADHD.
The primary goal of this study was to longitudinally evaluate the homework assignment completion patterns of middle school age adolescents with ADHD, their associations with academic performance, and malleable predictors of homework assignment completion. Analyses were conducted on a sample of 104 middle school students comprehensively diagnosed with ADHD and followed for 18 months. Multiple teachers for each student provided information about the percentage of homework assignments turned in at five separate time points and school grades were collected quarterly. Results showed that agreement between teachers with respect to students assignment completion was high, with an intraclass correlation of .879 at baseline. Students with ADHD were turning in an average of 12% fewer assignments each academic quarter in comparison to teacher-reported classroom averages. Regression analyses revealed a robust association between the percentage of assignments turned in at baseline and school grades 18 months later, even after controlling for baseline grades, achievement (reading and math), intelligence, family income, and race. Cross-lag analyses demonstrated that the association between assignment completion and grades was reciprocal, with assignment completion negatively impacting grades and low grades in turn being associated with decreased future homework completion. Parent ratings of homework materials management abilities at baseline significantly predicted the percentage of assignments turned in as reported by teachers 18 months later. These findings demonstrate that homework assignment completion problems are persistent across time and an important intervention target for adolescents with ADHD.


Profound hypothermia in golden hamsters (Mesocricetus auratus) induced by serotonergic potentiating and noradrenergic inhibiting drugs.
Profound hypothermia (6 degrees C) was induced in cold exposed golden hamsters (Mesocricetus auratus) by a combination of drugs that potentiate brain serotonergic activity (fluoxetine and pargyline) and inhibit noradrenergic activity (alpha-methyl-p-tyrosine). Individual drugs and combinations of 2 were ineffective.


Hematological and Hematopoietic Analysis in Fish Toxicology-A Review.
Hematological analysis is commonly used to assess the physiological state of fish. It includes red blood cell parameters, white blood cell parameters, and the number of thrombocytes per blood volume unit. Hematological analysis is one of the basic tools (often accompanied by biochemical and histopathological analyses) to assess the influence of organic and inorganic substances on fish. It is, therefore, applicable in both ecotoxicology and pharmacotoxicology. The advantages of this research method are the lack of need for specialized laboratory equipment and low costs, and the limitations are the need for extensive experience among the personnel performing the tests. One of the recommended methods of supplementing routinely determined hematological parameters is assessing the cellular composition and activity of hematopoietic tissue. As there is very little scientific data available on the issue of the effects of xenobiotics on the cellular structure of fish head kidney hematopoietic tissue, filling this gap should be considered an urgent need. Therefore, we recommend conducting research with the simultaneous use of hematological and hematopoietic analysis as reliable and complementary methods of assessing the impact of toxic substances on fish.


Psychological test and demographic variables associated with retention of narcotic addicts in treatment.
The relationships of psychological and demographic variables to retention in treatment of narcotic addicts were examined. Age and race were not related to retention. The IQ's of subjects retained longer seemed to be higher but the relationship did not reach statistical significance with this sample size. Legal pressure was clearly associated with longer retention as were higher scores on the Suitable for Treatment Scale. Legal pressure seemed to exert its major influence early in treatment. Treatment center variables and patient variables probably interact to determine retention.


Adeno-associated virus DNA replication complexes in herpes simplex virus or adenovirus-infected cells.
A complex which is active in in vitro synthesis of adeno-associated virus (AAV) DNA was solubilized from Vero cells that were co-infected with AAV and either adenovirus (Ad5) or a herpes simplex virus type 1 (HSV-1) as the helper virus. The complexes from the Ad5 and HSV-1-infected cells sedimented at 23 S and 28 S, respectively. The optimal conditions for in vitro DNA synthesis for the two types of complex using the endogenous AAV template and the endogenous DNA polymerase, differed with respect to the effect of KCl and K2SO4 concentration. In addition the complex from HSV-1-infected cells, but not that from Ad5-infected cells, was inhibited by phosphonoacetic acid. Thus, the two complexes appear to contain different DNA polymerase activities. This was verified by phosphocellulose chromatography of the DNA polymerases solubilized from the isolated complexes. The major activity in the complex from HSV-1 infected cells was the HSV-induced DNA polymerase with lesser amounts of cellular DNA polymerase alpha and gamma or both. The complex from the Ad5-infected cells contained mainly a cellular DNA polymerase gamma.


Discriminating drug-dependent women from alcoholic women and drug-dependent men.
The authors compared 99 drug-dependent women to 162 alcoholic women and 66 drug-dependent men entering an outpatient treatment program. They were assessed by a semistructured interview for demography, progression of dependence prior to entering treatment, prior suicidal behavior, and baseline functioning in different areas (alcohol/drug use, occupation, family relationships, and leisure activities). Discriminant analysis techniques were good at predicting group membership for all groups, with an overall correct classification of 69%; though at a lesser degree for the group of drug-dependent women (55%). Among those drug-dependent women misclassified, two-thirds were reclassified into the drug-dependent men group and the remaining third into the alcoholic women group. Taken together, these findings suggest that the drug-dependent women are a distinct group of substance users, who show more heterogeneous characteristics, as well as sharing more features with the drug-dependent men. This should be taken into account when devising treatment strategies for this specific population.


Oral health-related quality of life and related factors among residents in a disaster area of the Great East Japan Earthquake and giant tsunami.
Oral health is one of the most important issues for disaster survivors. The aim of this study was to determine post-disaster distribution of oral health-related quality of life (OHRQoL) and related factors in survivors of the Great East Japan Earthquake and Tsunami. Questionnaires to assess OHRQoL, psychological distress, disaster-related experiences, and current systemic-health and economic conditions were sent to survivors over 18 years of age living in Otsuchi, one of the most severely damaged municipalities. OHRQoL and psychological distress were assessed using the General Oral Health Assessment Index (GOHAI) and the Kessler Psychological Distress Scale (K6), Japanese version, respectively. Among 11,411 residents, 1,987 returned the questionnaire (response rate, 17.4%) and received an oral examination to determine number of present teeth, dental caries status, and tooth-mobility grade, and to assess periodontal health using the Community Periodontal Index. Relationships between GOHAI and related factors were examined by nonparametric bivariate and multinomial logistic regression analyses using GOHAI cutoff points at the 25(th) and 50(th) national standard percentiles. GOHAI scores were significantly lower in the 50-69-age group compared with other age groups in this study and compared with the national standard score. In bivariate analyses, all factors assessed in this study (i.e., sex, age, evacuation from home, interruption of dental treatment, lost or fractured dentures, self-rated systemic health, serious psychological distress (SPD), economic status, number of teeth, having decayed teeth, CPI code, and tooth mobility) were significantly associated with OHRQoL. Subsequent multinomial logistic regression analyses revealed that participants of upper-middle age, who had received dental treatment before the disaster, who had lost or fractured dentures, and who had clinical oral health problems were likely to show low levels of OHRQoL. In addition, perceived systemic health and SPD were also related with OHRQoL. OHRQoL of disaster survivors was associated with oral problems stemming from the disaster in addition to factors related to OHRQoL in ordinary times such as clinical oral status and perceived systemic health. Furthermore, SPD was also associated with OHRQoL, which suggests the disaster's great negative impact on both oral and mental health conditions.


Unusual headaches.
Headache represents one of the most common somatic complaints seen in the emergency department, accounting for 1% to 3% of all emergency department visits. Although most headaches seen in the emergency department are benign, as many as 10% of all headaches are secondary to an underlying pathologic condition. The emergency physician is well-trained to exclude stoke, subarachnoid hemorrhage, and meningitis as potential causes of headache. This article focuses on seven unusual headache syndromes, all of which are associated with significant morbidity and mortality. Particular emphasis is placed on clinical features and diagnostic modalities of choice.


Discovery of the antitumor activities of a potent DCN1 inhibitor compound 383 targeting LSD1 in gastric cancer.
Dual target compounds have become a hot spot in the treatment of cancer in recent years. Histone lysine specific demethylase 1 (LSD1) is identified as histone demethylase and acts as a key regulator involved in many other cellular activities through its demethylation function. We have reported a triazolo [1,5-α] pyrimidine-based DCN1(defective in cullin neddylation protein 1) inhibitor compound 383 (IC50 = 11 nM) which could selectively inhibit Cullin 3/1 neddylation in MGC-803 cells. In this research, we investigated that compound 383 could target LSD1 and inhibit the biological function of LSD1 in MGC-803 cells (IC50 = 0.53 μM). We found that compound 383 could induce the degradation of LSD1 and inhibit MGC-803 cell proliferation, migration and invasion in a dose-dependent manner. Compound 383 could cause cell cycle arrest at G2/M phase by down-regulating the expression of LSD1. In addition, compound 383 could significantly reverse epithelial-mesenchymal transition (EMT) through increase H3K4me methylation at E-cadherin promotor. Furthermore, the in vivo inhibitory effect of compound 383 without obvious toxicity was confirmed in nude mouse transplanted MGC-803 tumor cells model. Collectively, these results suggest that the DCN1 inhibitor compound 383 exhibits antiproliferative activity in gastric cancer cells by targeting LSD1 which promotes compound 383 as a good starting point for the development of dual-target therapeutics for gastric cancer.


Bone marrow spontaneous lesions in rodents from nonclinical 104-week carcinogenicity studies.
The authors performed a retrospective study to determine the incidences and range of spontaneous lesions in the bone marrow (sternum and femur) of control mice and rats. Data was collected from 2186 mice (Crl:CD-1(ICR)BR), and 2347 rats (Han Wistar and CD(SD) rats) from the control dose groups of 104-week carcinogenicity studies carried out between 2005 and 2014. The incidence of spontaneous lesions in the bone marrow was higher in mice than in rats, and in both species non-neoplastic lesions were more common than neoplastic lesions. In mice, the most common non-neoplastic lesions in the bone marrow were increased cellularity, pigmented macrophages, and decreased cellularity, and the most common neoplastic lesions were malignant lymphoma, granulocytic leukemia and histiocytic sarcoma. There were occasional sex and site differences (sternum marrow vs femur marrow) in the incidence of a few bone marrow lesions in mice. In rats, the most common non-neoplastic lesions were increased cellularity and stromal fibrosis, and the most common neoplastic lesion was malignant lymphoma. In rats, no sex predilection in the incidence of bone marrow lesions was apparent, and there were no significant site differences in the incidence of lesions. To the best knowledge of the authors, there are no recent reports on spontaneous pathological findings in bone marrow of rodents, and we believe that these results will facilitate the interpretation of background findings and/or their increased incidence in carcinogenicity studies.