Internet Addiction and Social Media Addiction in Medical Faculty Students: Prevalence, Related Factors, and Association with Life Satisfaction.
Internet addiction is a growing behavioral health problem in modern societies. In this study, we aimed to determine the prevalence of internet addiction (IA) and social media addiction (SMA) and their relationship with sociodemographic factors, lifestyle habits, and internet usage patterns among medical students. This cross-sectional study was conducted among 280 medical students in a medical faculty, in Istanbul. Self-report questionnaires comprised sociodemographic status, lifestyle habits, internet and social media usage behavior, the Young Internet Addiction Test-short form (s-IAT), and the Bergen Social media addiction scale. The total prevalence of IA was 16.1% (11.8-20.4%), 17.2% (12.8-21.7%) in males and 14.8% (10.7-19.0%) in females. The total prevalence of SMA was 6.1% (3.3-8.9%), 4.8% (2.3-7.3%) in males and 7.4% (4.3-10.5%) in females. No significant difference was found between the sexes in terms of IA and SMA. IA was higher in grade 3 students than in grade 6 students. Multivariate logistic regression analyses showed that reading books at least once per month, high life satisfaction, performing physical activity at least twice per week, and using the internet for communication purposes were independent preventive factors for IA. The current study shows that IA and SMA are common in medical school students. Moreover, IA is associated with socioeconomic characteristics and lifestyle habits such as reading books, life satisfaction, and physical activity. To protect medical school students from IA and develop healthy behaviors, it is necessary to develop prevention strategies and design and implement awareness and education programs.


Asymptomatic SARS-CoV-2 Infection in Nursing Homes, Barcelona, Spain, April 2020.
During the coronavirus disease pandemic in Spain, from April 10-24, 2020, a total of 5,869 persons were screened for severe acute respiratory syndrome coronavirus 2 at nursing homes. Among residents, 768 (23.9%) tested positive; among staff, 403 (15.2%). Of those testing positive, 69.7% of residents and 55.8% of staff were asymptomatic.


Determination of glucocorticoid receptors in leukemic myeloblasts by isoelectric focusing in polyacrylamide gel.
We investigated the optimal conditions for measuring glucocorticoid receptor in blast cells from patients with acute nonlymphocytic leukemia. Cytosol receptor measured with isoelectric focusing was saturated after 60 min of incubation at 0 degrees C with 100 nM of either dexamethasone or triamcinolone. Saturation was achieved when cytosol from at least 7 X 10(6) cells was used for incubation. Trypsin treatment of the cytosol resulted in a sharpened peak of receptor focusing at pH 5.6 with no loss of receptor-bound radioactivity. The two physical forms of glucocorticoid receptor were isolated with DEAE cellulose chromatography. They were both found to focus at pH 5.6 during isoelectric focusing.


Moderating Effects of Digital Citizenship on Problematic Digital Media Use and Children's Happiness: A Cross-Sectional Study.
Recently, the high prevalence of problematic digital media use among youth has become a public concern. Therefore, this study investigated digital citizenship's moderating effects on a supportive school environment, parental pressure to achieve, academic stress, problematic digital media use, and happiness in school-aged children. This cross-sectional study involved secondary data analysis of national data from the 11th Panel Study on Korean Children 2018 on 1342 families of fourth-grade students. Structural equation modeling assessed the relations among variables. A multigroup analysis verified that digital citizenship significantly moderated the paths from supportive school environment to problematic digital media use, supportive school environment to happiness, and problematic digital media use to happiness. Specifically, problematic digital media use had a significant positive effect on happiness in the low-digital citizenship group and a significant negative effect in the high-digital-citizenship group. These findings indicate that digital citizenship as a competency should be fostered to prevent problematic digital media use.


Green synthesis of copper nanoparticles using Celastrus paniculatus Willd. leaf extract and their photocatalytic and antifungal properties.
This research aimed to explore the eco-friendly green synthesis of copper nanoparticles (CuNPs) using Celastrus paniculatus leaves extract. Primarily, the biosynthesized CuNPs characterized by UV-vis spectroscopy showed an absorption peak at 269 nm. Further, The SEM and TEM studies revealed the spherical shape of particles with size ranged between 2-10 nm with an average particle diameter of 5 nm. FT-IR analysis confirmed the presence of functional groups -OH, C[bond, double bond]C and C-H triggers the synthesis of CuNPs. The negative zeta potential -22.2 mV indicated the stability of CuNPs was confirmed by DLS and the composition and purity by EDS studies. Further, the photocatalytic property of the CuNPs was divulged by their methylene blue dye degradation potential. The reaction kinetics followed pseudo-first-order with k-values (rate constant) 0.0172 min-1. In addition, this material was found to be a good antifungal agent against plant pathogenic fungi Fusarium oxysporum showed 76.29 ± 1.52 maximum mycelial inhibition.


Can Posterior Pericardial Incision Truly Improve Postoperative Complications After Cardiac Surgery? A Systematic Review and Meta-Analysis.
Postoperative atrial fibrillation (POAF) and pericardial effusion are important factors affecting prognosis after cardiac surgery. Recently, it has been reported that posterior pericardiotomy (PP) can effectively prevent the occurrence of POAF and pericardial effusion. To validate these conclusions and guide clinical practice, we conducted a systematic review with meta-analysis. We searched multiple databases for manuscripts published before July 2022 on the use of PP to prevent POAF and pericardial effusion and included only randomized controlled trials. The main outcome was atrial fibrillation after coronary artery bypass grafting, and secondary outcomes were included. This meta-analysis included 14 randomized controlled trials with a total of 2275 patients. Meta-analysis showed that the incidence of POAF after cardiac surgery in the PP group was significantly lower than that in the control group (risk ratio=0.48; 95% confidence interval=0.33~0.69; P<0.00001). PP effectively reduced postoperative pericardial effusion (risk ratio=0.34, 95% confidence interval=0.21-0.55; P<0.00001). PP has shown good results in preventing POAF, pericardial effusion, and other complications, which indicates that PP is a safe and effective surgical method, but attention still needs to be paid to the potential risk of coagulation dysfunction caused by PP.


Surgical and oncologic outcomes in surgically treated women 80 years and older with endometrioid endometrial cancer as a function of their comorbidities.
To describe the surgical and oncologic outcomes in surgically treated oldest old women (≥80 years) with endometrioid endometrial cancer as a function of their comorbidities. In this retrospective cohort study, patients aged 80-99 years who underwent surgical management of stage I endometrioid endometrial cancer between 2006 and 2018 were included. Low- and high-intermediate risk disease was defined using the Gynecologic Oncology Group-99 criteria. The validated, Combined Age-Charlson Comorbidity Index (CA-CCI) was used to quantify comorbidity burden. Logistic regression was used to identify the independent predictors of various surgical and oncologic outcomes. Kaplan-Meier survival analysis was performed to compare survival distributions based on mortality cause and comorbidity status. We identified 64 women who met the eligibility criteria. Median age was 84 years (IQR 80, 94 years). Among oldest old women undergoing a hysterectomy with or without lymph node dissection, women with a CA-CCI score of ≥7 had an 8 times higher risk of postoperative infections compared with oldest old women with a <7 score (95% CI 1.53-48.91, P = 0.015). Women with a CA-CCI score of ≥8 were 45% less likely to survive at 3 years (aRR 0.55, 95% CI 0.004-0.87; P = 0.039) than those with a lower CA-CCI score (three-year overall survival 73% vs 96%). Surgical and oncologic outcomes in oldest old women with early stage endometrioid endometrial cancer are largely determined by comorbidity status. Less comorbid women (CA-CCI score < 8) had a significantly higher five-year survival at 87% than their more comorbid counterparts. Use of age-comorbidity risk scoring such as CA-CCI, preoperative optimization, and careful selection for and counseling of patients about surgical treatment are paramount in providing optimal recovery and survival advantages in the oldest old.


Current status and potential application of navigated transcranial magnetic stimulation in neurosurgery: a literature review.
Transcranial magnetic stimulation (TMS) is a noninvasive neurophysiologic technique that can stimulate the human brain. Positioning of the coil was often performed based merely on external landmarks on the head, meaning that the anatomical target in the cortex remains inaccurate. Navigated transcranial magnetic stimulation (nTMS) combines a frameless stereotactic navigational system and TMS coil and can provide a highly accurate delivery of TMS pulses with the guidance of imaging. Therefore, many novel utilities for TMS could be explored due to the ability of precise localization. Many studies have been published, which indicate nTMS enables presurgical functional mapping. This review aimed to provide a comprehensive literature review on nTMS, especially the principles and clinical applications of nTMS. All articles in PubMed with keywords of "motor mapping," "presurgical mapping," "navigated transcranial magnetic stimulation," and "language mapping" published from 2000 to 2018 were included in the study. Frequently cited publications before 2000 were also included. The most valuable published original and review articles related to our objective were selected. Motor mapping of nTMS is validated to be a trustful tool to recognize functional areas belonging to both normal and lesioned primary motor cortex. It can offer reliable mapping of speech and motor regions at cortex prior to operation and has comparable accuracy as direct electrical cortical stimulation. nTMS is a powerful tool for mapping of motor and linguistic function prior to operation, has high application value in neurosurgery and the treatment of neurological and psychiatric diseases, and has gained increasing acceptance in neurosurgical centers across the world.


Insight into the early evolution of the avian sternum from juvenile enantiornithines.
The sternum is one of the most important and characteristic skeletal elements in living birds, highly adapted for flight and showing a diverse range of morphologies. New exceptional material of young juvenile specimens from the Early Cretaceous Jehol Group in northeastern China reveals the unique sequence of development in the sternum of Enantiornithes, the dominant clade of Cretaceous birds. We recognize six ossifications that together form the sternum, three of which were previously unknown. Here we show that although basal living birds apparently have retained the dinosaurian condition in which the sternum develops from a bilateral pair of ossifications (present in paravian dinosaurs and basal birds), the enantiornithine sternal body primarily develops from two unilateral proximo-distally arranged ossifications. This indicates that although superficially similar, the sternum formed very differently in enantiornithines and ornithuromorphs, suggesting that several ornithothoracine sternal features may represent parallelism. This highlights the importance of ontogenetic studies for understanding homology and the evolution of skeletal features in palaeontology.


Tetra-kis(di-cyclo-hexyl-amido)-zirconium(IV).
The reaction of ZrCl4 with three equivalents of LiNCy2 (Cy is cyclo-hex-yl) resulted in the formation of tris-(di-cyclo-hexyl-amido)-zirconium chloride and the title compound, [Zr(C12H22N)4]. The latter is isotypic with its cerium(IV) analogue and crystallizes with three independent mol-ecules in the asymmetric unit. One mol-ecule is located about a twofold rotation axis, and the other two on fourfold inversion axes. In each mol-ecule, the ZrIV atom has a distorted tetra-hedral coordination environment. The crystal under investigation was twinned by inversion in a 1:1 ratio.


Changes of drinking goals in a two-year out-patient alcoholic treatment program.
Choice of drinking goals were studied in a two-year out-patient alcoholic treatment program with a low attrition rate. Eighty-four percent of the alcoholics (N = 50) preferred abstinence during the first 3-month period and 64% during the last 3-month period. Forty-four percent changed drinking goals (abstinence or controlled drinking) during the 2-year period. Women had a more stable choice than men (p less than .1). Patients with an abstinence drinking goal during the total 2-year period were more often physically dependent on alcohol and had more drinks during abuse days than the other patients. Patients did not differ in number of abuse days during the 2-year program as a function of goal choice.


Design, Synthesis, Biological Evaluation and Molecular Docking Studies of Quercetin-Linker-H2 S Donor Conjugates for the Treatment of Diabetes and Wound Healing.
Based on the use of quercetin for treating diabetes and H2 S for promoting wound healing, a series of three quercetin-linker-H2 S donor conjugates was designed, synthesized and characterized by 1 H-NMR, 13 C-NMR and MS. Meanwhile, in vitro evaluation of these compounds was also researched by IR-HepG2 treatment experiment, MTT assay, scratch test and tubule formation experiment. The three compounds could be used to treat insulin resistance induced by high glucose and promote the proliferation of human umbilical vein endothelial cells, wound healing, and the formation of tubules in vitro under a high-glucose environment. Our results illustrate that these compounds could be used to treat diabetes and promote wound healing at the same time. Furthermore, molecular docking study results of the compounds were consistent with the evaluated biological activity. In vivo research of compounds is underway.


Treatment of aphasic perseveration (TAP) program. A new approach to aphasia therapy.
We have devised a new approach to the therapy of aphasia. Rather than focus on rehabilitation of linguistic errors, we treat perseveration, which may be an integral component of the aphasic symptoms. In this report we provide key elements of our Treatment of Aphasic Perseveration (TAP) technique, and the successful use of this method with three aphasic patients.


Two dimensional gel human protein databases offer a systematic approach to the study of cell proliferation and differentiation.
Human cellular protein databases have been established using computer-analyzed 2D gel electrophoresis. These databases, which include information on various properties of proteins, offer a global approach to the study of regulation of cell proliferation and differentiation. Furthermore, thanks to the advent of microsequencing the databases make it possible to directly link protein and DNA information.


Microbeam radiosurgery: An industrial perspective.
In spite of its long demonstrated potential, microbeam radiosurgery (MBRS) has yet to be developed into a clinical tool. This article examines the problems associated with MBRS, and potential solutions. It is shown that a path to a clinically useful device is emerging.


MR Imaging Biomarkers in Oncology Clinical Trials.
The authors discuss eight areas of quantitative MR imaging that are currently used (RECIST, DCE-MR imaging, DSC-MR imaging, diffusion MR imaging) in clinical trials or emerging (CEST, elastography, hyperpolarized MR imaging, multiparameter MR imaging) as promising techniques in diagnosing cancer and assessing or predicting response of cancer to therapy. Illustrative applications of the techniques in the clinical setting are summarized before describing the current limitations of the methods.


Molecular chaperones of the Hsp70 family assist in the assembly of 20S proteasomes.
The eukaryotic 26S proteasome is a large protease comprised of two major sub assemblies, the 20S proteasome, or core particle (CP), and the 19S regulatory particle (RP). Assembly of the CP and RP is assisted by an expanding list of dedicated assembly factors. For the CP, this includes Ump1 and the heterodimeric Pba1-Pba2 and Pba3-Pba4 proteins. It is not known how many additional proteins that assist in proteasome biogenesis remain to be discovered. Here, we demonstrate that two members of the Hsp70 family in yeast, Ssa1 and Ssa2, play a direct role in CP assembly. Ssa1 and Ssa2 interact genetically and physically with proteasomal components. Specifically, they associate tightly with known CP assembly intermediates, but not with fully assembled CP, through an extensive purification protocol. And, in yeast lacking both Ssa1 and Ssa2, specific defects in CP assembly are observed.


Staff in services for people with intellectual disabilities: the impact of stress on attributions of challenging behaviour.
There is a lack of a conceptual framework as to how stress and attribution variables interact and influence staff behaviour in response to challenging behaviour. To address this, a model is tested examining the impact of stress on attributions of challenging behaviour within Weiner's model of helping. A total of 107 staff working in community homes for people with intellectual disabilities completed a self-report questionnaire that measured stress, burnout, attributions, emotions, optimism and helping behaviour in response to challenging behaviour. Partial support was found for the role of attributions and emotions. However, although staff reported high stress levels and moderate burnout, this did not appear to relate to their reporting of thoughts and feelings regarding challenging behaviour predicted by Weiner's helping model. It was not possible to fully test the helping model, as the 'help' variable was not normally distributed. There was little evidence to suggest that stress has a primary role in determining staff responses when examined within Weiner's model of helping. Limited support in general was offered for Weiner's helping model. Potential conceptual difficulties and clinical implications are explored and alternative models for future research are discussed.


Molecular mechanics and dynamics of DNA-furocoumarin complexes: effect of the aromatization of the pyrone ring on the intercalation geometry.
Results of molecular mechanics and dynamics calculations on intercalation complexes of DNA with various furocoumarins (psoralen, angelicin, 7-methylpyrido[3,4-c]psoralen and 7-methylpyrido[4,3-c]psoralen) and their corresponding aromatized derivatives are presented. These calculations were undertaken with the aim to elucidate the roles of the pyrone and pyridine moieties in the interactions which tend to orient the furocoumarins and pyridopsoralens between DNA base pairs. It appears that the intercalation geometries are very similar for the furocoumarins and related aromatized compounds. Therefore the oxygen and nitrogen atoms of the pyrone and pyridine moieties are not important in the orientation of the drug within the oligonucleotide.


Clinical efficacy and safety of sunitinib after imatinib failure in Japanese patients with gastrointestinal stromal tumor.
Imatinib used to be the only effective treatment for advanced gastrointestinal stromal tumor. However, early clinical reports have shown that sunitinib has substantial anticancer activity in patients with advanced gastrointestinal stromal tumor after failure of imatinib. Eighteen Japanese patients with advanced gastrointestinal stromal tumor who were resistant or intolerant to previous treatment with imatinib were entered into this study. These patients were given sunitinib orally, once daily at a 50-mg starting dose, in 6-week cycles with 4 weeks on and 2 weeks off treatment. Tumor response and drug safety were then evaluated. Median time-to-treatment failure was 207 days. Overall, 5.6% (1/18) of patients achieved partial response, 38.9% (7/18) had stable disease and 44.4% (8/18) had progressive disease. The common adverse events were hand-foot syndrome, liver dysfunction, fatigue, anorexia and hypertension. Mild anemia, leukocytopenia and neutropenia were also noted. Nine patients required dose reduction or cessation because of adverse events. This study demonstrates that sunitinib may be an effective agent for advanced gastrointestinal stromal tumor after failure of imatinib in clinical practice.


ECG-based pulse detection during cardiac arrest using random forest classifier.
Sudden cardiac arrest is one of the leading causes of death in the industrialized world. Pulse detection is essential for the recognition of the arrest and the recognition of return of spontaneous circulation during therapy, and it is therefore crucial for the survival of the patient. This paper introduces the first method based exclusively on the ECG for the automatic detection of pulse during cardiopulmonary resuscitation. Random forest classifier is used to efficiently combine up to nine features from the time, frequency, slope, and regularity analysis of the ECG. Data from 191 cardiac arrest patients was used, and 1177 ECG segments were processed, 796 with pulse and 381 without pulse. A leave-one-patient out cross validation approach was used to train and test the algorithm. The statistical distributions of sensitivity (SE) and specificity (SP) for pulse detection were estimated using 500 patient-wise bootstrap partitions. The mean (std) SE/SP for nine-feature classifier was 88.4 (1.8) %/89.7 (1.4) %, respectively. The designed algorithm only requires 4-s-long ECG segments and could be integrated in any commercial automated external defibrillator. The method permits to detect the presence of pulse accurately, minimizing interruptions in cardiopulmonary resuscitation therapy, and could contribute to improve survival from cardiac arrest.


Erythropoietin (rhEPOa) promotes endothelial transdifferentiation of stem cells of the apical papilla (SCAP).
Mesenchymal stem cells (MSCs) have attracted worldwide attention for their capacity to repair damaged tissue, immunosuppression, ability to differentiate into several cell types and their secretome. Earlier studies have demonstrated their angiogenic potential in vitro and in vivo. However, little is known regarding pro-angiogenic inducers of stable endothelial transdifferentiation of MSCs. Here, we employed human MSCs from the Apical Papilla (SCAP) and investigated whether recombinant human erythropoietin-alpha (rhEPOa) could act as such inducer. Cultured SCAP cells were exposed to rhEPOa and assessed for cell growth kinetics, viability and morphology, as well as their capacity to form capillary tubule structures in selected microenvironments. RT-PCR was used to monitor endothelial markers and activation of EPO/EPOR pathway signaling components; while gelatin zymographies to assess activation of MMP-2. rhEPOa treatment initially (48 h) accelerated cell proliferation and allowed SCAP to sprout micro-tubular structures. Morphological and biochemical differentiation was accompanied by activation of MMP-2 and upregulation of PECAM-1, VEGFR2, vWF and VE-cadherin/CDH5. SCAP expressed the cognate EPO-R, while rhEPOa-treated SCAP exhibited higher expression of molecules involved in EPO/EPOR pathway (EPOR and JAK2). rhEPOa is capable of promoting endothelial transdifferentiation of SCAP which may be of clinical value in treating of ischemic disorders.


The reliability of video fluoroscopy, ultrasound imaging, magnetic resonance imaging and radiography for measurements of lumbar spine segmental range of motion in-vivo: A review.
Lower back pain (LBP) is a principal cause of disability worldwide and is associated with a variety of spinal conditions. Individuals presenting with LBP may display changes in spinal motion. Despite this, the ability to measure lumbar segmental range of motion (ROM) non-invasively remains a challenge. To review the reliability of four non-invasive modalities: Video Fluoroscopy (VF), Ultrasound imaging (US), Magnetic Resonance Imaging (MRI) and Radiography used for measuring segmental ROM in the lumbar spine in-vivo. The methodological quality of seventeen eligible studies, identified through a systematic literature search, were appraised. The intra-rater reliability for VF is excellent in recumbent and upright positions but errors are larger for intra-rater repeated movements and inter-rater reliability shows larger variation. Excellent results for intra- and inter-rater reliability are seen in US studies and there is good reliability within- and between-day. There is a large degree of heterogeneity in MRI and radiography methodologies but reliable results are seen. Excellent reliability is seen across all modalities. However, VF and radiography are limited by radiation exposure and MRI is expensive. US offers a non-invasive, risk free method but further research must determine whether it yields truly consistent measurements.


A strangulated umbilical hernia with perforated Meckel diverticulum: Case report.
Meckel's diverticulum (MD) is one of the most common gastrointestinal anomalies and affects 2-3 % of the population. Strangulated umbilical hernia with a perforated Meckel diverticulum is an extremely rare event. We reported here a case of one year old boy of a strangulated umbilical hernia with perforated MD that operated at the Mogadishu hospital. A wedge resection of the MD and anastomosis was performed. MD is one of the most common gastrointestinal anomalies and affects 2-3 % of the population. About 60 % of cases come to medical attention before the age of ten, with the remainder of patients presenting in adolescence and adulthood. It is more difficult to diagnose in males, especially in adulthood. Being aware of the likelihood that there could be a perforated Meckel's diverticulum in a sac of strangulated umbilical hernia has notable importance and may lead to innovative treatment and postoperative rehabilitation modalities.


Dihydrostreptomycin or streptomycin in combination with penicillin G in dairy cattle therapeutics: a review and re-analysis of published data. Part 1: clinical pharmacology.
Combination formulations of penicillin G salts and dihydrostreptomycin were developed during the 1960s and are currently marketed in New Zealand for parenteral and intramammary use in dairy cattle. In this paper, the clinical indications and efficacy, pharmacokinetics and potential for antimicrobial synergy of penicillin and dihydrostreptomycin or streptomycin, when combined, are discussed.


Transient appendiceal enlargement in a patient with colonic amebiasis: sonographic detection and follow-up.
A case of colonic amebiasis with no clinical signs of acute appendicitis but with sonographic visualization of an enlarged appendix is reported. As antiamebic therapy resolved the clinical signs and symptoms of the amebiasis, the sonographic appearance of the appendix returned to normal. Thus, an enlarged appendix does not necessarily indicate clinical appendicitis in patients with colonic amebiasis.


The pathogenetic significance of congophilic angiopathy.
Congophilic angiopathy has been separated into two forms. A primary vasculopathy is described in which amyloid deposition is the initial morphological brain change and is of pathogenetic importance in the development of dementia or brain hemorrhage. Another form occurs in Alzheimer's disease and is incidental to the brain damage resulting from senile plaques.


Differential sulfations and epimerization define heparan sulfate specificity in nervous system development.
Heparan sulfate proteoglycans (HSPG) are components of the extracellular matrix through which axons navigate to reach their targets. The heparan sulfate (HS) side chains of HSPGs show complex and differentially regulated patterns of secondary modifications, including sulfations of distinct hydroxyl groups and epimerization of an asymmetric carbon atom. These modifications endow the HSPG-containing extracellular matrix with the potential to code for an enormous molecular diversity. Attempting to decode this diversity, we analyzed C. elegans animals lacking three HS-modifying enzymes, glucuronyl C5-epimerase, heparan 6O-sulfotransferase, and 2O-sulfotransferase. Each of the mutant animals exhibit distinct as well as overlapping axonal and cellular guidance defects in specific neuron classes. We have linked individual HS modifications to two specific guidance systems, the sax-3/Robo and kal-1/Anosmin-1 systems, whose activity is dependent on different HS modifications in different cellular contexts. Our results demonstrate that the molecular diversity in HS encodes information that is crucial for different aspects of neuronal development.


[Lidoflazine derivatives with cycloaliphatic residues of coronary dilator activity].
The preparation of some derivatives of lidoflazine bearing a phenylcyclohexane residue in place of the m.xylene is described. Study of the coronary dilating activity on the isolated heart showed that this activity is markedly increased by the modification. Acute toxicity in rats is also strongly increased.


Providers' Behaviors and Beliefs on Prescribing Antipsychotic Medication to Children: A Qualitative Study.
Fragmentation in behavioral and mental health care to children has resulted in suboptimal care and high rates of psychotropic medication use, especially antipsychotic medications (APM). A qualitative study, based on the Theory of Planned Behavior (TPB), aimed to better understand prescribing practices, barriers to optimal treatment, and potential interventions to safeguard the use of APM for children in Kentucky. The most common barrier to optimal care was access to mental health specialists. Social norms and pressure from families contribute to increased medication use. We identify promising interventions to safeguard the use of APM through the lens of the TPB.


An en bloc technique for the resection of anterior uveal tumors.
We modified trabeculo-iridocyclosclerectomy in a technique for en bloc excision of anterior uveal tumor. A trabeculectomy-type of approach was used, which allowed excision of a rectangular block of sclera, cornea, and trabeculum with attached uveal tissue containing the tumor.


Experimental design of non-ionic hydrophobic DES-DLLME coupled with injector port silylation-GC-MS/MS for the quantitative determination of 13 bisphenols in food samples.
Non-ionic hydrophobic deep eutectic solvent based DLLME method with thymol and camphor (1:1 mole ratio) as extraction solvent and acetonitrile as disperser solvent was developed for the determination of 13 bisphenols (BPs) in food commodities by auto IPS-GC-MS/MS. Further, the influential parameters pH, vortex time, and volume of NIHDES for extraction of 13 BPs were optimized by employing the design of experiment. The LOQ and recoveries were observed to be 0.1 ng mL-1, and 77.8-109.2%, respectively. The expanded uncertainty was found to be 4.8-18.0% for the developed and validated method, which was applied to food commodities to determine 13 BPs and their levels were in the range of 0.01-1.24 ng mL-1 in liquid foods (milk, water, and beverages) and 0.29-3.25 ng g-1 in meat samples (goat, chicken, and fish). The present green analytical method is highly suitable for the rapid determination of 13 BPs in food commodities for routine analysis.


Theobroma cacao increases cells viability and reduces IL-6 and sVCAM-1 level in endothelial cells induced by plasma from preeclamptic patients.
This study aims to investigate whether an ethanolic extract of Theobroma cacao bean is able to increase cell viability and decrease IL-6 and sVCAM-1 in endothelial cells induced by plasma from preeclamptic patients. Endothelial cells were obtained from human umbilical vascular endothelial cells. At confluency, endothelial cells were divided into six groups, which included control (untreated), endothelial cells exposed to plasma from normal pregnancy, endothelial cells exposed to 2% plasma from preeclamptic patients (PP), endothelial cells exposed to PP in the presence of ethanolic extract of T. cacao (PP+TC) at the following three doses: 25, 50, and 100 ppm. The analysis was performed in silico using the Hex 8.0, LigPlus and LigandScout 3.1 software. Analysis on IL-6 and sVCAM-1 levels were done by enzyme linked immunosorbent assay (ELISA). We found that seven of them could bind to the protein NFκB (catechin, leucoanthocyanidin, niacin, phenylethylamine, theobromine, theophylline, and thiamin). This increase in IL-6 was significantly (P<0.05) attenuated by both the 50 and 100 ppm treatments of T. cacao extract. Plasma from PP significantly increased sVCAM-1 levels compared to untreated cells. This increase in sVCAM-1 was significantly attenuated by all doses of the extract. In conclusion, T. cacao extract prohibits the increase in IL-6 and sVCAM-1 in endothelial cells induced by plasma from preeclamptic patients. Therefore this may provide a herbal therapy for attenuating the endothelial dysfunction found in preeclampsia.


Effect of standardized post-coercion review session on symptoms of PTSD: results from a randomized controlled trial.
Post-coercion review is increasingly regarded as a mean to reduce the negative consequences of coercive interventions, including the development of posttraumatic symptoms. However, the efficacy of this intervention in preventing posttraumatic symptoms or PTSD has not been sufficiently studied. The objective of this study is to examine the influence of a single, standardized post-coercion review session on the development or exacerbation of PTSD symptoms in patients with psychotic disorders. In a multi-center, two-armed, randomized controlled trial, patients who experienced coercive interventions during current hospitalization were either randomized to standard treatment or an intervention group receiving a guideline-based, standardized reflecting review session. Factorial MANCOVA and subsequent ANCOVAs investigated the effects of the post-coercion reflecting review session on post-traumatic symptoms as measured by the subscales of the Impact of Events Scale-Revised (IES-R). Similarly, the effect of the intervention on the intensity of the peritraumatic reactions measured by the Peritraumatic Distress Inventory (PDI) was analyzed by conducting a factorial ANCOVA. N = 82 patients were included in an intention-to-treat analysis. MANCOVA and post hoc ANCOVAs revealed a significant main effect of the intervention for the IES-R subscales intrusion and hyperarousal, when controlling for levels of peritraumatic distress, whereby intervention group participants presented lower respective mean scores. There was no significant difference regarding the intensity of the peritraumatic reaction. Standardized post-coercion review contributes to a reduction of the burden of PTSD symptoms in patients with psychotic disorders experiencing coercive interventions in acute settings and shall be recommended as a measure of trauma-informed care. The trial was registered at ClinicalTrials.gov (ID NCT03512925) on 01/30/2018 (retrospectively registered).


Adaptive inflammatory microenvironment for cell-based regeneration in ischemic cardiovascular disease.
Cell-based therapy has emerged to be a promising strategy for alleviating the heavy burden of ischemic cardiovascular disease for nearly two decades, despite a variety of pending questions about its availability and efficacy. One question is whether and how the cells behave for regeneration in vivo, which could be limited or potentiated by the inflammatory microenvironment following myocardial infarction or critical limb ischemia. To this end, we hypothesize that the "adaptive inflammatory microenvironment" is pertinent to the cell-based regeneration, and make a brief comment on it based upon recent evidence.


Long-term clinical results of AMO PhacoFlex model SI-18 intraocular lens implantation.
The AMO PhacoFlex Model SI-18 was the first commercially available three-piece silicone intraocular lens (IOL) for use in small incision cataract surgery. Allergan Medical Optics' silicone IOLs have been implanted in more than 750,000 patients worldwide over the past eight years. This report of the FDA clinical investigation of the AMO PhacoFlex model SI-18 IOL summarizes one year follow-up data from the initial premarket approval clinical trial on 500 core patients implanted with the SI-18 lens. One-year follow-up data from 5,860 patients in the modified core group and three-year follow-up data on the 500 patient core/modified core group are also presented. At three years postoperatively, 91.3% of best case core/modified core patients achieved 20/40 or better corrected visual acuity. Overall incidence of persistent complications at three years was 3.2%.


Age-related alterations in duodenal calcium transport rate in rats.
To determine the age-related alterations in intestinal calcium transport under in vitro controlled conditions, we studied the calcium transport across duodenal segments of prepubertal (2 months), young adult (6 months) and aged (26 months) Fisher 344 male rats using the Ussing chamber technique. We also evaluated the effect of 10(-11) M 1,25-dihydroxycholecalciferol [1,25-(OH)2D3] in tissue bathing media. The calcium transport rate from mucosa-to-serosa (Jms) and from serosa-to-mucosa (Jsm) in 26-month-old rats (33.5 +/- 6.6 nmol/h per cm2 and 25.4 +/- 3.1 nmol/h per cm2, respectively) were significantly larger than that in 6-month-old animals (18.1 +/- 2.6 nmol/h per cm2 and 17.7 +/- 1.7 nmol/h per cm2 respectively). The Jms (46.1 +/- 12.0 nmol/h per cm2) and Jsm (50.8 +/- 7.2 nmol/h per cm2) in 2-month-old rats were significantly larger than the respective rates measured in 6-month-old animals. The addition of 1,25-(OH)2D3 minimized the age-related differences in mucosal calcium transport but did not significantly stimulate Jms. The magnitude of change in 1,25-(OH)2D3-stimulated Jsm in 6-month-old rats (17.7 +/- 1.7 vs. 29.4 +/- 2.2 nmol/h per cm2) was similar to that seen in 26-month-old rats (25.4 +/- 3.1 vs. 47.5 +/- 4.5 nmol/h per cm2). The results indicate that the maturational reduction in intestinal calcium transport capacity is followed by increased calcium fluxes in senescence.


Remodeled tumor immune microenvironment (TIME) parade via natural killer cells reprogramming in breast cancer.
Breast cancer (BC) is the main cause of cancer-related mortality among women globally. Despite substantial advances in the identification and management of primary tumors, traditional therapies including surgery, chemotherapy, and radiation cannot completely eliminate the danger of relapse and metastatic illness. Metastasis is controlled by microenvironmental and systemic mechanisms, including immunosurveillance. This led to the evolvement of immunotherapies that has gained much attention in the recent years for cancer treatment directed to the innate immune system. The long forgotten innate immune cells known as natural killer (NK) cells have emerged as novel targets for more effective therapeutics for BC. Normally, NK cells has the capacity to identify and eradicate tumor cells either directly or by releasing cytotoxic granules, chemokines and proinflammatory cytokines. Yet, NK cells are exposed to inhibitory signals by cancer cells, which causes them to become dysfunctional in the immunosuppressive tumor microenvironment (TME) in BC, supporting tumor escape and spread. Potential mechanisms of NK cell dysfunction in BC metastasis have been recently identified. Understanding these immunologic pathways driving BC metastasis will lead to improvements in the current immunotherapeutic strategies. In the current review, we highlight how BC evades immunosurveillance by rendering NK cells dysfunctional and we shed the light on novel NK cell- directed therapies.


Inflammatory bowel disease in patients with Hirschsprung's disease: a systematic review and meta-analysis.
Hirschsprung-associated enterocolitis (HAEC) continues to be an important cause of morbidity in patients with Hirschsprung's disease (HSCR). HAEC can occur at any time during the course of the disease. The reported incidence of HAEC before surgery ranges from 6 to 50%, and after surgery, it ranges from 2 to 35%. HAEC and inflammatory bowel disease (IBD) have similar clinical presentation including diarrhea, hematochezia, and abdominal pain. In recent years, isolated cases of IBD have been reported in patients who had surgical treatment for HSCR. The exact pathogenesis of HAEC or IBD is not known. However, both conditions are characterized by an abnormal intestinal mucosal barrier function, which may be a common pathway. The purpose of this meta-analysis was to determine the clinical presentation and outcome in patients with HSCR who developed IBD after pull-through operation. A systematic literature search for relevant articles was performed in four databases using the combinations of the following terms "inflammatory bowel disease", "Crohn/Crohn's disease", "ulcerative colitis", and "Hirschsprung disease/Hirschsprung's disease" for studies published between 1990 and 2017. The relevant cohorts of HSCR associated with IBD were systematically searched for clinical presentation and outcomes. 14 studies met defined inclusion criteria, reporting a total of 66 patients who had HSCR associated with IBD. Mean age at first operation for HSCR was 5.8 months, mean age at diagnosis of IBD was 7.7 years, and the majority of patients were male (73%). The extent of aganglionosis was total colonic aganglionosis in 41% of patients, long segment in 45%, and rectosigmoid in 14%. The majority of patients underwent a Duhamel procedure (84%) for HSCR. The distribution of IBD was Crohn's disease in 72.3% of patients, ulcerative colitis in 16.9%, and others in 10.8%. Eight articles (47 patients) reported about HAEC, and 22 patients (47%) had experienced HAEC after surgery for HSCR. Male patients with extensive colonic aganglionosis who continue to suffer from postoperative HAEC after a Duhamel procedure are more susceptible to develop IBD. Recognition of IBD may be important in the long-term follow-up of HSCR patients who have had postoperative HAEC.


Novel surgical technique to manage iStent inject over-implantation.
To describe a novel surgical technique to manage over-implantation of the iStent inject intra-operatively, utilizing only the iStent inject delivery system itself to perform both device extraction and reimplantation, without the need for additional instrumentation. A demonstration of managing over-implantation of the iStent inject, with two case examples. Over-implantation of the iStent inject can be successfully managed intra-operatively to ensure ideal positioning to optimise post-operative outcomes, with the use of only the iStent inject delivery system itself for both device extraction and reimplantation. This novel technique provides a cost-effective and feasible means to intra-operatively manage over-implantation of the iStent inject.


Regulatory control of the resolution of DNA recombination intermediates during meiosis and mitosis.
The efficient and timely resolution of DNA recombination intermediates is essential for bipolar chromosome segregation. Here, we show that the specialized chromosome segregation patterns of meiosis and mitosis, which require the coordination of recombination with cell-cycle progression, are achieved by regulating the timing of activation of two crossover-promoting endonucleases. In yeast meiosis, Mus81-Mms4 and Yen1 are controlled by phosphorylation events that lead to their sequential activation. Mus81-Mms4 is hyperactivated by Cdc5-mediated phosphorylation in meiosis I, generating the crossovers necessary for chromosome segregation. Yen1 is also tightly regulated and is activated in meiosis II to resolve persistent Holliday junctions. In yeast and human mitotic cells, a similar regulatory network restrains these nuclease activities until mitosis, biasing the outcome of recombination toward noncrossover products while also ensuring the elimination of any persistent joint molecules. Mitotic regulation thereby facilitates chromosome segregation while limiting the potential for loss of heterozygosity and sister-chromatid exchanges.


Tendon xanthoma: a physical manifestation of hyperlipidemia.
Tendon xanthoma, a nonneoplastic tumor of tendon is a significant physical manifestation of hyperlipidemia. These lesions may accompany rapidly progressive atherosclerosis and may signal the presence of life threatening hyperlipidemia. We have seen three patients with tendon xanthoma, and one patient was treated by surgical excision of large xanthomas arising from the substance of the extensor tendons over the metacarpophalangeal (MP) joints of the hand. Because these lesions arise from the substance of the extensor tendons complete removal may result in loss of tendon continuity and function. Surgery in the form of subtotal excision is advised for functional or cosmetic reasons. Although incomplete removal may be associated with recurrence, appropriate medical management may prevent or delay this recurrence.


Human herpesvirus 6.
HHV-6, the first T-lymphotropic human herpesvirus, is an important novel human pathogen. It is the cause of exanthem subitum in infants and may act as an opportunistic agent in immunocompromised patients. Moreover, several lines of clinical and experimental evidence suggest that HHV-6 may accelerate the progression of HIV infection. Progress in the study of HHV-6 has been rapid, in part as a consequence of the strong current interest in human lymphotropic viruses and their relationship with the immune system. Nonetheless, the full spectrum of diseases linked to this agent is still unknown (Table 2) and animal models of infection have not yet been exploited. The next few years will be crucial for a complete understanding of the potential role of HHV-6 in human disease.


The role of PDGF-dependent suppression of apoptosis in differentiating 3T3-L1 preadipocytes.
In a chemically defined serum-free culture system, platelet-derived growth factor (PDGF) as the only externally applied growth factor, in concert with corticosterone, 3-isobutyl-1-methylxanthine (IBMX) and low insulin (1nM), stimulates adipose conversion of 3T3-L1 preadipocytes. Omission of PDGF during the induction period results in loss of differentiation competence and apoptotic cell death. Induction of apoptosis is shown to be clearly mediated by PDGF withdrawal, since neither corticosterone nor IBMX affect the apoptotic behaviour of 3T3-L1 cells. Cell viability in the absence of the survival factor PDGF could be achieved by application of high insulin (1 microM) or ectopical expression of the anti-apoptotic proto-oncogene Bcl-2. However, PDGF-independent suppression of cell death does not trigger adipose conversion in the presence of corticosterone and IBMX. Therefore, we conclude that suppression of apoptosis per se is not permissive for differentiation of 3T3-L1 preadipocytes and PDGF might exert some additional differentiation-promoting effect(s).


N-Acylhomoserine lactone-mediated quorum sensing regulates biofilm structure in Methylobacterium populi P-1M, an isolate from a pink-pigmented household biofilm.
Numerous gram-negative bacteria have quorum-sensing systems and produce AHL as a quorum-sensing signal molecule. In this study, we demonstrated that Methylobacterium populi P-1M, an isolate from a pink-pigmented household biofilm, produced two AHLs, C14:1-HSL as a predominant product and 3OHC14-HSL as a minor product. The complete genome sequence of M. populi P-1M revealed the presence of genes that are predicted to encode an AHL synthase (mpoI) and AHL receptor (mpoR). M. populi P-1M formed a pellicle-like biofilm, which had a flat surface and was easily removable. In contrast, biofilms formed by mpoI and/or mpoR deletion mutants had a wavy surface structure and strongly adhered to the glass tube. When C14:1-HSL was added to the mpoI mutant culture, the biofilm structure resembled that of the wild-type strain. These results demonstrated that the structure and adhesion strength of M. populi P-1M biofilms are determined in part by AHL-mediated quorum sensing.Abbreviations: AHL: N-acyl-l-homoserine lactone; C14:1-HSL: N-tetradecenoyl-l-homoserine lactone; 3OHC14-HSL: N-(3-hydroxytetradecanoyl)-l-homoserine lactone; SAM: S-adenosyl-l-methionine; ACP: acyl-acyl carrier protein; EPS: extracellular polysaccharide; DMSO: dimethyl sulfoxide.


Fracture neck of the talus with isolated talonavicular dislocation: A case report.
Talar neck fractures are injuries which frequently result in adverse outcomes or impairment of functional activity. Four groups were identified according to Hawkins classification and Canale modification. We present a female patient with a fractured neck of the talus associated with talonavicular dislocation, but intact tibiotalar and subtalar joints; an injury pattern not fulfilling the criteria described in the Hawkins classification. A 46-year-old woman missed a step and fell down stairs with an immediate painful right ankle and inability to bear weight. Talar neck fracture with an unusual isolated talonavicular dislocation. Temporary closed reduction followed by open reduction and internal fixation were performed. The patient had excellent functional and radiological outcomes following surgical management. We discuss the management of this rare case in addition to a review of the current literature to provide the best evidence-based recommendations for this injury pattern.


Some advantages and limitations of mitosis as a phylogenetic criterion.
The advantages and disadvantages of mitosis as a phylogenetic character are discussed. Mitosis is suggested to be a good character on the grounds that it is universally applicable and that it reflects features of the basic organism since it is unlikely to have arisen through multiple endosymbiotic events. Since mitosis is an absolutely essential feature of the cell cycle it is subject to a great deal of evolutionary pressure and one would not expect a priori that relatively inefficient mitotic apparatuses would persist. It is suggested that supposedly primitive mitotic apparatuses are not inefficient and that the evidence that they are functionally different from those of higher organisms is largely negative electron microscopic evidence. This type of evidence is not very satisfactory since it can result from poor preservation and consequently it should be continually retested. Another weakness of mitosis as a phylogenetic criterion (shared with other essentially morphological criteria) is that there is no easy way to relate structural change with genetic change. Thus, while mitosis is a useful phylogenetic character, its usefulness is limited.


Prevalence and pattern of childhood abdominal pain in an Australian general practice.
Abdominal pain is a common problem in childhood and accounts for a significant workload in general practice. The aim of this study was assess the nature of abdominal pain in a sample of Australian children attending a Western Australian general practice for any reason, and to determine factors associated with the reporting of such pain. A prospective study of children and their families attending a rural general practice was undertaken using a parental survey to assess the frequency and nature of abdominal pain, demographic features, physical and behavioural characteristics. Abdominal pain was common in this population; 44% (70 of 164) of parents reported that the index child had experienced abdominal pain in the past 12 months. The average age of children who experienced recent abdominal pain was 9 years and 9 months. Multivariate analysis suggested that children experiencing abdominal pain in the preceding 12 months were more likely to be anxious (odds ratio (OR) = 3.74, P = 0.01), to have a family history of similar problems in siblings (OR = 4.26, P = 0.01) and to experience sleep disturbance (OR = 3.90, P = 0.02) than children without abdominal pain. Consumption of three or more serves of wholemeal bread or cereals per day had a significant protective effect on reported abdominal pain in children (OR = 0.12, P = 0.03). The majority of families (66%) dealt with the pain without resorting to medical care. Abdominal pain remains a common problem of children attending an Australian general practice, and was associated with features suggesting that it is related to anxiety and coping ability. Abdominal pain is not usually associated with disease; most families recognize this and cope with abdominal pain without medical consultation.


Oral Health Considerations of Children: Grandparent Caregiver Perceptions, Behaviors, and Knowledge.
In the United States, approximately 2.7 million grandparents have permanent custody of their grandchildren. Prevalence of primary dental caries has remained steady for those living in poverty, and among children of color. Children in the care of their grandparents frequently live in socioeconomically disadvantaged households, where dental disparities continue to exist. Research regarding the grandfamily dynamic as it relates to oral health, is limited. The purpose of this study was to investigate oral health perceptions, behaviors, and knowledge of grandparents raising/caring for their grandchildren; and explore how a grandparent caregiver's oral health knowledge influences their perceptions/behaviors regarding their grandchild's oral health. This descriptive, cross-sectional survey research used non-probability sampling strategies to recruit grandparents who were the primary caregiver of their grandchildren, aged birth to eighteen years. A validated questionnaire was employed, both in-person and electronically. A total of 75 grandparents participated and answered 52% (SD = 27%) of oral health knowledge questions correctly. The study showed a correlation between low-income grandparents (M = 3.94, SD = 1.02) having higher pediatric oral health knowledge. Additionally, results indicated the greater the knowledge, the more positive intent to assist grandchildren with routine brushing and in checking their teeth for cavities. This study demonstrated that regardless of socioeconomic status, grandparent caregiver's oral health knowledge can positively affect their oral health-related behaviors and values, which could influence their grandchildren's' oral health. Further research regarding grandparent caregiver utilization of public health pediatric services and dental education programs, and the potential influence of these programs on pediatric oral health, should be explored.


Co-regulation of lipoamide dehydrogenase and 2-oxoglutarate dehydrogenase synthesis in Escherichia coli: characterisation of an ArcA binding site in the lpd promoter.
The lipoamide dehydrogenase gene (lpdA) encoding the E3 subunits of both the pyruvate dehydrogenase and 2-oxoglutarate dehydrogenase complexes of Escherichia coli, is expressed from the upstream pdh and internal lpd promoters of the pdh operon (pdhR-aceEF-lpdA). Under aerobic conditions, the specific components of the 2-oxoglutarate dehydrogenase complex encoded by the sucAB genes in the sdhCDAB-sucABCD operon are expressed from the sdh promoter. The provision of lipoamide dehydrogenase subunits for assembly into the 2-oxoglutarate dehydrogenase complex could thus be controlled by co-regulation of the lpd promoter with the sdh promoter. Here, the transcription start point of the lpd promoter was defined by primer extension analysis, and an ArcA binding site, TGTTAACAAT, overlapping the lpd promoter and matching the consensus at 8 out of 10 positions, was identified by in vitro footprint analysis. PdhR was not bound to the lpd promoter nor was ArcA bound specifically to the pdh promoter. These results support the view that co-regulation of the lpd and sdh promoters is mediated primarily by ArcA.


Prevalence of male pattern hair loss in 18-49 year old men.
Previous studies investigating the prevalence of male pattern hair loss (MPHL) typically used biased samples of men recruited from clinical populations which may limit generalizability of findings to broader populations. To obtain an updated and improved estimate of the occurrence of MPHL in healthy men residing in the community. Community-based sample of healthy men aged 18-49 years participated in a study investigating the effects of MPHL. Participants completed a brief questionnaire self reporting degree of hair loss, general health-related quality of life (HRQL) and hair-loss-specific measures. A trained observer also rated each participant using standardized classification for MPHL. The proportion of men with moderate to extensive hair loss (type III or greater) was 42%. The proportion of men with moderate to extensive hair loss increased with increasing age, ranging from 16% for men 18-29 years of age to 53% of men 40-49. Twelve percent of the men were classified as having predominantly frontal baldness (type A variants). MPHL, especially frontal baldness, may be more common than previously reported.


A Randomized Clinical Trial of Single-Dose Versus Weekly Dalbavancin for Treatment of Acute Bacterial Skin and Skin Structure Infection.
Acute bacterial skin and skin structure infections (ABSSSIs) are a cause of significant morbidity and therapy can be a burden to the healthcare system. New antibiotics that simplify treatment and avoid hospitalization are needed. This study compared the safety and efficacy of a single intravenous infusion of 1500 mg of dalbavancin to the 2-dose regimen. This study was a randomized, double-blind trial in patients aged >18 years with ABSSSIs. Patients were randomized to dalbavancin 1500 mg either as a single intravenous (IV) infusion or 1000 mg IV on day 1 followed 1 week later by 500 mg IV. The primary endpoint was a ≥20% reduction in the area of erythema at 48-72 hours in the intent-to-treat population. Noninferiority was to be declared if the lower limit of the 95% confidence interval (CI) on the difference in the outcomes was greater than -10%. Clinical outcome was also assessed at days 14 and 28. Six hundred ninety-eight patients were randomized. Demographic characteristics were similar on each regimen, although there were more patients with methicillin-resistant Staphylococcus aureus (MRSA) at baseline on the 2-dose regimen (36/210 [17.1%] vs 61/220 [27.7%]). Dalbavancin delivered as a single dose was noninferior to a 2-dose regimen (81.4% vs 84.2%; difference, -2.9% [95% CI, -8.5% to 2.8%]). Clinical outcomes were also similar at day 14 (84.0% vs 84.8%), day 28 (84.5% vs 85.1%), and day 14 in clinically evaluable patients with MRSA in a baseline culture (92.9% vs 95.3%) in the single- and 2-dose regimens, respectively. Treatment-emergent adverse events occurred in 20.1% of the single-dose patients and 19.9% on the 2-dose regimen. A single 1500-mg infusion of dalbavancin is noninferior to a 2-dose regimen, has a similar safety profile, and removes logistical constraints related to delivery of the second dose. NCT02127970.


A simplified approach to detect a significant carbon dioxide reduction by phytoplankton in lakes and rivers on a regional and global scale.
Carbon dioxide (CO2) uptake by phytoplankton can significantly reduce the partial pressure of CO2 (pCO2) in lakes and rivers, and thereby CO2 emissions. Presently, it is not known in which inland waters on Earth a significant pCO2 reduction by phytoplankton is likely. Since detailed, comparable carbon budgets are currently not available for most inland waters, we modified a proxy to assess the pCO2 reduction by phytoplankton, originally developed for boreal lakes, for application on a global scale. Using data from 61 rivers and 125 lakes distributed over five continents, we show that a significant pCO2 reduction by phytoplankton is widespread across the temperate and sub-/tropical region, but absent in the cold regions on Earth. More specifically, we found that a significant pCO2 reduction by phytoplankton might occur in 24% of the lakes in the temperate region, and 39% of the lakes in the sub-/tropical region. We also showed that such a reduction might occur in 21% of the rivers in the temperate region, and 5% of the rivers in the sub-/tropical region. Our results indicate that CO2 uptake by phytoplankton is a relevant flux in regional and global carbon budgets. This highlights the need for more accurate approaches to quantify CO2 uptake by primary producers in inland waters, particularly in the temperate and sub-/tropical region.


Mating type loci inFusarium: structure and function.
Sex in fungi is regulated by highly dissimilar mating type loci named idiomorphs. The genus Fusarium harbours both sexual as well as esexual species and each appears to contain one or the other idiomorph. The structure of these loci is highly conserved, suggesting a cryptic sexual cycle in these socalled asexual species. Alternatively, idiomorphs could regulate additional hitherto unrecognized biological processes. Such processes could be elucidated by expression profiling using mutants disrupted in their mating type loci.


Use of botulinum toxin type A in symptomatic accessory soleus muscle: first five cases.
Symptomatic accessory soleus muscle (ASM) can cause exercise-induced leg pain due to local nerve/vascular compression, muscle spasm, or local compartment syndrome. As intramuscular injections of botulinum toxin type A (BTX-A) can reduce muscle tone and mass, we investigated whether local BTX-A injections relieve the pain associated with symptomatic ASM. We describe five patients presenting peri/retromalleolar exertional pain and a contractile muscle mass in the painful region. Com-pression neuropathy was ruled out by electromyo-graphic analysis of the lower limb muscles. Doppler ultrasonography was normal, excluding a local vascular compression. ASM was confirmed by magnetic resonance imaging. After a treadmill stress test, abnormal intramuscular pressure values in the ASM, confirmed the diagnosis of compartment syndrome only in one patient. All five patients received BTX-A injections in two points of the ASM. The treatment efficacy was evaluated based on the disappearance of exercise-induced pain and the resumption of normal physical and sports activities. After BTX-A injection, exertional pain disappeared and all five patients resumed their normal level of physical and sports performances. Neither side effects nor motor deficits were observed. BTX-A is well tolerated in patients with ASM and could be used as a new conservative therapeutic strategy for the treatment of symptomatic ASM before surgery.


Rectal carcinoma with solitary cerebral metastasis: report of a case and review of the literature.
A 54-year-old man underwent abdominoperineal resection for carcinoma of the rectum. Three months later, neurologic signs and symptoms developed. A brain scan, as well as angiographic studies, demonstrated a space-occupying lesion in the right parietal area. A solitary tumor was removed at craniotomy. Histologic examination revealed a metastatic adenocarcinoma with a rectal primary tumor. For two years the patient remained well, but then signs of local perineal recurrence developed. Treatment with cobalt irradiation and chemotherapy was unsuccessful. Autopsy revealed local recurrence with numerous distant metastases; however, examination of the brain failed to show a recurrent metastatic focus.


Biocompatibility, cytotoxicity and antibacterial effects of meropenem-loaded mesoporous silica nanoparticles against carbapenem-resistant Enterobacteriaceae.
The ever-increasing resistance to antimicrobial agents among bacteria associated with nosocomial infections indicate the necessity of new antimicrobial therapy. The nanoparticles are considered as new drug delivery systems to increase the efficiency and decrease the unfavourable effects of the antimicrobial agents. Herein we report the preparation and characterization of mesoporous silica nanoparticles (MSNs) loaded with meropenem against carbapenem-resistant Enterobacteriaceae. The antimicrobial effect of meropenem-loaded MSNs was determined against Enterobacteriaceae using the minimum inhibitory (MIC) method. The biocompatibility of meropenem-loaded MSNs was studied by the impact on the haemolysis and sedimentation rates of human red blood cells (HRBCs). Cytotoxicity of the meropenem-loaded MSNs was studied by the MTT test (hBM-MSC cell viability). The meropenem-loaded MSNs have shown antibacterial activity on all isolates at different MIC values lower than MICs of meropenem. Free MSNs did not show any significant antibacterial effect. Meropenem-loaded MSNs have no significant effect on haemolysis and ESR of HRBCs. The viability of hBM-MSC cells treated with serial concentrations of meropenem-loaded MSNs was 92-100%. Due to the desirable biocompatibility, low cytotoxicity and the improved antibacterial effect, MSNs can be considered as a promising drug delivery system for meropenem as a potential antimicrobial agent.


Management and Outcome of Febrile Infants ≤60 days, With Emphasis on Infants ≤21 Days Old, in Swedish Pediatric Emergency Departments.
Management of febrile infants ≤60 days of age varies, and the age for routine investigations and antibiotic-treatment is debated. The American Academy of Pediatrics recommended age threshold for lumbar puncture (LP) is 21 days and for blood culture 60 days. We describe management and adverse outcome of febrile infants ≤60 days old, in Sweden. Retrospective cross-sectional study of infants ≤60 days of age with fever without source evaluated in 4 University pediatric emergency departments, between 2014 and 2017. Adverse outcome was defined as delayed-treated invasive bacterial infection (IBI: meningitis or bacteremia). We included 1701 infants. In infants ≤21 days old, LP was performed in 16% (95% CI: 12-20) and blood culture in 43% (95% CI: 38-48). Meningitis was diagnosed in 5 (1.3%; 95% CI: 0.4-3.0) and bacteremia in 12 (4.5%; 95% CI: 2.6-7.0) infants. Broad-spectrum antibiotics were not administered to 66% (95% CI: 61-71), of which 2 (0.8%; 95% CI: 0.1-2.8) diagnosed with IBI (1 meningitis and 1 bacteremia). In the 29-60 days age group, blood culture was performed in 21% (95% CI: 19-24), and broad-spectrum antibiotics were not administered to 84% (95% CI: 82-86), with no case of delayed-treated bacteremia. The rates of LP, blood culture and broad-spectrum antibiotics were low. Despite that, there were few delayed-treated IBIs, but 2 of the 17 infants ≤21 days of age with IBI were not timely treated, which prompts the need for a safer approach for this age group. Also, the utility of routine blood culture for all febrile infants 29-60 days old could be questioned.


Current and future strategies for wine yeast lees valorization.
Wine lees is a sludge material mainly composed of dead yeast precipitated at the bottom of wine tanks. Along with grape pomace and grape stalks, it is one of the main by-products of the winemaking industry. Given that wine lees are considered a soil pollutant, their disposal represents a cost for wineries. Numerous wine lees recovery and valorization strategies have been proposed, with a particularly steep increase in published research in recent years. This attention is strictly linked to the concepts of circular economy and environmental sustainability that are attracting the interest of the scientific community. In this review, an overview on the available wine lees recovery and valorization strategies is reported. Additionally, the methods for the extraction and valorization of yeast's cell wall polysaccharides (β-glucans and mannoproteins) are discussed. Finally, current and future innovative applications in different sectors of yeast β-glucans and mannoproteins are described and critically discussed.


Prognostic implications of type and density of tumour-infiltrating lymphocytes in gastric cancer.
The study aims to determine whether type and density of tumour-infiltrating lymphocytes (TILs) can predict the clinical course in gastric cancer. Gastric carcinomas (n=220) were immunostained for CD3, CD8, CD20, and CD45RO and evaluated for clinicopathologic characteristics. Number of TILs that immunostained positively for each marker were counted using NIH ImageJ software. Tumours were grouped into low- and high-density groups for each marker (CD3, CD8, CD45RO). The densities of CD3(+), CD8(+), and CD45RO(+) TILs were found to be independent predictors of lymph node metastasis by multivariate analysis with odds ratios (95% CI) of 0.425 (0.204-0.885), 0.325 (0.150-0.707), and 0.402 (0.190-0.850), respectively. Kaplan-Meier survival analysis revealed that patients in the high-density groups for CD3, CD8, and C45RO had a significantly longer survival time than the patients in the corresponding low-density groups, respectively. In multivariate survival analysis, the densities of CD3(+), CD8(+), and CD45RO(+) TILs remained independent prognostic factors with hazard ratios (95% CI) of 0.549 (0.317-0.951), 0.574 (0.347-0.949), and 0.507 (0.298-0.862), respectively. In conclusion, density of TILs was found to be independently predictive of regional lymph node metastasis and patient survival in gastric cancer.


Selection for thiabendazole resistance in Ostertagia spp. by low efficiency anthelmintic treatment.
Thiabendazole (TBZ) treatment of grazing weaners infected with a predominantly susceptible strain of Ostertagia reduced worm burdens by 90%. The surviving sub population had a level of resistance four times greater than the original population when compared to similarly infected, but untreated, weaners. TBZ treated and control weaners were relocated to worm-free pasture so that the contamination on the plots grazed by TBZ treated weaners was from the survivors of the drench. The anthelmintic treated groups were subsequently managed under a two summer drench programme while control groups remained so throughout the experiment. Monitoring both parasite population size and the degree of resistance over the following 2 years indicated that after three anthelmintic treatments, resistance developed to a level where TBZ was ineffective. When compared to control groups, a mean reduction in population size of around 80% was maintained in the TBZ treated groups for 1 year. This difference, however, disappeared by the second year. A similar study over 1 year with a moderately TBZ resistant strain of Ostertagia indicated that TBZ treatment produced no significant reduction in population size but more than doubled the level of resistance. The study indicated the critical need for highly efficient anthelmintic treatment, particularly in situations where, through ecology or management, post treatment contamination is likely to contribute substantially to future generations of worms.


Bacteroidetes and Firmicutes levels in gut microbiota and effects of hosts TLR2/TLR4 gene expression levels in adult type 1 diabetes patients in Istanbul, Turkey.
The aim of this study was to determine and compare the levels of both Bacteroidetes and Firmicutes in the gut microbiota and TLR2/TLR4 gene expression in the blood of patients with type 1 diabetes mellitus (T1DM) and healthy individuals. These results may serve as a preliminary assessment to guide future research. Between January and October 2014, stool and blood samples were collected from 53 adult T1DM patients and 53 age- and gender-matched healthy individuals. Bacteroidetes and Firmicutes levels were assessed from stool sample DNA and TLR2 and TLR4 expression levels were analyzed via qPCR using RNA from EDTA blood samples from both patients and healthy controls. The amounts of Bacteroidetes and Firmicutes were statistically significantly higher and lower, respectively, in the T1DM group than in the healthy control group (p < 0.001 and p < 0.001, respectively). In addition, the Firmicutes/Bacteroidetes ratios in patients with T1DM were significantly lower than in healthy controls. The TLR4 and TLR2 gene expression levels in T1DM patients were significantly upregulated and downregulated, respectively, compared to those in the control group. Our data are the first to show a relationship between T1DM and gut microbiota in our country. In addition, our results provide information about the connections between T1DM, gut microbiota, and TLR2 and TLR4 expression. We believe that Bacteroidetes and Firmicutes in the gut microbiota may play a role in the autoimmune process of T1DM and that these findings should be further investigated in the future.


Zero effect of multiple dosage of olive leaf supplements on urinary biomarkers of oxidative stress in healthy humans.
We determined the effect of dietary supplementation with an olive leaf capsule or liquid extract on oxidative status of young and healthy male and female subjects. This was a single-center, randomized, single-blinded, prospective pilot comparison of the effect of dietary supplementation with olive leaf extracts. Healthy young adult male and female subjects (n = 45) were randomized into three groups and received daily doses of control, capsule, or liquid extract of olive leaf. Urinary F(2 alpha)-isoprostane, 8-hydroxy-2'-deoxyguanosine, and Folin-Ciocalteu total reducing power were measured to assess the impact of supplementation. Baseline values (mean +/- standard deviation) of the biomarkers were 0.24 +/- 0.13 microg, 9.16 +/- 2.94 microg, and 424.9 +/- 121.4 mg of gallic acid equivalents per gram of creatinine, respectively, for the control group. Using these markers, supplementation with liquid or capsule did not alter oxidative status compared with the control group. Possible reasons for the lack of an observed correlation are presented. Dietary supplementation with olive leaf extract did not alter the oxidative status of healthy young adults.


Phase II study of irinotecan plus S-1 combination for previously untreated advanced non-small cell lung cancer: Hokkaido Lung Cancer Clinical Study Group Trial (HOT) 0601.
Platinum-free regimens can represent an alternative for advanced non-small cell lung cancer (NSCLC) if similar efficacy is provided with better tolerability. This study evaluated the efficacy and safety of combined irinotecan and S-1 for chemotherapy-naïve advanced NSCLC. Chemotherapy consisted of 4-week cycles of intravenous irinotecan (100 mg/m(2), days 1 and 15) and oral S-1 (80 mg/m(2), days 1-14). The primary endpoint was response rate, while secondary endpoints were overall survival, progression-free survival (PFS), and safety. A total of 112 cycles was administered to 40 patients (median 3 cycles; range 1-6 cycles). Twelve patients showed partial response and 17 patients had stable disease, representing a response rate of 30% and a disease control rate of 72.5%. Median survival time and median PFS were 16.1 and 4.8 months, respectively. Hematological toxicities of grade 3 or 4 were neutropenia (32.5%) and anemia (5.0%). The most common nonhematological toxicities of grade 3 or 4 included diarrhea (15.0%) and anorexia (17.5%). Patients homo- or heterozygous for UGTA1A*6 tended to show a higher incidence of grade 3 diarrhea (p = 0.055). The combination of irinotecan and S-1 offers good efficacy and tolerability for previously untreated advanced NSCLC.


Chemokines and their receptors in esophageal cancer--the systematic review and future perspectives.
Esophageal cancer (EC) is an aggressive malignant solid tumor with rapid progression and unfavorable prognosis. The 5-year survival rate for EC patients was estimated to be less than 10 %. Therefore, there is an urgent need to improve diagnostic tool and effective treatment therapies for EC patients. In our paper, the general structure and function of chemokines and their receptors as well as their role in cancer progression were shortly presented. Moreover, the aim of our paper was to summarize and refer the current findings concerning the role of selected chemokines and their receptors as candidates for tumor markers of EC. Some clinical investigations have proved the involvement of these proteins in proliferation, migration, invasiveness and metastasis of tumor cells. Increasing evidence from previous studies suggested that C-X-C motif chemokine 12 (CXCL12), also known as stromal cell-derived factor 1 (SDF-1) and its receptor CXCR4 may provide novel diagnostic and prognostic strategies to reduce the burden of EC. Moreover, therapy targeting the CXCL12/CXCR4 axis may open a new direction for treatment of EC patients. However, given their nonspecific nature, the diagnostic value of chemokines and their receptors may be limited. Therefore, future larger investigations, especially in the blood of EC patients, still need to be continued to further clarify the significance of these proteins as potential candidates for tumor markers in diagnosis and prognosis of EC patients.


Kalman Filter-based Robust Closed-loop Carrier Tracking of Airborne GNSS Radio-Occultation Signals.
GNSS radio occultation (RO) signals have been demonstrated as a viable means to retrieve atmospheric profiles. Current GNSS-RO observations rely on open-loop (OL) processing of the signals, especially for signals propagating through the lower troposphere. The reason is that GNSS signals at low elevations are adversely affected by multipath effects due to propagation through lower troposphere structures and reflections and scattering from the Earth surface. The low-elevation RO signals are characterized by deep and fast amplitude fading and rapid signal carrier phase fluctuations, collectively referred to as signal scintillation. The conventional phase-lock loop (PLL) may lose lock of these signals. While OL tracking is known for its robustness, its accuracy is determined by the climatological models used to create the reference for the GNSS signal carrier tracking loop. The wide bandwidth typically associated with OL tracking also introduces large errors in signal parameters estimations. In this paper, we present an adaptive Kalman filter-based closed-loop (KFC) tracking method, which takes into consideration the tropospheric scintillation, platform vibration, and real-time C/N0 estimation of the RO signals. The KFC method has comparable robustness with and improved accuracy over the OL tracking, which are demonstrated through comparison using real GPS RO data collected on an airborne platform. Analysis of the excess Doppler estimation, retrieved bending angles and impact parameters also confirms the improved performances of the proposed algorithm over OL tracking.


HIF-P4H-2 deficiency protects against skeletal muscle ischemia-reperfusion injury.
We show here that mice hypomorphic for hypoxia-inducible factor prolyl 4-hydroxylase-2 (HIF-P4H-2) (Hif-p4h-2 (gt/gt)), the main regulator of the stability of the HIFα subunits, have normoxic stabilization of HIF-1α and HIF-2α in their skeletal muscles. The size of the capillaries, but not their number, was increased in the skeletal muscles of the Hif-p4h-2 (gt/gt) mice, whereas the amount of glycogen was reduced. The expression levels of genes for glycolytic enzymes, glycogen branching enzyme 1 and monocarboxylate transporter 4, were increased in the Hif-p4h-2 (gt/gt) skeletal muscles, whereas no significant increases were detected in the levels of any vasculature-influencing factor studied. Serum lactate levels of the Hif-p4h-2 (gt/gt) mice recovered faster than those of the wild type following exercise. The Hif-p4h-2 (gt/gt) mice had elevated hepatic phosphoenolpyruvate carboxykinase activity, which may have contributed to the faster clearance of lactate. The Hif-p4h-2 (gt/gt) mice had smaller infarct size following limb ischemia-reperfusion injury. The increased capillary size correlated with the reduced infarct size. Following ischemia-reperfusion, glycogen content and ATP/ADP and CrP/Cr levels of the skeletal muscle of the Hif-p4h-2 (gt/gt) mice were higher than in the wild type. The higher glycogen content correlated with increased expression of phosphofructokinase messenger RNA (mRNA) and the increased ATP/ADP and CrP/Cr levels with reduced apoptosis, suggesting that HIF-P4H-2 deficiency supported energy metabolism during ischemia-reperfusion and protection against injury. Key messages: HIF-P4H-2 deficiency protects skeletal muscle from ischemia-reperfusion injury. The mechanisms involved are mediated via normoxic HIF-1α and HIF-2α stabilization. HIF-P4H-2 deficiency increases capillary size but not number. HIF-P4H-2 deficiency maintains energy metabolism during ischemia-reperfusion.


Power-Frequency Magnetic Field Inhibits Adipogenic Differentiation in Human ADSC.
Semicircular lipoatrophy (SL) is an idiopathic condition characterized by atrophy of subcutaneous fatty tissue. Although several studies have suggested a possible association between SL and occupational exposure to power frequency magnetic fields (MF), no mechanism has been proposed so far that explains an influence of these fields on adipogenesis. The study investigates the effects of a 50 Hz, 100 µT MF on the adipogenesis of stem cells isolated from human adipose tissue (ADSC). Cells were plated in Petri dishes and either exposed intermittently to the field for 42 hours or sham-exposed. Field exposure significantly reduced lipid accumulation within the cells, revealed in Oil Red O stained samples by spectrophotometry and colorimetry. Early cell passages were particularly sensitive to the effect: 30.40 ± 5.77% and 47.96 ± 12.47% below controls in the spectrophotometric and colorimetric assays, respectively. Such antiadipogenic effect was accompanied by significant changes in the expression of key effectors/regulators of early adipogenesis: PPARx03B3;, p-ERK1/2 and Sox9, indicating that at least the ERK/PPARx03B3; signaling pathway could be involved in the effect. These results constitute an experimental support to the hypothesis that power frequency MF can be one of the factors involved in the etiology of SL.


[Destructive changes in the outer perimembrane layers (glycocalyx) of Zajdela ascites hepatoma cells under the action of UV radiation].
Immediately after far (254) nm and near (300--380 nm) UV light in small and moderate doses alcian blue sorption by glycocalix of Zaidela ascitic hepatoma cells decrease, which is indicative of destruction and solubilization. The effect of UV light on the cell surface is compared with the action of trypsin. Contribution of the damage of outer perimembrane layers to the lethal effect of UV light is discussed.


Delayed neutron counting of uranium pins using moderated neutrons from portable DD neutron generator in high frequency mode.
Delayed neutron counting is often used to verify the characteristics of nuclear material. Use of portable neutron generators in high frequency pulsing mode enables effective analysis with higher counting efficiency and lower radiation protection demands. The paper deals with delayed neutron counting of uranium pins with P385 portable DD neutron generator in polyethylene-based setup. Counting is performed in high frequency mode of neutron generator. The viability of such measurement in the frequency range from 100 Hz to 250 Hz was demonstrated and optimal pulsing parameters for P385 neutron generator were found. Delayed neutron counting was then performed for two types of uranium rods. Delayed neutrons were counted both inbetween neutron pulses during neutron generation and once the emission of neutrons stopped. The results were further validated by Monte Carlo (MCNP) simulations. For the geometry of studied rods, the MCNP calculation were done to calculate the dependence of the response to delayed neutrons on rod enrichment, to show the viability to use the method for rod enrichment verification. An option of using cadmium inset in irradiation channel to overcome the effect of self-shielding for samples with higher enrichment was proposed, experimentally tested, and evaluated through MCNP calculations.


Exploring perceived control and self-rated health in re-admissions among younger adults: A retrospective study.
Although health promotion calls for patient empowerment, it is not integrated in reducing re-admissions. This study examines the link among patient perceived control, self-rated health and fewer hospital re-admissions. An empirical explorative retrospective cross-sectional study with 208 respondents aged 40-65 with poor health and identical health plans. All measures hold good psychometric properties. Self-rated health was strongly related to fewer re-admissions. Perceived control moderated the relationship between self-rated health and fewer re-admissions. Perceived control and self-rated health, together, contributed 5.2% to the variance in re-admissions. Perceived control and perceived health status each explained a different share of the variance of re-admissions. Together, these perceptions reduced re-admissions by .40. Patient-clinician communication upon discharge may be a new direction to reduce re-admissions, improve delivery of care and promote health. To reduce re-admissions, managements need to invest in restructuring the patient discharge process. A physician-patient dialogue shaping patient perceptions about their health status, perceived room for health improvement, and available internal and external resources may make a difference. Findings stress the need to allocate more time and resources for discharge communication processes and for physician training on psycho-social skills that may empower patients upon discharge.


Ultra high performance liquid chromatography tandem mass spectrometric detection of glucuronides resistant to enzymatic hydrolysis: Implications to doping control analysis.
Controversial results have been reported in the literature regarding the behavior of two testosterone (T) metabolites (3α-glucuronide-6β-hydroxyandrosterone and 3α-glucuronide-6β-hydroxyetiocholanolone) excreted after T administration. Due to their potential as biomarkers of T misuse, a UHPLC-MS/MS method for the direct quantification of these glucuronides was developed and validated. In addition, the main phase II metabolites of T that compose the steroid profile used for doping control purposes (glucuronides of T, epitestosterone, androsterone and etiocholanolone) were included. The method was found to be linear and with suitable LODs and LOQs for all metabolites. The average accuracies were between 86% and 120%, the RSDs for the intra- and inter-day precision were below 15% and 25% respectively. The method showed low matrix effect. Samples obtained before and after the administration of T were analyzed by both the developed UHPLC-MS/MS method and the GC-MS/MS method currently used by anti-doping laboratories. Relevant disagreements between the results obtained for 3α-glucuronide-6β-hydroxyandrosterone and 3α-glucuronide-6β-hydroxyetiocholanolone quantitation were observed. These markers seemed to be more suitable for the screening of T misuse when detected by UHPLC-MS/MS. These discrepancies were further investigated in 50 urine samples from healthy volunteers. The two methods gave highly correlated results for all metabolites that are currently included in the athlete's steroid profile confirming the reliability of the UHPLC-MS/MS method. However, the quantification of 3α-glucuronide-6β-hydroxyandrosterone and 3α-glucuronide-6β-hydroxyetiocholanolone, was only possible by using the UHPLC-MS/MS method since three interfering compounds were observed when performing the GC-MS/MS analysis with the most intense ion transitions. These results confirm the potential of the resistant glucuronides as biomarkers of T misuse. Additionally, they suggest that previously reported reference ranges for these metabolites should be reevaluated.


Phenylacetylene macrocycles with two opposing bipyridine donor sites: syntheses, X-ray structure determinations, and Ru complexation.
Reaction of the known macrocycle 1a, which contains two bipyridine units in opposing sides, with two equivalents of [Ru(bipy)2Cl2] furnishes the doubly exocyclically complexed macrocycle 8a in 55% yield. Synthesis of the shape-persistent macrocycle 1c by Hagihara-Sonogashira cross-coupling chemistry of suitably functionalized building blocks is reported. This macrocycle was also converted into a Ru complex (8c). X-ray analysis of single crystals of 1b and 1c shows a layered structure that contains "channels" filled with solvent molecules and parts of the flexible chains, with which the cycle is decorated for solubility reasons.


The vacuolar iron transporter mediates iron detoxification in Toxoplasma gondii.
Iron is essential to cells as a cofactor in enzymes of respiration and replication, however without correct storage, iron leads to the formation of dangerous oxygen radicals. In yeast and plants, iron is transported into a membrane-bound vacuole by the vacuolar iron transporter (VIT). This transporter is conserved in the apicomplexan family of obligate intracellular parasites, including in Toxoplasma gondii. Here, we assess the role of VIT and iron storage in T. gondii. By deleting VIT, we find a slight growth defect in vitro, and iron hypersensitivity, confirming its essential role in parasite iron detoxification, which can be rescued by scavenging of oxygen radicals. We show VIT expression is regulated by iron at transcript and protein levels, and by altering VIT localization. In the absence of VIT, T. gondii responds by altering expression of iron metabolism genes and by increasing antioxidant protein catalase activity. We also show that iron detoxification has an important role both in parasite survival within macrophages and in virulence in a mouse model. Together, by demonstrating a critical role for VIT during iron detoxification in T. gondii, we reveal the importance of iron storage in the parasite and provide the first insight into the machinery involved.


Hearing loss screening tests for adults.
The early detection of hearing loss has been studied widely in newborns due to the emerging technologies for diagnosis and treatment. There are detailed protocols for this goal. Nonetheless, hearing loss screening in adults has become more important lately with the increase of the life expectancy, an expected change in the Mexican population pyramid towards a rectangular shape in the next 50 years (with increased hearing loss prevalence) and the creation of public policies for social security such as the "Seguro Popular". There are no Mexican studies about hearing loss screening in adults. The aim of this work was to assess a tone emission and a questionnaire as screening tools for hearing loss in adults. A sample size of 500 individuals without otology pathology from the outpatient clinics at a general hospital. An otoscopy, 2 screening tests (tone emission and questionnaire) and tonal audiometry were performed on all subjects. The questionnaire turned out to be a sensitive test but with low specificity, while the tone emission was less sensitive but more specific with a higher rate of precision. In this study, the best result was achieved by a combined strategy using the two tests above, with a precision of 90%. The best screening strategy proposed by this study for hearing loss in adults is a questionnaire and tone emission test, which guarantees complete hearing assessment in objective and subjective manners, performed quickly and without special training.


A Defective Nanotube Molecule of C552 H496 N24 with Pyridinic and Pyrrolic Nitrogen Atoms.
A 3-nm molecule comprising a cylindrical core and cross-shaped rims was designed and synthesized by developing a modular synthetic route. By using a cyclic precursor from previous studies as a starting material, multiple carbazole units were installed at the rims of the defective cylinder. The defective cylinder was synthetically doped with two types of nitrogen atoms, that is, pyridinic and pyrrolic nitrogen atoms, which resulted in solvatochromic shifts in fluorescence by charge-transfer interactions. The structure of the large, C552 H496 N24 molecule was fully disclosed by crystallographic analyses, and the unique helical arrangement of nitrogen-doped cylinders in the crystal was revealed.


Evaluation of an enumeration method for Listeria monocytogenes at low contamination levels in cold-smoked salmon.
For the enumeration of Listeria monocytogenes in cold-smoked salmon, a sensitive enumeration method, based on membrane filtration followed by transfer of the filter on a selective medium has been recently developed (Gnanou Besse et al., 2004, A contribution to the improvement of L. monocytogenes enumeration in cold-smoked salmon. International Journal of Food Microbiology, 91, 119-127). The aim of the study was to assess the performance of this enumeration method through an inter-laboratory study, using cold-smoked salmon artificially contaminated at 2 different levels (approximately 0.6 and 1.6 log10 CFU g(-1)). A reproducibility standard deviation of 0.23 log10 CFU g(-1)and 0.15 log10 CFU g(-1) was obtained for the method respectively at the lower level and the higher level. Under certain conditions, the uncertainty of measurement can be derived from the method reproducibility standard deviation and was calculated to be 0.46 log10 CFU g(-1) for the lower contamination level and 0.30 log10 CFU g(-1) for the higher contamination level. These values can be considered as satisfactory for such low contamination levels.


A spoonful of bitter helps the sugar response go down.
Sweet and bitter taste distinguishes good food sources from potential toxins, but what happens when these tastants are mixed? In this issue of Neuron, Jeong et al. (2013) show that in Drosophila, bitter compounds act through an extracellular odorant-binding protein to inhibit sweet-responsive neurons and block the response to sweet taste.


Human organ specimen banking--15 years of experience.
As a reaction to the lack of information concerning ranges of a 'normal xenobiotic burden' within the population and also the aquatic, terrestrial and atmospheric environments, the sampling and storage of environmental materials in Germany in 1974 as a possible tool for environmental observation and early recognizing of hazards was proposed. During subsequent years the collection of human specimens was undertaken in Münster. In a pilot phase (1978-1983) conditions of optimized storage were investigated, including reliable storage temperature and container materials. Since 1985 the Environmental Specimen Bank for Human Tissue in Münster has been institutionalized under the auspices of the Federal Ministry of Environment, Nature Protection and Nuclear Safety as well as the Federal Environmental Agency in Berlin. Up to 1991 about 300,000 samples had been collected and stored at -85 degrees C in a walk-in deep-freezer of 34 m3 comprising autopsy material as well as 'available' organs form living persons (e.g. blood, urine, hair, human milk, saliva, seminal plasma, sweat). Having fulfilled the tasks within the scope of environmental banking the Münster institution has proved to be an adequate scientific tool. It has been integrated into the logistic system of the Environmental Specimen Bank in Germany having the following main tasks (a) the development of Standard Operation Procedures (SOP) for sampling and sample handling, (b) evaluation of reliable analytical methods for inorganic and organic sample characterization, (c) collection of a sufficient data pool for reference ranges of xenobiotics, which are essential for environmental risk assessment, and (d) the evaluation of the efficacy of legislative xenobiotic restrictions: this could be proved for lead and some organochlorine pesticides.


Topical dihydrotestosterone to treat micropenis secondary to partial androgen insensitivity syndrome (PAIS) before, during, and after puberty - a case series.
X-linked partial androgen insensitivity syndrome (PAIS) causes under-virilization at all stages of development. In two thirds of males, this results in micropenis. Dihydrotestosterone (DHT) is a potent androgen that is critical for male genital development, which when applied topically, has been shown to increase penile length with micropenis of varying etiologies. We present the first case series using topical DHT gel to treat micropenis in 46,XY males with PAIS, before, during, and after puberty. Three related 46,XY males with confirmed p.L712F androgen receptor mutations exhibited varying degrees of micropenis post-surgical correction. They were of pre-pubertal, peri-pubertal and adult ages, respectively. Following baseline clinical and laboratory assessments all completed a 4-month course of daily DHT gel 2.5% (androstanolone) topically to penis (0.3 mg/kg body weight), with monitoring for adverse effects. Primary outcome was change in stretched penile length (SPL) following treatment. Mixed results were obtained following topical DHT therapy. In the pre- and peri- pubertal patients, SPL changed from 2.5 cm to 3.5 cm (+40%), and 3.5 cm to 5.7 cm (+63%), respectively. In the adult patient with 1 year of prior high-dose weekly testosterone therapy, no additional change in SPL was seen. No adverse effects of topical DHT were reported or observed throughout the 4 months of treatment. Topical DHT treatment appears to be a safe and well-tolerated method of virilising micropenis both prior to and during puberty in children with PAIS. Questions remain about long-term outcomes into adulthood, and efficacy in adults with prior lengthy exposure to high-dose testosterone.


Feyerabend's 'The concept of intelligibility in modern physics' (1948).
This essay introduces the transcription and translation of Paul Feyerabend's Der Begriff der Verständlichkeit in der modernen Physik [The concept of intelligibility in modern physics] (1948), which is an early essay written by Paul Feyerabend in 1948 on the topic of intelligibility (Verständlichkeit) and visualizability (Anschaulichkeit) of physical theories. The existence of such essay was likely. It is listed in his bibliography as his first publication. Yet the content of the essay was unknown, as no original or copy is extant in Feyerabend's Nachlass and no known published version was available to the community-until now. The essay has both historical and philosophical interest: it is, as far as our current knowledge goes, Feyerabend's earliest extant publication. It documents Feyerabend's philosophical interest as a physicist-to-be, in what he himself called his "positivist" phase; and it gives a rare if fragmentary insight into the early discussions of the 'Third Vienna Circle' and, more generally, the philosophical culture of discussion in Vienna.