Identifying the nurse characteristics that affect anticipated turnover.
Nurse turnover is a prevalent and serious issue in Jordan, with many nurses leaving their jobs to search for better opportunities outside the country. It is therefore important to assess anticipated nurse turnover and the factors that may affect this, to prevent the costly and unnecessary loss of staff. To assess anticipated nurse turnover and its predictors, and to compare these between public and university-affiliated (teaching) hospitals. A descriptive, cross-sectional and comparative design was used. Anticipated nurse turnover was measured using the Anticipated Turnover Scale, which consists of 12 items related to a nurse's intention to leave their job that are rated using a seven-point Likert-scale. Questionnaires were distributed to 280 nurses from three public hospitals and one university-affiliated hospital in the north of Jordan. Data were analysed using descriptive statistics, multiple regression and independent t-tests. Questionnaire responses were received from 250 nurses, yielding a response rate of 89%. This study identified that 68% of respondents intended to leave their job. Being older, more experienced and with a higher level of education increased the likelihood of nurse turnover. Nurses working in the university-affiliated hospital had a higher intent to leave compared with those working in public hospitals. This study found that a high proportion of nurses working in hospitals in the north of Jordan were considering leaving their jobs, and nurses' characteristics had a significant role in determining anticipated turnover. The results of this study could provide policymakers and stakeholders in Jordan with guidance to develop policies and retention programmes that could improve nurses' work environment and reduce turnover.


Environmental drift in health center dental practice management.
Federally qualified health centers, FQHCs, face a number of challenges providing low-cost health services and meeting their primary mission of being available to all users regardless of their ability to pay. In effect, health centers must provide services that border on free to minimal revenue-generating potential. This is especially challenging for health centers providing dental services that are often more costly on a case-by-case visit encounter than primary care services..


The Avon Longitudinal Study of Parents and Children (ALSPAC): an update on the enrolled sample of index children in 2019.
The Avon Longitudinal Study of Parents and Children (ALSPAC) is a prospective population-based study. Initial recruitment of pregnant women took place in 1990-1992 and the health and development of the index children from these pregnancies and their family members have been followed ever since. The eligible sampling frame was constructed retrospectively using linked recruitment and health service records. Additional offspring that were eligible to enrol in the study have been welcomed through major recruitment drives at the ages of 7 and 18 years; and through opportunistic contacts since the age of 7. This data note provides a status update on the recruitment of the index children since the age of 7 years with a focus on enrolment since the age of 18, which has not been previously described. A total of 913 additional G1 (the cohort of index children) participants have been enrolled in the study since the age of 7 years with 195 of these joining since the age of 18. This additional enrolment provides a baseline sample of 14,901 G1 participants who were alive at 1 year of age.


Major and trace-element geochemistry of Late Cretaceous clastic rocks in the Jitai Basin, southeast China.
Major, trace and rare earth element (REE) geochemistry of the late Cretaceous lower Zhoutian Formation from the Jitai Basin of Southeast China were measured by inductively coupled plasma mass spectrometry (ICP-MS) analysis to infer the provenance of the sediments and to reconstruct the palaeoenvironment and palaeoclimate. The wide range of Sr/Cu ratios point to a fluctuating palaeoclimate, and the negative correlation between the FeO/MnO and Al2O3/MgO ratios and the Sr/Cu ratio indicates that the late Cretaceous climate during the lower Zhoutian Formation in the Jitai Basin can be divided into two parts. The lower part experienced two cooling periods, whilst the upper part was dominated by warm-humid climate. Mostly corresponding trends of the B/Ga, Sr/Ba and Sr/Cu ratios show that the salinity changed consistently with the late Cretaceous climate during the lower Zhoutian Formation in the Jitai Basin. During the lower part, the salinity changed from salt water to fresh/brackish water. In the upper part, water was mainly fresh/brackish, and there were many changes from fresh/brackish water to salt water. The relatively stable Ni/Co, V/Cr, V/(V + Ni) and Ce/Ce* data indicate a long period of oxic conditions. The La-Th-Sc, Th-Sc-Zr/10 and La/Th-Hf data of the silt- and sandstones of the lower Zhoutian Formation show that its provenance was mainly a mixture of felsic upper crust sediments and older sedimentary rocks.


Monitoring your patients with chronic myeloid leukemia.
Chronic myeloid leukemia (CML), a hematopoietic stem cell disorder, which sometimes presents with fatigue, hepato-splenomegaly, and weight loss but is sometimes asymptomatic, is discussed. Diagnosis is suspected on the observation of an increased white blood cell count and is confirmed by the presence of the Philadelphia (Ph) chromosome. CML progresses through a series of three defined stages with survival times of 3-5 years if untreated. The chromosomal translocation creating the Ph chromosome creates the BCR-ABL fusion protein, which is the initiating factor for CML. BCR-ABL is a constitutively active tyrosine kinase, which transforms hematopoietic stem cells through dysregulation of proliferation, apoptosis, differentiation, and cell adhesion. The transformation process is then accelerated by the accumulation of additional translocations. This fusion protein has been used clinically as a therapeutic target and a sensitive marker for measuring residual disease. Techniques, such as cytogenetic analysis of chromosomes, allow for the visualization of the Ph chromosome and additional translocations and abnormalities. The more sensitive fluorescent in situ hybridization assay can directly visualize the bcr-abl translocation through merged fluorescent tags. Polymerase chain reaction, the most sensitive of the assays, can be used to detect minute amounts of bcr-abl mRNA and this has made it possible to monitor and detect minimal residual disease recurrence and disease progression, thus greatly enhancing patient care. A variety of monitoring techniques can be employed during CML therapy, providing degrees of quantifying disease burden or absence of disease.


Role of cortisol in menstrual recovery in adolescent girls with anorexia nervosa.
Neuroendocrine abnormalities in anorexia nervosa (AN) include hypercortisolemia, hypogonadism, and hypoleptinemia, and neuroendocrine predictors of menstrual recovery are unclear. Preliminary data suggest that increases in fat mass may better predict menstrual recovery than leptin. High doses of cortisol decrease luteinizing hormone (LH) pulse frequency, and cortisol predicts regional fat distribution. We hypothesized that an increase in fat mass and decrease in cortisol would predict menstrual recovery in adolescents with AN. Thirty-three AN girls 12-18 y old and 33 controls were studied prospectively for 1 y. Body composition [dual energy x-ray absorptiometry (DXA)], leptin, and urinary cortisol (UFC) were measured at 0, 6, and 12 mo. Serum cortisol was measured overnight (every 30 min) in 18 AN subjects and 17 controls. AN subjects had higher UFC/cr x m2 and cortisol area under curve (AUC), and lower leptin levels than controls. Leptin increased significantly with recovery. When menses-recovered AN subjects were compared with AN subjects not recovering menses and controls, menses-recovered AN subjects had higher baseline cortisol levels and greater increases in leptin than controls and greater increases in fat mass than AN subjects not recovering menses and controls (adjusted for multiple comparisons). In a logistic regression model, increasing fat mass, but not leptin, predicted menstrual recovery. Baseline cortisol level strongly predicted increases in the percentage of body fat. We demonstrate that 1) high baseline cortisol level predicts increases in body fat and 2) increases in body fat predict menses recovery in AN.


Liver granulomatosis: a case of Chlamydophila pneumoniae infection.
An 18-year-old man was referred to the Internal Medicine ward because of a 2-week history of intermittent high fever, weight loss and cough. Clinical examination revealed hepato-splenomegaly and multiple lymph nodes swelling while laboratory tests showed elevated C-reactive protein, gamma glutamyl transferase and lactate dehydrogenase. All serologic testes for auto-immune antibodies, viruses and bacteria were negative except for Chlamydophila pneumoniae. An 18-FDG PET computed tomography scanner showed hypermetabolism in the liver, spleen and lymph nodes. We therefore conducted a liver biopsy that demonstrated non-necrotizing granulomas. We conclude to a C. pneumoniae infection associated with a granulomatous hepatitis. After treatment with Doxyciclin the patient had no more fever, hepatosplenomegaly resolved and blood testes normalized. This case report is to our knowledge the first report of a granulomatous hepatitis associated with C. pneumoniae respiratory infection.


[Creutzfeldt-Jakob syndrome in the county of Storstrom during the period 1990-1999. Was there a significant accumulation of cases?].
In the county of Storstrøm with about 250,000 inhabitants, ten cases of Creutzfeldt-Jacob disease (CJD) were diagnosed at the Department of Neurology, Naestved County Hospital during the decade 1990-1999. Only one case is to be expected every four years in the county. Therefore we decided to investigate if a significant accumulation had occurred. Case records were examined to see whether the patients complied with the WHO criteria for possible, probable, or certain sporadic CJD. Poisson distribution with correction for age was used to compare the observed incidence with the expected incidence of 1 case/million/year. Eight cases complied with the diagnostic criteria: two certain, three probable, two possible, and one familial. The incidence of certain and probable cases was 1.9 per million per year during the period, which does not constitute a significant increase (p = 0.18). The result is consistent with the fact that all time or space clustering of CJD ever reported has proved ascribable to familial cases, and with the fact that case-control studies have never identified environmental risk factors for sporadic CJD.


Sugary drink consumption and dental caries in New South Wales teenagers.
The consumption of water, milk and various sugary drinks and their relationship with the caries experience of a random sample of teenagers aged 14 to 15 years living in New South Wales, Australia was investigated. Data were obtained from both clinical and questionnaire components of the NSW Teen Dental Survey, 2010. The analyses allowed for various demographic and behavioural risk factors using caries experience (DMFT >0) and mean DMFT as the key outcome variables. Males were more likely than females to consume large volumes of sugary drinks. Consuming two or more glasses of sugary drinks per day led to significantly increased caries experience amongst this sample of 14 and 15 year olds. Factors found to be associated with elevated sugary drink consumption included family income, gender, and mother's education level. There is a strong correlation between increased caries experience of NSW teenagers and high levels of consumption of sugary drinks.


A quantitative method for the high throughput screening for the soil adhesion properties of plant and microbial polysaccharides and exudates.
Understanding the structures and functions of carbon-based molecules in soils is an important goal in the context of soils as an ecosystem function of immense importance. Polysaccharides are implicated in maintaining soil aggregate status but have not been extensively dissected in terms of their structures and soil adhesion properties. This is largely because of the technical difficulties in identifying polysaccharide structures and quantifying any functional properties. Here, we describe the use of a novel nitrocellulose-based adhesion assay to determine the relative capacities for soil adhesion of over twenty plant and microbial polysaccharides that are likely to be present in soil and to contribute to organic matter content and properties. Weights of soil adhered to spots of known amounts of specific polysaccharides were quantified by scanning of the nitrocellulose sheets. The most effective polysaccharides identified from this survey included chitosan, β-1,3-glucan, gum tragacanth, xanthan and xyloglucan. We also demonstrate that the soil adhesion assay is suitable to assess the soil-binding properties of plant exudates. The soil adhesion assay will be useful for the functional dissection of the organic matter components of soils and also of the factors involved in soil attachment to plant roots and in rhizosheath formation.


Transjugular intrahepatic portosystemic shunt: indications, contraindications, and patient work-up.
The transjugular intrahepatic portosystemic shunt (TIPS) procedure is effective in achieving portal decompression and in managing some of the major complications of portal hypertension. While many clinicians are familiar with the two most common indications for TIPS placement, secondary prophylaxis of esophageal variceal hemorrhage and treatment of refractory ascites, evidence for its usefulness is growing in other entities, where it has been less extensively studied but demonstrates promising results. Newer indications include early utilization in the treatment of esophageal variceal hemorrhage, Budd-Chiari syndrome, ectopic varices, and portal vein thrombosis. The referring clinician and interventionist must remain cognizant of the contraindications to the procedure to avoid complications and potential harm to the patient. This review is designed to provide an in-depth analysis of the most common as well as less typical indications for TIPS placement, and to discuss the contraindications and appropriate patient evaluation for this procedure.


Multiple pathogenic and benign genomic rearrangements occur at a 35 kb duplication involving the NEMO and LAGE2 genes.
The X-linked dominant and male-lethal disorder incontinentia pigmenti (IP) is caused by mutations in a gene called NEMO (IKK-gamma). We recently reported the structure of NEMO and demonstrated that most IP patients carry an identical deletion that arises due to misalignment between repeats. Affected male abortuses with the IP deletion had provided clues that a second, incomplete copy of NEMO was present in the genome. We have now identified clones containing this truncated copy (Delta NEMO) and incorporated them into a previously constructed physical contig in distal Xq28. Delta NEMO maps 22 kb distal to NEMO and only contains exons 3-10, confirming our proposed model. A sequence of 26 kb 3' of the NEMO coding sequence is also present in the same position relative to the Delta NEMO locus, bringing the total length of the duplication to 35.5 kb. The LAGE2 gene is also located within this duplicated region, and a similar but unique LAGE1 gene is located just distal to the duplicated loci. Mapping and sequence information indicated that the duplicated regions are in opposite orientation. Analysis of the great apes suggested that the NEMO/LAGE2 duplication occurred after divergence of the lineage leading to present day humans, chimpanzees and gorillas, approximately 10-15 million years ago. Intriguingly, despite this substantial evolutionary history, only 22 single nucleotide differences exist between the two copies over the entire 35.5 kb, making the duplications >99% identical. This high sequence identity and the inverted orientations of the two copies, along with duplications of smaller internal sections within each copy, predispose this region to various genomic alterations. We detected four rearrangements that involved NEMO, Delta NEMO or LAGE1 and LAGE2. The high sequence similarity between the two NEMO/LAGE2 copies may be due to frequent gene conversion, as we have detected evidence of sequence transfer between them. Together, these data describe an unusual and complex genomic region that is susceptible to various types of pathogenic and polymorphic rearrangements, including the recurrent lethal deletion associated with IP.


Time to diagnostic certainty for saddle pulmonary embolism in hospitalized patients.
There is a lack of diagnostic performance measures associated with pulmonary embolism (PE). We aimed to explore the concept of the time to diagnostic certainty, which we defined as the time interval that elapses between first presentation of a patient to a confirmed PE diagnosis with computed tomography pulmonary angiogram (CT PA). This approach could be used to highlight variability in health system diagnostic performance, and to select patient outliers for structured chart review in order to identify underlying contributors to diagnostic error or delay. We performed a retrospective observational study at academic medical centers and associated community-based hospitals in one health system, examining randomly selected adult patients admitted to study sites with a diagnosis of acute saddle PE. One hundred patients were randomly selected from 340 patients discharged with saddle PE. Twenty-four patients were excluded. Among the 76 included patients, time to diagnostic certainty ranged from 1.5 to 310 hours. We found that 73/76 patients were considered to have PE present on admission (CT PA ≤ 48 hours). The proportion of patients with PE present on admission with time to diagnostic certainty of > 6 hours was 26% (19/73). The median (IQR) time to treatment (thrombolytics/anticoagulants) was 3.5 (2.5-5.1) hours among the 73 patients. The proportion of patients with PE present on admission with treatment delays of > 6 hours was 16% (12/73). Three patients acquired PE during hospitalization (CT PA > 48 hours). In this study, we developed and successfully tested the concept of time to diagnostic certainty for saddle PE.


Liver x receptors: potential novel targets in cardiovascular diseases.
The Liver X Receptors, LXRalpha and LXRbeta are members of the nuclear hormone receptor superfamily which have recently been implicated as novel pharmacological targets for the treatment of cardiovascular diseases. The identification of natural and synthetic ligands for LXRs and the generation of LXR-deficient mice have been crucial for our understanding of the function of these receptors and for the identification of LXR-regulated target genes, particularly with respect to the role of LXRs in regulating cholesterol homeostasis. Synthetic LXRalpha/beta agonists induce cholesterol efflux and reverse cholesterol transport, improve glucose metabolism, inhibit macrophage-derived inflammation, and suppress the proliferation of vascular smooth muscle cells. By regulating the expression of multiple genes involved in these pathways, LXR agonists prevent the development and progression of atherosclerosis and inhibit neointima formation following angioplasty of the arterial wall. In this review, we will summarize the important roles of LXR in metabolism and vascular biology and discuss its implications as potential molecular drug target for the treatment of cardiovascular diseases.


Histomorphometric characteristics of immune cells in small intestine of pigs perorally immunized with vaccine candidate F18ac nonenterotoxigenic E. coli strain.
Colidiarrhea and colienterotoxemia caused by F4(+) and/or F18(+) enterotoxigenic E. coli (ETEC) strains are the most prevalent infections of suckling and weaned pigs. Here we tested the immunogenicity and protective effectiveness of attenuated F18ac(+) non-ETEC vaccine candidate strain against challenge infection with F4ac(+) ETEC strain by quantitative phenotypic analysis of small intestinal leukocyte subsets in weaned pigs.We also evaluated levamisole as an immune response modifier (IRM) and its adjuvanticity when given in the combination with the experimental vaccine. The pigs were parenterally immunized with either levamisole (at days -2, -1 and 0) or with levamisole and perorally given F18ac(+) non-ETEC strain (at day 0), and challenged with F4ac(+) ETEC strain 7 days later.At day 13 the pigs were euthanatized and sampled for immunohistological/histomorphometrical analyses. Lymphoid CD3(+), CD45RA(+), CD45RC(+), CD21(+), IgA(+) and myeloid SWC3(+) cell subsets were identified in jejunal and ileal epithelium, lamina propria and Peyer's patches using the avidin-biotin complex method, and their numbers were determined by computer-assisted histomorphometry. Quantitative immunophenotypic analyses showed that levamisole treated pigs had highly increased numbers of jejunal CD3(+), CD45RC(+) and SWC3(+) cells (p<0.05) as compared to those recorded in nontreated control pigs.In the ileum of these pigs we have recorded that only CD21(+) cells were significantly increased (p<0.01). The pigs that were treated with levamisole adjuvanted experimental vaccine had significantly increased numbers of all tested cell subsets in both segments of the small intestine. It was concluded that levamisole adjuvanted F18ac(+) non-ETEC vaccine was a requirement for the elicitation of protective gut immunity in this model; nonspecific immunization with levamisole was less effective, but confirmed its potential as an IRM.


Management of the patient with multiple myeloma and renal failure.
Renal impairment is a common feature of multiple myeloma. Management of these patients requires an understanding of some of the basic principles of haematology and nephrology.


Acute mesenteric ischemia: classification, evaluation and therapy.
Mortality rates of acute mesenteric ischemia still range between 60 and 100%. Unfortunately, retrospective series have not shown any significant improvement in mortality in the past decades. With approximately 50%, superior mesenteric artery (SMA) embolism is the most common form of acute mesenteric ischemia, followed by SMA thrombosis (approximately 25%), nonocclusive mesenteric ischemia (approximately 20%) and mesenteric venous thrombosis (approximately 5%). Clinical presentation may be unspecific, but is often characterised by an initial discrepancy between severe subjective pain and relatively unspectacular findings on physical examination. The key to a better outcome (and the main problem in clinical practice) is early diagnosis. Up to now, helas, there are no simple and noninvasive diagnostic tests of sufficient sensitivity and specificity. Thus, angiography remains the cornerstone of diagnosis and should be performed early in all patients with a risk profile and a clinical presentation suspicious of AMI. The initial therapeutic step in all patients with AMI is resuscitation and a stabilization of circulation. If an advanced stage of ischemia is suspected, broad spectrum antibiotics have to be given. Nonocclusive mesenteric ischemia without signs of peritoneal infarction may be managed by pharmacological vasodilation, and vasodilators are also considered as a valuable supportive treatment option in patients with obstructive mesenteric ischemia. Patients with mesenteric venous thrombosis have to be treated by immediate anticoagulation, followed by laparotomy if peritoneal signs are present. Standard treatment for patients with obstructive mesenteric arterial syndromes is a laparotomy with embolectomy or revascularization and, if indicated, resection of infarcted bowel.--. This review will give an overview on the different forms of mesenteric ischemia and then focus on the diagnosis and on generally recommended forms of treatment.


The Value of Ultra-High-Frequency Ultrasound for the Differentiation between Superficial Basal Cell Carcinoma and Bowen's Disease.
The similar visual appearance of superficial basal cell carcinoma (sBCC) and Bowen's disease (BD) may cause confusion for diagnosis. The aim of the study was to investigate the value of ultra-high-frequency ultrasound (uHFUS) in differentiating sBCC from BD. This prospective study included a pilot cohort of 110 patients (73 BDs and 37 sBCCs) from November 2016 to October 2020 and a validation cohort of 42 patients (30 BDs and 12 sBCCs) from July 2021 to December 2021. Clinical and uHFUS features of pathologically confirmed sBCC and BD were assessed. A predictive model was developed based on the uHFUS features of the pilot cohort. Subsequently, the model was validated and compared with clinical diagnosis in the validation cohort. uHFUS features with significant differences between sBCC and BD included lesion surface, skin layer involvement, hyperkeratosis, and hyperechoic spots (all p < 0.05). A prediction model based on the above features was established to identify sBCC and BD in the pilot and validation cohorts with areas under the curve (AUC) of 0.908 and 0.923, sensitivity of 82.3% and 83.3%, specificity of 91.9% and 91.7%, and accuracy of 85.5% and 85.7%, respectively, which were significantly higher than those obtained by clinical diagnosis based on photographic pictures of lesions, with the AUC of 0.692, sensitivity of 63.3%, specificity of 75.3%, and accuracy of 66.7% (all p < 0.05). uHFUS provides detailed internal features of sBCC and BD, which facilitates the differentiation between sBCC and BD, and its diagnostic performance is superior to clinical diagnosis.


Bromopropylate: induction of hepatic cytochromes P450 and absence of covalent binding to DNA in mouse liver.
Oral administration of benzilic acid ester-based acaricide bromopropylate at daily doses of 3, 15, 100, and 300 mg/kg body wt to young adult male Tif:MAGf mice for 14 days caused slightly increased liver weights in the high-dose group. A dose-dependent increase of the microsomal cytochrome P450 content was accompanied by elevated ethoxycoumarin O-deethylase, ethoxyresorufin O-deethylase, pentoxyresorufin O-depentylase, and total testosterone hydroxylase activities. When compared with mice treated in parallel with the model compounds for hepatic xenobiotic metabolizing enzyme induction, phenobarbitone, and 3-methylcholanthrene, the enzyme activity changes observed with bromopropylate largely equalled those expressed in phenobarbitone-treated mice. Immunochemical studies with monoclonal antibodies against rat liver cytochrome P450 isoenzymes of the gene families 1A, 2B, 3A, and 4A confirmed that bromopropylate is a phenobarbitone-type inducer in the mouse liver. Titration of liver microsomal suspensions with bromopropylate yielded Type I substrate binding spectra. The specific amplitude was increased 1.5-fold when microsomes from bromopropylate-treated mice (300 mg/kg body wt) were used instead of control microsomes, indicating the induction of cytochromes P450 catalyzing the oxidative metabolism of the test compound. Single oral administration of 300 mg/kg body wt [14C]bromopropylate to male mice, without or following pretreatment for 14 days with 300 mg/kg body wt unlabeled bromopropylate, gave no indication for DNA binding of the test compound in the liver. This excludes a genotoxic potential via covalent DNA modification. The results suggest that, in analogy to phenobarbitone, bromopropylate acts as a tumor promotor rather than a tumor initiator in the mouse liver.


Required response time for variable air volume fume hood controllers.
This paper describes results from tests made with the aim of investigating how quickly the exhaust air flow rate through fume hoods needs to be controlled in order to prevent contaminants from leaking out of the fume hood and putting the safety of the laboratory personnel at risk. The measurements were made on a laboratory fume hood in a chemical laboratory. There were no other fume hoods in the laboratory, and the measurements were made without interference from persons entering or leaving the laboratory or walking about in it. A tracer gas method was used with the concentration of dinitrogen oxide (N(2)O) being recorded by a Foxboro Miran 101 infra-red gas analyser. In parallel with the tracer gas measurements, the air velocity through the face opening was also measured, as was the control signal to the damper controlling the air flow rate. The measurements show an increased outward leakage of tracer gas from the fume hood if the air flow rate is not re-established within 1-2 s after the sash is opened. If the delay exceeds 3 s the safety function is temporarily defeated. The measurements were made under virtually ideal conditions. Under more typical conditions, the fume hood could be exposed to various other external perturbations, which means that the control system should re-establish the correct exhaust flow more quickly than indicated by the measurement results obtained under these almost ideal conditions.


Immune mechanisms of hypertension.
Hypertension affects 30% of adults and is the leading risk factor for heart attack and stroke. Traditionally, hypertension has been regarded as a disorder of two systems that are involved in the regulation of salt-water balance and cardiovascular function: the renin-angiotensin-aldosterone system (RAAS) and the sympathetic nervous system (SNS). However, current treatments that aim to limit the influence of the RAAS or SNS on blood pressure fail in ~40% of cases, which suggests that other mechanisms must be involved. This Review summarizes the clinical and experimental evidence supporting a contribution of immune mechanisms to the development of hypertension. In this context, we highlight the immune cell subsets that are postulated to either promote or protect against hypertension through modulation of cardiac output and/or peripheral vascular resistance. We conclude with an appraisal of knowledge gaps still to be addressed before immunomodulatory therapies might be applied to at least a subset of patients with hypertension.


Seatbelt use is associated with lower risk of high-grade hepatic injury in motor vehicle crashes in a national sample.
Seatbelt use, alone and in conjunction with an airbag, is associated with lower risk of mortality, blunt abdominal trauma and kidney injury in motor vehicle crashes (MVCs). However, the effect of these protective devices on risk of severe liver injury is not well characterised. This retrospective cohort study included patient admissions with liver injuries from MVCs from the National Trauma Data Bank (NTDB), collected from 2010 to 2015 in the USA. We examined associations between injury severity and seatbelt use and airbag presence individually and in the presence of additive interaction. Secondary outcomes were mortality, complications and discharge disposition. We analysed 55 543 records from the National Trauma Data Bank. In adjusted analysis, seatbelt use alone was protective against severe (AAST VI or above) hepatic injury (risk ratio (RR) 0.79, 95% CI 0.75 to 0.84), while airbag presence alone was not (RR 1.05, 95% CI 0.8 to 1.12). The joint association of seatbelt use and airbag presence with injury severity was greater than seatbelts alone (RR 0.74, 95% CI 0.70 to 0.79), with 13% of the joint lower risk attributable to interaction (95% CI 3% to 24%). The adjusted mortality risk of those without protective devices (10.3%, n=2297) was nearly double that of patients who used a seatbelt in conjunction with a present airbag (5.3%, n=699, p<0.001). Seatbelts are associated with lower liver injury severity and are more protective with airbags present, while airbags without seatbelt use were not protective against severe injury among patients with liver injury.


Racial/ethnic differences in receipt of pelvic lymph node dissection among men with localized/regional prostate cancer.
Black and Hispanic men have a lower prostate cancer (PCa) survival rate than white men. This racial/ethnic survival gap has been explained in part by differences in tumor characteristics, stage at diagnosis, and disparities in receipt of definitive treatment. Another potential contributing factor is racial/ethnic differences in the timely and accurate detection of lymph node metastases. The current study was conducted to examine the association between race/ethnicity and the receipt of pelvic lymph node dissection (PLND) among men with localized/regional PCa. Logistic regression was used to estimate the adjusted odds of undergoing PLND among men who were diagnosed during 2000 to 2002 with PCa, who underwent radical prostatectomy or PLND without radical prostatectomy, and who were diagnosed in regions covered by the Surveillance, Epidemiology, and End Results database (n = 40,848). Black men were less likely to undergo PLND than white men (odds ratio [OR], 0.91; 95% confidence interval [CI], 0.84-0.98). When the analysis was stratified by PCa grade, black men with well differentiated PCa (OR, 0.48; 95% CI, 0.27-0.84) and poorly differentiated PCa (OR, 0.73; 95% CI, 0.60-0.89) were less likely to undergo PLND than their white counterparts, but racial differences were not observed among men with moderately differentiated PCa (OR, 0.96; 95% CI, 0.88-1.05). Among men with poorly differentiated PCa, failure to undergo PLND was associated with worse survival. Racial disparities in the receipt of PLND, especially among men with poorly differentiated PCa, may contribute to racial differences in prostate cancer survival.


The prospective contribution of childhood maltreatment to low self-worth, low relationship quality, and symptomatology across adolescence: A developmental-organizational perspective.
This research investigated the prospective contribution of childhood maltreatment to low self-worth, low relationship quality, and symptoms during adolescence. Further, the stability and cross-lagged effects of these sequelae of maltreatment were examined over time. History of maltreatment during childhood was obtained, and youth (407 maltreated, 228 nonmaltreated; 376 males, 259 females) completed 2 subsequent assessments spaced approximately 2 years apart during early-mid and mid-late adolescence. As anticipated, childhood maltreatment experiences predicted low self-worth, low relationship quality, and both internalizing and externalizing symptoms in early-mid adolescence. Beyond the stability paths of each outcome variable, significant cross-lagged effects were observed among low self-worth, low relationship quality, and internalizing symptoms across adolescence. In contrast, cross-lagged effects were not observed among adolescent externalizing symptoms. These findings support a developmental-organizational model in which childhood maltreatment creates multiple vulnerabilities that evince continuity and generate mutually influencing effects across adolescence.


MiR-140 Expression Regulates Cell Proliferation and Targets PD-L1 in NSCLC.
Programmed death ligand1(PD-L1) plays a role in the development and progression of non-small cell lung cancer (NSCLC). This study aimed to identify miRNA(s) that are responsible for regulation of expression of PD-L1 in NSCLC, and to investigate the role of PD-L1 in regulation of the cell cycle in NSCLC. We predicted the target miRNA of PD-L1, which was miR-140, using the online tools TargetScan and miBase. In NSCLC cells obtained from clinical specimens, in addition to A549 and NCI-H1650 cell cultures, western blots were used to detect the level of expression of proteins, while real-time PCR was used to determine the level of expression of PD-L1, miR-140, cyclin E, and β-actin. Transfection with miR-140 mimics, miR-140 inhibitors, and PD-L1 siRNA were conducted using commercial kits. To determine whether miR-140 directly binds PD-L1, a luciferase reporter gene with wild type or mutated PD-L1 was used. Cell viability was measured with the MTT assay, and PI staining was used for cell cycle analysis. We found low expression of miR-140 and high expression of PD-L1 and cyclin E in NSCLC cells. Over-expression of miR-140 suppressed the expression of PD-L1 by directly binding its 3' UTR, and was also associated with decreased expression of cyclin E and inhibition of cellular proliferation in A549 and NCI-H1650 cells. Inhibition of PD-L1, in the absence of manipulations to miR-140, also decreased the expression of cyclin E. We conclude that miR-140 directly suppresses PD-L1 and inhibits the miR-140/PD-L1/cyclin E pathway in NSCLC.


Factors Associated With Chronic Intestinal Inflammation Resembling Inflammatory Bowel Disease in Pediatric Intestinal Failure: A Matched Case-Control Study.
There is a subset of intestinal failure patients with associated chronic intestinal inflammation resembling inflammatory bowel disease. This study aimed to evaluate factors associated with chronic intestinal inflammation in pediatric intestinal failure. This was a single-center retrospective case-control study of children <18 years old with intestinal failure. Cases were defined by abnormal amounts of chronic intestinal inflammation on biopsies. Children with diversion colitis, eosinophilic colitis, or isolated anastomotic ulceration were excluded. Cases were matched 1:2 to intestinal failure controls based on sex, etiology of intestinal failure, and duration of intestinal failure. Multivariable conditional logistic regression was used to compare clinical factors between cases and controls, accounting for clustering within matched sets. A subgroup analysis was performed assessing factors associated with escalation of anti-inflammatory therapy. Thirty cases were identified and matched to 60 controls. On univariate analysis, longer parenteral nutrition (PN) duration (1677 vs 834 days, P = 0.03), current PN use (33.3% vs 20.0%, P = 0.037), and culture-proven bacterial overgrowth (53.3% vs 31.7%, P = 0.05) were associated with chronic intestinal inflammation. On multivariable analysis, no variable reached statistical significance. On subgroup analysis, duration of intestinal failure, location of inflammation, and worst degree of inflammation on histology were associated with escalation of therapy. PN dependence and intestinal dysbiosis are associated with chronic intestinal inflammation in children with intestinal failure. Severity of inflammation is associated with escalation of therapy. Further analysis is needed to assess these associations and the efficacy of treatments in this population.


Intra-abdominal sepsis following liver trauma.
Of 330 consecutive patients with liver trauma having a celiotomy over a 5-year period, 295 (89%) survived more than 72 hours. Of these 295, 35 (12%) developed sepsis, and 11 (31%) of these septic patients died. The sources of the sepsis in 30 of these patients included: abdominal abscesses--23, pneumonia or empyema--seven, acalculous cholecystitis--two, gangrene of right colon--two, and thigh abscess--one. In five other patients, the source of the sepsis was not found, even at autopsy. The mortality rate in the 30 patients with one or more identifiable foci of infection was 23%. In contrast, when the source of the sepsis could not be found, the mortality rate was 80% (4/5) (p less than 0.05). Factors associated with an increased incidence of abdominal abscess included: splenectomy, 75% (3/4); liver packs, 63% (5/8); 20+ units of blood, 57% (8/14); Class IV-V liver injury, 35% (8/23); 10-19 units of blood, 25% (7/28); colon injury, 19% (7/36); and open (Penrose) drainage of the abdomen, 11% (23/213). None of 82 patients without drains developed an intra-abdominal abscess. Thus early control of an identifiable source of infection provides the best results with sepsis following liver trauma. The most effective method for preventing intra-abdominal abscesses appears to be avoidance of drains in mild (Class I-II) liver injuries. The use of a closed system in the most severe injuries is still controversial and needs to be addressed in a prospective trial.


Benefits of Health Care Communication Training for Nurses Conducting Bedside Handovers: An Australian Hospital Case Study.
This study aimed to examine the effects of communication training on nurses' ability to conduct bedside handovers in hospital. Of the 26 participating nurses, 13 had recently completed specialized training in bedside handovers using the Connect, Ask, Respond, and Empathize (CARE) and Past, Present, and Future (PPF) of the patient journey and condition protocols for health care communication. The other 13 nurses did not participate in this training. Researchers videotaped and evaluated these nurses' handover practices using the Bedside Handover Evaluation Form. Nurses who had received the specific training in bedside handovers interacted with their patients to a far greater extent, asked more questions, and stated more complete information about their patient's medical journey. Nurses who participate in health care communication training on bedside handovers subsequently demonstrate a significantly better ability to lead these clinical interactions. This is evidenced by their articulation of more detailed medical information, their more respectful and multifaceted interactions with patients, and their more inclusive approach to all participants in the handover. J Contin Educ Nurs. 2018;49(7):329-336.


Longing to Belong: Hard of Hearing Young Adults' Experiences of Social Identity and Group Membership.
Studies on hard of hearing (HH) individuals have focused mostly on children's experiences in school. However, their lives as young adults have not received much attention. The present study therefore examined HH young adults' experiences of social identity and group membership. Semistructured interviews were conducted with 16 individuals (10 males, 6 females) with severe to profound hearing loss. They were from diverse cultural backgrounds. A qualitative content analysis was performed with a manifest analysis. Two categories emerged: Belonging to a Social Environment and Engaging in Important Communication. The results indicate that the HH individuals, either deliberately or unconsciously, chose to be with other HH individuals because of their longing for group membership and desire to avoid being misunderstood. The participants longed for inclusion, acceptance, and opportunities to create an inclusive social environment and to communicate with others.


Smad inhibition by the Ste20 kinase Misshapen.
The level of TGF-β/bone morphogenetic protein (BMP) signaling through Smad is tightly regulated to ensure proper embryonic patterning and homeostasis. Here we show that Smad activation by TGF-β/BMP is blocked by a highly conserved phosphorylation event in the α-helix 1 region of Smad [T312 in Drosophila Smad1 (MAD)]. α-helix 1 phosphorylation reduces Smad interaction with TGF-β/BMP receptor kinase and affects all receptor-activated Smads except Smad3. Tissue culture and transgenic studies in Drosophila further demonstrate that the biological activity of MAD is repressed by T312 phosphorylation in vivo. Through RNAi screening of the kinome, we have identified Misshapen (Msn) and the mammalian orthologs TNIK, MINK1, and MAP4K4 as the kinases responsible for α-helix 1 phosphorylation. Targeted expression of an active form of Msn in the wing imaginal disk disrupted activation of endogenous MAD by Dpp and expression of the Dpp/MAD target gene. Msn kinases belong to the Ste20 kinase family that has been shown to act as MAP kinase kinase kinase kinase (MAP4K). Our findings thus reveal a function of Msn independent of its impact on MAP kinase cascades. This Smad inhibition mechanism by Msn likely has important implications for development and disease.


Development of a centrifugal pump with thick blades.
We have developed a centrifugal blood pump with thick impeller blades (60% of pitch) to obtain a small tip clearance. An unshrouded impeller with 6 backward curved thick blades was used to reduce the dead zone between the shroud and upper casing. A streamline angle in volute was uniform in circumferential direction by continuity and angular momentum conservation. To prove the effectiveness of small tip clearance, performance and hemolysis tests were conducted on pumps with a tip clearance of 0.5, 1.5, and 2.0 mm at exit with the blade thickness of 60% of pitch, and with that of 1.0, 2.0, and 2.5 mm at exit with the thickness of 40% of pitch. The results showed that the smaller the tip clearance, the better the hydrodynamic and hemolytic performance. The best result was seen in the pump with tip clearance of 0.5 mm with a blade thickness of 60% of pitch. These results suggest that a centrifugal pump with thick blades and a small tip clearance can be a promising alternative as a cardiopulmonary bypass pump.


Synthesis and Evaluation of Antileishmanial and Cytotoxic Activity of Benzothiopyrane Derivatives.
In continuation of our efforts to identify promising antileishmanial agents based on the chroman scaffold, we synthesized several substituted 2H-thiochroman derivatives, including thiochromenes, thichromanones and hydrazones substituted in C-2 or C-3 with carbonyl or carboxyl groups. Thirty-two compounds were thus obtained, characterized, and evaluated against intracellular amastigotes of Leishmania (V) panamensis. Twelve compounds were active, with EC50 values lower than 40 µM, but only four compounds displayed the highest antileishmanial activity, with EC50 values below 10 µM; these all compounds possess a good Selectivity Index > 2.6. Although two active compounds were thiochromenes, a clear structure-activity relationship was not detected since each active compound has a different substitution pattern.


Lipase and esterase-catalyzed acylation of hetero-substituted nitrogen nucleophiles in water and organic solvents.
The lipase- and esterase-catalyzed acylations of hydroxylamine and hydrazine derivatives with octanoic acid and ethyl octanoate are described. The influence of solvent and nucleophile on the initial reaction rate was investigated for a number of free and immobilized enzymes. Initial rates were highest in water, but the overall productivity was optimal in dioxane. Octanoic acid (250 g/L) was converted for 93% into the hydroxamic acid in 36 h with only 1% (w/w) Candida antarctica lipase B (Novozym 435) in dioxane at 40 degrees C. This translates to a catalyst productivity of 68.5 g. g(-1). day(-1) and a space time yield of 149 g. L(-1). day(-1), unprecedented figures in the direct reaction of an acid with a nitrogen nucleophile in an organic solvent.


Effects of Temperature and Humidity on the Skin Permeation of Hydrophilic and Hydrophobic Drugs.
The humidity was a well-known method to hydrate the skin; however, the published data were varied, and systemic experiments in the previous papers were few. Therefore, the in vitro permeation of excised porcine ear skin by drugs with different polarities [aminopyrine (AMP), antipyrine (ANP), methylparaben (MP), and ibuprofen (IP)] was analyzed under a constant skin surface temperature with different temperatures and humidities to reveal the effects of temperature and humidity on the skin permeation enhancement effects. Applied formulations were prepared by mixing the drug and a hydrophilic vehicle containing glycerin. The disposition-distance profiles of water and the humectant glycerin in the stratum corneum were also investigated using confocal Raman microscopy. High absolute humidity (AH) significantly contributed to the high skin penetration of the hydrophilic penetrants AMP, ANP, and MP but not the hydrophobic penetrant IP. An increase in the partition parameter and a decrease in the diffusivity parameter occurred with an increase in AH, independent of drug polarity. Moreover, we found that dew condensation induced by high AH on temperature-controlled skin surface may effectively increase water content and may provide higher glycerin distribution in the skin barrier, the stratum corneum. Increasing the amount of water and hydrophilic vehicles such as glycerin in the stratum corneum may enhance the permeation of hydrophilic penetrants AMP, ANP, and MP. These data suggested a dew condensation on the skin surface induced by high AH at a constant skin surface temperature would be important to enhance hydrophilic penetrants.


Generation of airborne Listeria innocua from model floor drains.
Listeria monocytogenes can colonize floor drains in poultry processing and further processing facilities, remaining present even after cleaning and disinfection. Therefore, during wash down, workers exercise caution to avoid spraying hoses directly into drains in an effort to prevent the escape and transfer of drain microflora to food contact surfaces. The objective of this study was to examine the extent to which an inadvertent water spray into a colonized floor drain can cause the spread of airborne Listeria. Listeria innocua was used to inoculate a polyvinyl chloride model floor drain, resulting in approximately 10(8) cells per ml of phosphate-buffered saline and 10(4) attached cells per square centimeter of inner surface. Each model drain was subjected to a 2-s spray of tap water at 68.9 kPa from a distance of 1 m. Drains were sprayed while filled and again after emptying. Airborne cells were collected by using sedimentation plates containing Listeria selective agar which were placed on the floor and walls of a contained room at incremental horizontal and vertical distances of 0.6, 1.2, 2.4, or 4.0 m from the drain. Sedimentation plates were exposed for 10 min. A mechanical sampler was used to also collect air by impaction on the surface of Listeria selective agar to determine the number of cells per liter of air. The experiment was conducted in triplicate rooms for each of four replications. L. innocua was detected on sedimentation plates on the floor as far as 4.0 m from the drain and on walls as high as 2.4 m above the floor and 4 m from the drain. A 2-s spray with a water hose into a contaminated drain can cause airborne spread of Listeria, resulting in the potential for cross-contamination of food contact surfaces, equipment, and exposed product.


Healing of Osteochondral Defects Implanted with Biomimetic Scaffolds of Poly(ε-Caprolactone)/Hydroxyapatite and Glycidyl-Methacrylate-Modified Hyaluronic Acid in a Minipig.
Articular cartilage is a structure lack of vascular distribution. Once the cartilage is injured or diseased, it is unable to regenerate by itself. Surgical treatments do not effectively heal defects in articular cartilage. Tissue engineering is the most potential solution to this problem. In this study, methoxy poly(ethylene glycol)-block-poly(ε-caprolactone) (mPEG-PCL) and hydroxyapatite at a weight ratio of 2:1 were mixed via fused deposition modeling (FDM) layer by layer to form a solid scaffold. The scaffolds were further infiltrated with glycidyl methacrylate hyaluronic acid loading with 10 ng/mL of Transforming Growth Factor-β1 and photo cross-linked on top of the scaffolds. An in vivo test was performed on the knees of Lanyu miniature pigs for a period of 12 months. The healing process of the osteochondral defects was followed by computer tomography (CT). The defect was fully covered with regenerated tissues in the control pig, while different tissues were grown in the defect of knee of the experimental pig. In the gross anatomy of the cross section, the scaffold remained in the subchondral location, while surface cartilage was regenerated. The cross section of the knees of both the control and experimental pigs were subjected to hematoxylin and eosin staining. The cartilage of the knee in the experimental pig was partially matured, e.g., few chondrocyte cells were enclosed in the lacunae. In the knee of the control pig, the defect was fully grown with fibrocartilage. In another in vivo experiment in a rabbit and a pig, the composite of the TGF-β1-loaded hydrogel and scaffolds was found to regenerate hyaline cartilage. However, scaffolds that remain in the subchondral lesion potentially delay the healing process. Therefore, the structural design of the scaffold should be reconsidered to match the regeneration process of both cartilage and subchondral bone.


Structural consequences of ferroelectric nanolithography.
Domains of remnant polarization can be written into ferroelectrics with nanoscale precision using scanning probe nanolithography techniques such as piezoresponse force microscopy (PFM). Understanding the structural effects accompanying this process has been challenging due to the lack of appropriate structural characterization tools. Synchrotron X-ray nanodiffraction provides images of the domain structure written by PFM into an epitaxial Pb(Zr,Ti)O(3) thin film and simultaneously reveals structural effects arising from the writing process. A coherent scattering simulation including the superposition of the beams simultaneously diffracted by multiple mosaic blocks provides an excellent fit to the observed diffraction patterns. Domains in which the polarization is reversed from the as-grown state have a strain of up to 0.1% representing the piezoelectric response to unscreened surface charges. An additional X-ray microdiffraction study of the photon-energy dependence of the difference in diffracted intensity between opposite polarization states shows that this contrast has a crystallographic origin. The sign and magnitude of the intensity contrast between domains of opposite polarization are consistent with the polarization expected from PFM images and with the writing of domains through the entire thickness of the ferroelectric layer. The strain induced by writing provides a significant additional contribution to the increased free energy of the written domain state with respect to a uniformly polarized state.


DHPAC, a novel microtubule depolymerizing agent, suppresses angiogenesis and vasculogenic mimicry formation of human non-small cell lung cancer.
Angiogenesis and vasculogenic mimicry (VM) are the main causes of tumor metastasis and recurrence. In this study, we investigated the antiangiogenesis and anti-VM formation of a novel microtubule depolymerizing agent, DHPAC, as well as combretastatin A4 (CA4, a combretastatin derivate) in non-small-cell lung cancer (NSCLC), subsequently elucidating the underlying mechanisms. In human umbilical vein endothelial cells (HUVECs), DHPAC could enter cells and inhibit proliferation, migration, and angiogenesis in the presence and absence of conditioned medium from H1299 cells. Interestingly, the inhibition was enhanced under the stimulation of the conditioned medium. Under hypoxia or normoxia, DHPAC suppressed signal transducer and activator of transcription 3 phosphorylation and reduced vascular endothelial growth factor (VEGF) expression and secretion from HUVECs, thus impeding the activation of the downstream signal transduction pathway of VEGF/VEGFR2. However, JNK inhibitors reversed the inhibitory effect of DHPAC on the angiogenesis, suggesting that DHPAC regulated angiogenesis through activating JNK. In H1299 cells, DHPAC could inhibit proliferation, migration, invasion, and the formation of VM. In addition, DHPAC inhibited the phosphorylation of FAK and AKT and decreased the expressions of VEGF, matrix metalloproteinase 2 (MMP2), MMP9 and Laminin 5, suggesting that DHPAC inhibited VM formation via the FAK/AKT signaling pathway. In addition, CA4 showed a similar effect as DHPAC against angiogenesis and VM formation. These new findings support the use of microtubule destabilizing agents as a promising strategy for cancer therapy.


Prevalence of Metabolic Syndrome and Its Associated Factors among Vegetarians in Malaysia.
The prevalence and factors associated with metabolic syndrome (MetS) remain unknown in Malaysian vegetarians. This cross-sectional study aimed to determine the prevalence of MetS among vegetarians in Kuala Lumpur and Selangor and its associated factors. The data on socio-demographic characteristics, vegetarianism practises, lifestyle behaviours, body weight, height, waist circumference (WC), systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting blood glucose (FBG), and blood lipid profiles were collected from 273 vegetarians. A majority of the respondents were lacto-ovo vegetarians (44.0%), females (64.8%) and Chinese (54.9%). The prevalence of MetS was 24.2%. High BP (48.7%) and high WC (43.6%) were the most common MetS components. Females had lower WC, SBP, DBP, FBG, TG and higher HDL-c (p < 0.05) as compared to males. Multiple logistic regression analysis showed that being overweight and obese (Odds Ratio (OR) = 7.74, 95% Confidence Interval (CI): 4.04⁻14.82) was the main risk factor of MetS after being adjusted for sex and age. This study found that one in four vegetarians had MetS. An intervention programme should be developed to reduce Body Mass Index (BMI) among vegetarians, especially among those who are found to be overweight and obese.


Coexistent anti-GFAP and anti-MOG antibodies presenting with isolated meningitis and papillitis: more support for overlapping pathophysiology.
Anti-myelin oligodendrocyte glycoprotein (MOG)-associated disorders are heterogeneous and associated predominantly with central nervous system demyelination. Anti-glial fibrillar acidic protein (GFAP) conditions are much rarer and involve meningoencephalomyelitis with papillitis in addition to characteristic imaging findings and are generally a severe condition. Multiple autoantibodies can exist in patients and may support overlapping pathophysiological mechanisms. The co-occurrence of MOG and GFAP antibodies, however, is rare, with only two cases previously reported. A 53-year-old man presented with headache and fevers, with quick resolution, though with the later development of asymptomatic papillitis. He had a full recovery without the need for immunotherapy. He underwent extensive investigations and was found to have both anti-GFAP and anti-MOG antibodies in the cerebrospinal fluid. Extensive other immunological and infectious investigations were negative. Imaging was largely unremarkable. This is the third case of overlapping anti-GFAP and anti-MOG antibody-associated syndrome of self-limited lymphocytic meningitis, serving to expand the phenotype. Clinicians should consider testing for GFAP and MOG antibodies in otherwise unexplained meningitis, particularly with associated papillitis. This case may also help provide future insights into the pathophysiology of each condition.


Sigma-1 receptor maintains ATAD3A as a monomer to inhibit mitochondrial fragmentation at the mitochondria-associated membrane in amyotrophic lateral sclerosis.
Organelle contact sites are multifunctional platforms for maintaining cellular homeostasis. Alternations of the mitochondria-associated membranes (MAM), one of the organelle contact sites where the endoplasmic reticulum (ER) is tethered to the mitochondria, have been involved in the pathogenesis of neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). However, the detailed mechanisms through which MAM integrity is disrupted in ALS have not been fully elucidated. Here, we examined whether AAA ATPase domain-containing protein 3A (ATAD3A), a mitochondrial membrane AAA ATPase accumulating at the MAM, is involved in ALS. We found that sigma-1 receptor (σ1R), an ER-resident MAM protein causative for inherited juvenile ALS, required ATAD3A to maintain the MAM. In addition, σ1R retained ATAD3A as a monomer, which is associated with an inhibition of mitochondrial fragmentation. ATAD3A dimerization and mitochondrial fragmentation were significantly induced in σ1R-deficient or SOD1-linked ALS mouse spinal cords. Overall, these observations indicate that MAM induction by σ1R depends on ATAD3A and that σ1R maintains ATAD3A as a monomer to inhibit mitochondrial fragmentation. Our findings suggest that targeting σ1R-ATAD3A axis would be promising for a novel therapeutic strategy to treat mitochondrial dysfunction in neurological disorders, including ALS.


Development of oxidoreductases for amino acid quantification and mutagenesis techniques for heterologous soluble expression: screening and selection strategies.
The high stereo- and substrate specificities of enzymes have been utilized for microdetermination of amino acids. Here, I review the discovery of l-Arg oxidase from Pseudomonas sp. TPU 7192, l-Lys oxidase/decarboxylase from Burkholderia sp. AIU 395, and enzymes showing apparent l-His oxidase activity from Achromobacter sp. TPU 5009. I also discuss screening and uses of the selective enzymes for microdetermination of amino acids. In addition, functional modifications of l-amino acid oxidase/monooxygenase from Pseudomonas sp. AIU 813, l-Trp dehydrogenase from Nostoc punctiforme ATCC 29133, and l-Lys ε-oxidase from Marinomonas mediterranea NBRC 103028 by directed evolution are reviewed. Finally, I review the rational identification of aggregation hotspots based on secondary structure and amino acid hydrophobicity-this process enables the wider use of natural enzymes.


Is Primary Angioplasty the Best Treatment for AMI in the Elderly?
The elderly, particularly those over 80, are the fastest growing component of the population. Coronary artery disease accounts for 44% of all deaths in the elderly. Age is also one of the strongest predictors of mortality from acute myocardial infarction (AMI) and in those that survive, long term outcome is worse. In part, the poor inhospital mortality is due to difficulty in diagnosis, but is also likely to be caused by the widespread reluctance to use reperfusion therapy to treat the elderly. Reperfusion therapy has been shown to be equally effective in the elderly, despite an overall increased mortality. The results of randomized trials comparing thrombolysis to angioplasty show an advantage of primary angioplasty over thrombolysis. In the Global Use of Strategies to Open Occluded coronary Arteries in Acute Coronary Syndromes (GUSTO) IIb trial, the advantage was noted in all age groups, including the elderly. The Primary Angioplasty in Myocardial Infarction (PAMI) trial supports these findings. The trials also suggest that the risks are lower with angioplasty than thrombolysis, with a significant lower risk of stroke. Today, with improved outcomes using stents and glycoprotein IIb/IIIa agents, the advantages of primary angioplasty may be even greater than those reported in prior trials. The available data strongly support the use of primary angioplasty in the elderly as an effective reperfusion therapy and, due to improved safety and greater efficacy, should be the preferred treatment in the elderly. (c)1999 by CVRR, Inc.


Treatment of hepatocellular carcinoma in elderly patients.
The aim of this study was to compare the survival in elderly hepatocellular carcinoma (HCC) patients treated with curative modalities (radiofrequency ablation (RFA), percutaneous ethanol injection (PEIT) and surgery) to those treated with transcatheter arterial chemoembolization (TACE) and supportive care. Medical records of patients with HCC older than 75 years who had visited a single tertiary medical center from January 2000 to December 2011 were reviewed (n = 58). Multivariable-adjusted hazard ratios (HR) for mortality with 95% confidence intervals (CI) were estimated using Cox proportional hazard models. Twenty-nine patients were treated by TACE, 19 patients by supportive care, and 10 patients by curative treatment (four by PEIT, three by surgery and three by RFA).Variables associated with increased survival were better Child-Pugh class and lower TNM stage. Treatment with curative intent showed significant survival benefit compared to TACE (HR for mortality, 0.10; 95% CI, 0.01-0.95). In a subgroup analysis among patients with resectable HCC, supportive care showed significantly worse survival over TACE (HR for mortality, 6.47; 95% CI, 2.14-19.56) and curative intent (HR for mortality, 16.23; 95% CI, 1.92-136.83). Curative treatment seems to have a better survival benefit in comparison with other treatment modalities in elderly HCC patients.


Comparison of quality of life and mental health among elderly people in rural and suburban areas, Thailand.
This community based cross-sectional study design assessed the quality of life, mental and physical health among people aged > or = 60 years living in rural and suburban areas of northern Thailand. A cluster random sampling technique was used. The instruments used to assess quality of life were the Thai General Health Questionnaire (Thai-28), the WHO Quality of Life Assessment in Thai (WHOQOL-BREF-THAI), and a history and physical examination. The validity and reliability of the 2 written instruments (Thai-28 and WHOQOL-BREF-THAI) were detected and the Cronbach's alpha coefficient was 0.84 for the WHOQOL-BREF-THAI, and 0.94 for the Thai GHQ-28. The face-to face interview were conducted by trained interviewers. A chi-square test was used to determine significant differences at alpha = 0.05. Two hundred forty-seven subjects were recruited into the study, of which 225 were used for analysis. Forty-eight point five percent and 51.5% of subjects were from rural and semi-urban areas, respectively. Forty-five point three percent were males; the main age group was 70-79 years old (46.5%). The subjects from suburban areas had a higher quality of life in aspect to physical health (p = 0.011), mental health (p = 0.025), and social relationships (p = 0.012). Social relationships among females from difference areas were significantly different (p = 0.01). Subjects from rural areas had better mental health than those from suburban (p = 0.0001). Living in a suburban area had both positive and negative associations with quality of life that need to be further clarified to develop an elderly health care model for the community.


RUNX1/CEBPA Mutation in Acute Myeloid Leukemia Promotes Hypermethylation and Indicates for Demethylation Therapy.
Acute myeloid leukemia (AML) is a rapidly progressing heterogeneous disease with a high mortality rate, which is characterized by hyperproliferation of atypical immature myeloid cells. The number of AML patients is expected to increase in the near future, due to the old-age-associated nature of AML and increased longevity in the human population. RUNX1 and CEBPA, key transcription factors (TFs) of hematopoiesis, are frequently and independently mutated in AML. RUNX1 and CEBPA can bind TET2 demethylase and attract it to their binding sites (TFBS) in cell lines, leading to DNA demethylation of the regions nearby. Since TET2 does not have a DNA-binding domain, TFs are crucial for its guidance to target genomic locations. In this paper, we show that RUNX1 and CEBPA mutations in AML patients affect the methylation of important regulatory sites that resulted in the silencing of several RUNX1 and CEBPA target genes, most likely in a TET2-dependent manner. We demonstrated that hypermethylation of TFBS in AML cells with RUNX1 mutations was associated with resistance to anticancer chemotherapy. Demethylation therapy restored expression of the RUNX1 target gene, BIK, and increased sensitivity of AML cells to chemotherapy. If our results are confirmed, mutations in RUNX1 could be an indication for prescribing the combination of cytotoxic and demethylation therapies.


Pharmacotherapy of actinic keratosis.
Actinic keratosis (AK) represents the initial intraepidermal manifestation of abnormal keratinocyte proliferation with the potential of progression to squamous cell carcinoma (SCC). When in limited numbers, clinically visible AKs are treated individually with ablative and/or surgical procedures (lesion-directed treatment), while multiple and sublinical AKs are treated with field-directed therapies that use ablative, nonablating and other topically applied treatment modalities. Owing to difficulties in predicting which AK will progress to SCC, the general rule is to treat all AKs. The goals of treatment are to eliminate the AKs, minimizing their risk of progression to invasive SCC, while pursuing good cosmetic outcomes. Prevention is the most important treatment modality for AKs. Avoidance of sun and artificial sources of ultraviolet light, applying sunscreen and self-examination are among the most effective preventive measures. Chemopreventive modalities such as retinoids, 2-(Difluoromethyl)-dl-ornithine (DFMO), perillyl alcohol, T4 endonuclease V, and dl-alpha-tocopherol are described. Lesion-directed treatment modalities include cryotherapy, surgery and electrodessication with or without curettage. Field-directed treatment modalities include nonablative and ablative laser resurfacing, dermabrasion, chemical peels, topical immunomodulators (imiquimod, 5-fluorouracil and diclofenac) and photodynamic therapy. And, finally, newer and investigational treatment modalities such as ingenol mebutate, resiquimod and betulinic acid are also being discussed.


Critical behavior of a one-dimensional diffusive epidemic process.
We investigate the critical behavior of a one-dimensional diffusive epidemic propagation process by means of a Monte Carlo procedure. In the model, healthy (A) and sick (B) individuals diffuse on a lattice with diffusion constants D(A) and D(B), respectively. According to a Wilson renormalization calculation, the system presents a second-order phase transition between a steady reactive state and a vacuum state, with distinct universality classes for the cases D(A)=D(B) and D(A)<D(B). A first-order transition has been conjectured for D(A)>D(B). In this work we perform a finite size scaling analysis of order parameter data at the vicinity of the critical point in dimension d=1. Our results show no signature of a first-order transition in the case of D(A)>D(B). A finite size scaling typical of second-order phase transitions fits well the data from all three regimes. We found that the correlation exponent nu=2 as predicted by field-theoretical arguments. Estimates for beta/nu are given for all relevant regimes.


Classification of FLT3 inhibitors and SAR analysis by machine learning methods.
FMS-like tyrosine kinase 3 (FLT3) is a type III receptor tyrosine kinase, which is an important target for anti-cancer therapy. In this work, we conducted a structure-activity relationship (SAR) study on 3867 FLT3 inhibitors we collected. MACCS fingerprints, ECFP4 fingerprints, and TT fingerprints were used to represent the inhibitors in the dataset. A total of 36 classification models were built based on support vector machine (SVM), random forest (RF), eXtreme Gradient Boosting (XGBoost), and deep neural networks (DNN) algorithms. Model 3D_3 built by deep neural networks (DNN) and TT fingerprints performed best on the test set with the highest prediction accuracy of 85.83% and Matthews correlation coefficient (MCC) of 0.72 and also performed well on the external test set. In addition, we clustered 3867 inhibitors into 11 subsets by the K-Means algorithm to figure out the structural characteristics of the reported FLT3 inhibitors. Finally, we analyzed the SAR of FLT3 inhibitors by RF algorithm based on ECFP4 fingerprints. The results showed that 2-aminopyrimidine, 1-ethylpiperidine,2,4-bis(methylamino)pyrimidine, amino-aromatic heterocycle, [(2E)-but-2-enyl]dimethylamine, but-2-enyl, and alkynyl were typical fragments among highly active inhibitors. Besides, three scaffolds in Subset_A (Subset 4), Subset_B, and Subset_C showed a significant relationship to inhibition activity targeting FLT3.


Deaths following trauma: an audit of performance.
The TRISS methodology was applied to identify preventable trauma deaths in a retrospective audit of 267 (M = 0.908) patients admitted to a teaching hospital through the resuscitation room of its accident and emergency department during a 1-year period. No unexpected survivors were identified; of the 44 deaths (Z = 5.35), 25 (56.8%) were judged preventable by the TRISS method. Those deaths deemed preventable were subjected to peer review by a panel of six consultants. The findings are discussed in respect of recommendations made for UK trauma centre provision by the Working Party Report of the Royal College of Surgeons of England on the management of patients with major injuries.


The soluble extracellular domain of E-cadherin interferes with EPEC adherence via interaction with the Tir:intimin complex.
Enteropathogenic Escherichia coli (EPEC) causes watery diarrhea when colonizing the surface of enterocytes. The translocated intimin receptor (Tir):intimin receptor complex facilitates tight adherence to epithelial cells and formation of actin pedestals beneath EPEC. We found that the host cell adherens junction protein E-cadherin (Ecad) was recruited to EPEC microcolonies. Live-cell and confocal imaging revealed that Ecad recruitment depends on, and occurs after, formation of the Tir:intimin complex. Combinatorial binding experiments using wild-type EPEC, isogenic mutants lacking Tir or intimin, and E. coli expressing intimin showed that the extracellular domain of Ecad binds the bacterial surface in a Tir:intimin-dependent manner. Finally, addition of the soluble extracellular domain of Ecad to the infection medium or depletion of Ecad extracellular domain from the cell surface reduced EPEC adhesion to host cells. Thus, the soluble extracellular domain of Ecad may be used in the design of intervention strategies targeting EPEC adherence to host cells.-Login, F. H., Jensen, H. H., Pedersen, G. A., Amieva, M. R., Nejsum, L. N. The soluble extracellular domain of E-cadherin interferes with EPEC adherence via interaction with the Tir:intimin complex.


Percutaneous closure of a large patent ductus arteriosus in a preterm newborn weighing 1400 g without using arterial sheath: an innovative technique.
Percutaneous closure of patent ductus arteriosus is well established in infants weighing >5 kg, but data regarding outcome of preterm especially very low birth weight infants is minimal. Although surgical ligation of patent ductus arteriosus is the preferred and well-accepted modality of treatment after failure of drug therapy in preterm infants, it has also got its own demerits in such a small and fragile subset. Device closure in infants weighing <1.5 kg is rarely attempted because of high chances of complications, especially acute arterial injury due to the arterial sheath. We received a 1.4-kg ventilator-dependent infant for closure of large patent ductus arteriosus. Percutaneous closure of patent ductus arteriosus was done successfully and the infant was discharged on room air with a weight of 1.8 kg. We present here an innovative technique in which successful patent ductus arteriosus device closure was done in a 1.4-kg infant without using arterial sheath.


Strain differences in the diabetogenic activity of streptozotocin in mice.
We have already reported that slowly progressive non-insulin-dependent diabetes mellitus (NIDDM) is produced by a single i.p. injection of a subdiabetogenic dose (100 mg/kg) of streptozotocin (STZ) to 8-week-old male ICR mice. The aim of the present study was to clarify whether or not the progressive NIDDM is induced in ddY, BALB/c, C57BL/6 and ICR mice by the administration of STZ. Eight-week-old male mice of the 4 different strains were administered a single i.p. injection of STZ at various doses (ICR, ddY and BALB/c: 100-200 mg/kg; C57BL/6: 75-150 mg/kg). Among the ddY, BALB/c and C57BL/6 mice, a time course-related rise in non-fasting serum glucose levels throughout the observation period of 1-12 weeks after STZ administration was only induced in the 125 mg/kg STZ ddY and 100 mg/kg STZ ICR mice. In contrast with serum glucose levels, the area of islets and the percentage of the relative number of insulin-immunoreactive cells (beta-cells) to glucagon-immunoreactive cells (alpha-cells) in the 100 mg/kg STZ ICR and 125 mg/kg STZ ddY mice continued to decrease gradually over time. In addition, in low dose STZ mice of both strains, the insulin response to glucose stimulation was extremely impaired over time, although non-fasting serum insulin levels were maintained near normal levels. The rate of the progression of diabetes was faster in the 125 mg STZ ddY mice than in the 100 mg/kg STZ ICR mice.


Mechanical Thrombectomy Versus Best Medical Treatment in the Late Time Window in Non-DEFUSE-Non-DAWN Patients: A Multicenter Cohort Study.
We assessed the efficacy and safety of mechanical thrombectomy (MT) in adult stroke patients with anterior circulation large vessel occlusion presenting in the late time window not fulfilling the DEFUSE-3 (Thrombectomy for Stroke at 6 to 16 Hours With Selection by Perfusion Imaging trial) and DAWN (Thrombectomy 6 to 24 Hours After Stroke With a Mismatch Between Deficit and Infarct trial) inclusion criteria. Cohort study of adults with anterior circulation large vessel occlusion admitted between 6 and 24 hours after last-seen-well at 5 participating Swiss stroke centers between 2014 and 2021. Mismatch was assessed by computer tomography or magnetic resonance imaging perfusion with automated software (RAPID or OLEA). We excluded patients meeting DEFUSE-3 and DAWN inclusion criteria and compared those who underwent MT with those receiving best medical treatment alone by inverse probability of treatment weighting using the propensity score. The primary efficacy end point was a favorable functional outcome at 90 days, defined as a modified Rankin Scale score shift toward lower categories. The primary safety end point was symptomatic intracranial hemorrhage within 7 days of stroke onset; the secondary was all-cause mortality within 90 days. Among 278 patients with anterior circulation large vessel occlusion presenting in the late time window, 190 (68%) did not meet the DEFUSE-3 and DAWN inclusion criteria and thus were included in the analyses. Of those, 102 (54%) received MT. In the inverse probability of treatment weighting analysis, patients in the MT group had higher odds of favorable outcomes compared with the best medical treatment alone group (modified Rankin Scale shift: acOR, 1.46 [1.02-2.10]; P=0.04) and lower odds of all-cause mortality within 90 days (aOR, 0.59 [0.37-0.93]; P=0.02). There were no significant differences in symptomatic intracranial hemorrhage (MT versus best medical treatment alone: 5% versus 2%, P=0.63). Two out of 3 patients with anterior circulation large vessel occlusion presenting in the late time window did not meet the DEFUSE-3 and DAWN inclusion criteria. In these patients, MT was associated with higher odds of favorable functional outcomes without increased rates of symptomatic intracranial hemorrhage. These findings support the enrollment of patients into ongoing randomized trials on MT in the late window with more permissive inclusion criteria.


Pleiotropic control of secondary metabolism and morphological development by KsbC, a butyrolactone autoregulator receptor homologue in Kitasatospora setae.
The γ-butyrolactone autoregulator signaling cascades have been shown to control secondary metabolism and/or morphological development among many Streptomyces species. However, the conservation and variation of the regulatory systems among actinomycetes remain to be clarified. The genome sequence of Kitasatospora setae, which also belongs to the family Streptomycetaceae containing the genus Streptomyces, has revealed the presence of three homologues of the autoregulator receptor: KsbA, which has previously been confirmed to be involved only in secondary metabolism; KsbB; and KsbC. We describe here the characterization of ksbC, whose regulatory cluster closely resembles the Streptomyces virginiae barA locus responsible for the autoregulator signaling cascade. Deletion of the gene ksbC resulted in lowered production of bafilomycin and a defect of aerial mycelium formation, together with the early and enhanced production of a novel β-carboline alkaloid named kitasetaline. A putative kitasetaline biosynthetic gene cluster was identified, and its expression in a heterologous host led to the production of kitasetaline together with JBIR-133, the production of which is also detected in the ksbC disruptant, and JBIR-134 as novel β-carboline alkaloids, indicating that these genes were biosynthetic genes for β-carboline alkaloid and thus are the first such genes to be discovered in bacteria.


Oridonin-induced mitochondria-dependent apoptosis in esophageal cancer cells by inhibiting PI3K/AKT/mTOR and Ras/Raf pathways.
Oridonin, an active diterpenoid isolated from Rabdosia rubescens, has been reported for its antitumor activity on several cancers. However, its effect on human esophageal cancer remains unclear. In this study, we demonstrated that oridonin could inhibit the growth of human esophageal cancer cells both in vitro and in vivo. Oridonin not only suppressed the proliferation, but also induced cell cycle arrest and mitochondrial-mediated apoptosis in KYSE-30, KYSE-150, and EC9706 cells with dose-dependent manner. Further mechanism studies revealed that oridonin led cell cycle arrest in esophageal cancer cells via downregulating cell cycle-related proteins, such as cyclin B1 and CDK2, while upregulating p53 and p21. Oridonin also increased proapoptotic protein Bax and reduced antiapoptotic protein Bcl-2, as well as the increased expression of cleaved caspase-3, -8, and -9. In addition, oridonin treatment could significantly inhibit the PI3K/Akt/mTOR and Ras/Raf signaling pathway. In vivo results further demonstrated that oridonin treatment markedly inhibited tumor growth in the esophageal cancer xenograft mice model. Taken together, these results suggest that oridonin may be a potential anticancer agent for the treatment of esophageal cancer.


Validation of the Brazilian version of the 'Spanish Burnout Inventory' in teachers.
To assess factorial validity and internal consistency of the Brazilian version of the 'Spanish Burnout Inventory' (SBI). The translation process of the SBI into Brazilian Portuguese included translation, back translation, and semantic equivalence. A confirmatory factor analysis was carried out using a four-factor model, which was similar to the original SBI. The sample consisted of 714 teachers working in schools in the metropolitan area of the city of Porto Alegre, Southern Brazil, in 2008. The instrument comprises 20 items and four subscales: Enthusiasm towards job (5 items), Psychological exhaustion (4 items), Indolence (6 items), and Guilt (5 items). The model was analyzed using LISREL 8. Goodness-of-Fit statistics showed that the hypothesized model had adequate fit: chi2(164) = 605.86 (p<0.000); Goodness-of-Fit Index = 0.92; Adjusted Goodness-of-Fit Index = 0.90; Root Mean Square Error of Approximation = 0.062; Nonnormed Fit Index = 0.91; Comparative Fit Index = 0.92; and Parsimony Normed Fit Index = 0.77. Cronbach's alpha measures for all subscales were higher than 0.70. The study showed that the SBI has adequate factorial validity and internal consistency to assess burnout in Brazilian teachers.


Unrecognized fatalities related to colchicine in hospitalized patients.
Colchicine is commonly used for the treatment of gout and occasionally for other inflammatory diseases. It has a narrow therapeutic index and the potential for severe or fatal toxicity. We sought to determine (1) the frequency of colchicine toxicity among hospitalized patients taking colchicine who died during an admission, (2) the likelihood that colchicine contributed to death, (3) whether patients were taking interacting medications that could have contributed to toxicity, and (4) whether colchicine dosing among these patients adhered to established guidelines. We conducted an IRB-approved, retrospective chart review at an urban, tertiary care, 1228-bed, university hospital. Subjects included hospitalized patients who received colchicine and died in hospital between 1 January 2000 and 28 February 2007. We reviewed charts for signs and symptoms of colchicine toxicity. An expert panel reviewed each case and classified the likelihood of colchicine toxicity, the likelihood of a causal role of colchicine in the death using the WHO classification system, and the appropriateness of colchicine dosing. Thirty-seven hospitalized patients who died during the 86-month study period received colchicine. Toxicity was unlikely in 20/37, possible in 8/37, likely in 5/37, and certain in 4/37. A contributing role for colchicine in causing death was unlikely in 24/37, possible in 7/37, likely in 3/37, and certain in 3/37. Colchicine doses (based on creatinine clearance) exceeded the accepted range for 12 patients, including 10 of 17 cases of toxicity and 8 of 13 cases of death classified as possible or higher. Seventeen patients received interacting medications, including 8 of 17 cases of toxicity and 8 of 13 cases of death classified as possible or higher. Colchicine toxicity was frequent in this cohort and may have contributed to about one-third of the deaths. Inappropriate dosing of colchicine occurred frequently and was related to toxicity and death.


Synchronization waves in geometric networks.
We report synchronization of networked excitable nodes embedded in a metric space, where the connectivity properties are mostly determined by the distance between units. Such a high clustered structure, combined with the lack of long-range connections, prevents full synchronization and yields instead the emergence of synchronization waves. We show that this regime is optimal for information transmission through the system, as it enhances the options of reconstructing the topology from the dynamics. Measurements of topological and functional centralities reveal that the wave-synchronization state allows detection of the most structurally relevant nodes from a single observation of the dynamics, without any a priori information on the model equations ruling the evolution of the ensemble.


Ethnic differences in incidence of sudden infant death syndrome in Birmingham.
Among the 45,204 live births in Birmingham in the three calendar years 1981-3, there were 218 postneonatal deaths, giving a postneonatal mortality rate of 4.82 per 1000 live births. Postneonatal mortality rates were 4.22 for whites, 5.91 for Asians (relative risk 1.26, 95% confidence interval (CI) 1.04 to 1.53) and 8.20 for Afro-Caribbeans (relative risk 1.78, 95% CI 1.25 to 2.55). Among Asians malformations were common (3.36) and sudden infant death syndrome rare (1.18), in contrast to Afro-Caribbeans among whom the rates were 0.66 and 5.25, respectively. Logistic regression analysis demonstrated a significantly lower risk of sudden infant death syndrome (SIDS) in Asians and significantly raised risks of SIDS in very low birthweight babies and those with unemployed parent(s). Ethnic differences persisted after controlling for maternal age, social class, and birth weight. Studies of sociocultural differences in child rearing practices are needed and may uncover important aetiological factors of sudden infant death syndrome.


Tumor necrosis factor alpha activates human immunodeficiency virus type 1 through induction of nuclear factor binding to the NF-kappa B sites in the long terminal repeat.
Expression of human immunodeficiency virus type 1 (HIV-1) can be activated in a chronically infected T-cell line (ACH2 cells) by a cytokine, human tumor necrosis factor alpha (TNF-alpha). TNF-alpha treatment of ACH2 cells resulted in an increase in steady-state levels of HIV RNA and HIV transcription. Gel mobility shift assays demonstrated that the transcriptional activation of the HIV long terminal repeat (LTR) by TNF-alpha was associated with the induction of a nuclear factor(s) binding to the NF-kappa B sites in the LTR. Deletion of the NF-kappa B sites from the LTR eliminated activation by TNF-alpha in T cells transfected with plasmids in which the HIV LTR directed the expression of the bacterial chloramphenicol acetyltransferase gene. Thus, TNF-alpha appears to activate HIV RNA and virus production by ACH2 cells through the induction of transcription-activating factors that bind to the NF-kappa B sequences in the HIV LTR.


Esophageal perforations after anterior cervical surgery.
An esophageal perforation after anterior cervical surgery is an uncommon but well recognized complication. During the past 25 years, 44 patients have presented to Craig Hospital (Rocky Mountain Regional Spinal Injury Center) with esophageal perforations; this is the largest series reported to date. There were 34 patients whose esophageal injury was related to the operations performed for cervical fractures, of which 28 patients had plate and screw fixation. The most frequently occurring clinical symptoms were that of neck and throat pain, odynophagia, dysphagia, hoarseness, and aspiration. The most common clinical findings were an elevated temperature, localized induration and neck tenderness, crepitus or subcutaneous air in the neck and anterior chest wall, an unexplained tachycardia, and blood in the nasogastric tube. Imaging studies indicated an esophageal injury in only 32 (72.7%) patients. Twenty-two patients experienced cervical osteomyelitis or an abscess of the neck. Nonoperative treatment is fraught with a high mortality, and 42 patients required surgical repair of their esophageal injury. The length of hospital stay averaged 253 days. Successful management of esophageal perforations depends on the physicians' awareness of the causes, prompt recognition of the symptoms and clinical findings, and immediate institution of treatment.


[Sex- and age-related peculiarities of the morphometric characteristics of the lower part of facial skull in the adult persons].
Age-related changes and sexual differences of some of the morphometric characteristics of the lower part of facial skeleton were studied. It was shown that the height of the face lower part in the skulls with intact orthognathic occlusion remained unchanged during the age period from 22 to 70 years. In both men and women with full dentition and orthognathic occlusion aged from 22 to 35 years, the significant decrease was observed in the angle of the ramus of mandible due to the bone tissue formation in this region. The parameters of the height of the ramus of mandible, the projection height of the mandibular condylar process, and the least width of the mandibular ramus in men and women have significant age- and sex-related differences.


[Long-term study of gastroduodenal ulcer perforation].
One hundred forty-four patients, peptic (129 males and 15 females) treated for peptic ulcer perforation between 1972 and 1988 were reviewed. All were treated surgically, and in 28 the ulcer was also treated. The mean perforation time before treatment was 14 +/- 12.3 hours. The immediate postoperative results and long-term evolution were evaluated on the basis of the medical history, follow-up check-ups and home questionnaires. The were post-operative complications in 33 (23%) of the 137 patients who survived surgery; there was no difference in morbidity between the group in which only Closure and Epiploplasty (group C + E) were performed and group CD, where some type of definitive surgery was added, although the seven deaths belonged to the former. Of the 104 patients who were evaluated on a long-term basis (follow-up period of 55 +/- 44 months), poor results were obtained in 58 of the 82 belonging to group C + E and in four of the 28 in group CD, with a total of 13 re-operations (12 and one, respectively). Only a previous ulcer history dating from over three months had any effect on the appearance of recurrences in group C + E. We recommend performing a VGP within the first six hours as the preferred technique for pyloric or juxtapyloric perforations in patients with a previous ulcer history exceeding three months, since the rate of cure is satisfactory and there are few if any complications.


Evaluation of the efficacy of a peroxygen disinfectant-filled footmat for reduction of bacterial load on footwear in a large animal hospital setting.
OBJECTIVE-To compare the efficacy of a peroxygenbased disinfectant used in footbaths with the efficacy of the same disinfectant used in footmats for reducing bacterial contamination of footwear in a large animal hospital. DESIGN-Prospective study. SAMPLE POPULATION-Bacteria recovered from the soles of rubber boots after experimental microbial contamination and exposure to disinfectant solutions or water (water-treated control boots) or no treatment (untreated control boots). PROCEDURES-Investigators contaminated boots by walking through soiled animal bedding. Swab samples were collected from the sole of 1 untreated boot (right or left); the other boot was treated as investigators stepped through a disinfectant-filled footbath, a disinfectant-filled footmat, or water-filled footmat. Samples were collected 10 minutes after each treatment. Differences in numbers of bacteria recovered from treated and untreated boots were analyzed. RESULTS-Mean bacterial counts from peroxygentreated boots were 1.3 to 1.4 log(10) lower (95.4% to 99.8%) than the counts from untreated boots. Results were similar for footmat- and footbath-treated boots. In contrast, there were no statistically detectable differences in mean bacterial counts in samples collected from water-treated or untreated boots. CONCLUSIONS AND CLINICAL RELEVANCE-Results suggest that footmats and footbaths containing peroxygenbased disinfectant are effective in reducing bacterial contamination on the soles of boots when used in conditions representative of large animal hospitals. Similar results were achieved with use of either footmats or footbaths. The use of footbaths and footmats containing effective disinfectants may help decrease the risk for spread of nosocomial infection but should not be expected to sterilize footwear.


Fast synthesis of 1,3-DAG by Lecitase® Ultra-catalyzed esterification in solvent-free system.
Lecitase® Ultra, a phospholipase, was explored as an effective biocatalyst for direct esterification of glycerol with oleic acid to produce 1,3-DAG. Experiments were carried out in batch mode, and optimal reaction conditions were evaluated. In comparison with several organic solvent mediums, the solvent-free system was found to be more beneficial for this esterification reaction, which was further studied to investigate the reaction conditions including oleic acid/glycerol mole ratio, temperature, initial water content, enzyme load, and operating time. The results showed that Lecitase® Ultra catalyzed a fast synthesis of 1,3-DAG by direct esterification in a solvent-free medium. Under the optimal reaction conditions, a short reaction time 1.5 h was found to achieve the fatty acid esterification efficiency of 80.3 ± 1.2% and 1,3-DAG content of 54.8 ± 1.6 wt% (lipid layer of reaction mixture mass). The reusability of Lecitase® Ultra was evaluated via recycling the excess glycerol layer in the reaction system. DAG in the upper lipid layer of reaction mixture was purified by molecular distillation and the 1,3-DAG-enriched oil with a purity of about 75 wt% was obtained.Practical applications: The new Lecitase® Ultra catalyzed process for production of 1,3-DAG from glycerol and oleic acid described in this study provides several advantages over conventional methods including short reaction time, the absence of a solvents and a high product yield.


Gene drive for population genetic control: non-functional resistance and parental effects.
Gene drive is a natural process of biased inheritance that, in principle, could be used to control pest and vector populations. As with any form of pest control, attention should be paid to the possibility of resistance evolving. For nuclease-based gene drive aimed at suppressing a population, resistance could arise by changes in the target sequence that maintain function, and various strategies have been proposed to reduce the likelihood that such alleles arise. Even if these strategies are successful, it is almost inevitable that alleles will arise at the target site that are resistant to the drive but do not restore function, and the impact of such sequences on the dynamics of control has been little studied. We use population genetic modelling of a strategy targeting a female fertility gene to demonstrate that such alleles may be expected to accumulate, and thereby reduce the reproductive load on the population, if nuclease expression per se causes substantial heterozygote fitness effects or if parental (especially paternal) deposition of nuclease either reduces offspring fitness or affects the genotype of their germline. All these phenomena have been observed in synthetic drive constructs. It will, therefore, be important to allow for non-functional resistance alleles in predicting the dynamics of constructs in cage populations and the impacts of any field release.


State of play of CME in Europe in 2015: Proceedings from the Eighth Annual European CME Forum.
European CME Forum is a not-for-profit organisation that brings together all stakeholder groups with an interest in European continuing medical education (CME) and promote multichannel discussion in an independent and neutral environment. This report summarises the discussions that took place at the 8th Annual European CME Forum in Manchester on 11-12 November 2015. Held at a time of increased scrutiny on the quality and value of the CME, the forum provided a space for attendees to share perspectives on trends, challenges, and opportunities related to European CME accreditation, funding, and regulation. Discussions focused on specific "hot topics" identified through a pre-meeting survey and needs assessment conducted among CME stakeholders in Europe and beyond. Chief among these were issues related to managing the transparency of relationships between industry and healthcare professionals, evolving systems of European CME accreditation, and the future of CME funding. The programme structure included multiple workshops conducted by leaders in the CME field, and plenary sessions that facilitated multidisciplinary interactions with invited guests, including the very learners the CME field is designed to serve. Attendee feedback was gathered to begin shaping the programme for the 9th Annual European CME Forum (#9ECF), which will take place in Amsterdam, The Netherlands, on 9-11 November 2016.