A proposal of new therapeutic strategy for antenatally diagnosed congenital diaphragmatic hernia.
The prognosis of antenatally diagnosed congenital diaphragmatic hernia (ADCDH) is still very poor despite of innovation of various therapeutics. The authors reviewed their new therapeutic strategy of ADCDH from a viewpoint of cardiologic function. The cardiac function in 19 cases of ADCDH was reviewed. The patients, at the age of 0 days, were divided into 2 groups, PG (+) and PG (-), according to the requirement of prostaglandin E1 (PGE1) to attenuate pulmonary hypertension. The left ventricular (LV) end-diastolic dimension (LV diastolic diameter index [LVDI]) and bilateral pulmonary arterial diameters (total pulmonary artery index [TPAI]) were measured on days 0 and 2. Only 1 patient died of cardiac or respiratory failure, and the survivors' postoperative course was uneventful. Eleven patients needed inhalation of nitric oxide (NO), and in 9 of those, PGE1 was administered. The LVDI and TPAI of day 0 in PG (+) were significantly smaller than those in PG (-) and the controls. The LVDI increased from postnatal day 0 to day 2 in both PG (+) and PG (-). Although the LV was too small to output enough volume, the right ventricle successfully compensated for the low output through the ductus arteriosus, kept patent by NO and PGE1. For ADCDH with sever pulmonary hypertension, keeping patent ductus arteriosus with NO and PGE1 plays a critical role in obtaining excellent clinical outcome. Thus, the authors proposed a new therapeutic strategy for ADCDH based on a circulatory management.


The use of the sleep laboratory in the diagnosis of affective disorders.
Research over the past two decades has led to the development of standardized EEG sleep methodology, which in turn has proven useful for identification of characteristic sleep abnormalities for the affective disorders. Application of shortened REM latency (less than 60 minutes for most populations) or combination of EEG sleep variables as psychobiologic markers for endogenous depression has produced an accurate, reliable, and objective laboratory method to aid in differential diagnosis of affective states. In clinical practice, this method is not presently practical as a routine screening test for all depressed patients, but is very useful to help evaluate complex or diagnostically difficult cases. Beyond its role as a diagnostic aid, EEG sleep studies show great promise as a research strategy to help elucidate the pathophysiology of affective disorders and to understand mechanisms of antidepressant response. Continued application and development of EEG sleep methodology should yield further advances in diagnosis and treatment of affective disorders.


Can MRI biomarkers at 3 T identify low-risk ductal carcinoma in situ?
The objective was to explore whether 3-T magnetic resonance imaging (MRI) can identify low-risk ductal carcinoma in situ (DCIS). Dynamic contrast-enhanced and diffusion-weighted (DWI) MRI features of 36 DCIS lesions [8 low risk, Van Nuys Pathologic Classification (VNPC) 1; 28 high risk, VNPC 2/3] were reviewed. An MRI model that best identified low-risk DCIS was determined using multivariate logistic regression. Low-risk DCIS exhibited different DWI properties [i.e., higher contrast-to-noise ratio (P=.02) and lower normalized apparent diffusion coefficients (P=.04)] than high-risk DCIS. A model combining these DWI features provided best performance (area under receiver operating characteristic curve =0.86). DWI may help identify DCIS lesions requiring less therapy.


CD11c identifies microbiota and EGR2-dependent MHCII+ serous cavity macrophages with sexually dimorphic fate in mice.
The murine serous cavities contain a rare and enigmatic population of short-lived F4/80lo MHCII+ macrophages but what regulates their development, survival, and fate is unclear. Here, we show that mature F4/80lo MHCII+ peritoneal macrophages arise after birth, but that this occurs largely independently of colonization by microbiota. Rather, microbiota specifically regulate development of a subpopulation of CD11c+ cells that express the immunoregulatory cytokine RELM-α, are reliant on the transcription factor EGR2, and develop independently of the growth factor CSF1. Furthermore, we demonstrate that intrinsic expression of RELM-α, a signature marker shared by CD11c+ and CD11c- F4/80lo MHCII+ cavity macrophages, regulates survival and differentiation of these cells in the peritoneal cavity in a sex-specific manner. Thus, we identify a previously unappreciated diversity in serous cavity F4/80lo MHCII+ macrophages that is regulated by microbiota, and describe a novel sex and site-specific function for RELM-α in regulating macrophage endurance that reveals the unique survival challenge presented to monocyte-derived macrophages by the female peritoneal environment.


Combination chemotherapy versus melphalan plus prednisone as treatment for multiple myeloma: an overview of 6,633 patients from 27 randomized trials. Myeloma Trialists' Collaborative Group.
To compare combination chemotherapy (CCT) versus melphalan plus prednisone (MP) as treatment for multiple myeloma. In a collaborative worldwide overview of randomized trials of CCT versus MP, individual patient data on 4,930 patients from 20 trials were analyzed, with the addition of published data on a further 1,703 patients from seven trials. The main outcome measure was mortality, with response and recurrence rates being subsidiary end points. Taking all of the trials together, response rates were significantly higher with CCT than with MP (60.0% v 53.2%; P < .00001, two-tailed). There was no evidence of any difference in mortality between CCT and MP, with a nonsignificant 1.5% reduction in death rate in favor of CCT (P = .6, two-tailed). There is heterogeneity of design between the trials, but subgroup analyses by type of CCT or by dose-intensities of CCT, of melphalan, or of prednisone did not identify any particular forms of therapy that were either clearly beneficial or clearly adverse. Similarly, analysis of the presentation features of the patients did not find any categories in which CCT differed significantly from MP in its effects on mortality; in particular, there was no evidence that poor-risk patients benefited more from CCT. This overview found no difference, either overall or within any subgroup, in mortality between CCT and MP. In terms of survival, these therapeutic options, as tested in the trials considered, are approximately equivalent.


Vitamin D supplementation has minor effects on parathyroid hormone and bone turnover markers in vitamin D-deficient bedridden older patients.
to evaluate the effects of vitamin D supplementation on parathyroid function and bone turnover in aged, chronically immobile patients. a randomised double-blind controlled trial. two hundred and eighteen long-term inpatients aged over 65 years. the patients were randomised into treatment groups of I-III, each receiving 0 IU, 400 IU and 1200 IU cholecalciferol per day, respectively. In case of inadequate consumption of dairy products, patients received a daily calcium substitution of 500 mg. plasma concentrations of 25-hydroxyvitamin D (25-OHD), intact parathyroid hormone (PTH), amino-terminal propeptide of type I procollagen (PINP), a marker of bone formation, and carboxy-terminal telopeptide of type I collagen (ICTP), a marker of bone resorption, were measured at baseline and after 6 months. the patients (age 84.5 years) were chronically bedridden. The baseline 25-OHD was low (23 nmol/l), correlated inversely with PINP, and tended to associate inversely with PTH. The prevalence of vitamin D deficiency (VDD) (25-OHD < 50 nmol/l) was 98% and PTH was elevated in 23% of the patients. Vitamin D supplementation significantly increased 25-OHD concentrations (124% group II, 204% group III) and decreased PTH (-7% group II, -8% group III). PINP tended to decrease, but ICTP tended to increase, and only their ratio decreased significantly. The tendency of ICTP to increase was inconsistent. Changes in 25-OHD correlated inversely with those in PTH and PINP. vitamin D supplementation has minor effects on PTH and bone turnover in chronically immobilised aged patients with VDD. Further comparative studies and meta-analyses are warranted to elucidate the confounding effects of different mobility levels on the benefits of vitamin D supplementation in patients with differing baseline PTH levels.


Energy dispersive X-ray fluorescence detection of heavy metals in Bangladesh cows' milk.
It is considered that cow's milk is almost complete food for human as it provides most of the micronutrients and macronutrients. The cow's milks are essential for the growth and development especially for children. The main compositions of cow's milk are protein, fat, carbohydrates, vitamins and minerals which are well defined. Presently, the study of micronutrients and toxic elements in cow's milk has been widely carried out particularly in the industrialized and polluted regions because of its possibility of contamination, and thereby health risk of the consumers. The elemental composition in local cow's milk samples in Bangladesh is not well studied yet. The present study was therefore aimed to determine the level of heavy metals (Cr, Ni, As, Cd, Hg, Pb, Mn, Cu, Zn and Fe) in cow's milk using EDXRF technique. Subsequently, the experimental data was used to calculate the human health risk through the intake of both powder and liquid cows' milk available in Bangladesh. The results showed that powder milk contains significantly higher concentration of heavy metals than liquid milk samples. The HRI (health risk index) and HI (hazard index) values for most of the elements in all milk samples were within the safe limit (<1.0) or close to safe limit (≤1.0) with an exception of Hg. However, HRI value for Hg in powder milk samples for both children and adult showed a value higher than one (>1). MPI (metal pollution index) value for powder milk samples are very high compared to other type of milk samples analyzed in this study. Therefore, it has been suggested that heavy metal contamination through local powder milk samples might have significant negative impact (threat) on human health.


Perinatal tuberculosis and HIV-1: considerations for resource-limited settings.
Tuberculosis is the commonest HIV-1-related disease and the most frequent cause of mortality in young women in endemic regions. Tuberculosis and HIV-1 are independent risk factors for maternal mortality and adverse perinatal outcomes, and in combination have a greater impact on these parameters than their individual effects. In referral health centres in southern Africa around one-sixth of all maternal deaths are due to tuberculosis/HIV-1 coinfection. One-third (37%) of HIV-1-infected mothers with tuberculosis are severely immunocompromised, with CD4 counts of fewer than 200 cells/microL compared with 14-19% in mothers recruited into major mother-to-child intervention trials in Europe. Babies born to mothers with tuberculosis/HIV-1 also have higher rates of prematurity, low birthweight, and intrauterine growth restriction. Transmission rates of HIV-1 from mother to infant are around 25-45% in resource-limited settings, while that for mother-to-child-transmission of tuberculosis is 15% within 3 weeks of birth. We highlight this emergent problem, and discuss the dilemmas associated with diagnosis and management of pregnant HIV-1-infected mothers with tuberculosis, and their newborn babies.


Wound healing property of isolated compounds from Boesenbergia kingii rhizomes.
Boesenbergia kingii have been traditionally used in the treatment of inflammatory bowel disease, ulcerative colitis, aphthous ulcer, stomach discomfort, dysentery and abscess. Previously, we reported the B. kingii extract exert potential wound healing properties. Therefore the search of responsible constituents for wound healing property from these rhizomes is still relevant. This study was aimed to investigate for wound healing property of compounds from this plant in order to support its traditional uses. Wound healing activities were tested using in vitro assays including cell proliferation and migration assays, collagen production and H2O2-induced oxidative stress in mouse fibroblast L929 cells. The DPPH assay was also used to determine antioxidant activity. Fourteen compounds from the chloroform fraction possessed potent anti-oxidant and wound healing activities. Compound 11 exhibited the most potent anti-DPPH effect (IC50=21.0µM) and also active against 0.5mMH2O2-induced oxidative stress by increasing cell survival ability up to 60.3% at 10µM. In addition, compounds 3, 8 and 14 at 10µM significantly enhanced L929 viability with 119.2%, 122.7% and 113.7%, respectively. Compounds 2, 7, 8 and 14 markedly enhanced L929 migration on day 2 up to 60-76% at 10µM, whereas 7 and 14 strongly stimulated collagen production at 75.0 and 96.7µg/ml compared to the control group (57.5µg/ml), respectively. B. kingii is responsible for wound healing property via antioxidative effect, stimulation of fibroblast proliferation and migration as well as enhancement of collagen production.


Applying Rank Sum Ratio (RSR) to the Evaluation of Feeding Practices Behaviors, and Its Associations with Infant Health Risk in Rural Lhasa, Tibet.
To evaluate the status of feeding practices and analyze the association between feeding practice and health status among Tibetan infants, a cross-sectional survey of 386 women with children aged under 24 months was conducted in rural areas surrounding Lhasa, Tibet. All participants were selected using simple random sampling and were interviewed face-to-face by trained interviewers. Mothers were interviewed to collect information on their feeding practices. A feeding practices index was created using the rank sum ratio method. Most of the infants had been or were being breastfed at the time of the interview. The feeding practices index was significantly and inversely associated with the prevalence of acute upper respiratory infection, and the odds ratio for the qualified feeding practices index vs. the non-qualified feeding practices index was 0.43 (95% confidence interval: 0.20-0.94). There were no measurable associations observed between acute upper respiratory infection, diarrhea, and the feeding practices index after controlling for selected factors. The method of rank sum ratio provides a flexible way to evaluate feeding practices and is easy to understand. Furthermore, appropriate infant feeding practices might play a protective role in Tibetan infants' health.


Phylogenetic divisions among Collared peccaries (Pecari tajacu) detected using mitochondrial and nuclear sequences.
The Collared peccary (Pecari tajacu) is one of the three extant recognised species of the family Tayassuidae, living in the Americas. To understand phylogenetic relationships among Collared peccaries, the entire mitochondrial DNA control region and cytochrome b as well as partial nuclear GPIP and PRE-1 P27, PRE-1 P642 and TYR sequences from specimens from Colombia, Argentina, Bolivia, Mexico, United States and Australian zoo animals of unknown origin were analysed. Separate and combined analyses of the mitochondrial sequences provided good resolution of Collared peccary relationships. Nuclear sequences were partially informative when combined sequence analyses were performed. Maximum Likelihood analyses of mitochondrial sequences showed that Collared peccaries clustered in two major clades, representing North-Central American and South American specimens. Collared peccaries from Colombia are paraphyletic. Statistical Parsimony analysis of combined nuclear sequences showed a distribution of DNA variants consistent with mitochondrial sequence analyses. However, there is an uncoupling of nuclear and mitochondrial sequence variation in two specimens from Colombia. The present study suggests the recent contact of isolated populations within Colombia and possible mitochondrial introgression between the North/Central clade and the South clade. Pairwise genetic distances comparison of mitochondrial sequences show that divergence between the two major clades of the Collared peccary was higher and comparable respectively with that within and between the other two recognised peccary species. Divergence between the two major clades of the Collared peccary was also higher than that observed within and even between recognised species of the Suidae family. The divergence within the major clades of the Collared peccary showed comparable values with those observed within the other two species of Tayassuidae and within six species of Suidae. The results show that the geographically widespread and phenotypically diverse Collared peccary consists of two species or at least subspecies with implications for management of wild, zoo and captive populations.


Surgical management of splenic flexure cancer: is there an optimal technique? A bi-national registry analysis.
Splenic flexure tumours (SFC) are uncommon and present at more advanced disease stages. The optimal surgical technique for SFC remains controversial. We sought to compare the short-term outcomes of a left hemicolectomy (LHC) versus an extended resection (subtotal colectomy, STC) for SFCs. A retrospective analysis using the Binational Colorectal Cancer Audit (BCCA) registry was performed. All patients with SFC who underwent elective or emergency surgery for a SFC between 2010 and 2021 were included. Primary outcomes included short-term inpatient complications. Secondary outcomes included survival outcomes. Six hundred and ninety-nine patients underwent resections for SFCs. A LHC was more common, performed in 64.1%. Patients having a LHC were significantly older, with proportionally more LHCs done laparoscopically. Overall grade III/IV complications were similar between both operations. Prolonged ileus and return to theatre were significantly higher in patients undergoing a STC. On multivariate analysis, anastomotic leak and overall grade III/IV complications were not independently associated with the type of operation. There was no difference in medial survival based on type of operation. Higher tumour stage (Stage III/IV) were independently associated with worse survival. Segmental and extended resections are both oncologically sound procedures for SFCs. Segmental resections are associated with lower rates of prolonged ileus.


[Diamond-Forrester and cardiac CT : Is there a need to redefine the pretest probability of coronary artery disease?].
Apart from the Diamond-Forrester classification, which is widely used particularly in the USA for the pretest probability of coronary artery disease, other scores also exist, such as an updated version of the classification table by Genders et al., the Morise score and the Duke clinical risk score. These scores estimate the probability of coronary artery disease, defined as the presence of at least one high-grade stenosis, based on symptom characteristics, age, gender and other parameters. All of the scores were derived from patient cohorts in which invasive coronary angiography had been performed for clinical reasons. It has subsequently been shown that these scores, especially those developed several decades ago, substantially overestimate the pretest probability of coronary artery disease. When these risk scores are applied to patients for whom a non-invasive work-up of suspected coronary artery disease is planned, for example by coronary computed tomography (CT) angiography, the expected prevalence of significant coronary stenosis will be overestimated. This, in turn, influences the test characteristics and the significance of the non-invasive examination (positive and negative predictive values) and needs to be taken into account when interpreting test results.


Subcutaneous immunization with a novel immunogenic candidate (urease) confers protection against Brucella abortus and Brucella melitensis infections.
Brucellosis is a world prevalent endemic illness that is transmitted from domestic animals to humans. Brucella spp. exploits urease for survival in the harsh conditions of stomach during the gastrointestinal infection. In this study, we examined the immune response and the protection elicited by using recombinant Brucella urease (rUrease) vaccination in BALB/c mice. The urease gene was cloned in pET28a and the resulting recombinant protein was employed as subunit vaccine. Recombinant protein was administered subcutaneously and intraperitoneally. Dosage reduction was observed with subcutaneous (SC) vaccination when compared with intraperitoneal (IP) vaccination. rUrease induced mixed Th1-Th2 immune responses with high titers of specific IgG1 and IgG2a. In lymphocyte proliferation assay, splenocytes from IP and SC-vaccinated mice displayed a strong recall proliferative response with high amounts of IL-4, IL-12 and IFN-γ production. Vaccinated mice were challenged with virulent Brucella melitensis, B. abortus and B. suis. The SC vaccination route exhibited a higher degree of protection than IP vaccination (p value ≤ 0.05). Altogether, our results indicated that rUrease could be a useful antigen candidate for the development of subunit vaccines against brucellosis.


Necator americanus: temperature, pH, light, and larval development, longevity, and desiccation tolerance.
The effect of incubation temperature and pH on the hatch rate of eggs of Necator americanus, and the desiccation tolerance of the resulting infective stage-3 larvae were investigated in the laboratory under controlled conditions. Hatching did not occur below 15 C and above 35 C. A 21% hatch rate was obtained at 15 C while a 10.6% hatch rate was obtained at 35 C. The highest hatch rate (93.7%) was obtained at 30 C. The optimum pH for hatching was 6.0, but the larvae did not reach the infective stage. Incubation temperature of the eggs affected the longevity and desiccation tolerance of resultant infective larvae. Larvae hatched at 30 C and maintained at 26 C under bright fluorescent light had a 50% survival time (S50) of 4 days. In the dark or shade, the S50 for larvae raised at 30 C was 5 weeks, while that of larvae hatched at 20 C was 7 weeks. Incubation temperature also affected the desiccation tolerance of larvae. Larvae developed at 20 C were more resistant to desiccation at various relative humidity values than larvae hatched at 30 C.


Simulation of robotic hysterectomy utilizing the porcine model.
This article describes the simulation of robotically assisted hysterectomy utilizing the porcine model. Utilizing 3 domestic pigs, a technique for robotically assisted hysterectomy was developed. An edited video clip of the model was assessed by 6 gynecological surgeons. The steps of the operation are described in detail and are shown in a video clip. Overall the procedure simulated that done in the human both anatomically and surgically. Some of the evaluators rated the identification of the cervicovesical junction to be more difficult and division of the paracervical ligaments to be relatively easier in the model. Reported here is a technique for robotically assisted hysterectomy in the domestic pig that may be useful for training purposes.


The effect of Tarantula cubensis D6 on zone of stasis in a rat burn model.
Burn injuries are one of the most devastating injuries. Saving the zone of stasis decreases burn size, morbidity, and mortality. Tarantula cubensis (TC) increases epithelization of wounds, and increases wound contraction. In this study, we investigated the effects of TC on the stasis zone. 36 Wistar albino female rats were divided into 3 groups. Using brass comb burn model, at days 0 and 3, physiological serum solution in group 2, TC injection in group 3and no injection in group 1 was applied. Thermal and normal images were taken on day 10 and rats were sacrificed for histopathological examination. We found a statistically significant difference between the 1st and 3rd group, 2nd and 3rd group regarding viable wound areas (p < 0.05), temperature difference (body-stasis zone) and mean body temperature (p < 0.05). We found no statistically significant difference between groups regarding neovascularization, inflammatory density, and vital cutaneous appendages. We found a statistically significant difference in epithelial layer thickness between the1st and 3rd groups, 2nd and 3rd groups(p < 0.05). TC increases stasis zone viability macroscopically, increases epithelial layer thickness histopathologically, thus it promotes wound healing in burn wounds. This increase in stasis zone viability was also established with thermal imaging.


Digital Hepatic Iron Content: An Artificial Intelligence Model for Spatially Resolved Histologic Iron Quantitative Analysis in Liver Samples.
Currently, the precise evaluation of tissue hepatic iron content (HIC) requires laboratory testing using tissue-destructive methods based on colorimetry or spectrophotometry. To maximize the use of routine histologic stains in this context, we developed an artificial intelligence (AI) model for the recognition and spatially resolved measurement of iron in liver samples. Our AI model was developed using a cloud-based, supervised deep learning platform (Aiforia Technologies). Using digitized Pearl Prussian blue iron stain whole slide images representing the full spectrum of changes seen in hepatic iron overload, our training set consisted of 59 cases, and our validation set consisted of 19 cases. The study group consisted of 98 liver samples from 5 different laboratories, for which tissue quantitative analysis using inductively coupled plasma mass spectrometry was available, collected between 2012 and 2022. The correlation between the AI model % iron area and HIC was Rs = 0.93 for needle core biopsy samples (n = 73) and Rs = 0.86 for all samples (n = 98). The digital hepatic iron index (HII) was highly correlated with HII > 1 (area under the curve [AUC] = 0.93) and HII > 1.9 (AUC = 0.94). The percentage area of iron within hepatocytes (vs Kupffer cells and portal tract iron) identified patients with any hereditary hemochromatosis-related mutations (either homozygous or heterozygous) (AUC = 0.65, P = .01) with at least similar accuracy than HIC, HII, and any histologic iron score. The correlation between the Deugnier and Turlin score and the AI model % iron area for all patients was Rs = 0.87 for total score, Rs = 0.82 for hepatocyte iron score, and Rs = 0.84 for Kupffer cell iron score. Iron quantitative analysis using our AI model was highly correlated with both detailed histologic scoring systems and tissue quantitative analysis using inductively coupled plasma mass spectrometry and offers advantages (related to the spatial resolution of iron analysis and the nontissue-destructive nature of the test) over standard quantitative methods.


HUWE1 mutation explains phenotypic severity in a case of familial idiopathic intellectual disability.
The advent of next-generation sequencing has proven to be a key force in the identification of new genes associated with intellectual disability. In this study, high-throughput sequencing of the coding regions of the X-chromosome led to the identification of a missense variant in the HUWE1 gene. The same variant has been reported before by Froyen et al. (2008). We compare the phenotypes and demonstrate that, in the present family, the HUWE1 mutation segregates with the more severe ID phenotypes of two out of three brothers. The third brother has a milder form of ID and does not carry the mutation.


The Potential of Gelam Honey in Promoting the Proliferative Phase of Corneal Reepithelialization.
Advances in molecular diagnostic medicine have allowed for more rapid, accurate, and comprehensive methods for identifying microorganisms in a chronic wound, which led to the de- velopment and use of a tailored topical antibiotic gel aimed at treating this bioburden. This is a retrospective chart review evalu- ating the authors' early experience with the use of bacteria-speci c antimicrobial gel therapy on chronic lower extremity wounds that have not responded to standard therapy. All patients in the study were treated with a topical gel along with standard of care modalities. A total of 48 patients with 76 wounds (50/76 venous leg ulcers; 65.8%) were identi ed and analyzed. Of the 48 patients, 11 (22.9%) had complete wound closure at a mean of 101.6 days of treatment. The number of wounds decreasing in size improved from 45.3% to 77.6% after gel therapy. An analysis of all wounds showed an increase in size by 0.7% weekly with the topical gel; how- ever, a mean weekly healing rate of 6.5% was seen when analyzing only the subset of wounds that decreased in size. Although a minor improvement of weekly healing rate was seen for a subset of the wounds, the overall wound closure rate was low.


Diagnostic analysis of new quantitative parameters of low-dose dynamic myocardial perfusion imaging with CZT SPECT in the detection of suspected or known coronary artery disease.
The goal of this study is to explore and evaluate the diagnostic values of myocardial blood flow (MBF), myocardial flow reserve (MFR) and relative flow reserve (RFR) obtained with low-dose dynamic CZT SPECT for patients with suspected or known coronary artery disease (CAD). Fifty-seven consecutive patients who underwent low-dose dynamic CZT SPECT and CAG were enrolled. MBF, MFR and RFR were calculated on the vessel level with dedicated quantitative software, and the difference and correlation of each parameter was compared according to the reference standard of stenosis ≥ 50% or ≥ 75% on CAG, respectively. ROC curves were made by stress MBF (sMBF), rest MBF (rMBF), MFR and RFR. The optimal cut-off values and corresponding diagnostic efficacy were obtained and compared with each other. Results indicated that when stenosis ≥ 50% or ≥ 75% on CAG was used as the reference standard at the vessel level, there was no statistically significant difference in rMBF between the negative group and the positive group (P > 0.05), and the sMBF and MFR in positive groups were significantly lower than that in the negative group (all P < 0.05). There was a moderate to significant correlation between sMBF and MFR, sMBF and RFR, MFR and RFR (all P < 0.0001). These results indicate that low-dose dynamic CZT SPECT imaging can easily obtain the sMBF, MFR and RFR, and there is a good correlation among the three parameters, which has a certain diagnostic value for patients with suspected or known CAD, and is a useful supplement to the conventional qualitative or semi-quantitative diagnostic methods.


Assessing the relationships between nurse working conditions and patient outcomes: systematic literature review.
The purpose of the study was to systematically evaluate nurse working conditions and to review the literature dealing with their association with patient outcomes. Improving nurse working conditions is essential to address nursing shortages. Although general reviews of the literature support the positive link between working conditions and patient outcomes, definitive evidence has been lacking. A search of six electronic bibliographic databases was conducted for the primary research published in English, from January 2000 to October 2009. The concepts of working conditions were categorized into 10 groups of working conditions. A total of 69 relationships between working conditions and patient outcomes were examined. Increased attention has been drawn to nurse working conditions resulting from nursing shortages. The findings of this review suggested that the evidence supporting positive relationships between working conditions and patient outcomes is inconclusive. Further studies of a longitudinal and interventional nature in various settings are needed to advance knowledge of the complex contextual and multivariate influences among nurse working conditions and patient outcomes. Efforts to improve working conditions should be made in various health-care work settings to ensure patient safety and improve patient quality of outcomes.


Which lifestyle parameters discriminate high- from low-risk participants for coronary heart disease risk factors. Longitudinal analysis covering adolescence and young adulthood.
The purpose of this study was to analyse which lifestyle parameters (daily physical activity, dietary intake, smoking habits and alcohol consumption) discriminate between participants at high-risk and those at low-risk for coronary heart disease (CHD) [systolic and diastolic blood pressure (SBP/DBP), total serum cholesterol (TC), high-density lipoprotein cholesterol (HDL), the TC: HDL ratio, body fatness (sum of skinfolds [SSF]) and cardiopulmonary fitness (VO2-max)]. The data were derived from the Amsterdam Growth and Health Study (AGHS); an observational longitudinal study in which six repeated measurements were carried out over a period of 15 years on 181 participants aged 13 years at entry to the study. To assess possible discriminating factors, generalized estimating equations were used. This method makes use of risk group changing behaviour over time by using all available longitudinal data. For DBP no significant relationships were found; high risk for SBP was inversely related to smoking habits (OR=0.52; P<0.01). No significant relationships were found for TC; high risk for HDL was positively related to the intake of carbohydrates (OR=1.2; P=0.02) and to smoking habits (OR=1.6; P=0.04); high risk for the TC:HDL ratio was positively related to the intake of carbohydrates (OR=1.3; P=0.01). High risk for SSF was positively related to the intake of protein (OR=1.5; P<0.01) and smoking habits (OR=1.8; P=0.01) and inversely related to daily physical activity (OR=0.81; P=0.01). High risk for VO2-max was inversely related to daily physical activity (OR=0.67; P<0.01). In the relative young and healthy population of the AGHS during adolescence and young adulthood, physical inactivity was the most important lifestyle parameter related to high risk for CHD.


Recovery of normal topography in the somatosensory cortex of monkeys after nerve crush and regeneration.
After median nerve fibers to glabrous skin on the hands of monkeys were crushed and allowed to regenerate, normal topographical organization was recovered in the representation of the hand in primary somatosensory cortex. Similar recovery of normal cortical organization may underlie the sensory restoration that usually follows nerve crush injury in humans.


Estrogen dependent signaling in reproductive tissues - a role for estrogen receptors and estrogen related receptors.
Estrogens play a fundamental role in the development and normal physiological function of multiple tissue systems and have been implicated in the ontogeny of cancers. The biological effects of estrogens are classically mediated via interaction with cognate nuclear receptors. The relative expression of ER subtypes/variants varies between cells within different tissues and this alters the response to natural and synthetic ligands. This review focuses on the role of estrogen and estrogen related receptors in reproductive tissues.


Drug-eluting stent thrombosis: results from the multicenter Spanish registry ESTROFA (Estudio ESpañol sobre TROmbosis de stents FArmacoactivos).
This study sought to assess the incidence, predictors, and outcome of drug-eluting stent(DES) thrombosis in real-world clinical practice. The DES thromboses in randomized trials could not be comparable to those observed in clinical practice, frequently including off-label indications. We designed a large-scale, nonindustry-linked multicentered registry, with 20 centers in Spain. The participant centers provided follow-up data for their patients treated with DES, reporting a detailed standardized form in the event of any angiography-documented DES-associated thrombosis occurring. Of 23,500 patients treated with DES, definite stent thrombosis(ST) developed in 301: 24 acute, 125 subacute, and 152 late. Of the late, 62 occurred >1 year(very late ST). The cumulative incidence was 2% at 3 years. Antiplatelet treatment had been discontinued in 95 cases(31.6%). No differences in incidences were found among stent types. Independent predictors for subacute ST analyzed in a subgroup of 14,120 cases were diabetes, renal failure, acute coronary syndrome, ST-segment elevation myocardial infarction, stent length, and left anterior descending artery stenting, and for late ST were ST-segment elevation myocardial infarction, stenting in left anterior descending artery, and stent length. Mortality at 1-year follow-up was 16% and ST recurrence 4.6%. Older age, left ventricular ejection fraction <45%, nonrestoration of Thrombolysis In Myocardial Infarction flow grade 3, and additional stenting were independent predictors for mortality. The cumulative incidence of ST after DES implantation was 2% at 3 years. No differences were found among stent types. Patient profiles differed between early and late ST. Short-term prognosis is poor, especially when restoration of normal flow fails.


Possible ultraviolet A-induced lentigines: a side effect of chronic tanning salon usage.
A patient who developed lentigines after prolonged ultraviolet A (UVA) exposure in a tanning booth is described. The patient had no exposure to psoralens or furocoumarins. Histologic examination of a representative lentigo revealed melanocytic hyperplasia and cytologic atypia. Increased nevocytic activity with histologic dysplasia was present in several junctional nevi excised during the period of UVA exposure. Several studies have revealed significant effects of UVA on melanocytes. Patients should be cautioned to avoid tanning bed use in view of these potentially deleterious effects.


Genetic variation in human P450 oxidoreductase.
Catalysis by all 50 Type II (microsomal) P450 enzymes, including steroidogenic P450c17, P450c21, and P450aro and hepatic drug-metabolizing enzymes requires electron donation from P450 oxidoreductase (POR). POR knockout mice are embryonic lethal, but human POR mutations cause a complex disorder of steroidogenesis. Disorders of hepatic drug metabolism in human POR deficiency have not yet been described. To understand the potential contribution of POR to pharmacogenetics, we sequenced the POR gene in 842 normal persons from 4 ethnic groups. We detected 140 single nucleotide sequence variants of which 43 were in >1% of alleles, including 15 missense mutants; this brings the total of known POR missense mutants to 35. A503V was found on 28% of alleles, varying from 19% in African Americans to 37% in Chinese Americans. We expressed all 35 missense mutants in E. coli and assayed their activities to: oxidize NADPH, reduce cytochrome c, support the 17alpha-hydroxylase and 17,20 lyase activities of bacterially expressed human P450c17, and support the metabolism of fluorogenic EOMCC by bacterially expressed human CYP1A2 and CYP2C19. These data show that there are great differences in the activities of some POR mutants depending on the electron recipient assayed; for example, Q153R causes severely impaired steroid biosynthesis in human patients and in vitro, but is a gain-of-function mutant with CYP1A2 and 2C19. A503V reduces both activities of P450c17 in half, but had no effect on CYP1A2 or 2C19. POR variants are a previously unappreciated source of genetic variation in patterns of steroid synthesis and drug metabolism.


Optimizing point-of-care testing strategies for diagnosis and treatment of hepatitis C virus infection in Australia: a model-based cost-effectiveness analysis.
Timely diagnosis and treatment of hepatitis C virus (HCV) is critical to achieve elimination goals. This study evaluated the cost-effectiveness of point-of-care testing strategies for HCV compared to laboratory-based testing in standard-of-care. Cost-effectiveness analyses were undertaken from the perspective of Australian Governments as funders by modelling point-of-care testing strategies compared to standard-of-care in needle and syringe programs, drug treatment clinics, and prisons. Point-of-care testing strategies included immediate point-of-care HCV RNA testing and combined point-of-care HCV antibody and reflex RNA testing for HCV antibody positive people (with and without consideration of previous treatment). Sensitivity analyses were performed to investigate the cost per treatment initiation with different testing strategies at different HCV antibody prevalence levels. The average costs per HCV treatment initiation by point-of-care testing, from A$890 to A$1406, were up to 35% lower compared to standard-of-care ranging from A$1248 to A$1632 depending on settings. The average costs per treatment initiation by point-of-care testing for three settings ranged from A$1080 to A$1406 for RNA, A$960-A$1310 for combined antibody/RNA without treatment history consideration, and A$890-A$1189 for combined antibody/RNA with treatment history consideration. When HCV antibody prevalence was <74%, combined point-of-care HCV antibody and point-of-care RNA testing were the most cost-effective strategies. Modest increases in treatment uptake by 8%-31% were required for immediate point-of-care HCV RNA testing to achieve equivalent cost per treatment initiation compared to standard-of-care. Point-of-care testing is more cost-effective than standard of care for populations at risk of HCV. Testing strategies combining point-of-care HCV antibody and RNA testing are likely to be cost-effective in most settings. National Health and Medical Research Council.


Familial colorectal cancer, beyond Lynch syndrome.
Although 30% of individuals diagnosed with colorectal cancer (CRC) report a family history of the disease, only 5% to 6% carry germline mutations in genes associated with known hereditary cancer syndromes. The evaluation and management of families affected with CRC can be complicated by variability in disease phenotypes and limited sensitivity of genetic tests. In this review, we examine what is currently known about familial CRC and what we have yet to learn, and explore how novel genomic approaches might be used to identify additional genetic and epigenetic factors implicated in heritable risk for cancer.


Mortal hyperkalemia disturbances in rats are NO-system related. The life saving effect of pentadecapeptide BPC 157.
We demonstrate the full counteracting ability of stable gastric pentadecapeptide BPC 157 against KCl-overdose (intraperitoneal (i), intragastric (ii), in vitro (iii)), NO-system related. (i) We demonstrated potential (/kg) of: BPC 157 (10ng, 10μg ip, complete counteraction), l-arginine (100mg ip, attenuation) vs. L-NAME (5mg ip, deadly aggravation), given alone and/or combined, before or after intraperitoneal KCl-solution application (9mEq/kg). Therapy was confronted with promptly unrelenting hyperkalemia (>12mmol/L), arrhythmias (and muscular weakness, hypertension, low pressure in lower esophageal and pyloric sphincter) with an ultimate and a regularly inevitable lethal outcome within 30min. Previously, we established BPC 157-NO-system interaction; now, a huge life-saving potential. Given 30min before KCl, all BPC 157 regimens regained sinus rhythm, had less prolongation of QRS, and had no asystolic pause. BPC 157 therapy, given 10min after KCl-application, starts the rescue within 5-10min, completely restoring normal sinus rhythm at 1h. Likewise, other hyperkalemia-disturbances (muscular weakness, hypertension, low sphincteric pressure) were also counteracted. Accordingly with NO-system relation, deadly aggravation by L-NAME: l-arginine brings the values to the control levels while BPC 157 always completely nullified lesions, markedly below those of controls. Combined with l-arginine, BPC 157 exhibited no additive effect. (ii) Intragastric KCl-solution application (27mEq/kg) - (hyperkalemia 7mmol/L): severe stomach mucosal lesions, sphincter failure and peaked T waves were fully counteracted by intragastric BPC 157 (10ng, 10μg) application, given 30min before or 10min after KCl. (iii). In HEK293 cells, hyperkalemic conditions (18.6mM potassium concentrations), BPC 157 directly affects potassium conductance, counteracting the effect on membrane potential and depolarizations caused by hyperkalemic conditions.


Triclosan affects motor function in zebrafish larva by inhibiting ache and syn2a genes.
The widespread use of triclosan in personal care products as an antimicrobial agent is leading to its alarming tissue-bioaccumulation including human brain. However, knowledge of its potential effects on the vertebrate nervous system is still limited. Here, we hypothesized that sublethal triclosan concentrations are potent enough to alter motor neuron structure and function in zebrafish embryos exposed for prolonged duration. In this study, zebrafish embryos were used as vertebrate-animal model. Prolonged exposure (up to 4 days) of 0.6 mg/L (LC50, 96 h) and 0.3 mg/L (<LC50, Sublethal) triclosan produced aberrations in motor neuron innervations in skeletal muscles and reduced touch-evoked escape response in zebrafish larvae. This suggests motor dysfunction in treated embryos. To further explore the mechanisms of triclosan induced neurotoxicity, we determined the enzyme activity of acetylcholinesterase (AChE) and the expression of acetylcholinesterase (ache), myelin basic protein (mbp) and synapsin IIa (syn2a) genes which play an important role in the neural development and synaptic transmission. The ache and syn2a genes were down-regulated in triclosan treated larvae without any significant changes in mbp gene expression. At functional level, we observed a decrease in the AChE activity. Furthermore, docking results showed that triclosan can form a stable interaction with binding pocket of AChE and perhaps it can compete with natural acetylcholine for direct binding to AChE thereby inhibiting it and affecting cholinergic transmission. Therefore, triclosan can be regarded as a neurotoxic agent even at sublethal concentrations. Overall, the growing toxicological evidence against triclosan including ours suggest caution in its widespread use.


Development of a monolayer invasion assay for the discrimination and isolation of metastatic lymphoma cells.
A new in vitro invasion model system, based on monolayers of 10T1/2 fibroblastic mouse embryo cells, is presented. When inoculated onto such a confluent monolayer, cells from a nonmetastatic T-cell lymphoma line remained on top, whereas cells from metastatic derivative lines penetrated through the monolayer. Combined differential interference contrast and interference reflection microscopy were used to follow the relative vertical cell positions in the co-cultures. The number of underlying lymphoma cells per unit area can be used as a quantitative invasion index, allowing a systematic comparison between cell lines. Moreover, since the invasive cells could be recovered separately, this invasion system allowed the isolation of minor subpopulation of invasive cells from a 1000-fold excess of noninvasive cells.


G-Quadruplex Binders Induce Immunogenic Cell Death Markers in Aggressive Breast Cancer Cells.
DNA G-quadruplex (G4) structures represent potential anti-cancer targets. In this study, we compared the effect of two G4-targeting compounds, C066-3108 and the gold standard BRACO-19. In breast and prostate cancer cells, cytotoxicity induced by both molecules was measured by a sulforhodamine B assay. In breast cancer cells, cycle, apoptosis, the formation of G4 structures, calreticulin and high mobility group box 1 (HMGB1), as well as T cell activation, were analyzed by flow cytometry and adenosine triphosphate (ATP) by luminescence. Both ligands inhibited cell survival and induced DNA damage. In MCF-7 cells, G4 ligands increased the subG0/G1 phase of the cell cycle inducing apoptosis and reduced intracellular ATP. In untreated MCF-7 cells, we observed a slight presence of G4 structures associated with the G2/M phase. In MDA-MB231 cells, G4 ligands decreased the G1 and enhanced the G2/M phase. We observed a decrease of intracellular ATP, calreticulin cell surface exposure and an increase of HMGB1, accompanied by T cell activation. Both compounds induced G4 structure formation in the subG0/G1 phase. Our data report similar effects for both compounds and the first evidence that G4 ligands induce the release of danger signals associated with immunogenic cell death and induction of T cell activation.


Glucose and amino acid metabolism in rat brain during sustained hypoglycemia.
The metabolism of glucose in brains during sustained hypoglycemia was studied. [U-14C]Glucose (20 microCi) was injected into control rats, and into rats at 2.5 hr after a bolus injection of 2 units of insulin followed by a continuous infusion of 0.2 units/100 g rat/hr. This regimen of insulin injection was found to result in steady-state plasma glucose levels between 2.5 and 3.5 mumol per ml. In the brains of control rats carbon was transferred rapidly from glucose to glutamate, glutamine, gamma-aminobutyric acid and aspartate and this carbon was retained in the amino acids for at least 60 min. In the brains of hypoglycemic rats, the conversion of carbon from glucose to amino acids was increased in the first 15 min after injection. After 15 min, the specific activity of the amino acids decreased in insulin-treated rats but not in the controls. The concentrations of alanine, glutamate, and gamma-amino-butyric acid decreased, and the concentration of aspartate increased, in the brains of the hypoglycemic rats. The concentration of pyridoxal-5'-phosphate, a cofactor in many of the reactions whereby these amino acids are formed from tricarboxylic acid cycle intermediates, was less in the insulin-treated rats than in the controls. These data provide evidence that glutamate, glutamine, aspartate, and GABA can serve as energy sources in brain during insulin-induced hypoglycemia.


Renal water conservation and the volume kinetics of fluid-induced diuresis: A retrospective analysis of two cohorts of elderly men.
Renal water conservation after an overnight fast mirrors the habitual intake of liquid. The hypothesis in the present study was that water conservation influences the diuretic response to infusion of two types of crystalloid fluid. Twenty-three elderly male patients (mean age 72 years) underwent a total of 46 intravenous infusions of 1.0 or 1.5 L of either hypotonic non-electrolyte fluid (glycine 1.5%) or isotonic electrolyte fluid (Ringer's acetate or 0.9% saline). Urine osmolality (used to indicate renal water conservation) and plasma creatinine were measured before the infusions started. A two-volume model was fitted to repeated measurements of the blood haemoglobin concentration and the urinary excretion, using mixed-effects modelling software. Urine osmolality was examined as a potential covariate to the fixed kinetic parameters. The results show that distribution and redistribution of infused fluid occurred twice as fast for the non-electrolyte fluids as for the electrolyte-containing fluids, while the urine flow showed less difference. For both types of fluid, high urine osmolality served as a statistically significant covariate to the rate constant describing urinary excretion. Simulations showed that a high pre-infusion urine osmolality doubled the time required for the kidneys to excrete 50% of a 30-minute infusion. High plasma creatinine independently prolonged the elimination of non-electrolyte fluid. The use of 0.9% saline instead of Ringer's prolonged the excretion of electrolyte-containing fluid. In conclusion, renal water conservation is a determinant of the diuretic response to crystalloid fluid, regardless of whether the fluid contains electrolytes, and it should be considered in fluid balance studies.


Mutations in KANSL1 cause the 17q21.31 microdeletion syndrome phenotype.
The chromosome 17q21.31 deletion syndrome is a genomic disorder characterized by highly distinctive facial features, moderate-to-severe intellectual disability, hypotonia and friendly behavior. Here, we show that de novo loss-of-function mutations in KANSL1 (also called KIAA1267) cause a full del(17q21.31) phenotype in two unrelated individuals that lack deletion at 17q21.31. These findings indicate that 17q21.31 deletion syndrome is a monogenic disorder caused by haploinsufficiency of KANSL1.


[Morbidity and mortality conference in general practice: about an experiment in Rhône-Alpes].
A morbidity and mortality conference (MMC) is a collective analysis, retrospective and systemic cases marked by occurrence of death, complication, or event that could cause harm to patient (adverse event). Its aim is the implementation and monitoring of actions to improve the care of patients and patient safety. A group for analysis of adverse events in general practice was created in 2011 in the Rhone-Alps, in order to test the feasibility of a MMC with general practitioners (GPs). A charter setting out the ethical framework and the terminology, methodology and the role of individual players was drafted. Then a group of volunteers was created among the members of an association of continuing medical education. Each session has been the subject of a report. The evaluation was conducted through interviews with participants, and with an electronic survey of satisfaction. Since 2011, 12 physicians participated, analysing 36 cases during seven sessions. Reported events were most frequently interested women with a mean age of patients being 48 years (median 46 years). The situations reported were mixed (error diagnostic, therapeutic, adverse drug). Failures are related to care protocols, decision-making, the care environment (frequent disruptive pop) and human factors (caregiver stress). The participants were satisfied with the initiative. Analyses revealed some redundant causes that can be corrected to secure care. Beyond the non-stigmatising approach it may allow doctors to discuss their feelings without making them feel guilty (concept of second victim). If such initiatives are still not widespread in ambulatory, they should be promoted by organizations. Openness to other caregivers in Ambulatory is a fundamental change desired by the GP. The National Programme for Patient Safety recently published in February 2013 mentions these aspects, emphasizing the key role of the DPC for acquisition techniques analysis of the causes by caregivers.


Development and acceptability of the person-centred observation and reflection tool for supporting staff and practice development in dementia care services.
Observational tools can support the understanding of the complex needs of older people with dementia and aid delivery of person-centred care. However, existing tools are complex and resource intensive to use. To develop and evaluate the acceptability and feasibility of a low-resource, observational tool to support staff reflection and practice development. Intervention development of the Person-Centred Observation and Reflection Tool (PORT) and acceptability and feasibility study, using surveys and focus groups in the UK, Norway and Spain. PORT was reported as easy, accessible and acceptable to use. The observation was identified as powerful for individual staff development and provided an evidence-based source for underpinning individualised care planning. Potential time challenges associated with implementation were identified. Initial evaluation indicates PORT is an acceptable and feasible tool for use in health and social care settings for older people. Further research is needed on implementation models and the impacts of PORT use. PORT may be a useful tool to support individual staff development in care settings and person-centred care planning for people with dementia.


Correlation between clinical, endocrinologic and nuclear magnetic resonance findings in women with suspected pituitary adenomas.
Twenty-nine women with suspected pituitary adenomas were evaluated with nuclear magnetic resonance (NMR). Twenty-six had prolactin levels less than 100 ng/mL, and three had levels greater than 100. We tried to correlate the clinical findings with the prolactin levels and NMR findings. Pituitary adenomas were detected on NMR even with prolactin levels less than 100 ng/mL.


The Use of Person-Centered Language in Medical Research Journals Focusing on Psoriasis: Cross-sectional Analysis.
Person-centered language places a person's identity before any disability or medical condition they may have. Using person-centered language reduces stigma and improves the patient-physician relationship, potentially optimizing health outcomes. Patients with psoriasis often feel stigmatized due to their chronic skin condition. We seek to evaluate the use of person-centered language in psoriasis literature and to explore whether certain article characteristics were associated with non-person-centered language. We performed a systematic search on PubMed for recently published articles in journals that regularly publish psoriasis studies. After article reduction procedures, randomization, and screening, we reached our target sample of 400 articles. The following non-person-centered language terms were extracted from each article: "Psoriasis Patient," "Psoriasis subject," "Affected with," "Sufferer," "Suffering from," "Burdened with," "Afflicted with," and "Problems with." Screening and data extraction occurred in a masked duplicate fashion. Of the 400 included articles, 272 (68%) were not adherent to person-centered language guidelines according to the American Medical Association Manual of Style. The most frequent non-person-centered language term was "Psoriasis Patient," found in 174 (43.5%) articles. The stigmatizing language was associated with the type of article and funding status, with original investigations and funded studies having higher rates of stigmatizing language. Articles about psoriasis commonly use non-person-centered language terms. It is important to shift away from using stigmatizing language about patients with psoriasis to avoid potential untoward influences. We recommend using "patients with psoriasis" or "patient living with psoriasis" to emphasize the importance of person-centered care.


Anterior ectopic anus: a common cause of constipation in children.
Anterior ectopic anus is increasingly being recognized as a cause of constipation in infancy. Experience is reported with surgical treatment of 20 patients with anterior ectopic anus. This form of anal ectopia is associated with a syndrome of constipation that begins at birth, straining on defecation, and anterior displacement of an otherwise normal anus and sphincter. It is seen almost exclusively in females. Posterior anoplasty with sphincterotomy is curative.


Lactation in humans.
Postpartum milk secretion is a hormonally regulated process that reflects the highly coordinated actions of endocrine, neuroendocrine, and behavioral mechanisms. Structural development of the mammary gland during pregnancy is stimulated primarily by estrogen, progesterone, and prolactin (PRL), the secretion of which is controlled directly or indirectly by the fetoplacental unit. Following parturition, PRL also plays an important role in initiating and sustaining milk secretion and suppressing the resumption of cyclic hypothalamic-pituitary-ovarian function. Dynamic postpartum PRL secretion is in response to the neurogenic stimulus of suckling, which both acutely releases PRL and maintains the responsiveness of PRL regulatory pathways to subsequent nursing. The central control of PRL secretion at this time involves the integrated activities of inhibitory and stimulatory hypothalamic mechanisms. A major feature of lactation is the degree to which the entire process is controlled by the developing organism itself.


Ecological tannin assays: a critique.
The concept of protein precipitation potential has recently been introduced by Wisdom et al. (1987) as a means to combine chemical and protein precipitation assays of tannins for ecological studies. The definition of protein precipitation potential was not theoretically rigorous, and data analysis was obscure. Our attempts to repeat the tannin extraction procedure gave incomplete recovery (24% loss of quebracho) of condensed tannins, the only type considered by Wisdom et al. In contrast we found their method efficient for hydrolysable tannins (80% recovery of tannic acid) which were undetected by their chemical assay of tannins. Their protein precipitation assay was confounded by chemical interference from both types of tannins. We conclude with recommendations for this type of analysis.


Real-time stylistic prediction for whole-body human motions.
The ability to predict human motion is crucial in several contexts such as human tracking by computer vision and the synthesis of human-like computer graphics. Previous work has focused on off-line processes with well-segmented data; however, many applications such as robotics require real-time control with efficient computation. In this paper, we propose a novel approach called real-time stylistic prediction for whole-body human motions to satisfy these requirements. This approach uses a novel generative model to represent a whole-body human motion including rhythmic motion (e.g., walking) and discrete motion (e.g., jumping). The generative model is composed of a low-dimensional state (phase) dynamics and a two-factor observation model, allowing it to capture the diversity of motion styles in humans. A real-time adaptation algorithm was derived to estimate both state variables and style parameter of the model from non-stationary unlabeled sequential observations. Moreover, with a simple modification, the algorithm allows real-time adaptation even from incomplete (partial) observations. Based on the estimated state and style, a future motion sequence can be accurately predicted. In our implementation, it takes less than 15 ms for both adaptation and prediction at each observation. Our real-time stylistic prediction was evaluated for human walking, running, and jumping behaviors.


Gene expression of beta carotene genes in transgenic biofortified cassava.
Cassava is an important food for millions of people around the world. However, cassava is deficient in protein, iron, zinc, pro-vitamin A and vitamin E. Cassava biofortified with pro-vitamin A can help reduce Vitamin A Deficiency among the undernourished communities that rely upon it for sustenance. BioCassava Plus project has developed transgenic cassava that expresses beta carotene in roots using root specific patatin promoter. This study aimed at confirming expression of nptII, crtB and DXS genes. Leaf and roots samples were obtained from confined field trial at KARI Alupe at 12 months after planting. RNA was isolated from cassava roots and leaves using a modified Dellaporta protocol, analyzed for expression of DXS, crtB and the selectable marker, nptII using the one step RT-PCR kit (Qiagen) and analyzed through gel electrophoresis. DXS, crtB and nptII genes were expressed in the roots as anticipated. On the contrary, DXS and crtB genes were also expressed in the leaves of the transgenic cassava despite the use of root specific patatin promoter. This finding indicates that the promoter confers expression in leaves too. Intensive molecular screening of the biofortified transgenic cassava is important for risk assessment that informs on integrity of the promoter gene and confirms expression of the beta carotene genes.


Metabolic profiling during ex vivo machine perfusion of the human liver.
As donor organ shortages persist, functional machine perfusion is under investigation to improve preservation of the donor liver. The transplantation of donation after circulatory death (DCD) livers is limited by poor outcomes, but its application may be expanded by ex vivo repair and assessment of the organ before transplantation. Here we employed subnormothermic (21 °C) machine perfusion of discarded human livers combined with metabolomics to gain insight into metabolic recovery during machine perfusion. Improvements in energetic cofactors and redox shifts were observed, as well as reversal of ischemia-induced alterations in selected pathways, including lactate metabolism and increased TCA cycle intermediates. We next evaluated whether DCD livers with steatotic and severe ischemic injury could be discriminated from 'transplantable' DCD livers. Metabolomic profiling was able to cluster livers with similar metabolic patterns based on the degree of injury. Moreover, perfusion parameters combined with differences in metabolic factors suggest variable mechanisms that result in poor energy recovery in injured livers. We conclude that machine perfusion combined with metabolomics has significant potential as a clinical instrument for the assessment of preserved livers.


Patch exploitation in two dimensions: from Daphnia to simulated foragers.
We explore the variability that animals display in their movement choices as they forage in a finite-sized food patch with a uniform food distribution, and present a framework for how these choices may be adjusted to optimize foraging efficiency. Inspired by experimental studies of the zooplankton Daphnia, we model foraging animals as "agents" moving in two dimensions in repeated and successive sequences of hops, pauses, and turns. For Daphnia and other species, critical movement parameters such as hop lengths, pause times, and turning angles are typically reported as probability density functions. Similarly, the agents in our simulations choose their movement parameters at random from such distributions. Each distribution is defined by a characteristic width, which we interpret as a "noise width," available to be tuned for increased foraging efficiency. We investigate the sensitivity of the system by measuring the food gathered by the agents as the turning angle and hop length noise widths are varied. In all cases, we find a maximum in food gathered at some particular value of the noise width in question, suggesting that these results can be considered robust examples of natural stochastic resonance.


Neo-nicotinoid metabolic activation and inactivation established with coupled nicotinic receptor-CYP3A4 and -aldehyde oxidase systems.
Two important enzymes in metabolism of the principal neo-nicotinoid insecticide imidacloprid are liver microsomal CYP3 A4 and cytosolic aldehyde oxidase (AOX). CYP3A4 oxidation at several molecular sites and AOX reduction at the nitro substituent result in either an increase (activation) or decrease (inactivation) of agonist potency at nicotinic acetylcholine receptors (nAChRs), both insect and vertebrate alpha 4beta 2. This study evaluates activation or inactivation of 11 neo-nicotinoids in a continuous two-step system coupling metabolism and receptor binding. For metabolism, the neo-nicotinoid is incubated with CYP3A4 and NADPH or AOX with the cosubstrate N-methyl-nicotinamide, terminating the reaction with ketoconazole or menadione, respectively, to inhibit further conversion. For receptor assay, either the Drosophila nAChR and [(3)H]imidacloprid or the alpha4 beta2 nicotinic receptor and [(3)H](-)-nicotine are added to determine changes in neo-nicotinoid potency. With the Drosophila nAChR assay, the N-methyl compounds N-methyl-imidacloprid and thiamethoxam are activated 4.5-29-fold by CYP3 A4 whereas nine other neo-nicotinoids are not changed in potency. With the vertebrate alpha4 beta2 nAChR, AOX enhances imidacloprid potency but CYP3 A4 does not. The AOX system coupled with the Drosophila receptor strongly inactivates clothianidin, dinotefuran, imidacloprid, desmethyl-thiamethoxam, and thiamethoxam with some inactivation of nitenpyram and nithiazine, and little or no effect on four other compounds.


Analysis of the heat shock protein 70 (HSP70) genetic variants in nonsegmental vitiligo patients.
Vitiligo is an autoimmune disease that courses with skin depigmentation because of the destruction of melanocytes. Vitiliginous melanocyte is prone to damage because of oxidative stress which activates cellular stress response and the release of heat shock proteins such as HSP70 promoting immune activation against the melanocyte. Variants in HSP70 genes (HSPA) might alter their expression and thus modulate vitiligo susceptibility. Therefore, we sought to evaluate the role of the 5' untranslated region HSPA1A G/C (rs1043618) and the exonic HSPA1B A/G (rs1061581) and HSPA1L T/C (rs2227956) gene variants in nonsegmental vitiligo. A total of 200 nonsegmental vitiligo patients and 208 age/gender-matched healthy subjects were genotyped for rs1043618, rs1061581, and rs2227956 variants by PCR-RFLP. Variants rs1043618 and rs1061581 were not associated with vitiligo susceptibility. On the other hand, the rs2227956 C allele and TC genotype were associated with protection against vitiligo. A similar effect was observed for the GAC haplotype. Any of the aforementioned HSP70 gene variants were associated with the clinical characteristics of vitiligo. Our findings suggest that the HSPA1L rs2227956 gene variant might influence the susceptibility to vitiligo. Being the first study of HSP70 gene variants in vitiligo, further research is encouraged to corroborate these results.


Joint toxic impacts of cadmium and three pesticides on embryonic development of rare minnow (Gobiocypris rarus).
Although rare minnow (Gobiocypris rarus) has been employed in many toxicological investigations, most of them have only assessed the impacts of single chemical. In our current work, we investigated the single and joint toxic impacts of heavy metal cadmium (Cd) and three pesticides (thiamethoxam, bifenthrin, and tebuconazole) on G. rarus embryos. Results from the 96-h semi-static toxicity assay exhibited that bifenthrin possessed the highest intrinsic toxic effect on rare minnows with an LC50 value of 1.86 mg L-1, followed by tebuconazole with LC50 values of 4.07 mg L-1. Contrarily, thiamethoxam elicited the least toxic effect with an LC50 value of 351.9 mg L-1. Seven chemical mixtures (four binary mixtures of Cd-bifenthrin, thiamethoxam-bifenthrin, thiamethoxam-tebuconazole, and bifenthrin-tebuconazole, two ternary mixtures of Cd-thiamethoxam-tebuconazole and thiamethoxam-bifenthrin-tebuconazole, and one quaternary mixture of Cd-thiamethoxam-bifenthrin-tebuconazole) displayed synergistic impacts with equivalent concentration and equitoxic ratio on G. rarus. Our results offered valuable insights into ecological risk assessment of these chemical combinations to aquatic vertebrates. The simultaneous existence of a few chemicals in the aquatic ecosystem might result in elevated toxicity, leading to severe harm to the non-target organisms compared with single compound. The observed synergistic interactions underlined the necessity to revise water quality standards, in which the detrimental joint effects of these chemicals are likely to be underestimated.


Quantitative Analysis of Posttranslational Modifications of Plant Histones.
Reshaping of the chromatin landscape under oxidative stress is of paramount importance for mounting an effective stress response. Unbiased systemic identification and quantification of histone marks is crucial for understanding the epigenetic component of plant responses to adverse environmental conditions. We describe a detailed method for isolation of plant histones and subsequent bottom-up proteomics approach for characterization of acetylation and methylation status. By performing label-free quantitative mass spectrometry analysis, relative abundances of histone marks can be statistically compared between experimental conditions.


Failure of national antenatal vitamin D supplementation programme puts dark skinned infants at highest risk: A newborn bloodspot screening study.
To determine the prevalence of vitamin D deficiency on dried blood spots (DBS) obtained at newborn blood spot screening (NBS) and thereby test the efficacy of the UK national antenatal supplementation programme in an increasingly ethnically diverse English population. To evaluate the seasonal and ethnic variation in neonatal plasma 25 hydoxyvitamin D (25OHD) and its determinants. Three thousand random DBS samples received at a single regional newborn screening laboratory (52° N) over two one-week periods, one in winter (February 2019) and one in summer (August 2019), were collected. Data was collected from NBS cards on birth weight, gestational age, maternal age, ethnicity, and post code which was replaced with index of multiple deprivation (IMD). 25OHD concentrations were measured on 6 mm sub-punch from DBS using quantitative liquid chromatography tandem mass spectrometry adjusted to equivalent plasma values. 25OHD variation with season was assessed using Mann-Whitney U test and ethnic groups compared using Kruskal-Wallis test. Linear regression was used to assess the determinants of 25OHD concentrations. 25OHD measurements were available in 2999 (1580 males) subjects [1499 winter-born and 1500 summer-born]. The majority were white British (59.1%) and born at term (mean ± SD gestational age of 38.8 ± 1.8 weeks) with a mean (±SD) birth weight of 3306 (±565) grams. The overall prevalence of vitamin D deficiency [25OHD<30 nmol/L (12 μg/L)] was 35.7% (n = 1070) and insufficiency [30-50 nmol/L (12-20 μg/L)] 33.7% (n = 1010). The median (IQR) 25OHD concentration was significantly lower in the winter-born compared to summer-born [29.1 (19.8, 40.6) vs 49.2 (34.3, 64.8) nmol/L respectively; p < 0.001]. Across both seasons, when compared to white British babies (41.6 nmol/L), the median 25OHD concentrations were significantly lower in babies of black (30.3 nmol/L; p < 0.001), Asian (31.3 nmol/L; p < 0.001), any other mixed (32.9 nmol/L; p < 0.001), mixed white and black (33.7 nmol/L; p < 0.05) and any other white (37.7 nmol/L; p < 0.05) ethnicity. The proportion of deficiency was also higher in babies of Asian (48%), black (47%) and mixed ethnicity (38-44%) compared to any other white (34%) or white British (30%) ethnicity. Season of birth, ethnicity, gestation and maternal age accounted for almost 24% of the variation in 25OHD concentrations. The current UK antenatal supplementation programme fails to protect newborns from vitamin D deficiency, especially those from minority ethnic groups who are at high risk of vitamin D deficiency. Nearly 70% of all newborns and 85% of winter-borns had 25OHD concentrations below 50 nmol/L (20 μg/L). Almost 50% of babies of Black or Asian origin were deficient at birth, which explains their high risk of hypocalcaemic complications and rickets if left unsupplemented. Our findings call for an immediate review of the delivery of antenatal and infant vitamin D supplementation programmes and implementation of food fortification in the long term.


Preserving prion strain identity upon replication of prions in vitro using recombinant prion protein.
Last decade witnessed an enormous progress in generating authentic infectious prions or PrPSc in vitro using recombinant prion protein (rPrP). Previous work established that rPrP that lacks posttranslational modification is able to support replication of highly infectious PrPSc with assistance of cofactors of polyanionic nature and/or lipids. Unexpectedly, previous studies also revealed that seeding of rPrP by brain-derived PrPSc gave rise to new prion strains with new disease phenotypes documenting loss of a strain identity upon replication in rPrP substrate. Up to now, it remains unclear whether prion strain identity can be preserved upon replication in rPrP. The current study reports that faithful replication of hamster strain SSLOW could be achieved in vitro using rPrP as a substrate. We found that a mixture of phosphatidylethanolamine (PE) and synthetic nucleic acid polyA was sufficient for stable replication of hamster brain-derived SSLOW PrPSc in serial Protein Misfolding Cyclic Amplification (sPMCA) that uses hamster rPrP as a substrate. The disease phenotype generated in hamsters upon transmission of recombinant PrPSc produced in vitro was strikingly similar to the original SSLOW diseases phenotype with respect to the incubation time to disease, as well as clinical, neuropathological and biochemical features. Infrared microspectroscopy (IR-MSP) indicated that PrPSc produced in animals upon transmission of recombinant PrPSc is structurally similar if not identical to the original SSLOW PrPSc. The current study is the first to demonstrate that rPrP can support replication of brain-derived PrPSc while preserving its strain identity. In addition, the current work is the first to document that successful propagation of a hamster strain could be achieved in vitro using hamster rPrP.


Antioxidant, anti-inflammatory, and enzyme inhibitory activity of natural plant flavonoids and their synthesized derivatives.
The synthesized flavonoid derivatives were examined for their antioxidant, anti-inflammatory, xanthine oxidase (XO), urease inhibitory activity, and cytotoxicity. Except few, all the flavonoids under this study showed significant antioxidant activity (45.6%-85.5%, 32.6%-70.6%, and 24.9%-65.5% inhibition by DPPH, ferric reducing/antioxidant power, and oxygen radical absorption capacity assays) with promising TNF-α inhibitory activity (42%-73% at 10 μM) and IL-6 inhibitory activity (54%-81% at 10 μM) compared with that of control dexamethasone. The flavonoids luteolin, apigenin, diosmetin, chrysin, O3Ꞌ , O7 -dihexyl diosmetin, O4Ꞌ , O7 -dihexyl apigenin, and O7 -hexyl chrysin, showed an inhibition with IC50 values (4.5-8.1 μg/mL), more than allopurinol (8.5 μg/mL) at 5 μM against XO and showing more than 50% inhibition at a final concentration (5 mM) with an IC50 value of ranging from 4.8 to 7.2 (μg/mL) in comparison with the positive control thiourea (5.8 μg/mL) for urease inhibition. Thus, the flavonoid derivatives may be considered as potential antioxidant and antigout agents.


A novel FRET-based optical fiber biosensor for rapid detection of Salmonella typhimurium.
A biosensor that is portable and permits on-site analysis of samples would significantly reduce the large economical burden of food products recalls. A fiber optic portable biosensor utilizing the principle of fluorescence resonance energy transfer (FRET) was developed for fast detection of Salmonella typhimurium (S. typhimurium) in ground pork samples. Labeled antibody-protein G complexes were formed via the incubation of anti-Salmonella antibodies labeled with FRET donor fluorophores (Alexa Fluor 546) and protein G (PG) labeled with FRET acceptor fluorophores (Alexa Fluor 594). Utilizing silanization, the labeled antibodies-PG complexes were then immobilized on decladded, tapered silica fiber cores to form the evanescent wave-sensing region. The biosensors were tested in two different solutions: (1) PBS doped with S. typhimurium and (2) homogenized pork sample with S. typhimurium. The fiber probes tested in a S. typhimurium doped phosphate buffered solution demonstrated the feasibility of the biosensor for detecting S. typhimurium as well as determined the optimal packing density of the labeled antibody-PG complexes on the surface of fibers. The results showed that a packing density of 0.033 mg/ml produced the lowest limit of detection of 10(3)cells/ml with 8.2% change in fluorescence. The fiber probes placed in homogenized pork samples inoculated with S. typhimurium showed a limit of detection of 10(5)CFU/g with a 6.67% in fluorescence within a 5-min response time. These results showed that the FRET-based fiber optic biosensor can become a useful analytical tool for detection of S. typhimurium in real food samples.


The greenhouse gas footprints of China's food production and consumption (1987-2017).
As China urbanized and its economy grew rapidly, its food production and consumption patterns changed dramatically over the past three decades. With this in mind, we evaluate how the nation's greenhouse gas (GHG) emissions related to food production and consumption altered from 1987 to 2017. We further explore key factors that affect GHG emission changes from agricultural production and household diet perspectives. We find that the GHG emissions from China's food production rose 51 percent, while that from food consumption rose 64 percent. The rise in GHG footprint of China's food production was largely caused by the increasing material- and energy-intensive food production system. Agricultural modernization was a main cause of the rise in GHGs, as China was late to the game in improving agricultural productivity. But a more meat-intensive diet accompanied by a general rise in households' use of processed food also helped to drive these transformations. China's growing appetite for meat not only intensified GHG mitigation pressures domestically, but also abroad, as Chinese households began to demand greater variety that was satisfied via imports. Indeed, GHG emissions embodied in imported meats rose over eleven-fold from 2007 to 2017. Through this study, we highlight the importance of future policy-making focused on a more sustainable food system in China to benefit the world's environment, health, and climate.


Benchmarking Protocol Deviations and Their Variation by Major Disease Categories.
Little to no data exist quantifying and benchmarking the magnitude of protocol deviation experience. Nearly two-dozen companies provided the Tufts Center for the Study of Drug Development (Tufts CSDD) with data on the design and the performance of 187 protocols. The results of this working group study show that phase II and III protocols have a mean total of 75 and 119 protocol deviations, respectively, involving nearly one-third of all patients enrolled in each clinical trial. Oncology clinical trials have the highest relative mean number of protocol deviations affecting more than 40% of patients enrolled in each trial. The number of endpoints, the number of procedures per visit, and the number of countries were modestly positively associated with and predictive of, the incidence of deviations per protocol. A strong positive relationship was shown between the number of investigative sites and the number of protocol deviations. The results of this initial study provide useful measures that sponsor companies can use to benchmark their own protocol deviation experience, identify factors most associated with protocol deviations, and determine whether remediation is warranted.


On unsatisfied hydrogen bonds in the N-terminal subdomain of villin headpiece.
Villin headpiece is a small autonomously folding protein that has emerged as a model system for understanding the fundamental tenets governing protein folding. In this communication, we employ NMR and X-ray crystallography to characterize a point mutant, H41F, which retains actin-binding activity, is more thermostable but, interestingly, does not exhibit the partially folded intermediate observed of either wild-type or other similar point mutants.


Treatment of benign thyroid nodules by radiofrequency thermal ablation
Benign thyroid nodules are frequent findings in imaging studies, most of the time not requiring any intervention. Treatment is usually started when nodules increase in size, the patient becomes symptomatic or clinically relevant hyperthyroidism develops. Thermoablation is an effective alternative modality. In Hungary, our team has pioneered these interventions using radiofrequency ablation for decreasing the size of the nodules. We are presenting our results showing the effectiveness of this treatment after introducing the role, importance and technique of thermoablation in benign thyroid nodules. Between June of 2016 and September of 2019, 186 nodules of 140 patients were treated with radiofrequency ablation and had at least 6 months of follow up. The volume and diameter of all the ablated nodules were measured and calculated, then the decreases of these parameters were followed using ultrasonography. The mean follow-up time was 12.5 ± 5.9 months. The size measurements at the follow-up ultrasonography examinations showed a decrease in size and vascularity. The mean volume reduction was 44.7 ± 17.6% at one-month post-treatment and 72.9 ± 17.9% at 6 months. There were 3 minor complications. Radiofrequency ablation represents a feasible, effective, well tolerated method for outpatient treatment of benign thyroid nodules. This method is a valuable alternative to surgical treatments in selected cases. Orv Hetil. 2020; 161(27): 1131-1136.


Kaposi sarcoma presenting as a vulvar mass.
Kaposi sarcoma has become a common manifestation in people with AIDS, especially men. A few reports of Kaposi sarcoma in women with AIDS have involved nongenital areas. However, of the few patients with genital Kaposi sarcoma reported in the United States, none was believed to be human immunodeficiency virus (HIV)-positive. Genital Kaposi sarcoma associated with HIV has been reported in other parts of the world. A 29-year-old black woman presented with severe vulvar pain, vaginal discharge, and a vulvar mass. She had been diagnosed with AIDS 25 months earlier. Biopsy of the vulvar mass revealed Kaposi sarcoma; viral analysis of the tumor was positive for herpes simplex virus type 2. Sequencing of polymerase chain reaction product verified the presence of human papillomavirus 26. We report an HIV-associated Kaposi sarcoma presenting as a vulvar mass. This report should alert health care providers to include Kaposi sarcoma in the differential diagnosis of vulvar lesions.


Concanavalin A binds to puffs in polytene chromosomes.
CHANGES in transcriptional activity at defined loci are often correlated with significant local structural changes in the genome(1), and in polytene chromosomes, such changes are thought to be associated with compositional or conformational changes in the protein complement at these particular bands(2,3). Thus, various studies on Balfoiani rings and specific 'puffs' in such chromosomes are useful for elucidating the role of defined chromosomal components in both chromosome structure and gene activity. Such studies require specific probes which will allow in situ localisation of a chromosomal component during the various stages of puffing. Antibodies specific to purified histone fractions(4-7), HMG proteins(8), RNA polymerase(9) and non-histone protein subfractions(10) have been used in studies on chromatin and chromosome structure. We reported previously that concanavalin A (Con A) specifically binds to three types of non-histone proteins present in chromatin purified from rat liver nuclei and suggested that derivatives of Con A might serve as specific probes to study the in situ organisation of these non-histone proteins(11). We have now reacted fluorescein-labelled Con A with polytene chromosomes isolated from different developmental stages of Chironomus thummi and visualised the location of the bound Con A by fluorescence microscopy. We observed that the fluorescent lectin, which has an affinity for glucose- and mannose-containing molecules, specifically bound to the transcriptionally active regions of chromosome IV. The extent of binding of Con A to the Balbiani rings present in regions b and c of chromosome IV is proportional to the size of the respective ring. Our results indicate that glucose- or mannose-containing molecules are present in these Balbiani rings and that the availability of these sugars to interact with Con A can be correlated with the developmental stage of a puff. We suggest that lectins can be useful cytological tools with which to study the in situ organisation of defined chromosomal components during various functional states of the genome.


Safety profiles of percutaneous left atrial appendage closure devices: An analysis of the Food and Drug Administration Manufacturer and User Facility Device Experience (MAUDE) database from 2009 to 2016.
Percutaneous left atrial appendage closure (LAAC) is a viable option for AF patients who are unable to tolerate long-term oral anticoagulation (OAC). We sought to assess the safety of two commonly used percutaneous devices for LAA closure in the United States by analysis of surveillance data from the FDA Manufacturer and User Facility Device Experience (MAUDE) database. The MAUDE database was queried between May 1, 2006 and May 1, 2016 for LARIAT® (SentreHEART Inc., Redwood City, CA, USA) and WATCHMAN™ (Boston Scientific Corp., Marlborough, MA, USA) devices. Among 622 retrieved medical device reports, 356 unique and relevant reports were analyzed. The cumulative incidence of safety events was calculated over the study period and compared between the two devices. LAAC was performed with LARIAT in 4,889 cases. WATCHMAN was implanted in 2,027 patients prior to FDA approval in March 2015 and 3,822 patients postapproval. The composite outcome of stroke/TIA, pericardiocentesis, cardiac surgery, and death occurred more frequently with WATCHMAN (cumulative incidence, 1.93% vs. 1.15%; P = 0.001). The same phenomenon was observed when comparing the WATCHMAN pre- and postapproval experiences for the composite outcome, as well as device embolization, cardiac surgery, and myocardial infarction. MAUDE-reported data show that postapproval, new technology adoption is fraught with increased complications. Improved collaboration between operators, device manufacturers, and regulators can better serve patients through increased transparency and practical postmarket training and monitoring mechanisms.


Lay recommendations on how to treat mental disorders.
Beliefs about the helpfulness of interventions are influencing the individual help-seeking behavior in case of mental illnesses. It is important to identify these beliefs as professional helpers are asked to consider them in their treatment recommendations. Assessing lay proposals for an appropriate treatment of mental illnesses. We conducted a representative opinion survey in Switzerland. Eighteen treatment proposals were presented with respect to a vignette either depicting schizophrenia or depression. Respondents were asked to indicate the proposals considered to be helpful for treatment and those considered to be harmful, respectively. 'Psychologist,' 'general practitioner,' 'fresh air, and 'psychiatrist' were mostly proposed as being helpful. Among several psychiatric treatment approaches 'psychotherapy' was favored, while psychopharmacological treatment and electroconvulsive therapy were only proposed by less than one-fourth of the interviewees. Especially psychotropic drugs were considered to be harmful. Treatment by a psychiatrist was regarded as being more helpful for schizophrenic individuals than for depressive persons. For a person experiencing a life crisis, treatment by a psychiatrist and psychological treatment were viewed as being harmful, and non-medical interventions were preferred. However, for persons thought to be mentally ill, psychiatric and psychopharmacological treatments were recommended. Mental health professionals are regarded as being helpful although their treatment methods are seen as being less helpful. A clear distinction is made between lay proposals for depression and schizophrenia. However, the perception of whether a condition is considered to be an illness or a life crisis has significantly more influence on lay treatment proposals than the cited diagnosis in the vignette.


HDlive and HD-flow images of early-stage nonhydropic mole.
We present our first experience of constructing an image of an early-stage complete hydatidiform mole employing HDlive. Conventional 2D sonography showed massive, lobulated, and mixed masses and intrauterine anechoic fluid collection. Smooth, lobulated masses were clearly recognized using HDlive. Small, irregular, cystic spaces inside the masses were also evident. HDlive provided anatomically realistic features akin to macroscopic specimens for physicians and pathologists, owing to the complete depiction of the inner surface of an early-stage nonhydropic mole.


Pulmonary embolism during pregnancy and the postpartum period: report of 2 cases.
To investigate the high risk factors, clinical features, diagnosis and treatment of pulmonary embolism (PE) during pregnancy and the postpartum period. Two cases of PE during pregnancy and postpartum period were reported retrospectively. The first case was a pregnant woman with congenital heart disease at 39-week gestation. She underwent a successful cesarean section (CS) because of heart disease, but she manifested tachycardia, tachypnea, cyanosis, and dyspnea suddenly on the 10th day after CS and died soon after the onset of these symptoms. The diagnosis of PE was highly suspected clinically. The second case was a twin-pregnancy woman at 35-week gestation. Because of severe perinatal myocardiopathy, cesarean section was performed. Unfortunately, the patient died abruptly on the operation table. The diagnosis of PE was confirmed by autopsy. The maternal mortality of PE during pregnancy and postpartum period is quite high. Whenever there is any doubt, objective examinations for PE should be started early in order to strive for the chances of the anticoagulant therapy.


Tranexamic acid can reduce blood loss in adolescent scoliosis surgery: a systematic review and meta-analysis.
Tranexamic acid (TXA) has been widely used in orthopedic surgery, but its efficacy in adolescent scoliosis (AS) surgery remains unclear in the literature. The purpose of this systematic review and meta-analysis is to evaluate the safety and efficacy of TXA compared to placebo treatment during or after AS surgery, by gathering data from randomized both controlled trials (RCTs) and non-RCTs. English and Chinese electronic databases including PubMed, Web of Science, Embase, Cochrane, CNKI, and Wan Fang database were searched to identify the relevant literature up until August 2022. The primary outcomes were intraoperative blood loss and total blood loss. The secondary outcomes included the need for transfusion, postoperative hemoglobin (Hb) level, and change in Hb level. Stata 17 was used for data analysis and the risk of bias was assessed. We followed the PRISMA checklist to ensure the quality of this article. Twelve studies (795 participants) were included in the meta-analysis for intraoperative blood loss during surgery. The results suggest that TXA can reduce the intraoperative blood loss of the patients (MD = -306.40ml, 95%CI = -404.04ml to -208.77ml, p < 0.001). Six studies (2027 patients) were included in the meta-analysis for total blood loss. The pooled result shows that the total blood loss of the TXA group was significantly lower than that of the control group (MD = -779.24ml, 95% CI = -1157.10ml to -410.39ml, p < 0.001). Five studies (419 patients) were included in the meta-analysis for postoperative Hb level and shows a non-significant outcome (MD = 5.09 g/l, 95%CI = 2.92 g/l to 7.25 g/l, p = 0.611). Three studies (268 patients) were included in the meta-analysis for the postoperative Hb level. There is a non-significant decrease in the TXA group (MD = -0.23 g/l, 95%CI = -0.48 g/l to 0.01 g/l, p = 0.319). Eight studies (670 patients) reported data on the need for transfusion after surgery. The overall relative risks (RR) showed a significant difference between the TXA and control group, with a lower risk of transfusion in the TXA group (RR = 0.547, 95%CI = 0.308 to 0.972, p = 0.04). The meta-analysis of the data reveals that TXA usage is associated with a significant reduction in intraoperative and total blood loss, a lower risk of transfusion, and a non-significant change in postoperative Hb levels in AS surgery However, it should be noted that the surgical operation situations varied across different studies. Therefore, further research is required to investigate the effects of TXA on specific subgroups of gender, operation time, and blood transfusion indicators. Overall, our study provides valuable evidence for the clinical management of AS surgery and may inform the development of practice guidelines and protocols for the use of TXA in this setting.


Support for bereaved owners of pets.
The bond that exists between people and their pets and its impact on physical and mental health. To review the current literature and explore the clinical implications of bereavement related to pets. A comprehensive review of the bereavement, veterinarian, and agricultural literature related to attitudes and response patterns to pet and animal death. The death or loss of a beloved pet can be a life-changing event.


Brucellosis.
Brucellosis is a common Zoonosis affecting half a million people annually. The most common mode of infection is by consuming unpasteurized milk or milk products. The general manifestations are those of fever with generalized symptoms. The nervous system is affected in 4-7% of cases. The manifestations are protean and include meningo-encephalitis as well as peripheral nervous system involvement. The diagnosis relies on culture, which is cumbersome and can be falsely negative. Agglutination tests for the various species of the organism are the mainstay for diagnosis. Treatment is for 3-6 months with combination therapy including Doxycycline, Rifampicin and ceftriaxone. The main issue is prevention and better animal husbandry.


Squamous cell and basal cell carcinomas: preliminary study of 3,817 primary skin cancers.
A series of patients with 3,817 cutaneous carcinomas of different types observed in a private practice setting is reported. Preliminary computerized analyses indicate that 88% of these squamous cell and basal cell carcinomas were less than 25 mm. Scalpel surgery, curettage and desiccation, or radiation therapy was used for most tumors and an overall cure rate of greater than 98% was obtained. A pretreatment biopsy allowed for selection of the most appropriate management and authoritative instructions for long-term follow-up visits and prophylaxis.