Mebendazole mesylate monohydrate: a new route to improve the solubility of mebendazole polymorphs.
Mebendazole mesylate monohydrate, a new stable salt of mebendazole (MBZ), has been synthesized and fully characterized. It was obtained from recrystallization of MBZ forms A, B, or C in diverse solvents with the addition of methyl sulfonic acid solution. The crystal packing is first organized as a two-dimensional array consisting of rows of alternating MBZ molecules linked to columns of mesylate ions by hydrogen bonds. The three-dimensional structure is further developed by classical intermolecular interactions involving water molecules. In addition, nonclassical contacts are also found. The vibrational behavior is consistent with the crystal structure, the most important functional groups showing shifts to lower or higher frequencies in relation to the MBZ polymorphs. Thermal analysis indicates that the compound is stable up to 50°C. Decomposition occurs in five steps. Solubility studies show that the title compound presents a significant higher performance than polymorph C. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 102:3528-3538, 2013.


Genetic and environmental influences on anxiety dimensions in Italian twins evaluated with the SCARED questionnaire.
This study explored the factorial structure of the Italian version of the Screen for Child Anxiety-Related Emotional Disorders questionnaire (SCARED), and investigated the contributions of genetic and environmental influences of individual variation of anxiety dimensions as reported in the SCARED. Three hundred and seventy-eight twin pairs aged 8-17 from the Italian Twin Registry filled in the SCARED through a mail survey. Four, distinct empirical factors, that corresponded closely to the original SCARED subscales of Generalized Anxiety (GAD), Panic (PD), Social Phobia (SP), and Separation Anxiety (SAD) disorder emerged from Exploratory Factor Analysis. The empirically derived scores were analyzed by structural equation modeling; moderate-to-high heritability, without age or sex differences, emerged for all dimensions with the exception of GAD, for which an age effect was found. The DSM-IV anxiety dimensions identified by the SCARED have a psychometric structure that can be replicated in the Italian culture, and are influenced at different extents by genetic and nonshared environmental determinants.


Effects of Plasmodium falciparum mixed infections on in vitro antimalarial drug tests and genotyping.
Studying drug resistance in Plasmodium falciparum requires accurate measurement of parasite response to a drug. Factors such as mixed infection of drug-resistant and -sensitive parasites can influence drug test outcome. Polymorphic DNA sequences are frequently used to detect mixed infections; infections with a single genotype or having a minor allele smaller than a subjectively selected cut-off value are often considered single infection. We studied the effects of mixed parasite populations containing various ratios of parasites resistant and sensitive to chloroquine on outcomes of drug tests and how ratios of parasite mixtures correlated with genotypes using polymerase chain reaction-based methods. Our results show that a mixture with a resistant population as low as 10% could greatly impact a drug test outcome. None of the genotyping methods could reliably detect minor DNA alleles at < or = 10%. Mixed infection presents a serious problem for drug tests, and genotyping using microsatellite or other methods may not reliably reflect true ratios of alleles.


Using the NYHA Classification as Forecasting Tool for Hospital Readmission and Mortality in Heart Failure Patients with COVID-19.
During the COVID-19 pandemic, it was observed that patients with heart disease are more likely to be hospitalized and develop severe COVID-19. Cardiac disease takes the top position among patient comorbidities, heart failure (HF) prevalence reaching almost 5% in the general population older than 35 years in Romania. This retrospective study aimed to determine the potential use of the NYHA classification for HF in hospitalized patients with COVID-19 as prognostic tool for in-hospital mortality, length of hospitalization, and probability of rehospitalization for HF decompensation. We observed that patients with advanced HF had a history of significantly more comorbid conditions that are associated with worse disease outcomes than the rest of patients classified as NYHA I and II. However, regardless of existing diseases, NYHA III, and, especially, NYHA IV, patients were at greatest risk for mortality following SARS-CoV-2 infection. They required significantly longer durations of hospitalization, ICU admission for mechanical ventilation, and developed multiple severe complications. NYHA IV patients required a median duration of 20 days of hospitalization, and their in-hospital mortality was as high as 47.8%. Cardiac biomarkers were significantly altered in patients with SARS-CoV-2 and advanced HF. Although the study sample was small, all patients with NYHA IV who recovered from COVID-19 required a rehospitalization in the following month, and 65.2% of the patients at initial presentation died during the next six months. The most significant risk factor for mortality was the development of severe in-hospital complications (OR = 4.38), while ICU admission was the strongest predictor for rehospitalization (OR = 5.19). Our result highlights that HF patients continue to be vulnerable post SARS-CoV-2 infection. Physicians and policymakers should consider this population's high likelihood of hospital readmissions when making discharge, hospital capacity planning, and post-discharge patient monitoring choices.


Reductive half-reaction of aldehyde oxidoreductase toward acetaldehyde: Ab initio and free energy quantum mechanical/molecular mechanical calculations.
Energy and free energy barriers for acetaldehyde conversion in aldehyde oxidoreductase are determined for three reaction pathways using quantum mechanical/molecular mechanical (QM/MM) calculations on the solvated enzyme. Ab initio single-point QM/MM energies are obtained at the stationary points optimized at the DFT(B3LYP)/MM level. These ab initio calculations employ local correlation treatments [LMP2 and LCCSD(T0)] in combination with augmented triple- and quadruple-zeta basis sets, and the final coupled cluster results include MP2-based corrections for basis set incompleteness and for the domain approximation. Free energy perturbation (FEP) theory is used to generate free energy profiles at the DFT(B3LYP)/MM level for the most important reaction steps by sampling along the corresponding reaction paths using molecular dynamics. The ab initio and FEP QM/MM results are combined to derive improved estimates of the free energy barriers, which differ from the corresponding DFT(B3LYP)/MM energy barriers by about 3 kcal mol(-1). The present results confirm the qualitative mechanistic conclusions from a previous DFT(B3LYP)/MM study. Most favorable is a three-step Lewis base catalyzed mechanism with an initial proton transfer from the cofactor to the Glu869 residue, a subsequent nucleophilic attack that yields a tetrahedral intermediate (IM2), and a final rate-limiting hydride transfer. The competing metal center activated pathway has the same final step but needs to overcome a higher barrier in the initial step on the route to IM2. The concerted mechanism has the highest free energy barrier and can be ruled out. While confirming the qualitative mechanistic scenario proposed previously on the basis of DFT(B3LYP)/MM energy profiles, the present ab initio and FEP QM/MM calculations provide corrections to the barriers that are important when aiming at high accuracy.


Forgotten drugs: long-term prescriptions of thyroid hormones - a cross-sectional study.
Thyroid hormones are among the most prescribed drugs in Germany. Although iodine supply has been improving in the last decade, annual prescriptions for thyroid hormones are rising. The aim of this study was to provide prevalence of thyroid hormone prescribing and to explore reasons for thyroid hormone prescription in primary care settings. A cross-sectional study. Data collection took place in six general practitioner (GP) practices in Hesse, Germany. We used the records of six GP practices to estimate prevalence of thyroid hormone prescribing. All patients who received a prescription of the active ingredient levotyroxine during the preceding 3 months were mailed a study invitation. A proportion of the identified patients were interviewed. In addition, demographical data and all medical findings related to thyroid disease were recorded. On average, 9.2% (SD 4.6) of all patients from participating practices were taking thyroid hormones. The majority were female (82.5%). In 47.7% of the study participants, the GP's diagnosis, according to their records, was nonexistent. In 13.6% of cases, the documentation of the diagnostic information was incomplete. While 25% of interviewed patients with high educational background initiated further diagnostic investigation, only 4.4% of the patients with lower education did so. In the majority of patients treated with thyroid hormones, doctors had not documented the precise indication for prescription.


Skeletal muscle channelopathies: new insights into the periodic paralyses and nondystrophic myotonias.
To summarize advances in our understanding of the clinical phenotypes, genetics, and molecular pathophysiology of the periodic paralyses, the nondystrophic myotonias, and other muscle channelopathies. The number of pathogenic mutations causing periodic paralysis, nondystrophic myotonias, and ryanodinopathies continues to grow with the advent of exon hierarchy analysis strategies for genetic screening and better understanding and recognition of disease phenotypes. Recent studies have expanded and clarified the role of gating pore current in channelopathy pathogenesis. It has been shown that the gating pore current can account for the molecular and phenotypic diseases observed in the muscle sodium channelopathies, and, given that homologous residues are affected in mutations of calcium channels, it is possible that pore leak represents a pathomechanism applicable to many channel diseases. Improvements in treatment of the muscle channelopathies are on the horizon. A randomized controlled trial has been initiated for the study of mexiletine in nondystrophic myotonias. The class IC antiarrhythmia drug flecainide has been shown to depress ventricular ectopy and improve exercise capacity in patients with Andersen-Tawil syndrome. Recent studies have expanded our understanding of gating pore current as a disease-causing mechanism in the muscle channelopathies and have allowed new correlations to be drawn between disease genotype and phenotype.


Activation of the succinate receptor GPR91 in macula densa cells causes renin release.
Macula densa (MD) cells of the juxtaglomerular apparatus (JGA) are salt sensors and generate paracrine signals that control renal blood flow, glomerular filtration, and release of the prohypertensive hormone renin. We hypothesized that the recently identified succinate receptor GPR91 is present in MD cells and regulates renin release. Using immunohistochemistry, we identified GPR91 in the apical plasma membrane of MD cells. Treatment of MD cells with succinate activated mitogen-activated protein kinases (MAPKs; p38 and extracellular signal-regulated kinases 1/2) and cyclooxygenase 2 (COX-2) and induced the synthesis and release of prostaglandin E(2), a potent vasodilator and classic paracrine mediator of renin release. Using microperfused JGA and real-time confocal fluorescence imaging of quinacrine-labeled renin granules, we detected significant renin release in response to tubular succinate (EC(50) 350 microM). Genetic deletion of GPR91 (GPR91(-/-) mice) or pharmacologic inhibition of MAPK or COX-2 blocked succinate-induced renin release. Streptozotocin-induced diabetes caused GPR91-dependent upregulation of renal cortical phospho-p38, extracellular signal-regulated kinases 1/2, COX-2, and renin content. Salt depletion for 1 wk increased plasma renin activity seven-fold in wild-type mice but only 3.4-fold in GPR91(-/-) mice. In summary, MD cells can sense alterations in local tissue metabolism via accumulation of tubular succinate and GPR91 signaling, which involves the activation of MAPKs, COX-2, and the release of prostaglandin E(2). This mechanism may be integral in the regulation of renin release and activation of the renin-angiotensin system in health and disease.


A Case Study of Anisakiasis in the Palatine Tonsils.
Anisakidosis is a nematode infection caused by the ingestion of larvae-infected raw or undercooked fish. Although gastric anisakiasis is a common disease in Japan due to the popularity of eating raw and undercooked fish, reports of anisakiasis in the tonsils are extremely rare. A 68-year-old man presenting with clinical features of peritonsillitis was admitted for examination. The right peritonsillar region exhibited slight edematous swelling and rash, and a white foreign body was observed. This foreign body was removed, and pathological examination revealed Anisakis.


Temporal summation--the key to motor evoked potential spinal cord monitoring in humans.
Spinal motor evoked potentials (SMEP) were recorded from tibialis anterior muscle after epidural stimulation of the spinal cord at the low cervical or high thoracic level during scoliosis surgery. By using a double stimulus pulse to produce temporal summation within the spinal cord a maximal CMAP response was readily achieved despite good surgical anaesthesia.


Basic motifs target PSGL-1, CD43, and CD44 to plasma membrane sites where HIV-1 assembles.
HIV-1 incorporates various host membrane proteins during particle assembly at the plasma membrane; however, the mechanisms mediating this incorporation process remain poorly understood. We previously showed that the HIV-1 structural protein Gag localizes to the uropod, a rear-end structure of polarized T cells, and that assembling Gag copatches with a subset, but not all, of the uropod-directed proteins, i.e., PSGL-1, CD43, and CD44, in nonpolarized T cells. The latter observation suggests the presence of a mechanism promoting virion incorporation of these cellular proteins. To address this possibility and identify molecular determinants, in the present study we examined coclustering between Gag and the transmembrane proteins in T and HeLa cells using quantitative two-color superresolution localization microscopy. Consistent with the findings of the T-cell copatching study, we found that basic residues within the matrix domain of Gag are required for Gag-PSGL-1 coclustering. Notably, the presence of a polybasic sequence in the PSGL-1 cytoplasmic domain significantly enhanced this coclustering. We also found that polybasic motifs present in the cytoplasmic tails of CD43 and CD44 also promote their coclustering with Gag. ICAM-1 and ICAM-3, uropod-directed proteins that do not copatch with Gag in T cells, and CD46, a non-uropod-directed protein, showed no or little coclustering with Gag. However, replacing their cytoplasmic tails with the cytoplasmic tail of PSGL-1 significantly enhanced their coclustering with Gag. Altogether, these results identify a novel mechanism for host membrane protein association with assembling HIV-1 Gag in which polybasic sequences present in the cytoplasmic tails of the membrane proteins and in Gag are the major determinants. Nascent HIV-1 particles incorporate many host plasma membrane proteins during assembly. However, it is largely unknown what mechanisms promote the association of these proteins with virus assembly sites within the plasma membrane. Notably, our previous study showed that HIV-1 structural protein Gag colocalizes with a group of uropod-directed transmembrane proteins, PSGL-1, CD43, and CD44, at the plasma membrane of T cells. The results obtained in the current study using superresolution localization microscopy suggest the presence of a novel molecular mechanism promoting the association of PSGL-1, CD43, and CD44 with assembling HIV-1 which relies on polybasic sequences in HIV-1 Gag and in cytoplasmic domains of the transmembrane proteins. This information advances our understanding of virion incorporation of host plasma membrane proteins, some of which modulate virus spread positively or negatively, and suggests a possible new strategy to enrich HIV-1-based lentiviral vectors with a desired transmembrane protein.


Effect of cesarean section on relapse of childhood idiopathic nephrotic syndrome.
In parallel with the increase in the prevalence of childhood chronic diseases, the rate of cesarean delivery has risen during the past decades. This study tested the hypothesis that children delivered by cesarean section (CS) have a higher risk of relapse of idiopathic nephrotic syndrome (INS). Fifty-six children with INS were categorized into three groups. Group A consisted of patients with INS who had no relapses after the onset of INS; group B consisted of patients with INS who had infrequent relapse; and group C consisted of patients with INS who had frequent relapse. The number of enrolled patients in groups A, B, and C was 10, 14, and 32, respectively. The ratio of neonates delivered via CS was significantly higher in group C (37.5%, P < 0.001) than in groups A (0%) and B (7.1%). This study shows that CS is associated with an increased risk of relapse of childhood INS.


Evidence for a Genotype-Phenotype Correlation in Patients with Pathogenic GLUT2 (SLC2A2) Variants.
Fanconi-Bickel syndrome (FBS) is a very rare but distinct clinical entity with the combined features of hepatic glycogen storage disease, generalized proximal renal tubular dysfunction with disproportionately severe glucosuria, and impaired galactose tolerance. Here, we report five cases (out of 93 diagnosed in our lab) with pathogenic variants on both GLUT2 (SLC2A2) alleles. They come from 3 families and presented with an exceptionally mild clinical course. This course was correlated to data from old and most recent expression and transport studies in Xenopus oocytes. GLUT2 genotype in patients 1 and 2 was p.[153_4delLI];[P417R] with the first variant exhibiting normal membrane expression and partially retained transport activity (5.8%) for 2-deoxyglucose. In patient 3, the very first GLUT2 variant ever detected (p.V197I) was found, but for the first time it was present in a patient in the homozygous state. This variant had also shown unaffected membrane expression and remarkable residual activity (8%). The genotype in patient 4, p.[153_4delLI];[(E440A)], again included the 2-amino-acid deletion with residual transporter function, and patient 5 is the first found to be homozygous for this variant. Our results provide further evidence for a genotype-phenotype correlation in patients with GLUT2 variants; non-functional variants result in the full picture of FBS while dysfunctional variants may result in milder presentations, even glucosuria only, without other typical signs of FBS.


NO (nitric oxide): the ring master.
The migration and proliferation of endothelial cells affect the process of angiogenesis or the formation of blood vessels. Endothelial cells interact with each other to form ring-like structures in monolayers and tubular structures in matrigels. However, the transit phase between the individual endothelial cells and fully formed tubular structures is yet to be established. Guided by imaging, Western blot analysis, drug perturbation studies and siRNA studies we validate that endothelial ring structures are the fundamental and monomeric units of capillary tubes and nitric oxide is implicated in their fabrication. Giving input from experimental data, we used bagging classifier and information-gain to determine some of the physical and chemical parameters that define these biological structures. Further, we elucidated the implications of endothelial nitric oxide synthase and the NO/sGC/cGMP pathway in the formation of endothelial rings. We conclude that, formation of endothelial ring structure is important for angiogenesis and is mediated by the NO/sGC/cGMP pathway; and further endothelial rings can be used as in vitro models to study angiogenesis.


Sudden daytime sleep onset in Parkinson's disease: polysomnographic recordings.
Sleep attacks in Parkinson's disease are controversially discussed. This paper describes a patient with Parkinson's disease suffering from sudden, irresistible onset of sleep during daytime. Medication included levodopa, entacapone, budipine, and cabergoline. Introduction of entacapone was the last therapeutic action preceding onset of sleep events, suggesting increased bioavailabilty of levodopa to be provocative in this case. In contrast to previous cases, the sudden sleep events were witnessed by clinical staff members and documented by polysomnographic and video recordings. Polysomnography during these sleep events remarkably showed abrupt slowing of EEG-background activity and occurrence of slow eye movements and K-complexes within 10 seconds after stable wakefulness. Within 60 seconds, the polysomnographic pattern proceeded to stable sleep stage 2.


Educational Level, Anticoagulation Quality, and Clinical Outcomes in Elderly Patients with Acute Venous Thromboembolism: A Prospective Cohort Study.
Whether the level of education is associated with anticoagulation quality and clinical outcomes in patients with acute venous thromboembolism (VTE) is uncertain. We thus aimed to investigate the association between educational level and anticoagulation quality and clinical outcomes in elderly patients with acute VTE. We studied 817 patients aged ≥65 years with acute VTE from a Swiss prospective multicenter cohort study (09/2009-12/2013). We defined three educational levels: 1) less than high school, 2) high school, and 3) post-secondary degree. The primary outcome was the anticoagulation quality, expressed as the percentage of time spent in the therapeutic INR range (TTR). Secondary outcomes were the time to a first recurrent VTE and major bleeding. We adjusted for potential confounders and periods of anticoagulation. Overall, 56% of patients had less than high school, 25% a high school degree, and 18% a post-secondary degree. The mean percentage of TTR was similar across educational levels (less than high school, 61%; high school, 64%; and post-secondary, 63%; P = 0.36). Within three years of follow-up, patients with less than high school, high school, and a post-secondary degree had a cumulative incidence of recurrent VTE of 14.2%, 12.9%, and 16.4%, and a cumulative incidence of major bleeding of 13.3%, 15.1%, and 15.4%, respectively. After adjustment, educational level was neither associated with anticoagulation quality nor with recurrent VTE or major bleeding. In elderly patients with VTE, we did not find an association between educational level and anticoagulation quality or clinical outcomes.


Peripheral B lymphocyte percentage as an indicator of subclinical progression of bovine leukemia virus infection.
The relationship between percentage of B cells in peripheral blood and subclinical bovine leukemia virus infection was examined in a herd of 240 Holstein-Friesian cows. Absolute leukocyte count and absolute lymphocyte count were significantly positively correlated with B cell percentage in cows that were seropositive to bovine leukemia virus envelope glycoprotein, but these parameters were not correlated in seronegative cows. The B cell percentage was not affected by age. Cows that had persistent lymphocytosis and hematologically normal seropositive cows had greater mean B cell percentages (78 and 45%, respectively) than did seronegative herdmates (37%). To evaluate B cell percentage as a means of detecting subclinical progression of bovine leukemia virus infection, an index was developed based upon the distribution of B cell percentages in seronegative cows. When this index was compared with a standard hematological key (the European Community's Leukosis Key), which is based on absolute lymphocyte count and age, 29% of seropositive, hematologically normal cows had B cell percentages two standard deviations above the mean of their seronegative herdmates. The B cell percentage was thus shown to be more effective than absolute lymphocyte count for detecting subclinical progression of bovine leukemia virus infection in individual cows.


Association between variants of MTHFR genes and psychiatric disorders: A meta-analysis.
Psychiatric disorders have seriously affected human life, one of the risk genes related to psychosis is the methylenetetrahydrofolatereductase (MTHFR) gene. This gene has a potential role in psychiatric disorders. Therefore, a meta-analysis is conducted to investigate the correlations between two prevalent MTHFR single nucleotide polymorphisms (SNPs), MTHFR C677T, A1298C, severe psychological disorders (schizophrenia, major depression, bipolar disorder). A total of 81 published studies were screened and selected by a search of electronic databases up to April 2022. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the association between MTHFR polymorphism and psychiatric disorders susceptibility by using random effect models. We found that MTHFR C677T polymorphism is significantly related to schizophrenia and major depression in the overall population. MTHFR C677T has been linked to an increased risk of bipolar disorder in the recessive model (TT vs. CT + CC). Ethnic subgroup analysis shows that schizophrenia and major depression significantly correlate with MTHFR C677T and A1298C in Asian populations but not Caucasians. Besides, schizophrenia is correlated substantially with MTHFR C677T in the African population. However, the MTHFR A1298C polymorphism is only marginally linked to major depression. Findings of the current study revealed that MTHFR may contribute to the common pathogenesis of psychiatric diseases and that its variants may be essential in controlling the expression of psychosis-related genes. This study could help the researchers and health specialists in the early diagnosis and treatment of psychiatric disorders.


Immunosuppression minimization protocols: how should they be monitored?
This Practice Point commentary discusses the experience of Shapiro et al. with renal allograft recipients at a single center who underwent significant minimization of immunosuppressive treatment with alemtuzumab induction and tacrolimus monotherapy (weaned to three times weekly by 1 year after transplantation). Donor-specific antibodies (DSAs) against human leukocyte antigen were monitored after transplantation in some patients. Although 44% of patients did not develop acute rejection or DSAs and had excellent 2-year graft survival (96%), spaced weaning was not attempted in 20% of patients, generally those with early rejection and poor allograft function. During tapering, 20% of patients developed acute rejection and 15% developed DSAs. Two-year graft survival was 63% in patients for whom weaning was not attempted and 78% in patients who experienced acute rejection. Alemtuzumab preconditioning with tacrolimus monotherapy and spaced weaning increased the risk of acute rejection and development of DSAs. Patients should be carefully selected for this protocol and monitored closely for DSAs. Results of a long-term controlled trial that includes protocol biopsies are required to reach more-definitive conclusions.


Evaluation of two commercial loop-mediated isothermal amplification assays for detection of avian influenza H5 and H7 hemagglutinin genes.
Real-time reverse transcription loop-mediated isothermal amplification (real-time RT-LAMP) holds substantial potential as a highly sensitive, specific, and easy-to-perform molecular technique for pathogen detection in clinical samples. In the current study, the analytical and diagnostic performance of 2 commercial real-time RT-LAMP kits, Avian Flu H5 and Avian Flu H7, in detecting Avian influenza virus (AIV) infections were evaluated and compared with validated real-time reverse transcription polymerase chain reaction (RT-PCR) assays using RNA from reference virus isolates of subtypes H5 (n = 24) and H7 (n = 25) and of phylogenetically related subtypes (n = 20). When real-time RT-LAMP was carried out according to the recommendations of the manufacturer, 3 out of 24 H5 isolates and 8 out of 25 H7 reference strains were not detected. Prolonging the amplification phase resulted in detection of all H5 isolates but also in false positive detection of 2 non-H5 isolates. Real-time RT-LAMP specific to H7 failed to detect 2 H7 isolates after prolonged amplification. According to the examination of RNA log dilutions, the sensitivity of the real-time RT-LAMP assays, for a number of historic but also recent strains, was considerably lower compared with subtype-specific real-time RT-PCR assays. Application of the real-time RT-LAMP assays for analysis of diagnostic samples from wild birds confirmed their lower sensitivity. Commercial real-time RT-LAMP as tested in this study with a broad range of AIV H5 and H7 strains of phylogenetically diverse yet recent origin, holds some promise for routine veterinary diagnostic purposes, although real-time RT-LAMP was markedly more vulnerable to a reduction of detection limits because of strain-specific sequence variation than subtype-specific real-time RT-PCR.


Inhibition of tyrosylprotein sulfotransferase by sphingosine and its reversal by acidic phospholipids.
Although tyrosylprotein sulfation has been implicated in the processing of several secretory proteins, nothing is known about the regulation of the enzyme responsible for this event. When poly(Glu6, Ala3, Tyr1) (EAY; M(r) 47,000) was employed as sulfate acceptor, the tyrosylprotein sulfotransferase (TPST) from Golgi membranes of submandibular salivary gland was used to study the effect of various lipids on the expression of its activity. The TPST activity in the Golgi membrane was 38 pmol (mg of protein)-1 (30 min)-1. Approximately 90% of the total activity present in Golgi membranes was extracted by NaCl and Triton X-100 treatment. The Km values of solubilized TPST for EAY and 3'-phosphoadenosine 5'-phosphosulfate (PAPS) were 0.04 and 0.25 microM, respectively. Among the various lipids tested, sphingosine showed maximum inhibition of TPST activity followed by sphingomyelin and phosphatidylcholine (PC). Of the two sphingosine analogs tested, threosphinganine was as effective as sphingosine in TPST inhibition, while erythrosphinganine had little effect. In contrast, the acidic phospholipids phosphatidylinositol (PI) and phosphatidylserine (PS) and oleic acid showed slight stimulation. Half-maximal inhibition of TPST was obtained at 150 microM sphingosine (6 mol % when expressed as mole percent of sphingosine to total phospholipids plus Triton X-100). The inhibition was competitive with respect to EAY and uncompetitive with respect to PAPS. The inhibition caused by sphingosine could be reversed by PI, PS, and oleic acid but not by PC and sphingomyelin. Sphingosine inhibition of TPST activity was also observed in the enzyme isolated from several other tissues such as liver, lung, heart, and cerebellum.(ABSTRACT TRUNCATED AT 250 WORDS)


Machine Learning SNP Based Prediction for Precision Medicine.
In the past decade, precision genomics based medicine has emerged to provide tailored and effective healthcare for patients depending upon their genetic features. Genome Wide Association Studies have also identified population based risk genetic variants for common and complex diseases. In order to meet the full promise of precision medicine, research is attempting to leverage our increasing genomic understanding and further develop personalized medical healthcare through ever more accurate disease risk prediction models. Polygenic risk scoring and machine learning are two primary approaches for disease risk prediction. Despite recent improvements, the results of polygenic risk scoring remain limited due to the approaches that are currently used. By contrast, machine learning algorithms have increased predictive abilities for complex disease risk. This increase in predictive abilities results from the ability of machine learning algorithms to handle multi-dimensional data. Here, we provide an overview of polygenic risk scoring and machine learning in complex disease risk prediction. We highlight recent machine learning application developments and describe how machine learning approaches can lead to improved complex disease prediction, which will help to incorporate genetic features into future personalized healthcare. Finally, we discuss how the future application of machine learning prediction models might help manage complex disease by providing tissue-specific targets for customized, preventive interventions.


[Solitary hypermetabolic bone focus in the initial extension study of a prostate carcinoma].
56 year old male who was diagnosed of Prostatic Neoplasm by transrectal biopsy after elevated PSA level was found by chance in a routine control. The initial extension study with abdominal and pelvic CT did not show significant radiological abnormalities. This was followed by a whole body bone scintigraphy with 99mTc-MDP that showed a solitary hypermetabolic lesion within skull. A SPECT study placed this lesion at the left occipital region. An MRI and a CT head scan were carried out to characterize the isotopic lesion, finding no bone abnormalities to justify the mentioned uptake. Given the absence of a radiological benign diagnosis, a further FDG-PET scan was carried out which did not show either increased glycolytic activity at the left occipital region, or in the prostatic gland. In order to guide the biopsy, a CT head scan was repeated which showed what appeared to be an incipient blastic lesion in the scale of the left occipital bone, establishing the differential diagnosis between a metastasis and a benign process. The anatomopathologic analysis of the bone tissue describes a necrotic process without inflammatory reaction (osteonecrosis).


Angular spectral framework to test full corrections of paraxial solutions: erratum.
In our previous article [J. Opt. Soc. Am. A32, 1236 (2015)JOAOD60740-323210.1364/JOSAA.32.001236] there is an issue concerning the comparison of plane wave spectrum solutions of paraxial and Helmholtz equations. We compared the angular plane wave spectrum of Helmholtz solutions with the plane wave spectrum of the paraxial solutions in terms of normalized projections of paraxial wave vectors. We show that the proper comparison of plane wave spectra must be done in terms of angles. The results presented in our previous work are corrected accordingly. The most important change is that Wünsche's T2 operator leads to a valid method.


Homeward bound: Yemeni return migration.
The author discusses the return migration of Yemenis from Saudi Arabia during the period 1970-1989. "Through the use of original, empirical data collected in Yemen, this article sheds light on who these returning migrants are, where they have come from, and what sort of future awaits them.... The survey conducted on return migration was administered in the winter and spring of 1989 in a region of North Yemen called al-Hujariyya."


Mindfulness meditation research: issues of participant screening, safety procedures, and researcher training.
Increasing interest in mindfulness meditation (MM) warrants discussion of research safety. Side effects of meditation with possible adverse reactions are reported in the literature. Yet participant screening procedures, research safety guidelines, and standards for researcher training have not been developed and disseminated in the MM field of study. The goal of this paper is to summarize safety concerns of MM practice and offer scholars some practical tools to use in their research. For example, we offer screener schematics aimed at determining the contraindication status of potential research participants. Moreover, we provide information on numerous MM training options. Ours is the first presentation of this type aimed at helping researchers think through the safety and training issues presented herein. Support for our recommendations comes from consulting 17 primary publications and 5 secondary reports/literature reviews of meditation side effects. Mental health consequences were the most frequently reported side effects, followed by physical health then spiritual health consequences. For each of these categories of potential adverse effects, we offer MM researchers methods to assess the relative risks of each as it pertains to their particular research programs.


Determination of propranolol and carvedilol in urine samples using a magnetic polyamide composite and LC-MS/MS.
β-blockers are compounds that bind with adrenoreceptors hindering their interaction with adrenalin and noradrenalin. They are clinically relevant and they are also used in some sport as doping agents. A new method based on the combination of dispersive micro-solid phase extraction and LC-MS/MS has been developed to determine propranolol and carvedilol in urine samples. For this purpose a magnetic-polyamide composite is synthesized and used as sorbent. Working under the optimum conditions, the method provides limits of detection and quantification in the range of 0.1-0.15 μg/l and 0.3-0.5 μg/l, for carvedilol and propranolol, respectively. The precision, expressed as RSD, was better than 9.6% and the relative recoveries varied between 73.7 and 81.3%. The methodology is appropriate for the determination of β-blockers in urine samples at the low microgram per liter range for therapeutic purposes.


[Plasmocytoma of the skull base revealing multiple myeloma].
We report a case of sphenoidal plasmocytoma in a 57-year-old male revealing multiple myeloma. MRI showed a tumor located in the sphenoid sinus with local extension. Diagnosis was made by histology after transsphenoidal resection. We discuss the imaging features of plasmocytomas and review the principal differential diagnoses.


Effects of rhythmic auditory stimulation on vision: Oscillations in performance can be enhanced, but not induced.
A variety of reports suggest that rhythmic auditory stimulation can entrain visual perception, inducing perceptual oscillations as a function of time relative to the auditory rhythm. These effects have, to date, been reported only for stimulation frequencies at and below 3 Hz. Here we investigate the effects of rhythmic auditory stimulation on the detection of masked visual targets when this stimulation occurs at frequencies to which the visual system has been shown to entrain (8-12 Hz). Across four experiments, we found no consistent evidence of poststimulation modulations in performance induced by 8.5, 10.6, or 12.1 Hz auditory stimulation. This absence of a consistent auditory-to-visual effect was paralleled by an absence of unimodal effects (oscillations in auditory performance) following 12.1 Hz auditory stimulation. In a fifth experiment, we found that although auditory stimulation alone did not induce oscillations in visual performance, auditory stimulation did enhance the effects of concurrent visual stimulation. Notably, this enhancement did not require synchronous presentation of stimuli. These observations are consistent with recent reports that passive auditory stimulation beyond 5 Hz induces neither auditory perceptual oscillations nor visual cortical oscillations and suggest limits to the extent of cross-modal entrainment. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


Jeotgalicoccus halophilus sp. nov., isolated from salt lakes.
Two slightly halophilic bacterial strains, C1-52(T) and YD-9, were isolated from Daban and Aiding salt lakes in Xinjiang, China, respectively. The isolates were gram-positive, non-endospore-forming, non-motile, facultatively anaerobic cocci. Colonies were pale yellow, and a light pink, diffusible pigment was produced after a few additional days of incubation. The isolates grew optimally with 2-3 % (w/v) NaCl, at pH 7.5 and at 30-35 °C. The peptidoglycan type was L-Lys-Gly(3-4)-L-Ala(Gly). The menaquinones were MK-7 (83.2 %) and MK-6 (16.8 %). The major fatty acids (>10 %) were anteiso-C(15 : 0) and iso-C(15 : 0). The DNA G+C content of strains C1-52(T) and YD-9 was 41.2 and 41.0 mol%, respectively. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strains C1-52(T) and YD-9 were closely related to Jeotgalicoccus psychrophilus YKJ-115(T) (98.0 and 97.1 % 16S rRNA gene sequence similarity, respectively), followed by Jeotgalicoccus halotolerans YKJ-101(T) (97.1 and 96.8 %). Strains C1-52(T) and YD-9 shared, respectively, 20 and 11 % DNA-DNA relatedness with J. halotolerans JCM 11198(T) and 8 and 13 % with J. psychrophilus JCM 11199(T). DNA-DNA relatedness between the isolates was 91 %. On the basis of phenotypic and phylogenetic distinctiveness, strains C1-52(T) and YD-9 belonged to the same species, which should be placed in the genus Jeotgalicoccus as a novel species. The name Jeotgalicoccus halophilus sp. nov. is proposed, with the type strain C1-52(T) ( = CGMCC 1.8911(T) = NBRC 105788(T)).


Genetics of tolerance to heat stress in milk yield of dairy buffaloes assessed by a reaction norm model.
The objectives of this study were to assess the effects of heat stress on the milk yield and investigate the presence of genotype × environment interaction (G × E) in Brazilian Murrah buffaloes reared under tropical conditions. With this, 58,070 test-day (TD) records for milk yield from 3,459 first lactations of buffaloes collected between 1987 and 2018 were evaluated. A mixed model considering days in milk (DIM) and temperature-humidity index (THI) was applied to quantify milk yield losses due to heat stress. The most detrimental effect of THI on TD milk yield was observed in the mid-stages of lactation, after lactation peak, in DIM 105-154 and 155-204 days (-0.020 and -0.015 kg/day per THI, respectively). The least-squares means of TD milk yield were used to identify a heat stress threshold using a piecewise linear regression model. A substantial reduction in TD milk yield due to heat stress was observed for THI values above 77.8 (-0.251 kg/day per increase of 1 THI unit). An analysis using a single-trait random regression animal model was carried out to estimate variance components and genetic parameters for TD milk yield over THI and DIM values. Increased additive genetic variance and heritability estimates were observed for extreme THI values (THI = 60 and 80) combined with mid-lactation stages. The lowest genetic correlation (0.50) was observed between TD records at opposite extremes of the THI scale (THI = 60 vs. THI = 80). The genetic trends observed for the regression coefficients related to the general level of production (0.02) and specific ability to respond to heat stress (-0.002) indicated that selection to increase milk yield did not affect the specific ability to respond to heat stress until the present moment. These trends reflect the low genetic correlation between these components (0.05 ± 0.14). In this sense, monitoring trends of genetic components related to response to heat stress is recommended.


Participatory health research within a prison setting: a qualitative analysis of 'Paragraphs of passion'.
The purpose of this research was to engage, empower and enhance the health and well-being of incarcerated women. The integration of primary health care, community-based participatory research, a settings approach to health promotion, and transformative action research guided the design of this study. A partnership between incarcerated women who became peer-researchers, correctional staff, and academic researchers facilitated the equitable contribution of expertise and decision-making by all partners. The study was conducted in a short sentence (two years or less), minimum/medium security Canadian women's correctional centre. Of the approximately 200 women that joined the research team, 115 participated in writing a 'paragraph of passion' while incarcerated between November, 2005 and August, 2007. Participatory, inductive qualitative, narrative and content analysis were used to illuminate four themes: expertise, transformation, building self-esteem, as well as access and support. The women organized monthly health forums in the prison to share their new knowledge and life experience with other incarcerated women, correctional staff, academics, and community members, and in doing so have built bridges and relationships, some of which have lasted to the present day.


[Adverse effects of drugs in intensive care units: analysis of the administration of electrolyte solutions and antibiotics].
The aims of this study were: 1) to verify the incidence of adverse occurrences (AOs) with medication related to the time of electrolyte solutions infusion and the frequency of doses of antibiotics prescribed and administered to the patients; 2) to characterize the nature of those occurrences. The study was developed in two ICUs of a general hospital of São Paulo City. The population was composed by 51 patients that were in the ICUs in August of 1996. Sixty percent of the patients were older than 60 years, 58.8% were women, 49.1% remained in ICU from 1 to 4 days and 41.2% went to the Intermediate Care Units after ICU. Regarding the incidence of AOs related to the time of administration of the electrolyte solutions and the frequency of doses of antibiotics the non execution of the patient's medical prescriptions was verified in 76.3% and 38.8% respectively. The largest frequency of irregularities with the electrolyte solutions (60.2%) was the infusion faster than the prescribed time followed by the reduction of the number of doses of antibiotics administered. Taking these into consideration we have to invest in preventive measures to reduce those occurrences.


Hypoxia-specific gene expression for ischemic disease gene therapy.
Gene therapy for ischemic diseases has been developed with various growth factors and anti-apoptotic genes. However, non-specific expression of therapeutic genes may induce deleterious side effects such as tumor formation. Hypoxia-specific regulatory systems can be used to regulate transgene expression in hypoxic tissues, in which gene expression is induced in ischemic tissues, but reduced in normal tissues by transcriptional, translational or post-translational regulation. Since hypoxia-inducible factor 1 (HIF-1) activates transcription of genes in hypoxic tissues, it can play an important role in the prevention of myocardial and cerebral ischemia. Hypoxia-specific promoters including HIF-1 binding sites have been used for transcriptional regulation of therapeutic genes. Also, hypoxia-specific untranslated regions (UTRs) and oxygen dependent degradation (ODD) domains have been investigated for translational and post-translational regulations, respectively. Hypoxia-specific gene expression systems have been applied to various ischemic disease models, including ischemic myocardium, stroke, and injured spinal cord. This review examines the current status and future challenges of hypoxia-specific systems for safe and effective gene therapy of ischemic diseases.


Group II twintron: an intron within an intron in a chloroplast cytochrome b-559 gene.
The psbF gene of chloroplast DNAs encodes the beta-subunit of cytochrome b-559 of the photosystem II reaction center. The psbF locus of Euglena gracilis chloroplast DNA has an unusual 1042 nt group II intron that appears to be formed from the insertion of one group II intron into structural domain V of a second group II intron. Using both direct primer extension cDNA sequencing and cDNA cloning and sequencing, we have determined that a 618 nt internal intron is first excised from the 1042 nt intron of psbF pre-mRNA, resulting in a partially spliced pre-mRNA containing a 424 nt group II intron with a spliced domain V. The 424 nt intron is then removed to yield the mature psbF mRNA. Therefore, the 1042 nt intron of psbF is a group II intron within another group II intron. We use the term 'twintron' to define this new type of genetic element. Intermediates in the splicing pathway were detected by northern hybridization. Splicing of both the internal and external introns occurs via lariat intermediates. Twintron splicing was found to proceed by a sequential pathway, the internal intron being removed prior to the excision of the external intron. A possible mechanism for twintron formation by intron transposition is discussed.


Moxifloxacin Activates the SOS Response in Mycobacterium tuberculosis in a Dose- and Time-Dependent Manner.
Previous studies on Escherichia coli demonstrated that sub-minimum inhibitory concentration (MIC) of fluoroquinolones induced the SOS response, increasing drug tolerance. We characterized the transcriptional response to moxifloxacin in Mycobacterium tuberculosis. Reference strain H37Rv was treated with moxifloxacin and gene expression studied by qRT-PCR. Five SOS regulon genes, recA, lexA, dnaE2, Rv3074 and Rv3776, were induced in a dose- and time-dependent manner. A range of moxifloxacin concentrations induced recA, with a peak observed at 2 × MIC (0.25 μg/mL) after 16 h. Another seven SOS responses and three DNA repair genes were significantly induced by moxifloxacin. Induction of recA by moxifloxacin was higher in log-phase than in early- and stationary-phase cells, and absent in dormant bacilli. Furthermore, in an H37Rv fluoroquinolone-resistant mutant carrying the D94G mutation in the gyrA gene, the SOS response was induced at drug concentrations higher than the mutant MIC value. The 2 × MIC of moxifloxacin determined no significant changes in gene expression in a panel of 32 genes, except for up-regulation of the relK toxin and of Rv3290c and Rv2517c, two persistence-related genes. Overall, our data show that activation of the SOS response by moxifloxacin, a likely link to increased mutation rate and persister formation, is time, dose, physiological state and, possibly, MIC dependent.


Composition and thermochemistry of silver bromide vapor.
The mole fractions of AgBr and Ag3Br3 in the saturated vapor at 840 K have been evaluated from the vapor mass spectrum, by comparison with the corresponding spectrum of AgCl vapor, where the monomer/trimer ratio is known accurately from vapor molecular weight measurements. Combination of these results with new measurements of the vapor pressure of molten AgBr by the torsion-effusion method in the range 805-936 K yielded the third law enthalpies of vaporization and the standard enthalpies of formation DeltafH degrees 298(AgBr, g) = 27.8 +/- 0.3 kcal mol(-1) and DeltafH degrees 298(Ag3Br3, g) = -19.0 +/- 1 kcal mol(-1). The dissociation energy, D degrees 0(AgBr), is found to be 66.4 +/- 0.3 kcal mol(-1), or 2.88 +/- 0.01 eV, some 3.5-5 kcal mol(-1) lower than previous literature values. Approximate thermochemical stabilities of the dimer species Ag2Cl2 and Ag2Br2 have also been evaluated.


[Variability of the clinical expression of Ecstasy-induced hepatotoxicity].
3,4-methylenedioxymethamphetamine (MDMA) is an amphetamine derivative, known as ecstasy. Because of its euphoric effects, the use of this substance as a drug of abuse is becoming increasingly widespread. The development of hyperthermia, disseminated intravascular coagulation, rhabdomyolysis, acute renal failure, cardiac arrhythmia and neurotoxicity have been described in association with the use of this drug. Moreover, in the last few years, cases of liver involvement, associated or not with the above-mentioned entities, have been described, ranging from mild acute hepatitis to fulminant hepatic failure and death. We present four cases of ecstasy-induced hepatotoxicity. Outcome was favorable in three patients while the fourth required liver transplantation. Consequently, ecstasy ingestion should be ruled out as a cause of acute non-viral hepat


The effect of swimming on cartilage formation.
Swimming is a non-weight-bearing exercise. Therefore it has the advantage of maintaining skeletal integrity in aged persons with weakened skeletal structures. Unlike other weight-bearing aerobic exercises, however, it does not appear to exert sufficient stimulus on bone-remodeling activities because the local load-bearing on bone tissues is mild. The purpose of this study was to investigate the effect of swimming on bone remodeling, especially with the use of implanted pellets containing bone morphogenetic protein (BMP) and demineralized bone matrix during the initial stages of the differentiation of mesenchymal cells to cartilage cells. Six-week-old female rats were divided into the swimming group and a control, nonswimming group. Test animals were forced to swim in a water bath for 30 min daily for 2 wk. After the swimming protocol, pellets were implanted and harvested. Messenger RNA isolated from pellets was quantified by means of a reverse transcription-polymerase chain reaction. The expression of RNAs for bone sialoprotein and BMP-6 in pellets from the swimming group was apparently enhanced at 7 d after implantation. These results suggested that systemic hormonal and/or metabolic changes that promote cartilage formation might have occurred after swimming because the effect was observed after the swimming protocol had ended and the pellets were implanted at a non-weight-bearing site.


Microextensive chaos of a spatially extended system.
By analyzing chaotic states of the one-dimensional Kuramoto-Sivashinsky equation for system sizes L in the range 79 < or = L < or = 93, we show that the Lyapunov fractal dimension D scales microextensively, increasing linearly with L even for increments Delta L that are small compared to the average cell size of 9 and to various correlation lengths. This suggests that a spatially homogeneous chaotic system does not have to increase its size by some characteristic amount to increase its dynamical complexity.


Biglycan fragmentation in pathologies associated with extracellular matrix remodeling by matrix metalloproteinases.
The proteoglycan biglycan (BGN) is involved in collagen fibril assembly and its fragmentation is likely to be associated with collagen turnover during the pathogenesis of diseases which involve dysregulated extracellular matrix remodeling (ECMR), such as rheumatoid arthritis (RA) and liver fibrosis. The scope of the present study was to develop a novel enzyme-linked immunosorbent assay (ELISA) for the measurement of a MMP-9 and MMP-12-generated biglycan neo-epitope and to test its biological validity in a rat model of RA and in two rat models of liver fibrosis, chosen as models of ECMR. Biglycan was cleaved in vitro by MMP-9 and -12 and the 344'YWEVQPATFR'353 peptide (BGM) was chosen as a potential neo-epitope. A technically sound competitive ELISA for the measurement of BGM was generated and the assay was validated in a bovine cartilage explant culture (BEX), in a collagen induced model of rheumatoid arthritis (CIA) and in two different rat models of liver fibrosis: the carbon tetrachloride (CCL4)-induced fibrosis model, and the bile duct ligation (BDL) model. Significant elevation in serum BGM was found in CIA rats compared to controls, in rats treated with CCL4 for 16 weeks and 20 weeks compared to the control groups as well as in all groups of rats subject to BDL compared with sham operated groups. Furthermore, there was a significant correlation of serum BGM levels with the extent of liver fibrosis determined by the Sirius red staining of liver sections in the CCL4 model. We demonstrated that the specific tissue remodeling product of MMPs-degraded biglycan, namely the neo-epitope BGM, is correlated with pathological ECMR. This assay represents both a novel marker of ECM turnover and a potential new tool to elucidate biglycan role during the pathological processes associated with ECMR.


Role of arachidonic acid metabolites in oleic acid induced pulmonary injury in a canine model. Effect of ketoconazole (thromboxane synthetase inhibitor).
This study was designed to investigate the effects of ketoconazole, a thromboxane synthetase inhibitor, on pulmonary and systemic hemodynamics and pulmonary function in experimental respiratory distress syndrome. Pulmonary artery infusion of oleic acid (PAIOA), 0.1 ml/kg, was used to cause lung injury. Ten dogs were randomized into two groups (Gps): Gp I (n = 5) acted as control, whereas Gp II (n = 5) were treated with IV ketoconazole (2.5 mg/kg bolus then 10 mg/kg/hour for 2.5 hours). Hemodynamics, extravascular lung water (EVLW), serum levels of PGE2, and TxB2 were obtained at baseline (BL) and at 30-minute intervals for 2.5 hours (T30-T150). After 30 minutes of PAIOA the mean arterial pressure (MAP) decreased significantly in both Gps (131 +/- 17 vs. 88 +/- 9 mmHg Gp 1, 119 +/- 9 vs. 79 +/- 8 mmHg Gp II, P less than 0.05); however, while MAP returned to BL values in Gp II, it remained significantly lower throughout the experimental interval in Gp I. Mean pulmonary artery pressure (MAP) was not significantly affected by PAIOA in either Gp, while pulmonary vascular resistance increased significantly from BL at T120 in Gp II. Pulmonary function measured by partial pressure of arterial O2 (PaO2) and extravascular lung water (EVLW) were significantly affected by PAIOA. There was a significant decrease in PaO2 (66 +/- 6 vs. 96 +/- 8 mmHg, Gp I and 60 +/- 7 vs. 100 +/- 6 mmHg, Gp II) as well as an increase in EVLW (604 +/- 61 vs. 135 +/- 9 ml, Gp I and 641 +/- 110 vs. 117 +/- 18 ml, Gp II) in both Gps.(ABSTRACT TRUNCATED AT 250 WORDS)


The Bidirectional in Bilingual: Cognitive, Social and Linguistic Effects of and on Third-Age Language Learning.
Bilingualism has been put forward as a life experience that, similar to musical training or being physically active, may boost cognitive performance and slow down age-related cognitive decline. In more recent years, bilingualism has come to be acknowledged not as a trait but as a highly individual experience where the context of use strongly modulates any cognitive effect that ensues from it (cf. van den Noort et al., 2019). In addition, modulating factors have been shown to interact in intricate ways (Pot, Keijzer and de Bot, 2018). Adding to the complexity is the fact that control processes linked to bilingualism are bidirectional-just as language control can influence cognitive control, individual differences in cognitive functioning often predict language learning outcomes and control. Indeed, Hartsuiker (2015) posited the need for a better understanding of cognitive control, language control as well as the transfer process between them. In this paper, we aim to shed light on the bidirectional and individual cognitive, social and linguistic factors in relation to bilingualism and second language learning, with a special focus on older adulthood: (1) we first show the intricate clustering of modulating individual factors as deterministic of cognitive outcomes of bilingual experiences at the older end of the lifespan; (2) we then present a meta-study of work in the emergent field of third-age language learning, the results of which are related to lifelong bilingualism; (3) objectives (1) and (2) are then combined to result in a blueprint for future work relating cognitive and social individual differences to bilingual linguistic outcomes and vice versa in the context of third-age language learning.


Biomechanical concepts of fracture healing in weight-bearing long bones.
Fracture healing is a complex process in which mechanical forces are essential for the regeneration of bone tissue. Mechanical loading can induce osteogenesis through the process of mechanotransduction. Current data on how mechanical loading stimulates fracture healing in weight-bearing long bones are presented. The role of mechanosensors, loading-induced interstitial fluid flow, streaming potentials, the biophysical environment of the fracture gap and the significance of timing, strains and distribution of mechanical stimulation in long bone fractures are reviewed. Remodelling and biomechanical concepts of fracture healing are discussed from a clinical perspective.


Hypertension as the presenting feature of the antiphospholipid syndrome.
The antiphospholipid or Hughes syndrome is the association between antiphospholipid antibodies (aPL), venous and arterial thromboses and pregnancy morbidity. Antiphospholipid syndrome (APS) commonly coexists with autoimmune diseases usually systemic lupus erythematosus (SLE), when it is known as secondary APS. When present in isolation it is known as primary APS (PAPS). Although the kidney may be affected in APS, its involvement is perhaps not as well described as that of other organs. Thrombotic microangiopathy (TMA) affecting the kidney has been reported as a manifestation in both primary and secondary APS. This report describes hypertension related to underlying renal TMA as a presenting symptom of APS.


Inhibition of gastrointestinal lipolysis by Orlistat during digestion of test meals in healthy volunteers.
The inhibition of digestive lipases by the antiobesity drug Orlistat along with lipolysis levels and fecal fat excretion were measured in healthy humans. Orlistat was found to be a powerful gastric lipase inhibitor, achieving 46.6--91.4% enzyme inhibition and thus greatly reducing gastric lipolysis of solid and liquid meals (11--33% of respective controls). Gastric lipase inhibition by Orlistat was extremely fast (half-inhibition time < 1 min). Duodenal lipolysis was reduced significantly by Orlistat given with the solid meal (32.6--37.6% of controls) but was only slightly reduced by Orlistat given with the liquid meal (74.5--100% of controls). Human pancreatic lipase (HPL) inhibition was found to be high (51.2--82.6%), however, regardless of the meal. These paradoxical results were explained when in vitro lipolysis experiments were performed. The rates of HPL inhibition by Orlistat were found to be similar with both types of meals (half-inhibition time 5--6 min), but the preemulsified triglycerides of the liquid meal were rapidly hydrolyzed by HPL before the enzyme was significantly inhibited by Orlistat. With the solid meal, the rate of hydrolysis of the meal triglycerides by HPL was slower than the rate of HPL inhibition by Orlistat. As predicted from the previous results, the effects of Orlistat on fat excretion levels were found to be much greater with the solid (40.5--57.4% of ingested fat) than with the liquid (4.2--18.8%) test meal.


Consequences of pandemic-associated social restrictions: Role of social support and the oxytocin system.
During pandemics, governments take drastic actions to prevent the spreading of the disease, as seen during the present COVID-19 crisis. Sanctions of lockdown, social distancing and quarantine urge people to exclusively work and teach at home and to restrict social contacts to a minimum; lonely people get into further isolation, while families` nerves are strained to the extreme. Overall, this results in a dramatic and chronic increase in the level of psychosocial stress over several months mainly caused by i) social isolation and ii) psychosocial stress associated with overcrowding, social tension in families, and domestic violence. Moreover, pandemic-associated social restrictions are accompanied by loss of an essential stress buffer and important parameter for general mental and physical health: social support. Chronic psychosocial stress and, in particular, social isolation and lack of social support affect not only mental health, but also the brain oxytocin system and the immune system. Hence, pandemic-associated social restrictions are expected to increase the risk of developing psychopathologies, such as depression, anxiety-related and posttraumatic stress disorders, on the one hand, but also to induce a general inflammatory state and to impair the course of infectious disorders on the other. Due to its pro-social and stress-buffering effects, resulting in an anti-inflammatory state in case of disease, the role of the neuropeptide oxytocin will be discussed and critically considered as an emerging treatment option in cases of pandemic-induced psychosocial stress, viral infection and during recovery. In this review, we aim to critically focus on possible short- and long-term consequences of social restrictions on mental health and the immune system, while discussion oxytocin as a possible treatment option.


Antibody responses to Onchocerca volvulus in Ecuadorian Indians and blacks.
In Ecuador, previous epidemiological studies of onchocerciasis affecting a population consisting of Blacks of African origin and Amerindians of the Chachi tribe, have demonstrated different frequencies of clinical disease manifestations in each racial group. To explore the possibility of differential antibody responses to O. volvulus antigens in this population, a subset of sera from these two groups of Ecuadorians with onchocerciasis was analyzed for antibody to O. volvulus antigens using ELISA and Western blot techniques. Significantly higher levels of immunoglobulin against O. volvulus were demonstrated in Chachi Indians compared to native Blacks of African origin: total Ig (p = 0.049), IgG (P = 0.002) IgG4 (p = 0.019) and IgA (p = 0.035). Western blot analysis of sera from 41 persons demonstrated more intense and more frequent recognition of low molecular weight parasite antigens in the Chachi compared to a similar group of male and female Ecuadorian Blacks. These data suggest that the intensity of antibody responses to O. volvulus antigens may reflect the influence of racial factors in the pathogenesis of onchocerciasis in Ecuador.


Physician Beliefs and Patient Preferences: A New Look at Regional Variation in Health Care Spendingf.
There is considerable controversy about the causes of regional variations in health care expenditures. Using vignettes from patient and physician surveys linked to fee-for-service Medicare expenditures, this study asks whether patient demand-side factors or physician supply-side factors explain these variations. The results indicate that patient demand is relatively unimportant in explaining variations. Physician organizational factors matter, but the most important factor is physician beliefs about treatment. In Medicare, we estimate that 35 percent of spending for end-of-life care and 12 percent of spending for heart attack patients (and for all enrollees) is associated with physician beliefs unsupported by clinical evidence. (JEL D83, H75, I11, I18).


Immunological mechanisms of scarring and their psychological impact on patients.
A scar is a local symptom, which results from severe physical, biological and chemical damage to human skin and soft tissue. Scars can affect both skin appearance and function. The affected skin or soft tissue cannot be completely repaired normally by itself and is replaced by formed fibrous tissue. Patients with scars can develop physical pain and mental conditions, especially those with scars left after burns, scalds and severe traumas. The scar proliferation phase can be up to several years which could be almost unbearable for patients. Also, the atrophic period afterwards makes the patient's face unrecognizable and dysfunctional, causing great physical and mental impairment. Therefore, scar repair is of great clinical importance for patients, and understanding the immunological mechanisms of scar repair is an important prerequisite for the effective treatment of scars. This study is a systematic review of current research advances about the immunological mechanisms of scar repair, so as to provide a reference for the selection of regimens in clinical treatment.


Methicillin-resistant Staphylococcus aureus strains in Buenos Aires teaching hospitals: replacement of the multidrug resistant South American clone by another susceptible to rifampin, minocycline and trimethoprim-sulfamethoxazole.
The aim of this study was to characterize methicillin-resistant Staphylococcus aureus (MRSA) isolates recovered from different infectious sites of hospitalized patients at two university hospitals. Fourteen isolates were analyzed by repetitive sequence based PCR (Rep-PCR), randomly amplified polymorphic DNA assay (RAPD-PCR), and pulsed-field gel electrophoresis (PFGE). We found that a prevalent clone of MRSA, susceptible to rifampin, minocycline, and trimethoprim/sulfamethoxazole (RIF(s), MIN(s), TMS(s)) was present in both hospitals in replacement of the multiresistant MRSA South American clone, previously described in these hospitals. The staphylococcal chromosomal cassette (SCCmec) type I element was detected in this new clone.


Effects of Aqueous Extract of Three Cultivars of Banana (Musa acuminata) Fruit Peel on Kidney and Liver Function Indices in Wistar Rats.
Background:Musa acuminata fruit peels are used in the northern part of Nigeria for the treatment of hypertension and other cardiovascular related diseases. The effects of aqueous extracts of ripped fruit peel of three cultivars of Musa acuminata (Saro, Ominni and Oranta) on the hepatic and renal parameters of normal rats were examined. Methods: Fruit peel aqueous extracts (FPAE) of the 3 cultivars of Bananas (100 mg/kg b.w.) were administered by oral intubation (that is through esophageal cannula) to normal rats (140-180 g) for a period of 28 days. Blood samples were collected for determination of plasma aspartate amino transferase (AST), alanine amino transferase (ALT), alkaline phosphatase ALK-P), total protein, albumin, creatinine as well as urea. Results: From the results obtained, there were no significant (p < 0.05) changes in the ALK-P, AST, ALT, total protein and albumin among the experimental rats administered FPAE of the 3 cultivars of Musa acuminata when compared with the normal control group. There was a significant (p < 0.05) increase in the level of serum creatinine (in mg/dL) (1.53 ± 0.23) when compared to the normal control (0.72 ± 0.15), Ominni (0.92 ± 0.39) and Oranta (0.74 ± 0.22). Similarly, there was a significant (p < 0.05) increase in the level of serum urea (in mg/dL) of Saro (41.56 ± 4.68) when compared to the normal control (26.05 ± 0.73), Ommini (28.44 ± 2.43) and Oranta (26.10 ± 2.94). Conclusion: The findings reveal the Saro cultivar of Musa acuminata to be nephrotoxic and not a good potential drug candidate among the cultivars studied hence should be discouraged in the treatment of hypertension and other cardiovascular related diseases.


Early efforts of blacks in the fight against heart disease and stroke.
This article highlighted the early efforts of some individuals whose vision and dedication helped to set the stage for later progress in the fight against heart disease, who forged links to those who eagerly took up the cause of creating an appropriate place for minority participation in the specialty of cardiovascular diseases, and to contribute to efforts to establish programs for the reduction of morbidity and mortality and for prevention in African Americans. This is only one view of what was an exciting period of fitful progress and controversy. Dr Wilson reviewed the still deplorable state of affairs in regard to minorities and the medical profession in 1986, stating: A meaningful role for minorities will not exist until there is access to academic postgraduate training programs that will lead to faculty positions and research opportunities for minorities to serve as role models for future students. The Association of Academic Minority Physicians was established to foster greater progress in this regard across disciplines. Again, while much has been accomplished, including Donald Wilson's becoming the first African-American dean of a nonminority medical school, much remains to be done as we approach the end of the 20th century.


Identification and validation of EPHX2 as a prognostic biomarker in hepatocellular carcinoma.
Hepatocellular carcinoma (HCC) is one of the most common types of cancer, which is associated with a poor prognosis. It is necessary to identify novel prognostic biomarkers and therapeutic targets to improve the survival of patients with HCC. In the present study, a seven‑gene signature associated with HCC progression was identified using weighted gene co‑expression network analysis and least absolute shrinkage and selection operator, and its prognostic prediction value was confirmed in The Cancer Genome Atlas‑liver HCC and International Cancer Genome Consortium liver cancer‑RIKEN, Japan cohorts. Subsequently, a rarely reported gene, epoxide hydrolase 2 (EPHX2), was selected for further validation. Downregulation of EPHX2 in HCC was revealed using multiple expression datasets. Furthermore, reduced expression of EPHX2 was confirmed in HCC tissue samples and cell lines using reverse transcription‑quantitative polymerase chain reaction and western blotting. Additionally, Kaplan‑Meier survival curves indicated that patients with higher EPHX2 expression exhibited better prognosis, and clinicopathological analysis also revealed elevated EPHX2 levels in patients with early‑stage HCC. Notably, EPHX2 was identified as an independent prognostic biomarker for overall survival of patients with HCC. Gene Ontology analysis, Kyoto Encyclopedia of Genes and Genomes analysis and gene set enrichment analysis were performed to elucidate the functions of EPHX2. The results suggested that EPHX2 expression was closely associated with metabolic reprogramming. Finally, the prognostic value of EPHX2 was evaluated using HCC tissue microarrays. In conclusion, downregulation of EPHX2 was significantly associated with the development of HCC; therefore, EPHX2 may be considered a putative therapeutic candidate for the targeted treatment of HCC.


[Features of ontogenetic development of Drosophila melanogaster in the dysgenetic cross system].
Three families of mobile elements that induce P-M, H-E, and I-R hybrid dysgenesis in Drosophila melanogaster were activated by crossing files of different cytotypes. Manifestation of gonadal sterility in F1 hybrid progeny was dependent on the temperature of development. The systems differed significantly in lethality of F2 hybrids at various stages of ontogeny (embryos, larvae, pupae, and adult flies). The highest embryo lethality was found in the P-M system at the cleavage stage. In the I-R and H-E systems, the peak of embryonic death corresponded to the stages of blastoderm and organogenesis, respectively. Experimental results are discussed in view of molecular and cytological characteristics of interacting strains and existing hypotheses for regulation xof transposition of P, hobo, and I mobile elements.


Sulfuric acid at workplaces--applicability of the new Indicative Occupational Exposure Limit Value (IOELV) to thoracic particles.
Until 2009, the limit values for airborne sulfuric acid in Europe were based on the inhalable particle fraction (e.g. MAK (Maximum allowed concentration at workplace) value 0.1 mg m(-3) as the inhalable fraction). With the publication of the Commission Directive 2009/161/EU, an Indicative Occupational Exposure Limit Value (IOELV) of 0.05 mg m(-3) for sulfuric acid aerosols was based for the first time on the thoracic particle fraction. To permit a comparison of the measured values for the inhalable fraction with those of the thoracic fraction and to quantify the thoracic fraction, a cyclone was fabricated out of sulfuric-acid-resistant stainless steel that achieves suitable collection characteristics (PM(10)) at a flow rate of 5.34 L min(-1). 49 measurements were carried out in parallel in 21 companies. At concentrations well below the IOELV, there is little difference between the thoracic and inhalable particle concentrations. At higher concentrations (>0.1 mg m(-3) inhalable aerosol), larger droplets have a marked effect on the measured values and the thoracic fraction accounts for only 32.1 ± 12.5% of the inhalable fraction. The EU's IOELV and the proposal of the MAK Commission therefore provide a comparable level of protection. In the transposition of the IOELV into national law, an air limit of 0.1 mg m(-3) could therefore be implemented for the inhalable fraction.


Femoral neck fracture following hardware removal.
It is uncommon for femoral neck fractures to occur after proximal femoral hardware removal because age, osteoporosis, and technical error are often noted as the causes for this type of fracture. However, excessive alcohol consumption and failure to comply with protected weight bearing for 6 weeks increases the risk of femoral neck fractures.This article describes a case of a 57-year-old man with a high-energy ipsilateral inter-trochanteric hip fracture, comminuted distal third femoral shaft fracture, and displaced lateral tibial plateau fracture. Cephalomedullary fixation was used to fix the ipsilateral femur fractures after medical stabilization and evaluation of the patient. The patient healed clinically and radiographically at 6 months. Despite conservative treatment for painful proximal hardware, elective hip screw removal was performed 22.5 months after injury. Seven weeks later, he sustained a nontraumatic femoral neck fracture.In this case, it is unlikely that the femoral neck fracture occurred as a result of hardware removal. We assumed that, in addition to the patient's alcohol abuse and tobacco use, stress fractures may have attributed to the femoral neck fracture. We recommend using a shorter hip screw to minimize hardware prominence or possibly off-label use of an injectable bone filler, such as calcium phosphate cement.


The Association Between State Value-Added Taxes and Tobacco Use in India-Evidence From GATS and TCP India Survey.
State value-added taxes (VAT) on tobacco products have been increased significantly in recent years in India. Evidence on how these VATs were associated with smoking is highly needed. State bidi and cigarette VAT rates were linked to Global Adult Tobacco Survey (GATS) India 2009-2010 and Tobacco Control Policy (TCP) India Survey waves 1 (2010-2011) and 2 (2012-2013), respectively. These linked data were used to analyze the associations between bidi VAT rates and bidi smoking, between cigarette VAT rates and cigarette smoking, and between the two VAT rates and dual use of bidis and cigarettes. Weighted logistic regressions were employed to examine GATS cross-sectional data, whereas generalized estimating equations (GEE) were employed to examine longitudinal TCP data. We further stratified the analyses by gender. A 10% increase in cigarette VAT rates was associated with a 6.5% (p < .001) decrease in dual use of cigarettes and bidis among adults and a 0.9% decrease (p < .05) in cigarette smoking among males in TCP; and with a 21.6% decrease (p < .05) in dual use among adults and a 17.2% decrease (p < .001) in cigarette smoking among males in GATS. TCP analyses controlling for state fixed effects are less likely to be biased and indicate a cigarette price elasticity of -0.44. As female smoking prevalence was extremely low, these associations were nonsignificant for females. Higher state cigarette VAT rates in India were significantly associated with lower cigarette smoking and lower dual use of cigarettes and bidis. Increasing state VAT rates may significantly reduce smoking in India. Both Global Adult Tobacco Survey and Tobacco Control Policy (TCP) India datasets suggest that higher state cigarette value-added tax rates were significantly associated with lower male cigarette smoking and lower dual use of cigarettes and bidis among all adults in India. TCP analyses indicate a cigarette price elasticity of -0.44. As shown in this study, state tobacco taxes in the current taxation system are likely effective in reducing smoking. Given this, a future central goods and service tax (GST) system could consider keeping states' authority in implementing local tobacco taxes or designing a GST system that is equally or more effective in reducing tobacco use.


The accuracy of magnetic resonance cholangiopancreatography in the diagnosis of biliary atresia in preterm infants with cholestasis.
Magnetic resonance cholangiopancreatography (MRCP) is a useful and non-invasive method to diagnose biliary atresia (BA) in term infants, however few studies have investigated its use in preterm infants. This study aimed to evaluate the accuracy of MRCP in the diagnosis of BA in preterm infants with cholestasis. Infants aged less than 6 months who received MRCP for cholestasis at a tertiary medical center were enrolled from 2011 to 2020. Demographic and laboratory data were retrospectively obtained. One pediatric radiologist reviewed the MRCP images. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of MRCP to diagnose BA based on surgical proof or at least 6 months of follow-up were assessed. A total of 80 infants (36 preterm and 44 term) were analyzed. The mean post-chronological age was 1.8 months, and the female-to-male ratio was 0.78. Six (16.7%) preterm and 16 (36.4%) term infants were confirmed to have BA. BA was obscured by a choledochal cyst preoperatively in two term infants. In the preterm infants, the sensitivity, specificity, PPV, NPV, and accuracy of MRCP to diagnose BA were 100%, 77%, 46%, 100%, and 81%, respectively, compared to 81%, 86%, 76%, 89%, and 84% in the term infants. Using MRCP to differentiate BA from other cholestasis in the preterm infants had superior sensitivity (100% vs. 81%) and NPV (100% vs. 89%), and lower specificity (77% vs. 86%) and PPV (46% vs. 76%) than in the term infants. Negative MRCP findings can be used to exclude BA in preterm infants with cholestasis based on a favorable NPV.


Rheumatologic aspects of lysosomal storage diseases.
Lysosomal storage diseases are rare metabolic disorders, some of which can now be treated using enzyme replacement therapies. Because the time point of treatment initiation significantly influences the outcome in Gaucher disease, Fabry disease, and mucopolysaccharidosis type I, early diagnosis is of utmost importance. All three disorders can present with musculoskeletal symptoms in early stages, therefore, the rheumatologist may be the first to be contacted by these patients. Here, we present three characteristic lysosomal storage disease cases to increase awareness in the rheumatological community of the typical symptom constellations associated with these rare but treatable disorders.


Measurement of static and vibration-induced phase noise in UHF thin-film resonator (TFR) filters.
Measurements of the static phase noise and vibration sensitivity of thin-film resonator (TFR) filters operating at 640 and 2110 MHz have been made. They show that the short-term frequency instability of the filters is small compared with that induced in the oscillator signal by the sustaining stage amplifier PM (phase modulation) noise. In-oscillator measurement of filter performance under vibration indicates that fractional frequency vibration sensitivities (deltafo/fo) are on the order of several parts in 10(-9)/g. Because the percentage bandwidth and order (number of poles) of the filters was fairly constant, so was the product of the center frequency and group delay. Thus, the fractional frequency vibration sensitivity of the filters can be expressed alternatively as carrier signal phase sensitivity to vibration. The tau-omega0 product for the filters that were tested was on the order of 300 rad, so that the equivalent phase sensitivity to vibration was approximately 1 microrad/g.


Sleep duration is reduced in elite athletes following night-time competition.
This study examined the impact of competition on the sleep/wake behaviour of elite athletes. The sleep/wake behaviour of Australian Rules Football players was assessed with wrist activity monitors on the night immediately before, and the night immediately after, a day game and an evening game. The time of day that a game occurred had a marked influence on sleep/wake behaviour later that night. After the evening game, sleep onset was later, time in bed was shorter and total sleep obtained was less than after the day game. It is yet to be determined whether a reduction in sleep after evening games impairs recovery.


A New Sliding-Loop Technique in Renorrhaphy for Partial Nephrectomy: A Feasibility Study in a Porcine Model.
We developed a sliding-loop technique that narrowed both sides of the parenchyma in a porcine model and compared it with the conventional sliding-clip technique. Three pigs (30-40 kg) were reused following another experiment conducted by the same researchers. Bilateral kidneys were harvested within 30 minutes after euthanasia. Two partial nephrectomies per kidney were performed on opposite surfaces. All kidney defects were of the same size (diameter of 2.5-3 cm with a depth of 1.0-1.5 cm). The sliding-clip technique and sliding-loop technique were performed separately. In the sliding-loop technique, we created a 1-cm loop at the end of a Vicryl and placed a tetrafluoroethylene polymer pledget in front of the knots passing through the needle. The needle then crossed the loop after passing through the renal parenchyma. A Weck clip was placed and slid on one side to tighten the suture. Tightening was controlled with an equivalent force using a digital push-pull gauge. Three stitches were placed at each renorrhaphy site. The distance between repaired renal surfaces was measured at 5 different points (3 suture sites and 2 middle sites between sutures). The results of the 2 techniques were compared by using the independent t test. The mean distance between renal surfaces was significantly narrower in the sliding-loop technique than in the conventional technique (1.80 ± 1.08 mm vs 5.28 ± 2.46 mm, P < .001). In the porcine model, the sliding-loop technique more effectively closed the partial nephrectomy defects compared with the conventional sliding-clip technique.


Multicenter survey on the use of device-assisted enteroscopy in Portugal.
Device-assisted enteroscopies (DAEs) are recent endoscopic techniques that enable direct endoscopic small-bowel evaluation. The objective of this article is to evaluate the implementation of DAEs in Portugal and assess the main indications, diagnoses, diagnostic yield, therapeutic yield and complication rate. We conducted a multicenter retrospective series using a national Web-based survey on behalf of the Portuguese Small-Bowel Study Group. Participants were asked to fill out two online databases regarding procedural data, indications, diagnoses, endoscopic therapy and complications using prospectively collected institutional data records. A total of eight centers were enrolled in the survey, corresponding to 1411 DAEs. The most frequent indications were obscure gastrointestinal bleeding (OGIB), inflammatory bowel disease and small-bowel tumors. The pooled diagnostic yield was 63%. A relation between the diagnostic yield and the indications was clear, with a diagnostic yield for OGIB of 69% (p = 0.02) with a 52% therapeutic yield. Complications occurred in 1.2%, with a major complication rate of 0.57%. Perforations occurred in four patients (0.28%). DAEs are safe and effective procedures, with complication rates of 1.2%, the most serious of which is perforation. Most procedures are performed in the setting of OGIB. Diagnostic and therapeutic yields are dependent on the indication, hence appropriate patient selection is crucial.


Septicemia with Streptococcus pseudopneumoniae: report of three cases with an apparent hepatic or bile duct association.
Streptococcus pseudopneumoniae was described in 2004 as a new human pathogen, acknowledged in a range of clinical infections typically associated to the respiratory tract. This report demonstrates that S. pseudopneumoniae has the potential to cause invasive infection. In blood cultures from three patients, growth of an atypical Streptococcus pneumoniae (non-capsular, non-serotypeable, optochin susceptible under ambient atmosphere and bile-intermediately soluble) was recovered. All three patients had a history of a haematological disease (myelodysplastic syndrome and multiple myeloma) and an apparent origin of infection related to the liver or bile duct. All isolates were genome sequenced and subsequently identified as S. pseudopneumoniae by multi-locus sequence analysis (MLSA). Multi-locus sequence typing (MLST) based on the S. pneumoniae scheme revealed unknown sequence types and the antibiogram and resistome revealed no antibiotic resistance.


In-Depth Studies of Ground- and Excited-State Properties of Re(I) Carbonyl Complexes Bearing 2,2':6',2″-Terpyridine and 2,6-Bis(pyrazin-2-yl)pyridine Coupled with π-Conjugated Aryl Chromophores.
In the current work, comprehensive photophysical and electrochemical studies were performed for eight rhenium(I) complexes incorporating 2,2':6',2″-terpyridine (terpy) and 2,6-bis(pyrazin-2-yl)pyridine (dppy) with appended 1-naphthyl-, 2-naphthyl-, 9-phenanthrenyl, and 1-pyrenyl groups. Naphthyl and phenanthrenyl substituents marginally affected the energy of the MLCT absorption and emission bands, signaling a weak electronic coupling of the appended aryl group with the Re(I) center. The triplet MLCT state in these complexes is so low lying relative to the triplet 3ILaryl that the thermal population of the triplet excited state delocalized on the organic chromophore is ineffective. The attachment of the electron-rich pyrenyl group resulted in a noticeable red shift and a significant increase in molar absorption coefficients of the lowest energy absorption of the resulting Re(I) complexes due to the contribution of intraligand charge-transfer (ILCT) transitions occurring from the pyrenyl substituent to the terpy/dppy core. At 77 K, the excited states of [ReCl(CO)3(Ln-κ2N)] with 1-pyrenyl-functionalized ligands were found to have predominant 3ILpyrene/3ILCTpyrene→terpy character. The 3IL/3ILCT nature of the lowest energy excited state of [ReCl(CO)3(4'-(1-pyrenyl)-terpy-κ2N)] was also evidenced by nanosecond transient absorption and time-resolved emission spectroscopy. Enhanced room-temperature emission lifetimes of the complexes [ReCl(CO)3(Ln-κ2N)] with 1-pyrenyl-substituted ligands are indicative of the thermal activation between 3MLCT and 3IL/3ILCT excited states. Deactivation pathways occurring upon light excitation in [ReCl(CO)3(4'-(1-naphthyl)-terpy-κ2N)] and [ReCl(CO)3(4'-(1-pyrenyl)-terpy-κ2N)] were determined by femtosecond transient absorption studies.


Characterization and photocatalytic activity of Ag-Cu/TiO2 nanoparticles prepared by sol-gel method.
In this study, monometallic and bimetallic silver and copper doped TiO2 nanoparticles were prepared by sol-gel method. Structural and morphological characterizations of prepared nanoparticles were performed by X-ray diffraction (XRD), transmission electron microscopy (TEM), scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDX) and N2 physisorption techniques. Co-doped TiO2 nanoparticles displayed pure anatase phase with 20-30 nm particle size and a humdrum distribution. The stability of anatase phase was increased with co-doping of silver and copper to TiO2 lattice. In addition, the co-doped TiO2 nanoparticles had a mesoporous structure with slit-shaped pores. The photocatalytic activity of all samples was evaluated in the photocatalytic removal of C.I. Acid Orange 7. Co-doped TiO2 nanoparticles by Ag and Cu were shown to have highest activity as compared with the Ag/TiO2, Cu/TiO2 and pure TiO2 nanoparticles. The best performance of co-doped TiO2 nanoparticles was observed for a sample calcined under 550 degrees C, containing optimum molar contents of silver (0.08 mol%) and copper (0.01 mol%) dopant ions.


Determination of the neutralizing potency of horse antivenom against bothropic and crotalic venoms by indirect enzyme immunoassay.
The use of ELISA to determine antisnake venom potency of horse immune sera should provide benefits of costs and reproducibility compared to in vivo assays. In the present investigation we evaluated the correlation between ELISA antibody levels and in vivo neutralization assays. For the indirect ELISA method, 0.016 micrograms/well of Bothrops jararaca or Crotalus durissus terrificus venom were used to coat the plates and 100 microliters/well of each sample of antibothropic or anticrotalic venom sera were used at 1:10,000 dilution. Sheep anti-horse IgG conjugated to peroxidase was added and the substrate H2O2/o-phenylenediamine produced the color that was read at 492 nm. A correlation coefficient of r = 0.97 was found for anticrotalic venom antibodies and no significant correlation was observed for antibothropic venom sera using 16 serum samples from immunized horses. However, when three antibothropic venom sera showing high in vivo neutralization potency and low absorbance in ELISA or high absorbance values and low in vivo protection were not included in the correlation analysis the coefficient value was r = 0.88. The correlation coefficient did not improve for all 16 antibothropic sera when a partially purified Bothrops jararaca venom fraction was used to coat the ELISA plates. The results indicate that ELISA could be used to determine the neutralizing potency of anticrotalic venom sera. For the antibothropic venom sera further studies are needed.


Study on the interaction between 3 flavonoid compounds and alpha-amylase by fluorescence spectroscopy and enzymatic kinetics.
The interaction between alpha-amylase and 3 flavonoid compounds from tartary buckwheat bran, namely, quercetin (Que), its monoglycoside isoquercetin (Iso), and its diglycoside rutinb (Rut), has been studied by fluorescence spectroscopy and enzymatic kinetics. The results indicate that Que, Iso, and Rut could bind with alpha-amylase to form a new complex, which exhibits an obvious fluorescence quenching. We deduce that such a quenching is a static quenching via nonradiation energy transfer. Results from plots and calculations show that the sequence of binding constants (KA) is Iso > Que > Rut. Calculation on thermodynamic parameters reveals that the main driving force of above-mentioned interaction is hydrophobic. Enzyme activity measurements show that all of the 3 flavonoid compounds are effective inhibitors toward alpha-amylase, and the inhibitory mode belongs to a competitive type. The sequence of affinity (1/Ki) is in accordance with the results of binding constants (KA) from fluorescence experiments.


A retrospective audit of referrals of 16-17 year olds with reference to substance abuse.
Emerge is an innovative Child and Adolescent Mental Health Service that provides support for 16-17 year olds. The team provide a community based multi-disciplinary, open access model, texting young people and travelling to locations convenient to them. There is an enhanced duty system providing a rapid flexible response within working hours. To examine the referral data as part of the ongoing annual audit cycle and to establish prevalence of alcohol, cigarettes and substance use among young people referred to the service. Data from the case notes was analysed using Statistical Package for Social Science. Demographic details, referrer profession, reason for referral, other services involved and substance use were examined. There were 437 patients referred to Emerge between 1/4/2010 and 31/3/2011, and 387 patients were accepted while 50 were signposted on. Cases were not accepted if they fell outside the age and geographical area, or were not in need of a mental health service. Overall, 24% of young people were reported to consume alcohol, 19% used cannabis and 9% reported using cigarettes. In all categories there were areas where documentation was not complete, and we suggest that these figures are an underestimate. This data has been fed back to the team, a full morning of teaching regarding drugs and alcohol has been delivered. Emerge often works with young people who are marginalised and may be harder to reach, consequently early sessions require neutral and supportive questions, thus if young people do not return after the first appointment, histories may be incomplete. The team will be reflecting on the lessons learned and considering ways to optimise their work.


Comparative study of the microvascular blood flow in the intestinal wall during conventional negative pressure wound therapy and negative pressure wound therapy using paraffin gauze over the intestines in laparostomy.
Higher closure rates of the open abdomen have been reported with negative pressure wound therapy (NPWT) than with other kinds of wound management. We have recently shown that NPWT decreases the blood flow in the intestinal wall, and that the blood flow could be restored by inserting a protective disc over the intestines. The aim of the present study was to investigate whether layers of Jelonet™ (Smith & Nephew) dressing (paraffin tulle gras dressing made from open weave gauze) over the intestines could protect the intestines from hypoperfusion. Midline incisions were made in ten pigs and were subjected to treatment with NPWT with and without four layers of Jelonet over the intestines. The microvascular blood flow was measured in the intestinal wall before and after the application of topical negative pressures of -50, -70 and -120 mmHg, using laser Doppler velocimetry. Baseline blood flow was defined as 100% in all settings. The blood flow was significantly reduced, to 61 ± 7% (P < 0·001), after the application of -50 mmHg using conventional NPWT, and to 62 ± 7% (P < 0·001) after the application of -50 mmHg with Jelonet dressings between the dressing and the intestines. The blood flow was significantly reduced, to 38 ± 5% (P < 0·001), after the application of -70 mmHg, and to 42 ± 6% (P < 0·001) after the application of -70 mmHg with Jelonet dressings. The blood flow was significantly reduced, to 34 ± 9% (P < 0·001), after the application of -120 mmHg, and to 38 ± 6% (P < 0·001) after the application of -120 mmHg with Jelonet dressings. The use of four layers of Jelonet over the intestines during NPWT did not prevent a decrease in microvascular blood flow in the intestinal wall.