Role of Cripto-1 during epithelial-to-mesenchymal transition in development and cancer.
Epithelial-to-mesenchymal transition (EMT) is a critical multistep process that converts epithelial cells to more motile and invasive mesenchymal cells, contributing to body patterning and morphogenesis during embryonic development. In addition, both epithelial plasticity and increased motility and invasiveness are essential for the branching morphogenesis that occurs during development of the mammary gland and during tumor formation, allowing cancer cells to escape from the primary tumor. Cripto-1, a member of the epidermal growth factor-Cripto-1/FRL-1/Cryptic (EGF/CFC) gene family, together with the transforming growth factor (TGF)-β family ligand Nodal, regulates both cell movement and EMT during embryonic development. During postnatal development, Cripto-1 regulates the branching morphogenesis of the mouse mammary gland and enhances both the invasive and migratory properties of mammary epithelial cells in vitro. Furthermore, transgenic mouse models have shown that Cripto-1 promotes the formation of mammary tumors that display properties of EMT, including the down-regulation of the cell surface adherens junctional protein E-cadherin and the up-regulation of mesenchymal markers, such as vimentin, N-cadherin, and Snail. Interestingly, Cripto-1 is enriched in a subpopulation of embryonal, melanoma, prostate, and pancreatic cancer cells that possess stem-like characteristics. Therefore, Cripto-1 may play a role during developmental EMT, and it may also be involved in the reprogramming of differentiated tumor cells into cancer stem cells through the induction of an EMT program.


Stem cell based delivery of IFN-beta reduces relapses in experimental autoimmune encephalomyelitis.
Interferon-beta (IFN-beta), an approved treatment of multiple sclerosis (MS), produces only partial clinical responses. IFN-beta therapy has been limited by its short serum half-life and limited ability to cross the blood brain barrier. We have developed a means of delivering the IFN-beta gene both systemically and into the central nervous system (CNS) using bone marrow stem cells (BMSCs) as a vehicle and examined the therapeutic efficacy of this approach in experimental autoimmune encephalomyelitis (EAE), an animal model of MS. A retroviral expression vector (pLXSN-IFNbeta) was used to stably transfect virus producer PA317 cells to generate retrovirus containing the IFN-beta gene which then was used to transduce BMSCs. IFN-beta engineered BMSCs were transplanted (i.v.) into mice that then were immunized with proteolipoprotein (PLP) to initiate EAE. IFN-beta-engineered BMSCs transplanted mice showed a significant inhibition of EAE onset, and the overall clinical severity was less compared to control groups. IFN-beta delivery strongly reduced infiltration of mononuclear cells possibly by inhibiting cell adhesion molecules. Reduced demyelination and increased remyelination were also observed in the IFN-beta treated group. Furthermore, inhibition of the pro-inflammatory cytokines TNF-alpha, IFN-gamma and IL-12 and enhanced expression of the anti-inflammatory cytokines IL-10, IL-4 and TGF-beta was observed in CNS tissue. In addition, mice receiving IFN-beta had reduced apoptosis and increases in growth promoting factors including BDNF, CNTF, PDGF and VEGF. These results suggest that BMSCs can be used as vehicles to deliver the IFN-beta into the CNS. This is a potentially novel therapeutic approach which might be used in MS and other diseases of the CNS in which drug access is limited.


A Sox17 downstream gene Rasip1 is involved in the hematopoietic activity of intra-aortic hematopoietic clusters in the midgestation mouse embryo.
During mouse embryonic development, definitive hematopoiesis is first detected around embryonic day (E) 10.5 in the aorta-gonad-mesonephros (AGM) region. Hematopoietic stem cells (HSCs) arise in the dorsal aorta's intra-aortic hematopoietic cell clusters (IAHCs). We have previously reported that a transcription factor Sox17 is expressed in IAHCs, and that, among them, CD45lowc-Kithigh cells have high hematopoietic activity. Furthermore, forced expression of Sox17 in this population of cells can maintain the formation of hematopoietic cell clusters. However, how Sox17 does so, particularly downstream signaling involved, remains poorly understood. The purpose of this study is to search for new Sox17 targets which contribute to cluster formation with hematopoietic activity. RNA-sequencing (RNA-seq) analysis was done to identify genes that are upregulated in Sox17-expressing IAHCs as compared with Sox17-negative ones. Among the top 7 highly expressed genes, Rasip1 which had been reported to be a vascular-specific regulator was focused on in this study, and firstly, the whole-mount immunostaining was done. We conducted luciferase reporter assay and chromatin immunoprecipitation (ChIP) assay to examine whether Sox17 regulates Rasip1 gene expression via binding to its enhancer element. We also analyzed the cluster formation and the multilineage colony-forming ability of Rasip1-transduced cells and Rasip1-knockdown Sox17-transduced cells. The increase of the Rasip1 expression level was observed in Sox17-positive CD45lowc-Kithigh cells as compared with the Sox17-nonexpressing control. Also, the expression level of the Rasip1 gene was increased by the Sox17-nuclear translocation. Rasip1 was expressed on the membrane of IAHCs, overlapping with the endothelial cell marker, CD31, and hematopoietic stem/progenitor marker (HSPC), c-Kit. Rasip1 expression was observed in most part of c-Kit+Sox17+ cells in IAHCs. Luciferase reporter assay and ChIP assay indicated that one of the five putative Sox17-binding sites in the Rasip1 enhancer region was important for Rasip1 expression via Sox17 binding. Rasip1 knockdown in Sox17-transduced cells decreased the cluster formation and diminished the colony-forming ability, while overexpression of Rasip1 in CD45lowc-Kithigh cells led to a significant but transient increase in hematopoietic activity. Rasip1 knockdown in Sox17-transduced CD45lowc-Kithigh cells displayed a significant decrease in the multilineage colony-forming ability and the cluster size. Rasip1 overexpression in Sox17-untransduced CD45lowc-Kithigh cells led to a significant but transient increase in the multilineage colony-forming ability, suggesting the presence of a cooperating factor for sustained hematopoietic activity.


Regulation of rat liver type 1 iodothyronine deiodinase mRNA levels by testosterone.
To investigate the underlying mechanisms of sex-related differences in liver type 1 iodothyronine deiodinase (ID1), we studied the sex-related differences and roles of sex steroids in liver ID1 mRNA levels in the rat. In both euthyroid and thyroidectomized rats, liver ID1 activity and ID1 mRNA levels in female rats were less than those in male rats. A positive correlation was observed between liver ID1 activity and ID1 mRNA levels. Liver ID1 activity and ID1 mRNA levels in male rats decreased after orchiectomy, and were increased to control levels by testosterone administration. Ovariectomy of beta-estradiol administration did not alter liver ID1 activity or ID1 mRNA levels in female rats. ID1 mRNA levels in cultured rat hepatocytes were significantly increased by testosterone, but not by beta-estradiol. These results suggest that the sex-related differences in liver ID1 activity are attributable to differences in ID1 mRNA levels, and that testosterone plays an important role in the sex-related differences in liver ID1 mRNA levels.


Effects on hearing during prolonged oral contraceptive use.
Different hearing defects have been attributed to prolonged use of oral contraceptives. The aim of the present investigation has been the evaluation by means of a number of audiological tests and of brain-stem evoked responses (BSER) of the possible incidence of subclinical pathology of the nervous hearing structures in these subjects. Twenty healthy subjects taking oral contraceptives from 9 to 30 months and 10 paired controls have been studied. No hearing loss was found but the study of BSER showed the presence of a significantly shorter latency of waves I and III which could be attributed to a functional alteration. Other, less significant, alterations are described and the conclusion is reached that prolonged oral contraception does not affect the hearing function, even if it is investigated with sophisticated techniques. However, the significant alterations of BSER responses and of the stapedial reflex might be considered as an initial non-organic sign of impairment of the central hearing pathways and therefore deserve further investigation.


Rooming-in improves breastfeeding initiation rates in a community hospital in Puerto Rico.
Several studies have shown that rooming-in can have a positive impact on lactation success. The objective of this study was to assess if the establishment of rooming-in in a community hospital has an impact on breastfeeding success. Participants included volunteer women who delivered babies at a community hospital. The participants answered a survey. Sixty females were included. The mean age was 23 years (18-38) and the mean gestational age 38 weeks (34-41). Breastfeeding in the hospital was reported by 54% with 6% doing it exclusively. Rooming-in was practiced by 70%. Rooming-in was associated to breastfeeding (OR 5.0, 95% CI 1.5-16.9, p = 0.0069). Thirty-percent of the babies in rooming-in started breastfeeding during the first 6 hours after delivery as compared to none of those not roomed-in. The advantages offered by the rooming-in practice in the maternity ward of this hospital resulted in successful breastfeeding in this group of mothers.


[Expression of a novel immunoglobulin gene SNC73 in human cancer and its significance].
To investigate the expression of a new immunoglobulin gene SNC73 in malignant tumor and normal tissue and its significance. Expression level of SNC73 in tumors and normal tissues was determined by reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay (RT-PCR-ELISA) in 90 malignant tumors, including colorectal cancer, gastric cancer, breast cancer, lung cancer and liver cancer. Analysis on relation of SNC73 expression with age, sex, site, differentiation grade, depth of invasion and metastasis of colorectal cancer was made to assess the clinical significance of SNC73. Mean ratio of SNC73 expression level in normal mucosa and colorectal cancer tissue was 7.134 (P < 0.01). Expression of SNC73 showed no significant difference among gastric cancer, breast cancer, lung cancer or liver cancer as compared with the control normal tissues (P > 0.05). Down-regulation of SNC73 expression is a relatively specific phenomenon in colorectal cancer for which development SNC73 may be a potential genetic marker. The study on relationship of SNC73 expression with development of colorectal cancer is promising.


A rat model of organophosphate-induced status epilepticus and the beneficial effects of EP2 receptor inhibition.
This review describes an adult rat model of status epilepticus (SE) induced by diisopropyl fluorophosphate (DFP), and the beneficial outcomes of transient inhibition of the prostaglandin-E2 receptor EP2 with a small molecule antagonist, delayed by 2-4 h after SE onset. Administration of six doses of the selective EP2 antagonist TG6-10-1 over a 2-3 day period accelerates functional recovery, attenuates hippocampal neurodegeneration, neuroinflammation, gliosis and blood-brain barrier leakage, and prevents long-term cognitive deficits without blocking SE itself or altering acute seizure characteristics. This work has provided important information regarding organophosphate-induced seizure related pathologies in adults and revealed the effectiveness of delayed EP2 inhibition to combat these pathologies.


Intravenous lipid emulsions and liver function in adult chronic intestinal failure patients: Results after 5 y of home parenteral nutrition.
Intravenous lipid emulsions (ILE) are an essential component of parenteral nutrition (PN); however, pure soybean oil emulsion is considered a risk factor for intestinal failure-associated liver disease (IFALD). Limited data are available on the effect of different ILEs on the liver during long-term PN, and to our knowledge, no study has evaluated outcomes beyond 12 mo. Therefore, the aim of the present study was to assess the influence of mixed ILEs on liver function during long-term PN. A randomized, open-label clinical trial was performed at the Intestinal Failure Center in Skawina, Poland. Sixty-seven patients (35 F, 32 M; mean age, 53.2 years) receiving home parenteral nutrition (HPN) due to stable chronic intestinal failure (CIF) were randomized to receive one of the following three ILEs: medium/long-chain triacylglycerides (MCT/LCT), olive oil/soybean oil (OO/SO), or a combination of SO/MCT/OO/fish oil (FO) (SMOFlipid). Patients were followed for 5 y. Liver function was assessed clinically and with biochemical parameters (total bilirubin, serum glutamyl oxalate transaminase, serum glutamyl pyruvate transaminase, γ-glutamyl transpeptidase, and alkaline phosphatase) at baseline and after 24 and 60 mo. The most common etiology for CIF was vascular, followed by Crohn's disease, surgical complications, and radiation enteritis. HPN was effective in improving nutritional status and was associated with low rates of catheter infections and clinical complications. No significant differences were observed between groups in median concentrations serum glutamyl oxalate transaminase, serum glutamyl pyruvate transaminase, γ-glutamyl transpeptidase, or alkaline phosphatase at 24 or 60 mo. A significant reduction in median bilirubin concentration was observed in the SMOFlipid group at 60 mo compared with baseline (6.8 umol/L; interquartile range, 5.2-8.5 versus 7.7 umol/L; interquartile range, 4.9-12.4; P = 0.0138). Mixed ILEs are safe and effective for use in patients on long-term HPN. A multicomponent ILE with FO can provide additional benefits in terms of liver function during long-term HPN.


[Development of tolerance of phenobarbital after administration over several days (author's transl)].
In mice daily testing by maximal electroshock (MES) and pentylenetetrazole infusion (PTZ) 2 h after an i.p. injection of 25 mg/kg penobarbital (PB) was performed on days 1, 2, 4 through 8. The first twitch was delayed as compared to NaCl controls (50.4 +/- 4.8 s; 36.6 +/- 3.6 s; n = 53) on day 2, 4, 6 through 8. There was no tolerance of the PTZ induced tonic extension with Pb-treatment. In contrast, MES-tested mice developed tolerance, at day 5 the number of protected animals fell to about 50%. In view of the constant phenobarbital levels in plasma, a functional tolerance was assumed. The development of tolerance seemed to be connected with the spread of the discharge but not with discharge of the neurones themselves since it was observed only with MES but not wih PTZ-testing.


Affibody-conjugated 5-fluorouracil prodrug system preferentially targets and inhibits HER2-expressing cancer cells.
Overexpression of HER2 is associated with cancer phenotypes, such as proliferation, survival, metastasis and angiogenesis, and has been validated as a therapeutic target. However, only a portion of patients benefited from anti-HER2 treatments, and many would develop resistance. A more effective HER2 targeted therapeutics is needed. Here, we adopted a prodrug system that uses 5-fluorocytosine (5-FC) and a HER2-targeting scaffold protein, ZHER2:2891, fused with yeast cytosine deaminase (Fcy) to target HER2-overexpressing cancer cells and to convert 5-FC to a significantly more toxic chemotherapeutic, 5-fluorouracil (5-FU). We cloned the coding gene of ZHER2:2891 and fused with those of ABD (albumin-binding domain) and Fcy. The purified ZHER2:2891-ABD-Fcy fusion protein specifically binds to HER2 with a Kd value of 1.6 nM ZHER2:2891-ABD-Fcy binds to MDA-MB-468, SKOV-3, BT474, and MC38-HER2 cells, which overexpress HER2, whereas with a lower affinity to HER2 non-expresser, MC38. Correspondingly, the viability of HER2-expressing cells was suppressed by relative low concentrations of ZHER2:2891-ABD-Fcy in the presence of 5-FC, and the IC50 values of ZHER2:2891-ABD-Fcy for HER2 high-expresser cells were approximately 10-1000 fold lower than those of non-HER2-targeting Fcy, and ABD-Fcy. This novel prodrug system, ZHER2:2891-ABD-Fcy/5-FC, might become a promising addition to the existing class of therapeutics specifically target HER2-expressing cancers.


Fecal Incontinence in the Elderly.
Fecal incontinence can be a challenging and stigmatizing disease with a high prevalence in the elderly population. Despite effective treatment options, most patients do not receive care. Clues in the history and physical examination can assist the provider in establishing the diagnosis. Direct inquiry about the presence of incontinence is key. Bowel disturbances are common triggers for symptoms and represent some of the easiest treatment targets. We review the epidemiology and impact of the disease, delineate a diagnostic and treatment approach for primary care physicians to identify patients with suspected fecal incontinence and describe appropriate treatment options.


Avian influenza virus H5N1: a review of its history and information regarding its potential to cause the next pandemic.
Avian influenza virus H5N1, which has been limited to poultry, now has spread to migrating birds and has emerged in mammals and among the human population. It presents a distinct threat of a pandemic for which the World Health Organization and other organizations are making preparations. This article reviews information about the virus itself and its spread among poultry, migrating birds, mammals, and humans.


Scaling up Mental Healthcare for Perinatal Populations: Is Telemedicine the Answer?
Telemedicine has transformed our ability to access and offer mental healthcare. There remain key questions to facilitate scalable, patient-centered solutions for perinatal mental health. We critically evaluate the recent literature and propose potential future directions. The current literature highlights the promise of telemedicine in the prevention and treatment of perinatal depression, including the preference for and the potential efficacy of telemedicine-delivered mental healthcare when compared to in-person treatments. There remains a need for large, adequately powered randomized controlled trials; integration of trauma into depression and anxiety trials, transdiagnostic treatment of perinatal women, and scaling up these effective treatments into existing health and payer systems. Pragmatic, evidence-based solutions exist to effectively scale-up treatments for perinatal mental health. While research is underway to address the growing treatment gap, questions remain regarding who will deliver and pay for these treatments and how we can leverage telemedicine to treat perinatal mental health transdiagnostically.


Effect of Reproductive and Lifestyle Factors on Anti-Mullerian Hormone Levels in Women of Indian Origin.
Infertility is a world-wide problem and one third females. Over the years, anti-mullerian hormone (AMH) has emerged as a major marker of ovarian reserve. There is also increasing interest in determining the factors which can impact AMH levels. To correlate the association of reproductive and lifestyle factors on AMH levels in women of Indian origin. Multicentric cross sectional study. The study was conducted using data extracted from the patient records of seven private fertility practices located in North India. Women who were attending these clinics for fertility treatment were requested to fill the questionnaire related to reproductive and lifestyle factors. Our outcome variable was level of AMH measured in the past 3 months, and was assessed as normal or low. All analyses were conducted using STATA 17. We found a direct association of low AMH with increasing age, short cycles, amenorrhea and women with family history of premature menopause. We found a direct correlation of high AMH and women with polycystic ovary syndrome and those whose partners had Oligoasthenoteratozoospermia (OATS) or azoospermia. There was no correlation with smoking, sleep, diet, body mass index, cell phone or laptop use in our study. Reproductive and lifestyle factors may affect ovarian reserve and but there was a dearth of human studies in this area. To the best of our knowledge this is the first human study on the effect of AMH on Laptop and Cell phone use. We urgently need more studies to confirm or refute our findings so that we can counsel our patients well.


A deep learning model for accurately predicting cancer-specific survival in patients with primary bone sarcoma of the extremity: a population-based study.
Primary bone and joint sarcomas of the long bone are relatively rare neoplasms with poor prognosis. An efficient clinical tool that can accurately predict patient prognosis is not available. The current study aimed to use deep learning algorithms to develop a prediction model for the prognosis of patients with long bone sarcoma. Data of patients with long bone sarcoma in the extremities was collected from the Surveillance, Epidemiology, and End Results Program database from 2004 to 2014. Univariate and multivariate analyses were performed to select possible prediction features. DeepSurv, a deep learning model, was constructed for predicting cancer-specific survival rates. In addition, the classical cox proportional hazards model was established for comparison. The predictive accuracy of our models was assessed using the C-index, Integrated Brier Score, receiver operating characteristic curve, and calibration curve. Age, tumor extension, histological grade, tumor size, surgery, and distant metastasis were associated with cancer-specific survival in patients with long bone sarcoma. According to loss function values, our models converged successfully and effectively learned the survival data of the training cohort. Based on the C-index, area under the curve, calibration curve, and Integrated Brier Score, the deep learning model was more accurate and flexible in predicting survival rates than the cox proportional hazards model. A deep learning model for predicting the survival probability of patients with long bone sarcoma was constructed and validated. It is more accurate and flexible in predicting prognosis than the classical CoxPH model.


Validation of a T1 and T2* leakage correction method based on multiecho dynamic susceptibility contrast MRI using MION as a reference standard.
A combined biophysical- and pharmacokinetic-based method is proposed to separate, quantify, and correct for both T1 and T2* leakage effects using dual-echo dynamic susceptibility contrast (DSC) acquisitions to provide more accurate hemodynamic measures, as validated by a reference intravascular contrast agent (CA). Dual-echo DSC-MRI data were acquired in two rodent glioma models. The T1 leakage effects were removed and also quantified to subsequently correct for the remaining T2* leakage effects. Pharmacokinetic, biophysical, and combined biophysical and pharmacokinetic models were used to obtain corrected cerebral blood volume (CBV) and cerebral blood flow (CBF), and these were compared with CBV and CBF from an intravascular CA. T1 -corrected CBV was significantly overestimated compared with MION CBV, while T1 + T2*-correction yielded CBV values closer to the reference values. The pharmacokinetic and simplified biophysical methods showed similar results and underestimated CBV in tumors exhibiting strong T2* leakage effects. The combined method was effective for correcting T1 and T2* leakage effects across tumor types. Correcting for both T1 and T2* leakage effects yielded more accurate measures of CBV. The combined correction method yields more reliable CBV measures than either correction method alone, but for certain brain tumor types (e.g., gliomas), the simplified biophysical method may provide a robust and computationally efficient alternative. Magn Reson Med 76:613-625, 2016. © 2015 Wiley Periodicals, Inc.


Disintegration of isolated cells.
A simple device has been developed for the disintegration of isolated cells in isotonic or hypertonic media. It is based on the extrusion of a cell suspension through a small orifice under controlled pressure. The diameter of this interchangeable orifice has to be adapted to the cell type to be disrupted. The conditions fulfill the requirements for an efficient disruption of the plasma membranes and for good preservation of the particularly fragile subcellular components, lysosomes and peroxisomes, of rat hepatocytes and rat Leydig cells.


Characterization and genomics identification of key genes involved in denitrification-DNRA-nitrification pathway of plant growth-promoting rhizobacteria (Serratia marcescens OK482790).
A wide variety of microorganisms, including bacteria, live in the rhizosphere zone of plants and have an impact on plant development both favorably and adversely. The beneficial outcome is due to the presence of rhizobacteria that promote plant growth (PGPR). In this study, a bacterial strain was isolated from lupin rhizosphere and identified genetically as Serratia marcescens (OK482790). Several biochemically and genetically characteristics were confirmed in vitro and in vivo to determine the OK482790 strain ability to be PGPR. The in vitro results revealed production of different lytic enzymes (protease, lipase, cellulase, and catalase), antimicrobial compounds (hydrogen cyanide, and siderophores), ammonia, nitrite, and nitrate and its ability to reduce nitrate to nitrite. In silico and in vitro screening proposed possible denitrification-DNRA-nitrification pathway for OK482790 strain. The genome screening indicated the presence of nitrite and nitrate genes encoding Nar membrane bound sensor proteins (NarK, NarQ and NarX). Nitrate and nitrite reductase encoding genes (NarI, NarJ, NarH, NarG and NapC/NirT) and (NirB, NirC, and NirD) are also found in addition to nitroreductases (NTR) and several oxidoreductases. In vivo results on wheat seedlings confirmed that seedlings growth was significantly improved by soil inoculation of OK482790 strain. This study provides evidence for participation of S. marcescens OK482790 in nitrogen cycling via the denitrification-DNRA-nitrification pathway and for its ability to produce several enzymes and compounds that support the beneficial role of plant-microbe interactions to sustain plant growth and development for a safer environment.


Epigenetic modulation of metabolism in glioblastoma.
Epigenetic and metabolic alterations incancer cells are highly associated. Glioblastoma multiforme (GBM) is a complicated pathological process with dysregulated methylation and histone modifications. Metabolic modulation of epigenetics in gliomas was previously summarized. However, epigenetic modulation is also important in metabolic decision. Recently, there has been a tremendous increase in understanding of DNA methylation, chromatin modulation, and non-coding RNAs in the regulation of cell metabolism, especially glycolytic metabolism in GBM. In this review, we summarize DNA methylation, histone alteration, and non-coding RNA mediated epigenetic modulation of metabolism in GBM and discuss the future research directions in this area and its applications in GBM treatment.


REDUCING ER USE THROUGH A TRAINEE-DESIGNED, INTERPROFESSIONAL CARE GROUP FOR HIGH-UTILIZING CHRONICALLY ILL PATIENTS: A PILOT PROGRAM.
Healthcare utilization is skewed to a subset of high-need, high-use patients, but optimal models of care are not known. To reduce emergency room (ER) use and hospital readmissions, trainees designed an innovative model of care delivery for chronically ill, high-utilizing adult patients. Enrolled patients (N = 65) joined an interprofessional care program (nutrition, behavioral health, pharmacy, and care coordination), located in a single ambulatory clinic with extended hours. Evaluated by generalized linear mixed-effects models, the primary outcome of all-cause ER visits showed a significant decreasing trend after enrollment, from an increasing odds of ER visits (OR 1.07) in the 12-months prior to the program, compared to a decreasing trend post-enrollment (OR 0.88). Implementation and completion of the program was cost neutral. This pilot supports team-based ambulatory care models that address the diverse needs of chronically ill patients, with a focus on improving select health services utilization.


Effects of a sound source moving in a vertical plane on postural responses in humans.
The effects of moving sound sources on postural responses were studied. Sound source movement was simulated by sequential switching of loudspeakers located along an arch positioned in the sagittal plane relative to the subject. The total durations of the sound stimulus movement were 1.6, 3.2, and 4.8 sec. Signals of 1.6 and 3.2 sec led to decreases in the mean amplitude of oscillogram oscillations in the sagittal and frontal planes. Stabilogram curves averaged for all subjects for the signal of duration 4.8 sec showed that the center of gravity deviated during exposure to the sound stimulus towards the side opposite the direction of movement of the sound source.


High-risk human papillomavirus infection in the prediction of poor treatment response and disease recurrence in patients with vulvovaginal condyloma.
To determine the predictive factors for progression and recurrence of vulvovaginal condyloma (VVC), with a specific focus on high-risk HPV (HR-HPV) infections. Retrospective data were collected from 48 patients who were diagnosed with VVC and treated with topical trichloroacetic acid application or laser therapy during 2003-2014 at a hospital in South Korea. The diagnoses were made based on the presence of exophytic condylomatous lesions as assessed by direct visual inspection regardless of whether a biopsy was performed. Overall, 18 patients (50.0% of those with a test result) were positive for HR-HPV. Three-quarters of the patients with a poor treatment response had abnormal cytologies, and abnormal cytology was a risk factor for a poor response (odds ratio, 4.33 [95% confidence interval, 1.05-17.84]). During a median follow-up of 24months, VVC recurred in seven (14.6%) patients. A high viral load (more than 50 relative light units) of HR-HPV was significantly associated with recurrence (odds ratio, 7.42, 95% confidence interval, 1.19-46.18). A high HR-HPV load is a risk factor for recurrence, but is not related to treatment response. A poor treatment response is more related to abnormal cytology than it is to viral load.


Noncontrast T2-Weighted Magnetic Resonance Imaging Sequences for Long-Term Monitoring of Asymptomatic Convexity Meningiomas.
Gadolinium-based contrast agents (GBCAs) used to enhance magnetic resonance imaging (MRI) scans have been linked to tissue deposition, including in the brain. The management of indolent tumors such as meningiomas requires frequent MRI scans to monitor for interval growth. Given concern regarding GBCA deposition, we sought to determine if noncontrast MRI scans in patients with asymptomatic meningiomas were equivalent to GBCA-enhanced MRI scans in surveillance monitoring. This institutional review board-approved retrospective chart review included 106 MRI sequences from 18 patients. Inclusion criteria were adult patients with asymptomatic meningiomas who received baseline contrast-enhanced and noncontrast axial brain MRI scan. Exclusion criteria included the following: 1) baseline or follow-up axial images were not available for review, 2) baseline scan was obtained without contrast, and 3) diagnosis of meningioma was uncertain. Percent tumor growth was measured by comparing cross-sectional area at maximum tumor diameter from the earliest and most recent scans. For each patient, change in tumor size over time was compared using T1 + contrast, T2, and T2 fluid-attenuated inversion recovery (FLAIR) sequences. These were compared with a qualitative consensus reading by a neurosurgeon and a neuroradiologist. Measured change of greater than 10% was taken to represent tumor growth. In 17 out of 18 patients, measurement of noncontrast studies (T2 and T2 FLAIR) matched consensus. For one patient, imaging on T2 suggested 11% growth, whereas T2 FLAIR and overall consensus was stability. Our study provides evidence that noncontrasted MRI scans are equivalent to contrast-weighted MRI scans to follow change in tumor size over time in asymptomatic meningiomas.


The phagocytic role of macrophage following myocardial infarction.
Myocardial infarction (MI) is one of the cardiovascular diseases with high morbidity and mortality. MI causes large amounts of apoptotic and necrotic cells that need to be efficiently and instantly engulfed by macrophage to avoid second necrosis. Phagocytic macrophages can dampen or resolve inflammation to protect infarcted heart. Phagocytosis of macrophages is modulated by various factors including proteins, receptors, lncRNA and cytokines. A better understanding of mechanisms in phagocytosis will be beneficial to regulate macrophage phagocytosis capability towards a desired direction in cardioprotection after MI. In this review, we describe the phagocytosis effect of macrophages and summarize the latest reported signals regulating phagocytosis after MI, which will provide a new thinking about phagocytosis-dependent cardiac protection after MI.


Lithium augmentation therapy in refractory depression-update 2002.
Lithium has been used to augment the efficacy of antidepressant medications for more than 20 years. The present study examines whether evidence exists to support the clinical efficacy of lithium augmentation in refractory, treatment resistant depression. Studies were identified by searching Medline (1980 to August 2002) and by scanning the references of published reviews and standard textbooks. Studies were selected if they were open-labeled or double-blind, placebo-controlled or comparator trials that involved patients who had not responded to conventional antidepressants. 27 prospective studies were identified that included a total of 803 depressed patients displaying the following designs: 10 double-blind, placebo-controlled trials, 2 randomized, double-blind comparator trials, 2 randomized, open comparator trials, and 13 open-label trials. The majority of randomized controlled trials has demonstrated substantial efficacy of lithium augmentation in partial and non responders to antidepressant treatment. In the placebo-controlled trials, the response rate in the lithium group was 45% and in the placebo group 18% (p<0.001). Summarizing all open and controlled studies, approximately 50% of patients responded to lithium augmentation within 4 weeks. In conclusion, lithium is the foremost and most well-documented augmentation strategy in refractory depression.Therefore, it should be considered a first-line treatment strategy in patients with major depression who do not adequately respond to standard antidepressants.


One Year Outcomes and Longitudinal Changes in Voice Improvement With Single High Dose Intracordal Trafermin Injections for Age-Related Vocal Fold Atrophy.
Although intracordal trafermin injection has been performed in the treatment of age-related vocal fold atrophy, the effects of single high dose trafermin injections are unknown. In this study, we examined the 1 year outcomes and longitudinal changes in voice improvement with single high dose intracordal trafermin injections. Retrospective study with approval by our Ethics Committee. The medical records of 34 patients who underwent single high dose (50ug per side) intracordal trafermin injections under local anesthesia for vocal fold atrophy were retrospectively reviewed at 1 month pre-injection and 1 month, 6 months and 1 year post injection. Maximum phonation time (MPT), pitch range (PR), Japanese version of voice handicap index (VHI), grade of GRBAS evaluation, and jitter% improved significantly at 1-year post-injection compared to 1-month pre-injection. MPT and PR improved as early as 1-month post-injection and continued to improve most at 1-year post-injection. VHI showed negative progression from 6-months to 1-year post-injection, during which time the speaking fundamental frequency (SFF) changed to the high pitch in men. Single high dose intracordal trafermin injections can be expected to improve voice in the early post-injection period and to maintain its effect for 1 year. SFF may play a role in worsening VHI in men. level 4.


Epidemiological study and dairy farmers' knowledge, attitudes, and practices on foot and mouth disease in central Ethiopia.
Foot and mouth disease (FMD) is consistently ranked as the most economically significant viral disease and one of the top five livestock diseases in Ethiopia. Although FMD is endemic in Ethiopia, the epidemiology and the farmers' knowledge, attitudes, and practices regarding FMD were poorly quantified. Thus, a cross-sectional study was conducted from November 2021 to April 2022 to estimate the seroprevalence, identify the FMD serotypes, and assess the farmers' knowledge, attitudes, and practices on FMD in Addis Ababa city and Sebeta special zone, central Ethiopia. A total of 384 serum samples were collected from cattle and tested using a 3ABC enzyme-linked immunosorbent assay (ELISA). In this study, an overall 56% seroprevalence was recorded. Two types of FMD serotypes were detected in which serotype O was the dominant serotype (75.5%) followed by serotype A (45.5%). A significantly higher seroprevalence (P = 0.00) was recorded in Addis Ababa (85%) compared to Sebeta (28.7%). Seropositivity in older and semi-intensively managed cattle was 2.9 (95% CI: 1.36-6.50; P = 0.006) and 2.1 (95% CI: 1.34-3.26; P = 0.001) times higher compared to young and intensively managed cattle, respectively. A survey on knowledge, attitude, and practice of 103 farmers revealed that 90.2% knew of FMD and the majority of them can recognize its clinical pictures. However, 12.7% of farmers who knew FMD didn't practice any prevention methods. Additionally, 70% of the farmers responded that their cattle roamed outside of their farms for communal grazing, watering, breeding purposes, and vaccination which might put them more at risk of FMD. The current study demonstrated that the majority of farmers have gaps in biosecurity practices and vaccination of cattle against FMD. Therefore, educating farmers on FMD prevention measures is necessary for successful disease control programs.


Coupling of laser excitation and inelastic neutron scattering: attempt to probe the dynamics of light-induced C-phycocyanin dynamics.
Excitation energy transfer (EET) in light-harvesting antennae is a highly efficient key event in photosynthesis, where light-induced dynamics of the antenna pigment-protein complexes may play a functional role. So far, however, the relationship between EET and protein dynamics remains unknown. C-phycocyanin (C-PC) is the main pigment/protein complex present in the cyanobacterial antenna, called "phycobilisome". The aim of the present study was to investigate light-induced C-PC internal thermal motions (ps timescale) measured by inelastic neutron scattering. To synchronize the beginning of the laser flash (6 ns duration) with that of the neutron test pulse ( approximately 87 micros duration), we developed a novel type of "time-resolved" experimental setup on MIBEMOL time-of-flight neutron spectrometer (LLB, France). Data acquisition has been modified to get quasi-simultaneously "light" and "dark" measurements (with and without laser, respectively) and eliminate many spurious effects that could occur on the sample during the experiment. The study was carried out on concentrated C-PC ( approximately 135 g/L protein in D(2)O phosphate buffer), contained in an aluminium/sapphire sample holder (almost "transparent" for neutrons) and homogeneously illuminated inside an "integrating sphere". We observed very similar incoherent dynamical structure factors of C-PC with or without light. The vibrational density of states showed two very slightly increased vibrational modes with light, at approximately 30 and approximately 50 meV ( approximately 240 and approximately 400 cm(-1), respectively). These effects have to be verified by further experiments before probing any temporal evolution, by introducing a time delay between the laser flash and the neutron test pulse.


Effect of alkyl polyglycosides on the performance of thermophilic bacteria pretreatment for saline waste sludge hydrolysis.
In this study, alkyl polyglycosides (APG) was used to further accelerate the hydrolysis of saline waste sludge with thermophilic bacteria (TB) pretreatment. In the presence of 0.4 g/g TSS APG, the concentrations of soluble chemical oxygen demand (SCOD), soluble carbohydrate and soluble protein in dissolved organic matters (DOM) were 0.4, 2.4 and 1.3 times of that without APG addition, respectively. Excitation emission matrix (EEM) fluorescence spectroscopy revealed that the addition of APG led to the increase of soluble microbial materials and the decrease of fulvic acid-like substances in DOM, which was beneficial for the subsequent process of anaerobic digestion. Using APG promoted the releasing of enzymes trapped in saline waste sludge and improved the activity of enzymes during hydrolysis. The activities of α-glucosidase and protease increased by 8.8% and 21.3% respectively in the presence of 0.4 g/g TSS APG comparing no APG addition.


Clinical utilization of a sous vide device in the acute rewarming of frostbitten extremities.
The current standard of care for acute frostbite rewarming is the use of a circulating warm water bath at a temperature of 37 °C to 39 °C. There is no standardized method to achieve this. Manual management of a warm water bath can be inefficient and time consuming. This case describes the clinical use of a sous vide cooking device to create and maintain a circulating warm water bath to rewarm acute frostbite. A 34 year-old male presented to the emergency department with acute frostbite. Each of the patient's feet were placed in a water bath with a sous vide device attached to the side of the basin and set to 38 °C. Temperatures were recorded every 2 m from 2 thermometers. Once target temperature was achieved, the extremities were rewarmed for 30 m. The water baths required an average of 25 m to reach target temperature and maintained the target temperature within ±1 °C for the duration of the rewarming. The extremities were clinically thawed in one session and there were no adverse events. The patient was seen by plastic and vascular surgery and admitted to the hospital for conservative management. He was discharged on hospital day 3 and did not require any amputations. A sous vide device can be used clinically to heat and maintain a water bath and successfully rewarm frostbitten extremities in one 30 m cycle. No adverse events were reported and providers rated this as a convenient method of water bath management.


What is New in the Management of Acute Preterm Labor?: Best Articles From the Past Year.
This month we focus on current research in the management of acute preterm labor. Dr. Malone discusses four recent publications, which are concluded with a "bottom line" that is the take-home message. The complete reference for each can be found in on this page, along with direct links to the abstracts.


New cancer therapies and jaw necrosis.
Osteonecrosis of the jaw (ONJ) has a number of causes, the most familiar being radiation or bisphosphonate induced. Various other novel anti-neoplastic and bone-targeting therapies that can also cause jaw necrosis have recently become available. This has led to the suggested acronym MRONJ for medication-related osteonecrosis of the jaw. This article summarises the available information on these drugs and their implications for the dental surgeon.


A novel indole ethyl isothiocyanate (7Me-IEITC) with anti-proliferative and pro-apoptotic effects on platinum-resistant human ovarian cancer cells.
A novel indole ethyl isothiocyanate derivative (7Me-IEITC) was defined as a potent growth-suppressing agent to cell lines derived from ovarian cancers. Key mechanisms of the cellular response in vitro were studied and suggest a potential of 7Me-IEITC as a therapeutic drug. The viability of ovarian cancer cell lines (SKOV-3, OVCAR-3) in comparison to pancreatic and prostate cancer cell lines, primary fibroblast and immortalized trophoblasts after treatment with 7Me-IEITC was analyzed. Morphological and apoptotic responses of SKOV-3 were studied by fluorescence microscopy (DAPI staining, TUNEL assay). SKOV-3 proliferation was estimated by a standardized BrdU incorporation assay. The phosphorylation of MAP-Kinases, pro-survival factors and the activation of caspases and PARP-1 were analyzed by western blotting. Changes of the mitochondrial transmembrane-potential and in cell-cycle progression were studied by FACS analysis. MAP-Kinase and caspase inhibitors were employed in cytotoxicity studies. 7Me-IEITC selectively reduced the viability of SKOV-3, OVCAR-3, BXPC-3 and PC-3 cells (IC(50) values < or = 5 microM), while the viability of fibroblasts or trophoblasts remained un-affected at concentrations below 20 microM. 7Me-IEITC treatment down-regulated pro-survival kinases and transcription factors (STAT-3, IKKalpha and NF-kappaB), caused rapid loss of the mitochondrial transmembrane-potential and inactivation of PARP-1 along with activation of caspases. The use of p38 MAP-Kinase-and caspase inhibitors suppressed the cytotoxicity of the drug. 7Me-IEITC acted as an anti-proliferative agent and arrested the cell-cycle progression of SKOV-3 in G2/M phase. 7Me-IEITC is a potent and growth-suppressing agent to cell lines derived from ovarian cancers by causing deactivation of survival signals, apoptosis, and cell-cycle arrest.


Calcium citrate, a nonaluminum-containing phosphate-binding agent for treatment of CRF.
Calcium citrate was evaluated as a dietary phosphate binder in 81 patients with end-stage renal disease. These patients were grouped as follows: Group 1, 43 patients who were treated with calcium citrate; and Group 2 (the control group), 38 patients who were treated with aluminum-containing compounds. Blood chemistries were measured monthly and medications adjusted to maintain the following levels: serum calcium, greater than 9 mg/dl; serum phosphorus, less than 5.5 mg/dl; and total CO2 content, greater than 22 mmol/liter. At the end of the treatment period, the following serum values were obtained in Groups 1 and 2, respectively: calcium, 9.6 +/- 1.2 mg/dl (mean +/- SD) versus 8.9 +/- 0.8 mg/dl (P less than 0.001); phosphorus 5.5 +/- 1.9 mg/dl versus 7.0 +/- 2.3 mg/dl (P less than 0.005); and calcium-phosphate product, 52 +/- 18 versus 61 +/- 21 (P less than 0.05). Differences in alkaline phosphatase, total CO2 content, and C-terminal parathyroid hormone (C-PTH) values were not statistically significant between the two groups. Fifteen patients in Group 1 were then switched to aluminum-containing compounds and chemistries were compared one month later. During calcium citrate therapy, serum calcium was significantly higher, while C-PTH and serum alkaline phosphatase were significantly reduced. No difference was noted in serum phosphorous and total CO2 content. A questionnaire completed by 17 patients in Group 1 documented excellent patient tolerance to calcium citrate. Hypercalcemia (greater than 10.5 mg/dl) was the only significant complication, but only one patient became symptomatic. We conclude that, as a phosphate binder, calcium citrate is at least as effective as aluminum-containing compounds.


Gradient Hydrogels.
Gradient hydrogels represent a pivotal and expanding direction of three-dimensional cell culture. Since various types of gradients play an important role in physiological and pathological processes in vivo, recreation of these gradients in vitro allows a better understanding of cellular behavior, intercellular and cell-matrix interactions. Moreover, gradient hydrogels can advance the creation of functionally improved and physiologically relevant tissue engineered constructs. Another application of gradient hydrogels is the optimization of the 3D in vitro microenvironment (e.g., in terms of hydrogel stiffness or concentration of adhesion ligands). Tunable hydrogels provide researchers with a versatile toolbox to manufacture such gradients in vitro. In this chapter different types of in vivo and in vitro gradients in hydrogels will be presented. Equipment and methods for various gradient fabrications will be discussed. Furthermore, methods of gradient characterizations in hydrogels will be reported. As one of the most recent developments, the influence of low oxygen concentration on cells, as well as the creation and characterization of oxygen gradients in hydrogels will be described. In the last part, achievements in the creation of multiple combinatorial gradients will be presented. The aim of this chapter is to give the reader an overview on existing techniques and biological importance of gradient hydrogels in basic science as well as in applied research.


Spontaneous testicular recrudescence of Syrian hamsters: role of stimulatory photoperiods.
The gonads of hamsters maintained in short photoperiods first undergo regression and then spontaneous recrudescence. The latter is indicative of refractoriness of the neuroendocrine axis to short day lengths. We tested the hypothesis that the absence of long-day stimulation contributes to the development of refractoriness to short photoperiods. Male Syrian hamsters were maintained for 26 weeks in a short-day photoperiod (8 hr light/day). Testicular regression was confirmed in all animals at week 10; thereafter different groups of hamsters were stimulated with one long day (16 hr light) every 10, 15, 20 or 30 days until week 26. Control groups were maintained continuously in long or short photoperiods, respectively. The rate of gonadal recrudescence of short-day hamsters was not affected by intermittent stimulation with long photoperiods. After 26 weeks, testes in all short-day groups had undergone recrudescence. Refractoriness to short day lengths is not counteracted by long photoperiods. The role of the pineal gland in the development of refractoriness is considered.


Monocyte CD169 Expression as a Biomarker in the Early Diagnosis of Coronavirus Disease 2019.
We assessed the expression of CD169, a type I interferon-inducible receptor, on monocytes (monocyte CD169 [mCD169]) in 53 adult patients admitted to the hospital during the coronavirus disease 2019 (COVID-19) outbreak for a suspicion of severe acute respiratory syndrome coronavirus 2 infection. Monocyte CD169 was strongly overexpressed in 30 of 32 (93.7%) confirmed COVID-19 cases, compared with 3 of 21 (14.3%) patients in whom the diagnosis of COVID-19 was finally ruled out. Monocyte CD169 was associated with the plasma interferon-alpha level and thrombocytopenia. Monocyte CD169 testing may be helpful for the rapid triage of suspected COVID-19 patients during an outbreak.


False discovery rate estimation using candidate peptides for each spectrum.
False discovery rate (FDR) estimation is very important in proteomics. The target-decoy strategy (TDS), which is often used for FDR estimation, estimates the FDR under the assumption that when spectra are identified incorrectly, the probabilities of the spectra matching the target or decoy peptides are identical. However, no spectra matching target or decoy peptide probabilities are identical. We propose cTDS (target-decoy strategy with candidate peptides) for accurate estimation of the FDR using the probability that the spectrum is identified incorrectly as a target or decoy peptide. Most spectrum cases result in a probability of having the spectrum identified incorrectly as a target or decoy peptide of close to 0.5, but only about 1.14-4.85% of the total spectra have an exact probability of 0.5. We used an entrapment sequence method to demonstrate the accuracy of cTDS. For fixed FDR thresholds (1-10%), the false match rate (FMR) in cTDS is closer than the FMR in TDS. We compared the number of peptide-spectrum matches (PSMs) obtained with TDS and cTDS at a 1% FDR threshold with the HEK293 dataset. In the first and third replications, the number of PSMs obtained with cTDS for the reverse, pseudo-reverse, shuffle, and de Bruijn databases exceeded those obtained with TDS (about 0.001-0.132%), with the pseudo-shuffle database containing less compared to TDS (about 0.05-0.126%). In the second replication, the number of PSMs obtained with cTDS for all databases exceeds that obtained with TDS (about 0.013-0.274%). When spectra are actually identified incorrectly, most probabilities of the spectra matching a target or decoy peptide are not identical. Therefore, we propose cTDS, which estimates the FDR more accurately using the probability of the spectrum being identified incorrectly as a target or decoy peptide.


Tuberculosis infection transmitted at autopsy.
Tuberculosis can be a risk to staff and students in the autopsy room. We report three medical students and one technician who were infected with tuberculosis during two autopsies. In both cases pulmonary tuberculosis had not been diagnosed before death.


Cyanosalvianin, a supramolecular blue metalloanthocyanin, from petals of Salvia uliginosa.
A metalloanthocyanin, cyanosalvianin, was found in blue petals of Salvia uliginosa. Cyanosalvianin consisted of 3-O-(6-O-p-coumaroylglucopyranosyl)-5-O-(4-O-acetyl-6-O-malonylglucopyranosyl) delphinidin, 7,4'-di-O-glucopyranosylapigenin and magnesium ion. We reproduced the same blue color as the petals by mixing the three components together. An ESI-MS measurement gave a molecular weight of 9014 indicating the composition of cyanosalvianin to be six molecules of the anthocyanin component, six molecules of the flavone component and two magnesium ions. The special arrangement of the organic components in cyanosalvianin was analyzed by CD and 2D-NMR spectroscopy. It was clarified that cyanosalvianin has a similar structure to that of commelinin, a metalloanthocyanin isolated from blue dayflower, Commelina communis.


Feeding Practices and Dietary Diversity in the First Year of Life: PreventADALL, a Scandinavian Randomized Controlled Trial and Birth Cohort Study.
Breastmik is considered the optimal source of nutrition in early infancy. However, recommendations and practices for when and how complementary food should be introduced in the first year of life vary worldwide. Early introduction of allergenic foods may prevent food allergies, but if early food introduction influences infant feeding practices is less known. We sought to assess infant feeding practices in the first year of life and to determine if early interventional food introduction influences breastfeeding and dietary diversity. Dietary intake was assessed in infants from the population-based clinical trial Preventing Atopic Dermatitis and ALLergies (PreventADALL) in children study. A total of 2397 infants were cluster-randomized at birth into 4 different groups: 1) control, 2) skin intervention, 3) introduction to 4 allergenic foods between 3 and 4 mo of age: peanut, cow milk, wheat, and egg, as small tastings until 6 mo, and 4) combined skin and food interventions. Dietary data were available from at least one of the 3-, 6-, 9-, and 12-mo questionnaires in 2059 infants. In the present analysis, groups 1 and 2 constitute the No Food Intervention group, whereas groups 3 and 4 constitute the Food Intervention group. We used the log-rank test and Cox regression to assess the impact of food intervention on age of breastfeeding cessation. Mixed effects logistic regression was used to compare dietary diversity, defined as the number of food categories consumed, between intervention groups. At 3, 6, 9, and 12 mo, 95%, 88%, 67%, and 51% were breastfed, respectively, and breastfeeding duration was not affected by the food intervention. In the No Food Intervention group, mean age of complementary food introduction was 18.3 wk (confidence interval [CI]: 18.1, 18.5). In the Food Intervention group, the dietary diversity score was 1.39 units (CI: 1.16, 1.62) higher at 9 mo (P < 0.001) and 0.7 units (CI: 0.5, 0.9) higher at 12 mo (P < 0.001) compared to the No Food Intervention group. Early food intervention did not affect breastfeeding rates and increased dietary diversity at 9 and 12 mo.


NBD peptides protect against ischemia reperfusion after orthotopic liver transplantation in rats.
NBD (NEMO binding domain) peptides could selectively inhibit the inflammation induced NF-κB activity, while sparing the protective functions of basal NF-κB activity. The aim of this study was to determine whether NBD peptides inhibited the transcriptional activity of nuclear factor-κB (NF-κB) during liver transplant ischemia-reperfusion injury (IRI), without affecting its basal function. Sprague Dawley (SD) rats were performed orthotropic liver transplantation according to the Kamada technique. Donors were given NBD peptides (8 mg/kg, intraperitoneal) 2 h before surgery (n = 24) and the controls were treated with the same volume of physiologic saline (n = 24). An additional 16 animals in normal condition (did not undergo any surgery) were also divided into two groups and given the same treatment as above to assess the effect of NBD peptides on basal function. We analyzed levels of alanine aminotransferase (ALT), tumor necrosis factor (TNF-α), IKK (IκB kinase) complex phosphorylation, IκBα degradation, NF-κB transcriptional activity, apoptosis, and performed a morphologic study of liver tissues at 3, 6, and 24 h after portal vein reperfusion and in normal condition (n = 8). Pretreatment with NBD peptides significantly improved liver function, attenuating liver parenchymal cell damage, apoptosis by down-regulating TNF-α level, inhibiting IKK complex phosphorylation, IκBα degradation, and NF-κB transcriptional activity, but had no effect in normal condition. NBD peptides attenuated hepatic IRI by preventing NF-κB activation, without affecting basal NF-κB activity.


[Mono- or bilateral abducens paralysis as the initial symptom of sinus vein thrombosis].
Sinus vein thrombosis is a rare intracerebral complication of mastoiditis. We report on the clinical ophthalmologic symptomatology of this secondary illness. two young female patients, aged 14 and 3.5 years, presented at our pediatric ophthalmology section due to diplopia. Both girls had suffered 1-2 weeks earlier from otitis media, which had been treated with antibiotics. Other neurological symptoms were not reported. Best corrected visual acuity was 20/20 OD/OS in both patients. Ocular alignment revealed a bilateral abduction deficit in the 14-year-old girl and a monolateral abduction deficit of the right eye in the younger patient. Ophthalmoscopic examination evidenced bilateral papilledema in both patients. Magnetic resonance tomography and magnetic resonance angiography showed mastoiditis and thrombosis of the sigmoid and transverse sinuses. Following mastoidectomy, high-dose antibiotic therapy, and full-dose heparin therapy, rapid improvement occurred. Thrombosis of the sigmoid sinus following mastoiditis is a rare but severe complication of middle ear inflammation. Immediate surgical and antibiotic therapy is necessary. Symptoms can possibly occur even when the primary focus seems to resolve.


D-dimer concentrations during normal pregnancy, as measured by ELISA.
In pregnant women a number of changes in blood clotting and fibrinolysis proteins have been reported so indicating the existence of a state of hypercoagulability. In addition to fibrinogen and antithrombin III (AT), D-dimer is frequently checked during pregnancy, in particular during at risk pregnancy, but the exact pattern of D-dimer modifications during uncomplicated pregnancy is not definitively described. The aim of this study was to establish the range values in three different periods of uncomplicated pregnancy (A: 1-20 wks; B: 21-30 wks; C: 31-40 wks). We measured plasma levels of D-dimer, clottable fibrinogen and AT in 108 consecutive normal pregnant women aged 16 to 42 years. In period A, the range of D-dimer values was 43-211 ng/mL, not different from controls, while fibrinogen levels were significantly higher (p < 0.05) than in matched non pregnant women. Mean D-dimer levels were higher in periods B (p < 0.05) and C (p < 0.05) vs period A. Similarly, mean fibrinogen levels were found more elevated in periods B and C vs period A (p < 0.05). A significant correlation was found between fibrinogen and D-dimer levels (p < 0.001). No differences in AT levels were found among the three periods of pregnancy. The results of this study indicate that levels of D-dimer up to 685 micrograms/L may be reached at the end of physiological pregnancy. This fact should be taken into account in the evaluation of hemostatic studies performed in uncomplicated and complicated pregnant women.


Rating analysis and BERTopic modeling of consumer versus regulated mHealth app reviews in Germany.
Germany introduced prescription-based mobile health (mHealth) apps in October 2020, becoming the first country to offer them fully reimbursed by health insurance. These regulated apps, known as DiGAs, undergo a rigorous approval process similar to pharmaceuticals, including data protection measures and sometimes clinical trials. This study compares the user experience of DiGAs with non-prescription mHealth apps in Germany, analyzing both average app store ratings and written reviews. Our study pioneers the use of BERTopic for sentiment analysis and topic modeling in the mHealth research domain. The dataset comprises 15 DiGAs and 50 comparable apps, totaling 17,588 German-language reviews. Results reveal that DiGAs receive higher contemporary ratings than non-regulated apps (Android: 3.82 vs. 3.77; iOS: 3.78 vs. 3.53; p < 0.01; non-parametric Mann-Whitney-Wilcoxon test). Key factors contributing to positive user experience with DiGAs are customer service and personalization (15%) and ease of use (13%). However, challenges for DiGAs include software bugs (24%) and a cumbersome registration process (20%). Negative user reviews highlight concerns about therapy effectiveness (11%). Excessive pricing is the main concern for the non-regulated group (27%). Data privacy and security receive limited attention from users (DiGAs: 0.5%; comparators: 2%). In conclusion, DiGAs are generally perceived positively based on ratings and sentiment analysis of reviews. However, addressing pricing concerns in the non-regulated mHealth sector is crucial. Integrating user experience evaluation into the review process could improve adherence and health outcomes.


Hypoglycaemia in an adult male: a surprising finding in pursuit of insulinoma.
A 50-year-old man who had suffered several episodes of early morning sweats and tremors was diagnosed as having hyperinsulinaemic hypoglycaemia. Cross-sectional imaging and endoscopic ultrasound revealed no pancreatic lesion. A selective intra-arterial calcium infusion study showed a two-fold increase of insulin secretion after infusion of the splenic and superior mesenteric arteries. Laparotomy was performed, no lesion was identified after full mobilisation of the pancreas, and nothing was evident with intra-operative ultrasound. A distal pancreatectomy was performed. Microscopically, the pancreas exhibited diffuse islet cell hyperplasia consistent with nesidioblastosis. The patient remains euglycaemic eight months post-operatively.


Hemodynamic characterization in experimental liver cirrhosis induced by thioacetamide administration.
Systemic and splanchnic hemodynamics in experimental liver cirrhosis in rats induced by thioacetamide were evaluated by the radioactive microsphere method. Cardiac output and regional blood flow were measured in conscious and anesthetized control and cirrhotic rats. The conscious thioacetamide-treated rats had hyperdynamic circulation with an increased cardiac index (300 +/- 10 vs 258 +/- 3 ml/min/kg body weight, P < 0.001) and increased portal venous inflow compared with the controls (64.60 +/- 2.4 vs 48.39 +/- 0.88 ml/min/kg body weight, P < 0.001). Under pentobarbital anesthesia, the hyperdynamic circulation of the cirrhotic rats was maintained, with an increased cardiac index (276 +/- 7 vs 229 +/- 5 ml/min/kg body weight, P < 0.001) and increased protal venous inflow compared with the controls (72.47 +/- 3.0 vs 54.08 +/- 1.2 ml/min/kg body weight, P < 0.001). Portal pressure, portal venous resistance, and portal systemic shunting increased significantly while splanchnic arterial resistance decreased significantly in cirrhotic rats. Thioacetamide-induced cirrhosis is a useful model for the hemodynamic study of portal hypertension and remains useful in hemodynamic studies in the basal state under pentobarbital anesthesia.


Elevated levels of apolipoprotein D predict poor outcome in patients with suspected or established coronary artery disease.
Apolipoprotein D (apoD) is a lipocalin exerting neuroprotective effects. However, the relevance of apoD in respect to cardiovascular risk is largely unexplored. Therefore, this study aimed to evaluate the ability of apoD to predict future all-cause mortality, cardiovascular mortality, and cardiovascular events. Serum apoD levels were measured in a cohort of 531 Caucasian individuals who underwent coronary angiography (356 males, 175 females; mean age 65 ± 10 years). Fatal and non-fatal events were recorded over a median follow-up period of 5.8 years. ApoD concentrations at baseline correlated significantly with age, presence of the metabolic syndrome, body mass index, lipoprotein levels, fasting glucose, and estimated glomerular filtration rate. Kaplan-Meier curve analyses by gender-stratified quartiles of apoD revealed that the cumulative incidence rates of mortality and cardiovascular events become higher with increasing apoD levels. The adjusted hazard ratios for participants in the highest quartile of apoD compared to those in the lowest quartile were 4.00 (95% confidence interval [CI] 1.49-10.74) for overall mortality, 5.47 (95% CI 1.20-25.00) for cardiovascular mortality, and 2.52 (95% CI 1.28-5.00) for cardiovascular events. High circulating levels of apoD are an indicator of poor prognosis in patients with suspected or established coronary artery disease.


Alleviating Drought Stress in Brassica juncea (L.) Czern & Coss. by Foliar Application of Biostimulants-Orthosilicic Acid and Seaweed Extract.
Agricultural productivity is negatively impacted by drought stress. Brassica is an important oilseed crop, and its productivity is often limited by drought. Biostimulants are known for their role in plant growth promotion, increased yields, and tolerance to environmental stresses. Silicon in its soluble form of orthosilicic acid (OSA) has been established to alleviate deteriorative effects of drought. Seaweed extract (SWE) also positively influence plant survival and provide dehydration tolerance under stressed environments. The present study was conducted to evaluate the efficacy of OSA and SWE on mitigating adverse effects of drought stress on Brassica genotype RH-725. Foliar application of OSA (2 ml/L and 4 ml/L) and SWE of Ascophyllum nodosum (3 ml/L and 4 ml/L) in vegetative stages in Brassica variety RH 725 under irrigated and rainfed condition revealed an increase in photosynthetic rate, stomatal conductance, transpirational rate, relative water content, water potential, osmotic potential, chlorophyll fluorescence, chlorophyll stability index, total soluble sugars, total protein content, and antioxidant enzyme activity; and a decrease in canopy temperature depression, proline, glycine-betaine, H2O2, and MDA content. Application of 2 ml/L OSA and 3 ml/L SWE at vegetative stage presented superior morpho-physiological and biochemical characteristics and higher yields. The findings of the present study will contribute to developing a sustainable cropping system by harnessing the benefits of OSA and seaweed extract as stress mitigators.


Years of life lost to drug overdose in the Latinx community during the most recent wave of overdose deaths.
This study estimated years of life lost (YLL) among US Latinx individuals during the most recent wave of drug overdose deaths. A serial cross-sectional study of YLL (life expectancy minus age at death) from death certificate records of Latinx individuals who died from drug overdoses from 2015 to mid-2022. Over the study period, 58,209 Latinx individuals aged 15-64 years died from drug overdoses resulting in 2,266,784 YLL. Age-group YLL differences remained stable, but gender YLL trajectories diverged. This study extends our understanding of the immense loss to Latinx communities from preventable drug deaths.


High pre-treatment static and dynamic alpha-fetoprotein values predict reduced overall survival in hepatocellular carcinoma.
Hepatocellular carcinoma is one of the most lethal cancers worldwide. Novel prognostic and/or predictive biomarkers are urgently needed to improve patient management. Alpha-fetoprotein is a well-established and widely used biomarker for hepatocellular carcinoma. However, diagnostic accuracy of static alpha-fetoprotein values is limited and the clinical potential is a matter of ongoing scientific discussion. We here evaluated the prognostic impact of pre-treatment static and dynamic alpha-fetoprotein variables on overall survival of hepatocellular carcinoma patients in a Western cohort. Patients with confirmed hepatocellular carcinoma (n = 809) treated at the Johannes Gutenberg-University Mainz between 1998 and 2014 and two available pre-treatment alpha-fetoprotein-values (AFP-slope) were retrospectively analysed. Clinico-pathological baseline parameters, pre-treatment static values and AFP-slope were assessed. Prognostic impact was determined by Kaplan-Meier analyses and Cox regression models. High static and dynamic alpha-fetoprotein variables prior to therapy were associated with reduced survival rates of hepatocellular carcinoma patients. Several known clinical parameters such as Child-Pugh B (p < 0.01) and C stage (p < 0.001), portal vein thrombosis (p < 0.001) and extrahepatic spread (p < 0.001) were confirmed as independent predictors for overall survival. Addition of static and/or dynamic alpha-fetoprotein variable resulted in higher time-dependent area under the curves. Notably, in patients with more favourable prognosis, AFP-slope prior to therapy was a slightly stronger predictor for overall survival compared with static alpha-fetoprotein values. Static and dynamic alpha-fetoprotein variables prior to therapy are predictive for overall survival of hepatocellular carcinoma patients. Addition of AFP-slope to established prognostic parameters might improve prognostic classification for a subgroup of hepatocellular carcinoma patients with preserved liver function and without portal vein tumour thrombosis.


Effects of emotion and sex difference on item-method directed forgetting.
It is crucial to remember or forget others' faces in daily life. People can intentionally forget things they wish to forget, a phenomenon called directed forgetting (DF). This study examined the effects of stimuli's emotions and sex differences in participants and stimuli on DF. We used happy and angry faces as the items in a typical item-method paradigm and conducted three behavioral experiments. In Experiment 1, we recruited 60 participants to examine how emotions of stimuli and sex differences in participants and stimuli affected DF. In Experiment 2, we recruited 60 female participants and manipulated the durations of items presented during the study phase to examine whether the selective rehearsal theory was held. In Experiment 3, we recruited 50 female participants and attached recognition cues to the items presented during the test phase to examine whether the inhibitory control theory was held. We treated the sex of participants in Experiment 1, the durations of items presented during the study phase in Experiment 2 as the between-subject factors, and emotion and sex of stimuli as the with-subject factors. We conducted the mixed-design ANOVA for corrected hit rate, sensitivity, and bias based on the signal detection theory. As a result, we found that DF occurred easily for male participants, whereas not for female participants because of females' superior memorial performances and stronger sensitivities. Furthermore, we found that female participants owned the best and worst recognition rates for angry female faces and happy male faces, respectively. Our results supported the selective rehearsal theory, suggesting manipulations during the study phase had the potential to help females forget what they wished to forget. We presumed that psychologists and therapists should pay attention to the roles of sex difference in twofold, self and others, when studying people's memory and forgetting. Furthermore, the sensitivity of self and the emotion of others should be considered as well.


Effects of edible coatings and ultrasonic pretreatment on the phenolic content, antioxidant potential, drying rate, and rehydration ratio of sweet cherry.
The target of this study was to examine the influence of ultrasound pretreatment and edible coatings (xanthan, guar, and wild sage seed gums) on the total phenols content, antioxidant potential, mass transfer rate, effective moisture diffusivity (Deff), and rehydration rate of sweet cherries (SC). For the edible coating of SC, a 0.2% gum solution (xanthan, guar, and wild sage seed) was prepared and the SC were dipped into the aqueous solution. Also, the ultrasound process (40 kHz and 150 W) was performed in an ultrasonic bath for 3 min. The gums coating increased the total phenols content, antioxidant properties, and drying time and decreased the Deff values. The highest value of DPPH (2,2-Diphenyl-1-picrylhydrazyl) radical scavenging activity (61.04 ± 2.09%) was observed on coated SC by guar gum. The mean drying times for uncoated, xanthan gum-coated, guar gum-coated, and wild sage seed gum-coated SC were 130, 160, 175, and 140 min, respectively. In this study, the SC Deff as determined by the second Fick law varied from 1.39 × 10-9 m2/s to 2.46 × 10-9 m2/s. The Midilli model gave the best results for describing single-layer drying of SC. The mean rehydration ratio for uncoated, xanthan gum-coated, guar gum-coated, and wild sage seed gum-coated SC were 141.81, 167.26, 176.21, and 156.87 %, respectively. Considering the total phenols content, antioxidant activity, and rehydration ratio, edible coating and ultrasonic pretreatment will be more promising for SC pretreatment before drying and other processes.


The effects of self-care education based on the health literacy index on self-care and quality of life among menopausal women: a randomized clinical trial.
Aging is associated with many different health-related challenges for women such as menopause and its associated problems. Self-care (SC) is a factor with potential effects on menopause and its consequences. SC education based on health literacy has the potential to improve menopausal women's SC. The aim of this study was to evaluate the effects of SC education based on the health literacy index (HLI) on SC and quality of life (QOL) among menopausal women. This randomized clinical trial was conducted in Iran. Participants were 100 menopausal women purposively recruited from five comprehensive healthcare centers in the south of Tehran. They were randomly allocated to a control and an intervention group through block randomization. Intervention was an HLI-based SC education program implemented in four 1.5-hour weekly sessions through the lecture, group discussion, and question and answer methods. Data were collected before and eight weeks after the intervention using a demographic questionnaire, the Health Literacy for Iranian Adults scale, the Menopause-Specific Quality of Life Questionnaire, and the Menopausal Self-Care Questionnaire. The SPSS software (v. 22.0) was used to analyze the data through the Chi-square, Fisher's exact, paired-sample t, and the independent-sample t tests as well as the analysis of covariance at a significance level of less than 0.05. There were no significant differences between the intervention and the control groups respecting the pretest mean scores of QOL (88.15 ± 32.36 vs. 79.6 ± 36.99) and SC (104.75 ± 12.31 vs. 103.32 ± 13.8) (P > 0.05). However, the posttest mean scores of QOL and SC in the intervention group significantly differed from the control group (66.44 ± 28.41vs. 81.3 ± 38.04 and 125.6 ± 11.23 vs. 102.6 ± 14.34) (P < 0.05). HLI-based SC education is effective in significantly improving menopausal women's QOL and SC and can be used to improve health-related outcomes among menopausal women. Clinical trial registration This research was registered (24/03/2020) in the www.thaiclinicaltrials.org with registration number: TCTR20200324002.


Kierkegaard and psychology as the science of the "multifarious life".
The aim of this paper is to demonstrate the actuality of some considerations around psychology made by the Danish philosopher Søren Kierkegaard (1813-1855). According to him psychology is about the "multifarious" life, which is a term that pinpoints the challenges psychology still have when it comes to including changes and genetic perspectives on its understanding of actual living. Yet Kierkegaard discusses psychology in relationship to metaphysics, which is an almost forgotten perspective. His understanding opens up for narrowing the definition of psychology down to the science of subjectivity, which at the same time elevates psychology to being the only science that focuses on the actual human life. Yet Kierkegaard's most important contribution to psychology is to maintain a radical distinction between subjectivity and objectivity, and in this respect the psychology of today is challenged.


Spatiotemporal visualization of DNA replication dynamics.
The ability of cells to copy their DNA allows them to transmit their genetic information to their progeny. In such, this central biological process preserves the instructions that direct the entire development of a cell. Earlier biochemical analysis in vitro and genetic analysis in yeast laid the basis of our understanding of the highly conserved mechanism of DNA replication. Recent advances on labeling and live-cell microscopy permit now the dissection of this fundamental process in vivo within the context of intact cells. In this chapter, we describe in detail how to perform multiple DNA replication labeling and detection allowing high spatial resolution imaging, as well as how to follow DNA replication in living cells allowing high temporal resolution imaging.


Oxidation by rat brain of N-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP) coupled to tetrazolium nitro blue.
The present study shows that the dehydrogenation of N-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP) can be coupled to tetrazolium nitro blue (TNB), a substance used as electron acceptor in many dehydrogenase reactions. The MPTP-TNB reductase system has an apparent Km value and inhibitor sensitivity similar to those of monoamine oxidase (MAO) type B. MPTP oxidation in the brain may very well be mediated by MAO-B.


Effect of sport-tinted contact lenses for contrast enhancement on retinal straylight measurements.
To investigate the effect of two tinted contact lenses (CL) designed for outdoor sports activity on the psychometric determination of retinal straylight using the compensation comparison method. Thirteen emmetropic subjects were randomly fitted with two different tinted Nike Maxsight (Bausch & Lomb, Rochester, NY, USA) CL in one eye, while the contralateral eye was fitted with a clear lens made of the same material (Optima 38, Bausch & Lomb). Three valid straylight measurements were taken on each eye before and a few minutes after lens insertion, when lens stabilization had occurred. The subjects' mean straylight values were 0.90 +/- 0.09 at baseline and 0.95 +/- 0.10 with the clear Optima 38 CL. Straylight values were 0.97 +/- 0.10 and 1.0 +/- 0.10 log units with the amber and grey-green tinted CL, respectively. Differences in straylight between baseline (without CL) and with the clear CL in place were neither statistically significant (p = 0.066) nor was there a significant difference between baseline and the amber CL (p = 0.052). However, the grey-green CL showed a statistically significant difference from baseline (p = 0.006). Differences in straylight with the clear CL compared with the grey-green CL were also statistically different from zero (p = 0.002) showing an increased straylight value for the tinted CL. These differences were variable, but consistent for each subject, thus those showing higher or lower changes with one tinted lens tended to show the same trend with the second lens (r(2) = 0.736). Despite increases having been found in straylight values with tinted contact lenses, those changes are not likely to induce clinically significant changes in visual function under photopic conditions, even for the grey-green CL, which seems to increase straylight values more significantly than the amber CL. This difference between the tinted CL could suggest a wavelength dependence of straylight values, although this should be investigated further by controlling for pupil size and subjects' pigmentation, as well as by using neutral density filters.


Application of photoacoustic calorimetry to the determination of volume changes in reactions involving radical anions in aqueous solutions.
The particular features of the application of photoacoustic calorimetry to the determination of volume changes in reactions involving radical anions in aqueous solutions are addressed. Analysis of recent literature data on volume changes of redox pairs, including our previous results on the couples NO2(-)/NO2 and SO4(2-)/(SO4)*-, together with known values of molal volume changes for ionization reactions, allow us to derive an empirical correlation for these categories of reactions. Finally, the pertinence of describing the volume changes of complex processes as a simple sum of separable terms is critically examined.


Inducing Propulsion of Colloidal Dimers by Breaking the Symmetry in Electrohydrodynamic Flow.
We show that dielectric colloidal dimers with broken symmetry in geometry, composition, or interfacial charges can all propel in directions that are perpendicular to the applied ac electric field. The asymmetry in particle properties ultimately results in an unbalanced electrohydrodynamic flow on two sides of the particles. Consistent with scaling laws, the propulsion direction, speed, and orientation of dimers can be conveniently tuned by frequency. The new propulsion mechanism revealed here is important for building colloidal motors and studying collective behavior of active matter.


Gap junction-mediated cell-cell communication modulates mouse neural crest migration.
Previous studies showed that conotruncal heart malformations can arise with the increase or decrease in alpha1 connexin function in neural crest cells. To elucidate the possible basis for the quantitative requirement for alpha1 connexin gap junctions in cardiac development, a neural crest outgrowth culture system was used to examine migration of neural crest cells derived from CMV43 transgenic embryos overexpressing alpha1 connexins, and from alpha1 connexin knockout (KO) mice and FC transgenic mice expressing a dominant-negative alpha1 connexin fusion protein. These studies showed that the migration rate of cardiac neural crest was increased in the CMV43 embryos, but decreased in the FC transgenic and alpha1 connexin KO embryos. Migration changes occurred in step with connexin gene or transgene dosage in the homozygous vs. hemizygous alpha1 connexin KO and CMV43 embryos, respectively. Dye coupling analysis in neural crest cells in the outgrowth cultures and also in the living embryos showed an elevation of gap junction communication in the CMV43 transgenic mice, while a reduction was observed in the FC transgenic and alpha1 connexin KO mice. Further analysis using oleamide to downregulate gap junction communication in nontransgenic outgrowth cultures showed that this independent method of reducing gap junction communication in cardiac crest cells also resulted in a reduction in the rate of crest migration. To determine the possible relevance of these findings to neural crest migration in vivo, a lacZ transgene was used to visualize the distribution of cardiac neural crest cells in the outflow tract. These studies showed more lacZ-positive cells in the outflow septum in the CMV43 transgenic mice, while a reduction was observed in the alpha1 connexin KO mice. Surprisingly, this was accompanied by cell proliferation changes, not in the cardiac neural crest cells, but in the myocardium- an elevation in the CMV43 mice vs. a reduction in the alpha1 connexin KO mice. The latter observation suggests that cardiac neural crest cells may have a role in modulating growth and development of non-neural crest- derived tissues. Overall, these findings suggest that gap junction communication mediated by alpha1 connexins plays an important role in cardiac neural crest migration. Furthermore, they indicate that cardiac neural crest perturbation is the likely underlying cause for heart defects in mice with the gain or loss of alpha1 connexin function.


A Quantum Inspired GVNS: Some Preliminary Results.
GVNS is a well known and widely used metaheuristic for solving efficiently many NP-Hard Combinatorial Optimization problems. In this paper, the qGVNS, which is a new quantum inspired variant of GVNS, is being introduced. This variant differs in terms of the perturbation phase because it achieves the shaking moves by adopting quantum computing principles. The functionality and efficiency of qGVNS have been tested using a comparative study (compared with the equivalent GVNS results) in selected TSPLib instances, both in first and best improvement.


Association of the methylene-tetrahydrofolate reductase gene rs1801133 C677T variant with serum homocysteine levels, and the severity of coronary artery disease.
This study aimed to investigate whether the single nucleotide polymorphism C677T (rs1801133) of the methylene-tetrahydrofolate reductase (MTHFR) gene was associated with the risk of coronary artery disease (CAD) and circulating homocysteine (Hcy) levels in Tunisian population. 310 angiografically diagnosed CAD patients and 210 controls were enrolled in this study. The MTHFR C677T (rs1801133) polymorphism was genotyped, and the Hcy concentrations were measured. The severity of CAD was evaluated using the Gensini scoring system. Compared to the CC genotype, the TT genotype confers a higher risk for CAD severity with an OR = 9.07 and 95% CI = 3.78-21.8. The T allele was the predisposing allele for CAD and that it was probably associated with CAD severity. The area under the ROC curve for Hcy was 0.764 (95% CI 0.660 to 0.868, p = 0.001). The receiver operating characteristics curve (ROC) for Hcy showed its useful prediction of CAD. Hcy levels were not significantly associated with CAD severity expressed by Gensini Score (GS). The MTHFR C677T (rs1801133) polymorphism influences circulating Hcy levels. The MTHFR C677T polymorphism and hyperhomocysteinemia could have an important role in the prediction of the presence and not the severity expressed by GS of CAD.


Acid-producing capacity from sugars and sugar alcohols among Lactobacillus isolates collected in connection with radiation therapy.
To investigate the acid-producing capacity from sugars and sugar alcohols of oral Lactobacillus collected in connection with radiation therapy (RT) to the head and neck region. Lactobacillus were collected from the tongue, buccal mucosa and supragingival plaque in 24 patients before, during, and after RT. The acid-producing capacity of Lactobacillus isolates (n=211) was analyzed using a colorimetric fermentation test in microtiter plates. Solutions containing 2% sugars (sucrose, glucose, fructose, lactose) or sugar-alcohols (sorbitol and xylitol) were used. After 24h of incubation, bacterial acid-producing capacity was determined as strong (pH<5), weak (pH ≥5-≤ 6) or low/absent (pH>6). Data regarding intake frequency of sugar-rich products and products with sugar-alcohols was collected. The highest acid-producing capacity using the sugars was seen for isolates collected during RT. Sorbitol was fermented to a higher extent during and post RT, especially among isolates from plaque. Lactobacillus fermenting xylitol showed the highest acid-producing capacity during RT (p<0.05). No statistically significant correlations between stimulated whole salivary secretion rate and acid-producing capacity, or between the intake frequency of sugar-rich products or sugar-alcohol containing products and Lactobacillus acid-producing capacity, were found. The results suggest that Lactobacillus isolates, collected from the tongue, buccal mucosa and supragingival plaque, have a higher acid-producing capacity using sugars and sugar-alcohols during RT than one year post RT.


Do newspaper reports of coroners' inquests incite people to commit suicide?
A statistical association has been found between reports of suicide inquests in a local paper and the subsequent suicide of men under 45 years.


Bacterial consumption of humic and non-humic low and high molecular weight DOM and the effect of solar irradiation on the turnover of labile DOM in the Southern Ocean.
The decomposition of dissolved organic matter (DOM) in pelagic ecosystems is mediated primarily by heterotrophic bacteria, but transformation by short-wave solar radiation may play an important role in surface waters, in particular when humic substances constitute a substantial fraction of the DOM pool. Most of the studies examining bacterial decomposition and photochemical transformation of DOM stem from limnetic and coastal marine systems and much less information is available from oceanic environments. To examine the bacterial decomposition of humic and non-humic DOM in the Southern Ocean we carried out microcosm experiments in which we measured bacterial growth on isolated fractions of humic and non-humic DOM of the size classes <3 kDa and >3 kDa. Experiments carried out at the Polar Front showed a preferential bacterial growth on non-humic DOM and in particular on the size fraction <3 kDa. Bacterial growth, measured as bacterial biomass production, on non-humic DOM accounted for 74% to 88% of the total growth on all four DOM fractions. In experiments in the Antarctic circumpolar current and the coastal current under pack ice, bacterial growth was 6x lower than at the Polar Front, and humic and non-humic DOM was consumed to equal amounts. The size fraction <3 kDa was always preferred. Experiments examining the effect of solar radiation on the release of dissolved amino acids (DAA) and carbohydrates (DCHO) and their subsequent bacterial utilization showed a stimulating effect on glucose uptake and the release of DAA at the Polar Front but an inhibition in the eastern Weddell Sea. Ultraviolet-B was the most effective component of the solar radiation spectrum tested. Effects of UV-B on glucose uptake and release of DAA were positively correlated with concentrations of humic-bound DAA. The data imply that at low concentrations, e.g., <100 nM (amino acid equivalent), UV-irradiation reduces, whereas at concentrations >100 nM UV-irradiation stimulates glucose uptake and release of DAA as compared to dark conditions.


Scanning electron microscope observations of heat-treated human bone.
This report describes the heat-induced alterations in human bone tissue observed using scanning electron microscopy and microradiography. Femoral bone samples were taken from persons varying in age from 1 year to 97 years at the time of their death. The bone was heated at selected temperatures in the range 200-1600 degrees C for periods of 2, 12, 18 and 24 h. Macroscopically, changes in colour occurred, together with some shrinkage, fracturing and distortion. However, dramatic changes occurred at the ultrastructural level. These changes included the progressive combustion of the organic portion of the bone tissue up to 400 degrees C and recrystallisation of the bone mineral beginning at 600 degrees C. Recrystallisation produced a range of crystal morphologies: spherical, hexagonal, platelets, rosettes and irregular. Crystal growth occurred at temperatures > 600 degrees C. Sintering led to fusion of crystals at 1000 degrees C. This process continued up to temperatures > 1400 degrees C. At 1600 degrees C the bone mineral melted. On heating, the morphology of crystals formed, and the ultrastructural changes which occurred, were found to be related to the age of the deceased, the temperature to which the bone had been heated and the duration of heating. These results are of importance to forensic scientists, arson investigators and paleoarcheologists in their investigation of cremated human bones, particularly when only fragments of bone are available, in order to determine something of the life history of the deceased and the circumstances surrounding the death.


Functional expression of an antimicrobial peptide, belonging to halocin C8 family, from Natrinema sp. RNS21 in Escherichia coli.
Halocins, the proteinaceous antimicrobial agents produced by haloarchaea, may be used for the preservation of salted foods and the treatment of diseases. For their application and function explanation, it is necessary to produce the active recombinants. In this work, a haloarchaeal strain producing halocin was isolated from the salt-fermented shrimp and identified as Natrinema sp. RNS21 by 16S rRNA gene sequence analysis. From 1 L of RNS21 culture, about 0.32 mg of halocin with 96% purity was obtained. Based on the molecular weight, stability and amino acid sequence alignment, the antimicrobial peptide belonged to the halocin C8 (HalC8) family. HalC8 was expressed by fusion with glutathione-S-transferase (GST) in E. coli, followed by affinity purification and enterokinase (EK) cleavage. About 6.2 mg of recombinant HalC8 with 95% purity was obtained from 1 L of E. coli culture. MALDI-TOF-MS and RP-HPLC analysis indicated that the molecular weight and folding pattern of purified recombinant HalC8 were the same as those of native HalC8. Recombinant HalC8 showed obvious inhibitory activity against Haloferax volcanii. Contrast to native HalC8, the active recombinant HalC8 could be easily produced in a short time with a high yield.


Effect of ergotamine on cranial arteriovenous shunting in experiments with constant flow perfusion.
The effect of the antimigraine drug, ergotamine, was studied on the distribution of flow throughout the cranial microcirculation of the cat, using microspheres suitable in size to separate capillary flow from flow through the arteriovenous anastomoses. A constant flow perfusion experiment was used in order to eliminate the secondary effect of ergotamine on the microcirculation through a reduction in carotid blood flow per se. Under the experimental conditions, ergotamine decreased in a dose-dependent way the fraction of perfusion flow shunted through the arteriovenous anastomoses. This mode of action of ergotamine sheds new light on the so-called migraine shunt theory.


Increasing isolation of rapidly growing mycobacteria in a low-incidence setting of environmental mycobacteria, 1994-2015.
To determine trends in incidence and clinical relevance of rapidly growing mycobacteria (RGM) in a low-prevalence region of non-tuberculous mycobacteria. We retrospectively identified all patients with RGM-positive cultures between January 1994 and December 2015. Trends in incidence, clinical significance, and outcomes were assessed. One hundred and forty patients had RGM-positive cultures (116 respiratory and 24 extra-respiratory sources). The incidence of RGM isolates increased steadily from 2003 (0.34 per 100,000) to 2015 (1.73 per 100,000), with an average annual increase of 8.3%. Thirty-two patients (22.9%) had clinical disease, which trended to cluster in the second half of the study period. A positive acid-fast bacilli smear (odds ratio [OR] 97.7, 95 % CI 13.8-689.4), the presence of extra-respiratory isolates (OR 19.4, 95 % CI 5.2-72.7), and female gender (OR 5.9, 95 % CI 1.9-19.1) were independently associated with clinical disease. Cure rates were 73.3 and 87.5% for pulmonary and extra-pulmonary disease respectively. Although the burden of disease remains low, the presence of RGM isolates is increasing in our geographical setting. Whether this rise will be sustained over time and will coincide with an increase in clinical disease, or whether it is merely a cycle in the poorly understood epidemiological behaviour of environmental mycobacteria, will be seen in the near future.


"I did not know I was gay": sexual identity development and fluidity among married tongzhi in China.
This study aimed to analyse the life experiences of married tongzhi (defined here as men who are sexually attracted to men) in mixed-orientation marriages in mainland China. The study used a life course perspective to understand sexual identity development among tongzhi, born in the 1970s or thereabouts, in heterosexual marriage and rural China. The study focused on identifying the experiences of the 13 tongzhi participants. Using thematic analysis, we found sexual identity development was influenced by China's historical and social context and, in particular, internal (e.g. internalised heteronormativity), informational (e.g. Internet), and cultural (e.g. family-oriented) factors. Some tongzhi did not follow an identity development trajectory as "out and proud" since their identities were embedded in the complexity of family life and social pressure, the invisibility of "gay circles", and normative social roles. They chose instead to maintain their heteronormative marriages, while seeking to explore and fulfil their homoerotic desires. Implications are discussed for epistemology, methodology and advocacy.