Trends in emergency department visits attributable to acetaminophen overdoses in the United States: 1993-2007.
With the heightened concern over acetaminophen overdose induced liver toxicity, it is important to track the overdose incidences over time. We estimated the trends in emergency department (ED) visits attributable to acetaminophen overdoses and compared the risk across sociodemographic groups and geographic regions. ED visits attributable to acetaminophen overdoses were identified using physician diagnosis codes and cause of injury codes from the National Hospital Ambulatory Medical Care Survey (1993-2007). Annual rates of ED visits for acetaminophen overdoses per 100,000 persons in the U.S. population and by subgroups (age, gender, race, insurance coverage, geographic region, and presence of alcohol abuse and dependence) were calculated. Bivariate analysis and logistic regressions were used to examine the associations of patient demographic characteristics with ED visits for acetaminophen overdoses. Data were analyzed using STATA 9.2 accounting for complex survey design. From 1993 through 2007, an estimated 751,552 ED visits (0.05% of all ED visits) were attributable to acetaminophen overdoses. The annual rate per 100,000 persons was significantly higher prior to 2000 (21.0 visits in 1993-1999 vs. 15.2 visits in 2000-2007, p = 0.017). Rates were particularly high in young children under 5 years (72.4 visits, 95% confidence interval (CI): 49.1-95.8) and for adolescents between 15-17 years (61.8 visits, 95%CI: 35.4-88.3). Rates also varied cross gender, insurance coverage, and geographic regions. ED visits attributable to acetaminophen overdose decreased in recent years. Children less than 5 years of age, adolescents and young adults account for the overwhelming majority of these visits.


Lost in Translation: The Impact of Language Barriers on the Outcomes of Patients Receiving Coronary Artery Revascularization.
Clear and effective communication is vital in discussions regarding coronary revascularization. Language barriers may limit communication in healthcare settings. Previous studies on the influence of language barriers on the outcomes of patients receiving coronary revascularization have produced conflicting results. The aim of this systematic review was to evaluate and synthesise the existing evidence regarding the effects of language barrier on the outcomes of patients receiving coronary revascularization. A systematic review was conducted, including a search of the PubMed, EMBASE, Cochrane, and Google Scholar databases on 01/10/2022. The review was conducted in accordance with PRISMA guidelines. This review was also prospectively registered on PROSPERO. Searches identified 3983 articles of which a total 12 studies were included in the review. Most studies describe that language barriers result in delayed presentation, but not delays in treatment following hospital arrival with respect to coronary revascularization. The findings with respect to the likelihood of receiving revascularization have varied significantly; however, some studies have indicated that those with language barriers may be less likely to receive revascularization. There have been some conflicting results with respect to the association between language barrier and mortality. However, most studies suggest that there is no association with increased mortality. In studies that evaluated length of stay variable results have been reported based on geographical location. Namely Australian studies have suggested no association between language barrier and length of stay, but Canadian studies support an association. Language barriers may also be associated with readmissions following discharge, and major adverse cardiovascular and cerebrovascular events (MACCE). This study demonstrates that patients with language barriers may have poorer outcomes from coronary revascularization. Future interventional studies will be required to consider the sociocultural context of patients with language barriers, and may be targeted at timepoints including prior to, during, or after hospitalisation for coronary revascularization. Further examination of the adverse health outcomes of those with language barriers in fields outside of coronary revascularization are required in view of the stark inequities identified in this field.


The implications of Project 2000 and the formation of links with higher education for the professional and academic needs of nurse teachers in the United Kingdom.
A national study was conducted between 1991 and 1994 to explore and describe the changing role of the nurse teacher following the introduction of Project 2000 pre-registration nursing courses. Multiple methods were used to collect data from a wide variety of respondents (nurse teachers, midwife teachers, clinical nurses, health service managers and higher education lecturers). This paper presents the findings relating to the impact of Project 2000 and the move into higher education on the continuing educational needs of nurse teachers. Views on college strategies for staff development, the changing nature of teachers' academic and professional development needs and the problems of the conflicting demands experienced are reported. The research highlights the need for clinical credibility to be clearly defined in relation to nurse teachers and for educational institutions to place more emphasis on teachers' clinical development if the rhetoric of policy is to become a reality.


Survival in patients with Parkinson's disease: a ten-year follow-up study in northern China.
A thorough understanding of the factors that influence patient survival in Parkinson's disease (PD) will aid in prognosis prediction and provide a new direction for disease modification treatment. Currently, there are no standardized mortality ratio (SMR) data for PD patients in the northern Chinese mainland. The main focus of this study was to determine which factors in the prospectively collected baseline characteristics can affect the survival of PD patients. In addition, for the first time, we investigated the SMR of PD patients in northern China. Between 2009 and 2012, 218 PD patients were continuously recruited from the movement disorder clinic of the First Affiliated Hospital of Dalian Medical University and followed up until death or May 31, 2021. The prespecified prognostic variables were demographics, clinical features, lifestyle factors, and drug dose prospectively collected at baseline. To determine the independent predictors of survival during follow-up, the Cox proportional hazards model was used. Kaplan-Meier analysis was applied to estimate the overall survival curve and to compare survival between layers based on statistically significant predictors. The SMR of this northern Chinese mainland PD cohort was calculated. After a mean follow-up of 9.58 ± 2.27 years, 50 patients (22.90%) died. Factors that could individually predict shortened survival during follow-up included older age at onset (hazard ratio [HR] 1.10, 95% confidence interval [CI] 1.06-1.15), Hoehn and Yahr (H&Y) stage ≥ 3 (HR 9.36, 95% CI 2.82-31.03) and severe cognitive impairment (HR 6.18, 95% CI 2.75-13.88). Univariate Cox regression revealed that a certain amount of physical activity was associated with better survival (HR 0.41, 95% CI 0.22-0.74), while fatigue was associated with an increased risk of death (HR 2.54, 95% CI 1.37-4.70). The overall SMR was 1.32 (95% CI 0.98-1.74). Older age at onset, higher baseline H&Y stage, and severe cognitive impairment have a negative impact on survival. The 10-year survival of PD patients is not significantly different from that of the general population in China.


Factors Influencing the Vietnamese Older Persons in Choosing Healthcare Facilities.
The rapidly growing aging population poses major challenges for health systems in Vietnam. This study was therefore aimed to examine factors influencing the choices of healthcare facilities among older patients in Vietnam, using a national survey on older people. We applied multinomial logistic regression models based on Andersen's Behavioral Model with various predisposing factors, enabling factors and healthcare-needs factors associated with different types of healthcare facilities where older patients utilized services. We used data from the Vietnam Aging Survey (VNAS) in 2011. This was the first-ever nationally representative survey on older persons in Vietnam. Among those who used healthcare services, 15.1% visited central hospitals; 23.6% visited provincial hospitals; 28.0% visited district hospitals; 8.8% visited commune heath centres; 18.3% visited private hospitals/clinics; and 6.2% visited other facilities. The results showed that "having to pay cost" and "having sufficient income" were strong predictors for using commune health centres, district hospitals, and private facilities, while "having health insurance" was not a significant predictor for using these facilities. Also, we showed that apart from enabling factors (such as age, gender, educational levels, employment status, living regionand place of residence), predisposing factor (such as health insurance, perceived sufficient income, household wealth and having to pay medical cost) as well as need factors (such as self-rated health and chronic disease) were also associated with the choice of healthcare facilities. Based on the findings, we discussed the implications of the results for organizing healthcare finance and delivery to achieve efficiency and equity for older people in Vietnam.


Infection of cultured rat hepatoma cells by mouse mammary tumor virus.
A continuous line of buffalo rat hepatoma (HTC) cells has been successfully infected with mouse mammary tumor virus (MMTV) produced by the GR mammary tumor cell line. Uniform infection required initial exposure of the HTC cells to greater than 10(5) MMTV particles per cell. The resultant chronically infected cell population was found to have stably acquired 20-30 copies of MMTV DNA. The infected cells contain viral RNA and express viral antigens; however, very few MMTV particles are released into the culture medium. In spite of the biochemical evidence for infection, we have not detected any alterations in the morphology or growth properties of the infected HTC cells. As is the case in mammary tumor cells, the intracellular concentration of viral RNA is strongly stimulated (50-150 fold) by the synthetic glucorcorticoid, dexamethasone. Thus it appears that the mechanisms by which glucorticoids regulate MMTV gene expression in mouse cells are maintained when this virus infects nonmurine cells.


The brain as a symbol-processing machine.
The knowledge accumulated about the biochemistry of the synapsis in the last decades completely changes the notion of brain processing founded exclusively over an electrical mechanism, toward that supported by a complex chemical message exchange occurring both locally, at the synaptic site, as well as at other localities, depending on the solubility of the involved chemical substances in the extracellular compartment. These biochemical transactions support a rich symbolic processing of the information both encoded by the genes and provided by actual data collected from the surrounding environment, by means of either special molecular or cellular receptor systems. In this processing, molecules play the role of symbols and chemical affinity shared by them specifies the syntax for symbol manipulation in order to process and to produce chemical messages. In this context, neurons are conceived as message-exchanging agents. Chemical strings are produced and stored at defined places, and ionic currents are used to speed up message delivery. Synaptic transactions can no longer be assumed to correspond to a simple process of propagating numbers powered by a factor measuring the presynaptic capacity to influence the postsynaptic electrical activity, but they must be modeled by more powerful formal tools supporting both numerical and symbolic calculations. It is proposed here that formal language theory is the adequate mathematical tool to handle such symbolic processing. The purpose of the present review is therefore: (a) to discuss the relevant and recent literature about trophic factors, signal transduction mechanisms, neuromodulators and neurotransmitters in order (b) to point out the common features of these correlated processes; and (c) to show how they may be organized into a formal model supported by the theory of fuzzy formal languages (d) to model the brain as a distributed intelligent problem solver.


Comparative study between omentopexy and omental plugging in treatment of giant peptic perforation.
Giant peptic perforation is a life threatening surgical emergency with high mortality.. This study aims to compare the success rate between omental plugging and standard omentopexy in the emergency management of giant perforations. A prospective non-randomized study of 23 patients with giant peptic perforation (≥2 cm in diameter) was carried out over a period of 18 months. The highest incidence was seen in the age group of 41-50 years. Intestinal fistula occurred in 23.08% of the omentopexy group compared to none in the omental plugging group. The mean hospital stay was slightly higher in the omentopexy group. Three patients died in the omentopexy group post operatively after 24 h compared to none in the omental plugging group and this was statistically significant (p < 0.05). Omental plugging is associated with lesser morbidity and mortality compared to omentopexy in the management of giant peptic perforations.


A combined ITS rDNA and beta-tubulin phylogeny of Thai species of Hypocrella with non-fragmenting ascospores.
A combined ITS and beta-tubulin gene phylogeny has revealed new species of Hypocrella and Aschersonia related to the type species Hypocrella discoidea from natural forest in Thailand. As a result, Hypocrella calendulina and Hypocrella luteola are named as new species with Aschersonia sensu stricto anamorphs for specimens previously identified as Hypocrella discoidea sensu Petch. Hypocrella siamensis and Aschersonia minutispora are described as new species, both exhibiting brown stromata, with the former producing whole ascospores.


Patients' experiences of dialysis services: are national health strategy targets being met?
The National Health Strategy envisages a health system incorporating patient views; and providing accessible, consultant-led dialysis services with patient choice of dialysis modality, in all regions. To describe patients' experiences of renal services against National Health Strategy objectives. Telephone interviews with 192 dialysis patients from three hospitals in the Eastern region. One-quarter of participants (16% of haemodialysis [HD] and 46% of peritoneal dialysis patients) lived outside the Eastern region, and travelled there because dialysis was not available locally. Two-thirds (65%) had a choice of dialysis modality. High satisfaction with interpersonal care was observed (83-98% satisfaction). Dissatisfaction with physical environment included parking (39-56%), waiting areas (62-69%), HD unit space (74%). Regarding support services, dietary services were satisfactory (92-95%), with lower satisfaction ratings for social and financial support services (62%). Structural and management issues must be addressed to advance a quality agenda for renal care in Ireland.


Establishment of a non-human primate Campylobacter disease model for the pre-clinical evaluation of Campylobacter vaccine formulations.
Campylobacter jejuni is a common cause of enteritis worldwide. The mechanisms by which C. jejuni causes disease are unclear. Challenge studies in humans are currently considered unethical due to the possibility of severe complications, such as Guillain-Barré syndrome. Campylobacter infection in non-human primates closely mimics the disease and immune response, seen in humans. In this study, we attempted to determine the minimal dose of a pathogenic C. jejuni 81-176 strain required for clinical signs and symptoms of disease (> or = 80% attack rate) in Macaca mulatta monkeys using an escalating dosage (three doses for three monkey groups: 10(7), 10(9) and 10(11) cfu). Eighty percent of the monkeys challenged with highest dose (10(11) cfu) had mild disease, but the 80% attack rate (moderate diarrhea in 80% of the monkeys) was not achieved. However, 100% of monkeys showed IgA seroconversions (three-fold over pre-challenge titers). The elicited immune response was challenge dose-dependent. Campylobacter antigen specific fecal s-IgA responses were observed in all challenged groups but the response was not dose-dependent. Only IgM antibody secreting cells response was observed against Campylobacter antigens. The elicited immune response in three groups of rhesus monkeys was dose-dependent, indicating this monkey model can be used for pre-clinical evaluation of Campylobacter candidate vaccines, however these adult rhesus monkeys are less prone to Campylobacter infection.


Oral combined hydrochlorothiazide and lisinopril vs nifedipine for postpartum hypertension: a comparative-effectiveness pilot randomized controlled trial.
Angiotensin-converting enzyme inhibitors and diuretics may be underutilized for postpartum hypertension because of their teratogenicity during pregnancy. We evaluated whether combined oral hydrochlorothiazide and lisinopril therapy produced superior short-term blood pressure control when compared with nifedipine among postpartum individuals with hypertension requiring pharmacologic treatment. We performed a pilot randomized controlled trial (October 2021 to June 2022) that included individuals with chronic hypertension or hypertensive disorders of pregnancy with 2 systolic blood pressure measurements ≥150 mm Hg and/or diastolic blood pressure measurements ≥100 mm Hg within 72 hours after delivery. Participants were randomized to receive either combined hydrochlorothiazide and lisinopril therapy or nifedipine therapy after stratifying the participants by diagnosis (chronic hypertension vs hypertensive disorders of pregnancy). The primary outcome was stage 2 hypertension (systolic blood pressure ≥140 mm Hg and/or diastolic blood pressure ≥90 mm Hg) determined using a home blood pressure monitor on days 7 to 10 after delivery or at readmission to the hospital for blood pressure control. The secondary outcomes included severe maternal morbidity (any of the following: intensive care unit admission; hemolysis, elevated liver enzymes, low platelet count syndrome; eclampsia; stroke; cardiomyopathy; or maternal death), need for intravenous medications after randomization, hospital length of stay, blood pressure during first clinic visit, medication compliance, and adverse events. A pilot trial with 70 individuals was planned given the limited available data on combined hydrochlorothiazide and lisinopril therapy use in postpartum care. We calculated relative risks and 95% credible intervals in an intention-to-treat analysis. Finally, we conducted a preplanned Bayesian analysis to estimate the probability of benefit or harm with a neutral informative prior. Of 111 eligible individuals, 70 (63%) agreed and were randomized (31 in the hydrochlorothiazide and lisinopril group and 36 in the nifedipine group; 3 withdrew consent after randomization), and the characteristics were similar at baseline between the groups. The primary outcome was unavailable for 9 (12.8%) participants. The primary outcome occurred in 27% of participants in the hydrochlorothiazide and lisinopril group and in 43% of the participants in the nifedipine group (posterior adjusted relative risk, 0.74; 95% credible interval, 0.40-1.31). Bayesian analysis indicated an 85% posterior probability of a reduction in the primary outcome with combined hydrochlorothiazide and lisinopril therapy relative to nifedipine treatment. No differences were noted in the secondary outcomes or adverse medication events. The results of the pilot trial suggest a high probability that combined hydrochlorothiazide and lisinopril therapy produces superior short-term BP control when compared with nifedipine. These findings should be confirmed in a larger trial.


Assessing morphokinetic parameters via time lapse microscopy (TLM) to predict euploidy: are aneuploidy risk classification models universal?
To determine if Aneuploidy Risk Classification Models are predictive of euploidy/aneuploidy amongst IVF facilities. We retrospectively applied key time lapse imaging events of embryos (Campbell et al.[5, 6]) to stratify embryos into 3 groups: low, medium and high risk of aneuploidy. The actual ploidy results (from array comparative genomic hybridization) were compared with expectations [5, 6]. Sources of variability in morphokinetic parameters were determined using Analysis of Variance (ANOVA). The model failed to segregate euploid embryos from aneuploid embryos cultured at our facility. Further analysis indicated that the variability of embryos among patients was too great to allow selection of euploid embryos based on simple morphokinetic thresholds. Clinical selection of embryos based on morphokinetics alone is unlikely to identify euploid embryos accurately for transfer or yield higher rates of live delivery. The use of non-invasive morphokinetics is unlikely to discriminate aneuploid from euploid embryos. Further, it does not approach the accuracy of preimplantation genetic screening with array comparative genomic hybridization.


Object identification and attention training for treating tinnitus.
We hypothesize that abnormal attention and auditory scene analysis contribute to the severity of tinnitus and that the incongruence between tinnitus and normal auditory perception is responsible for its resistance to traditional sound-based habituation therapies. New methods of treatment using auditory and visual attention training are proposed as a means to augment counseling and sound therapies for tinnitus management. Attention training has been demonstrated to improve an individuals' ability to attend to relevant sounds while ignoring distracters. The main aim of the current study was to determine the effectiveness of structured Auditory Object Identification and Localization (AOIL) tasks to train persons to ignore their tinnitus. The study looked at the effects of a 15-day (30 min/day) take-home auditory training program on individuals with severe tinnitus. Pitch-matched tinnitus loudness levels (TLLs), tinnitus minimum masking levels (MMLs) and measures of attention were compared before and after the auditory training. The results of this study suggest that short-duration auditory training which actively engages attention, object identification and which requires a response from participants, reduces tinnitus. There was a greater effect on pitch-matched tinnitus MMLs than on actual TLLs. The reason(s) for this are unclear, although a correlation found between changes in MMLs and improvements in the ability to shift attention may be one underlying reason. Although this study followed a small number of participants over a limited time-span, it is believed that the training and accompanying model are a promising approach to investigate and treat some forms of tinnitus.


Software system for calibrating examiners in cephalometric point identification.
The literature has shown that subjective concepts lead to interobserver variations in the definitions and identifications of cephalometric landmarks. Observers must be trained and calibrated to conduct scientific research using cephalometric comparisons. In this study, we aimed to develop and test a computational model called Cyclops cephalometry in radiographic cephalometry training and calibration. This system uses the concepts of evaluation process managers, examiners, and testers, thus affording uniformity in cephalometric evaluations. The system was tested with 5 orthodontists and 5 postgraduate students who located 28 landmarks in 10 lateral cephalometric radiographs before and after training. Before training, the Student t test showed significant differences (P <0.05) in accuracy between the orthodontists and the students (71.4% and 54.9%, respectively). However, considerable improvement in accuracy was observed after training in both groups (86.5% and 83%, respectively), without significant differences (P = 0.30) between groups. Users of the system agreed about its usability aspects such as effectiveness, efficiency, and satisfaction. This model was shown to be a useful and efficient tool in the calibration process, and might be helpful in various comparative cephalometric investigations.


Strategies of hemopoietic stress adaptation within the medullary cavity.
Gravimetric determination of total bone water space was used as an index of available bone marrow space in mice following various specific stressors, i.e., splenectomy, hypoxia, bone fracture, and estrone-induced osteosclerosis. Data was corrected for bone weight and was reported as specific bone marrow volume (total bone water space/mg dry bone X 100). A direct relationship was observed between specific bone marrow volume and medullary hemopoietic activity induced by stress. Absolute and/or relative marrow space increased following splenectomy, hypoxia, and fracture. Osteosclerotic animals shift most hemopoietic activity from marrow to spleen, and splenectomized osteosclerotic animals become anemic. Both intact and splenectomized hypoxic animals develop increased specific bone marrow volume and successfully compensate for hypoxia with enhanced erythropoiesis. Animals sustaining a fracture callus increase both specific bone marrow volume and hemopoietic activity at the callus without an increase in hemopoietic demand. Increased specific bone marrow volume extends the marrow bone interface, where primitive stem cells accumulate, while expanding marrow stromal space, where stem cells lodge, proliferate and differentiate. Therefore, it would appear that availability of competent marrow space may play an integral part in passively permitting hematopoiesis and in determining hemopoietic reserve capacity. Stem cell migration increases during intensified hemopoietic demand, which also may be related to available marrow space. Mice have a low medullary hemopoietic reserve capacity; subsequently, when available medullary hematopoietic stroma becomes occupied, stem cells are more likely to migrate from the marrow to extra-medullary sites where they mature before entering the circulating pool.


Public health significance of zoonotic Cryptosporidium species in wildlife: Critical insights into better drinking water management.
Cryptosporidium is an enteric parasite that is transmitted via the faecal-oral route, water and food. Humans, wildlife and domestic livestock all potentially contribute Cryptosporidium to surface waters. Human encroachment into natural ecosystems has led to an increase in interactions between humans, domestic animals and wildlife populations. Increasing numbers of zoonotic diseases and spill over/back of zoonotic pathogens is a consequence of this anthropogenic disturbance. Drinking water catchments and water reservoir areas have been at the front line of this conflict as they can be easily contaminated by zoonotic waterborne pathogens. Therefore, the epidemiology of zoonotic species of Cryptosporidium in free-ranging and captive wildlife is of increasing importance. This review focuses on zoonotic Cryptosporidium species reported in global wildlife populations to date, and highlights their significance for public health and the water industry.


Effects of Flammulina velutipes polysaccharides on gut microbiota composition and metabolism in vitro fermentation.
Flammulina velutipes polysaccharides (FVP) exhibit many biological activities, but the effects on gut microflora and metabolism were still unclear. Here, we explored the composition of FVP, their influence on human gut microflora composition and metabolites. FVP were used to vitro fermentation through human fecal inoculums. In addition, 16S rRNA sequencing were used to assess the effects of FVP on the gut microbiota. The metabolic profiles were investigated using untargeted metabolomics approaches in the LC-MS platform. The results showed that FVP was mainly consisted of glucose, mannose, xylose, fucose and galactose. FVP is shown to increase the relative abundances of Bifidobacteriaceae, as well as Bacteroidaceae and remarkably decrease the numbers of genera Lachnospiraceae coupled with Enterococcaceae. The differential metabolites were identified and mainly involved the metabolism of glycerophospholipid, linoleic acid and synthesis of unsaturated fatty acids. FVP may exhibit biological activity function by regulating gut microflora composition and metabolites. The online version contains supplementary material available at 10.1007/s10068-022-01192-y.


The effects of aqueous and ethanolic extracts of Rheum ribes on insulin-resistance and apolipoproteins in patients with type 2 diabetes mellitus: a randomized controlled trial.
Previous studies have shown that Rheum ribes (R. ribes) could be effective in controlling the blood glucose levels. This study was conducted to determine the effects of R. ribes supplementation on glycemic indices and apolipoproteins in patients with type 2 diabetes mellitus (T2DM). In the present randomized double-blind controlled trial, 60 type 2 diabetic patients aged 30-60 years with a body mass index (BMI) of 20-30 kg/m2 and hemoglobin A1c (HbA1c) of 6-8% were enrolled. Patients were randomly assigned to receive 450 mg of aqueous R. ribes extract (AG), 450 mg of ethanolic R. ribes extract (EG), or placebo (PG) three times daily for 6 weeks. At the baseline and at the end of the study, blood glucose levels, homeostatic model assessment of insulin resistance (HOMA-IR) and the homeostatic model assessment of β-cell dysfunction (HOMA-B), as well as apolipoprotein A-I (ApoA1) and apolipoprotein B (ApoB) were measured. There was a significant decrease in the serum levels of insulin in AG and EG groups (P = 0.003 and P = 0.001, respectively), HOMA-IR (P = 0.01 and P = 0.001, respectively), HOMA-B (P = 0.002 and P = 0.001, respectively), ApoB (P = 0.006 and P = 0.03, respectively), ApoB/ApoA1 ratio (P = 0.016 and P = 0.04, respectively). However, a significant increase in ApoA1 (P = 0.08 and P = 0.05, respectively) with no significant changes in blood glucose, at the end of study compared to beginning values, were observed. None of the variables showed a significant change in PG. At the end of the study; while there were significant differences in insulin (P = 0.04), HOMA-IR (P = 0.03), HOMA-B (P = 0.01), ApoB (P = 0.02), and ApoB/ApoA1 ratio (P = 0.03) among the groups but ApoA1 had no significant change. Consumption of R. ribes intake could have beneficial effects on insulin resistance and apolipoproteins in type 2 diabetic patients. (Registered at en.irct.ir, identification number: IRCT201410142709N31).


Molecular mimicry of host short linear motif-mediated interactions utilised by viruses for entry.
Viruses are obligate intracellular parasites that depend on host cellular machinery for performing even basic biological functions. One of the many ways they achieve this is through molecular mimicry, wherein the virus mimics a host sequence or structure, thereby being able to hijack the host's physiological interactions for its pathogenesis. Such adaptations are specific recognitions that often confer tissue and species-specific tropisms to the virus, and enable the virus to utilise previously existing host signalling networks, which ultimately aid in further steps of viral infection, such as entry, immune evasion and spread. A common form of sequence mimicry utilises short linear motifs (SLiMs). SLiMs are short-peptide sequences that mediate transient interactions and are major elements in host protein interaction networks. This work is aimed at providing a comprehensive review of current literature of some well-characterised SLiMs that play a role in the attachment and entry of viruses into host cells, which mimic physiological receptor-ligand interactions already present in the host. Considering recent trends in emerging diseases, further research on such motifs involved in viral entry can help in the discovery of previously unknown cellular receptors utilised by viruses, as well as help in the designing of targeted therapeutics such as vaccines or inhibitors directed towards these interactions.


The associations between uric acid with BMDs and risk of the 10-year probability of fractures in Chinese patients with T2DM stratified by age and gender.
Accumulating evidence suggests that serum uric acid (SUA) plays a beneficial role in bone health in the general population through antioxidant mechanisms. However, there is controversy over the association between SUA and bone in patients with type 2 diabetes mellitus (T2DM). We aimed to investigate the association of serum UA with BMDs and future fracture risks and its potential influencing factors in those patients. This was a cross-sectional study of 485 patients. BMDs at femoral neck (FN), Troch and the lumbar spine (LS) were measured by DXA. The 10-year probability of fracture risk was assessed using the fracture risk assessment tool (FRAX). SUA level and other biochemical indexes were measured. There were lower SUA concentrations in patients with osteoporosis/osteopenia compared with those in the normal group, which only existed in non-elderly men and elderly women with T2DM. After adjustment for potential confounders, SUA was positively associated with BMD and negatively with 10-year probability of fracture risk only in non-elderly men and elderly women with T2DM. Multiple stepwise regression analysis showed that SUA was an independent determinant of BMD and 10-year probability of fracture risk, which also occurred in the above patients. These results implied that relatively high SUA is a protective factor for bone in T2DM patients, but the osteoprotective effect of SUA was mediated by age and gender, and persisted only in non-elderly men and elderly women. Large intervention studies are needed to further confirm the outcomes and provide possible explanations.


White sturgeon (Acipenser transmontanus) acid-base regulation differs in response to different types of acidoses.
White sturgeon (Acipenser transmontanus) completely protect intracellular tissue pH (pHi) despite large reductions in extracellular (blood) pH (pHe), termed preferential pHi regulation, in response to elevated environmental PCO2 (hypercarbia) and in general appear to be relatively resilient to stressors. Preferential pHi regulation is thought to be associated with hypercarbia tolerance in general, but has also recently been observed to protect pHi against metabolic acidoses induced by exhaustive exercise and anoxia in a tropical air breathing catfish. We hypothesized that preferential pHi regulation may also be a general strategy of acid-base regulation in sturgeon. To address this hypothesis, severe acidoses were imposed to reduce pHe, and the presence or absence of preferential pHi regulation was assessed in red blood cells (RBC), heart, brain, liver and white muscle. A respiratory acidosis was imposed using hyperoxia, while metabolic acidoses were induced by exhaustive exercise, anoxia or air exposure. Reductions in pHe occurred following hyperoxia (0.15 units), exhaustive exercise (0.30 units), anoxia (0.10 units) and air exposure (0.35 units); all acidoses reduced RBC pHi. Following hyperoxia, heart, brain and liver pHi were preferentially regulated against the reduction in pHe, similar to hypercarbia exposure. Following all metabolic acidoses heart pHi was protected and brain pHi remained unchanged following exhaustive exercise and air exposure, however, brain pHi was reduced following anoxia. Liver and white muscle pHi were reduced following all metabolic acidoses. These results suggest preferential pHi regulation may be a general strategy during respiratory acidoses but during metabolic acidoses, the response differs between source of acidoses and tissues.


The efficacy of oral piroxicam fast-dissolving tablets versus sublingual fentanyl in incident breakthrough pain due to bone metastases: a double-blinded randomized study.
Breakthrough pain (BTP) is a transient exacerbation of pain occurring in a patient with chronic, persistent pain. The most common type is incident pain that is mostly related to bone metastases. The oral mucosa is an attractive route for drug delivery. Sublingual fentanyl preparations are a very attractive agent in controlling attacks of BTP due to its rapid absorption through the oral mucosa. Non-steroidal anti-inflammatory drugs (NSAIDs) play a key role as a first step in treatment of cancer pain; piroxicam sublingual formulations could be a useful alternative in controlling incident pain. Our study hypothesis is to evaluate the efficacy of sublingual fentanyl versus oral piroxicam fast-dissolving tablets in patients with incident pain and its impact on functional status. A cohort of 100 adults of both genders suffering from bone metastases. Patients were assigned to receive either sublingual fentanyl tablet (group 1) or oral piroxicam fast-dissolving tablets (group 2). The pain intensity reduction on a 0-10 visual analog scale (VAS), frequency of BTP attacks, and onset of pain relief. Secondary end points included the functional interference items of the Brief Pain Inventory (BPI). There is no significant difference between the two groups regarding the patients' demographics. Significant decline of the VAS in each group in comparison to the pretreatment values (p = 0.001). Non-significant changes of the VAS, duration of pain attacks, and number of rescue doses in comparing both groups were measured. There was significant reduction in group 2 BPI regarding the relation with others, sleep pattern and enjoyment of life parameters at 2 and 4 weeks (p = 0.001). Our study demonstrated that oral piroxicam fast-dissolving tablet is an analgesic alternative to sublingual fentanyl in patients with bone metastasis to control incidental BTP attacks with more favorable cost-benefit values.


Geospatial analysis of unmet pediatric surgical need in Uganda.
In low- and middle-income countries (LMICs), an estimated 85% of children do not have access to surgical care. The objective of the current study was to determine the geographic distribution of surgical conditions among children throughout Uganda. Using the Surgeons OverSeas Assessment of Surgical Need (SOSAS) survey, we enumerated 2176 children in 2315 households throughout Uganda. At the district level, we determined the spatial autocorrelation of surgical need with geographic access to surgical centers variable. The highest average distance to a surgical center was found in the northern region at 14.97km (95% CI: 11.29km-16.89km). Younger children less than five years old had a higher prevalence of unmet surgical need in all four regions than their older counterparts. The spatial regression model showed that distance to surgical center and care availability were the main spatial predictors of unmet surgical need. We found differences in unmet surgical need by region and age group of the children, which could serve as priority areas for focused interventions to alleviate the burden. Future studies could be conducted in the northern regions to develop targeted interventions aimed at increasing pediatric surgical care in the areas of most need. Level III.


California adults increase fruit and vegetable consumption from 1997-2007.
To determine whether fruit and vegetable consumption among California adults significantly increased from 1997-2007. Biennial telephone surveillance surveys of California adults' dietary practices. California adults (n = 9,105 total all 6 surveys). Surveillance data reporting. Changes in fruit and vegetable consumption over time between 1997-2007, measured by mean servings and percentage of adults eating ≥ 5 servings on any given day. Comparisons of subsets both within the same year and across years were made using t tests, chi-square, and Tukey Studentized Range tests at 5% procedure-wise error rate. California adults significantly increased mean daily servings of fruits and vegetables from 3.8 servings in 1997 to 5.2 servings in 2007. Since 1998, notable improvements in fruit and vegetable consumption have occurred to California populations, including the target audience groups of the Network for a Healthy California.


Enzymatic synthesis of nucleoside analogues using immobilized 2'-deoxyribosyltransferase from Lactobacillus reuteri.
Covalent attachment of recombinant Lactobacillus reuteri 2'-deoxyribosyltransferase to Sepabeads EC-EP303 leads to the immobilized biocatalyst SLrNDT4, which displayed an enzymatic activity of 65.4 IU/g of wet biocatalyst in 2'-deoxyadenosine synthesis from 2'-deoxyuridine and adenine at 40°C and pH 6.5. Response surface methodology was employed for the optimization of SLrNDT4 activity. Optimal conditions for SLrNDT4 highest activity were observed at 40°C and pH 6.5. Immobilized biocatalyst retained 50% of its maximal activity after 17.9 h at 60°C, whereas 96% activity was observed after storage at 40°C for 110 h. This novel immobilized biocatalyst has been successfully employed in the enzymatic synthesis of different natural and therapeutic nucleosides effective against cancer and viral diseases. Among these last products, enzymatic synthesis of therapeutic nucleosides such as 5-ethyl-2'-deoxyuridine and 5-trifluorothymidine has been carried out for the first time. Importantly for its potential application, SLrNDT4 could be recycled for 26 consecutive batch reactions in the synthesis of 2,6-diaminopurine-2'-deoxyriboside with negligible loss of catalytic activity.


Central neurotoxicity after exposure to organic lead: susceptibility to seizures.
Organic leads are present in the environment from a variety of sources and produce metabolites such as triethyl lead (TEL) which have relatively long half-lives in the brain. However, little is known at present about the possible neurological consequences of exposure to these compounds. The susceptibility of an animal to experimentally induced seizures has been used as a reliable index of neural function to assess neurotoxic insult, and the present study assessed the effect of TEL upon this index. Adult male rats of the Fischer-344 strain were divided into groups and treated with 7.88 mg/kg of TEL or the control vehicle at 1, 7, 14 or 28 days prior to a single challenge with 35 mg/kg of pentylenetetrazole (PTZ). The rats treated with TEL were more susceptible to PTZ-induced seizures than were the controls. This effect was statistically significant on days 7, 14 and 28 after treatment, although some elevation of seizure scores was observed among TEL-treated animals on day 1. These results demonstrate a functional change in the central nervous system after exposure to TEL, which persists for at least 4 weeks after exposure.


PTGS-2-PTGER2/4 signaling pathway partially protects from diabetogenic toxicity of streptozotocin in mice.
Prostanoids are suggested to participate in diabetes pathology, but their roles are controversially discussed. The purpose of the current study was to examine the role of cyclooxygenase (prostaglandin synthase [PTGS]) enzymes and prostaglandin (PG) E(2) signaling pathways in streptozotocin (STZ)-induced type 1 diabetes. Blood glucose, insulin, and survival rate were studied in mice with targeted disruption of the genes for PTGS and PGE receptors (PTGERs). PGE(2) was found as the main prostanoid formed by the pancreas. Contrarily to PTGS-1, deficiency of PTGS-2 activity significantly amplified STZ effect, causing dramatic loss of insulin production and rise in blood glucose and death rate. STZ metabolism was unaffected by PTGS deficiency. Diabetogenicity of STZ in PTGER1(-/-), PTGER2(-/-), PTGER3(-/-), and PTGER4(-/-) mice was comparable to control mice. In striking contrast, combined knockout of PTGER2 and PTGER4 by blocking PTGER4 in PTGER2(-/-) mice strongly enhanced STZ pathology. Treatment of PTGS-2(-/-) and wild-type mice with PTGER2/PTGER4 agonists partially protected against STZ-induced diabetes and restored β-cell function. Our data uncover a previously unrecognized protective role of PTGS-2-derived PGE(2) in STZ-induced diabetes mediated by the receptor types PTGER2 and PTGER4. These findings offer the possibility to intervene in early progression of type 1 diabetes by using PTGER-selective agonists.


Assessment of predictors of renal cell carcinoma progression after nephrectomy at short- and medium-term follow-up and implication on surveillance protocols.
Prediction of risk of RCC progression after surgery is important for follow-up planning. We identified predictors of progression-free survival (PFS) and cancer-specific survival (CSS) in a large single institutional cohort and investigated patterns and sites of progression according to stage and grade. Node-negative non-metastatic clear-cell RCC (ccRCC) patients treated with radical or partial nephrectomy from 2000 to 2020 were included. Sites of progression were defined as thoracic, abdominal and others (bone/brain). Kaplan-Meier curves and multivariable Cox regression (MCR) models tested for PFS and CSS. Of 384 clear cell RCC N0M0 patients, 301 (78.4%) vs. 83 (21.6%) were pT1-2 vs. pT3-4, respectively; 253 (65.9%) vs. 130 (33.9%) were G1-G2 vs. G3-G4. Thoracic progressions occurred in 2.7% pT1-T2 vs. 21.7% pT3-T4 and 2.8% G1-G2 vs. 14.6% G3-G4 tumors. Abdominal progressions occurred in 4.0% pT1-T2 vs. 13.3% pT3-T4 and 4.3% G1-G2 vs. 9.2% G3-G4. Other progressions occurred in 0.3% pT1-T2 vs. 9.6% pT3-T4 and 0.8% G1-G2 vs. 5.4% G3-G4 (5.4%). Five-year PFS and CSS were 81.7 and 90.6%, respectively. At MCR models, pT3-4 (HR 9.1, P<0.001), G3-G4 (HR 2.7, P=0.003) and PSMs (HR 6.1, P<0.001) independently predicted PFS. Similarly, pT3-4 (HR 10.1, P<0.001), G3-G4 (HR 4.1, P=0.02), and PSMs (HR 5.2, P=0.04) independently predicted CSS. In ccRCC N0M0 patients, G3-G4, pT3-4, PSMs were independent predictors of progression after surgery. Lower stage and grade ccRCCs progress predominantly in the abdominal sites and may be followed with less frequent extra-abdominal imaging compared to more advanced/aggressive tumors.


A chromatography-focused bioprocess that eliminates soluble aggregation for bioactive production of a new antimicrobial peptide candidate.
Human beta defensins (hBDs) are an important class of antimicrobial peptides (AMPs), which provide the host with innate protection from bacteria, fungi and viruses. Human β-defensin-25 (hBD25) is a new hBD variant which has been recently discovered in the male genital tract. Since its discovery, hBD25 was hypothesized to play a key role in protection against genital tract infection, which has significantly increased mortality rates in the last decade. However, further studies to confirm the role of hBD25 are hindered by the lack of sufficient amounts of pure hBD25 for clinical studies. This study reports the first successful development of an efficient and low cost chromatography-oriented bioprocess for production of hBD25. hBD25 was expressed predominantly as soluble aggregates although the peptide was co-expressed with a Maltose Binding Protein (MBP) fusion tag in E. coli. The soluble aggregates were disrupted by denaturation-reduction of the hBD25, followed by an in vitro size exclusion chromatography refolding step which readily yielded bioactive and purified hBD25 peptides at 90% purity. The refolded hBD25 showed antimicrobial activity against E. coli K12 at a minimal inhibitory concentration of 60 μg/mL. With an overall hBD25 bioprocess yield of 48% obtained, this bioprocess will open the way for detailed clinical studies of hBD25, and serve as a generic platform for efficient recovery of other 'fusion protein'-derived peptides that inevitably exist as soluble aggregates.


Binaural response characteristics of single neurons in the medial superior olivary nucleus of the albino rat.
Binaural response properties of single neurons in the medial superior olivary nucleus (MSO) were investigated in the anesthetized rat. Stimulus parameters studied included interaural time difference and interaural intensity difference. In the present study, of the two cell types observed in the rat MSO nucleus, EE and EI, variations in the binaural response properties of the MSO neurons permitted further subclassifications, which may be related to the dendritic dominance of the MSO neurons.


Postoperative delirium is a risk factor for complications and poor outcome after total hip and knee arthroplasty.
Background and purpose - Improving health care and demographic change have resulted in a steady increase in geriatric patients undergoing total hip (THA) and knee (TKA) arthroplasty. Postoperative delirium (POD) is a frequent and severe complication after major surgery. Therefore, we analyzed the impact of POD on outcome after THA and TKA.Patients and methods - In a consecutive series of 10,140 patients who had undergone elective THA or TKA between 2011 and 2020, rates of reoperation within 90 days, readmission within 90 days, complications, and responder rate as defined by the OMERACT-OARSI criteria were compared between patients with and without POD. Multivariable logistic regression models were used to assess the relationship between POD and other postoperative complications.Results - Patients with POD showed higher rates of reoperation (12% vs. 5%), readmission (15% vs. 5%), surgical complications (7% vs. 2%), non-surgical complications (8% vs. 4%), Clavien-Dindo IV° complications (10% vs. 2%) and transfusion (14% vs. 2%). POD led to lower responder rate (76% vs. 87%) 1 year after total joint replacement. All previous comparisons statistically significant. Multivariable logistic regression analyses revealed POD as an independent risk factor for reoperation (OR = 2; CI 1-3), readmission (OR = 2; CI 2-4) and Clavien-Dindo IV° complications (OR = 3; CI 2-5).Interpretation - POD is a serious problem in elective joint replacement. Affected patients suffer more complications and show poor patient-reported outcome 1 year postoperatively. Systematic prevention strategies and standardized therapy protocols are mandatory to avoid burden to patients and healthcare providers.


Signal Peptide-rheostat Dynamics Delay Secretory Preprotein Folding.
Sec secretory proteins are distinguished from cytoplasmic ones by N-terminal signal peptides with multiple roles during post-translational translocation. They contribute to preprotein targeting to the translocase by slowing down folding, binding receptors and triggering secretion. While signal peptides get cleaved after translocation, mature domains traffic further and/or fold into functional states. How signal peptides delay folding temporarily, to keep mature domains translocation-competent, remains unclear. We previously reported that the foldon landscape of the periplasmic prolyl-peptidyl isomerase is altered by its signal peptide and mature domain features. Here, we reveal that the dynamics of signal peptides and mature domains crosstalk. This involves the signal peptide's hydrophobic helical core, the short unstructured connector to the mature domain and the flexible rheostat at the mature domain N-terminus. Through this cis mechanism the signal peptide delays the formation of early initial foldons thus altering their hierarchy and delaying mature domain folding. We propose that sequence elements outside a protein's native core exploit their structural dynamics to influence the folding landscape.


Timing of food consumption in Hispanic adolescents with obesity.
Little is known about the normal eating time periods in adolescents with obesity and how these patterns change throughout development. As the obesity epidemic continues to rise in adolescence, it becomes imperative to understand developmentally appropriate eating behaviours and to create weight management strategies that build on those innate patterns and preferences. The purpose of this study was to determine the most common habitual eating windows observed in adolescents with obesity. Participants were 101 Hispanic adolescents (mean age 14.8 ± 2.1 years; 48 male/53 female) with obesity (BMI ≥95th percentile) who were recruited as part of a larger clinical trial. Dietary intake and meal timing was determined using multiple pass 24-hours recalls. Histograms were utilized to determine the natural distribution of percent consumption of total kilocalories, carbohydrates and added sugar per hour. The majority of total kilocalories (65.4%), carbohydrates (65.3%) and added sugar (59.1%) occurred between 11:00 and 19:00. Adolescents were 2.5 to 2.9 times more likely to consume kilocalories, carbohydrates, and added sugar during the 8-hour window between 11:00 am and 19:00 pm than other time windows examined (all P < .001). The consumption of these calories did not differ between weekdays and weekend (P > .05) or by sex. In this cohort, more than 60% of calories, carbohydrates and added sugar were consumed between 11:00 am and 19:00 pm, which is concordant with an afternoon/evening chronotype that is common in adolescents. Our findings support this 8-hour period as a practical window for weight loss interventions that target pre-specified eating periods in this population.


Mild hypoglycemia is independently associated with increased mortality in the critically ill.
Severe hypoglycemia (blood glucose concentration (BG) < 40 mg/dL) is independently associated with an increased risk of mortality in critically ill patients. The association of milder hypoglycemia (BG < 70 mg/dL) with mortality is less clear. Prospectively collected data from two observational cohorts in the USA and in The Netherlands, and from the prospective GLUCONTROL trial were analyzed. Hospital mortality was the primary endpoint. We analyzed data from 6,240 patients: 3,263 admitted to Stamford Hospital (ST), 2,063 admitted to three institutions in The Netherlands (NL) and 914 who participated in the GLUCONTROL trial (GL). The percentage of patients with hypoglycemia varied from 18% to 65% among the different cohorts. Patients with hypoglycemia experienced higher mortality than did those without hypoglycemia even after stratification by severity of illness, diagnostic category, diabetic status, mean BG during intensive care unit (ICU) admission and coefficient of variation (CV) as a reflection of glycemic variability. The relative risk (RR, 95% confidence interval) of mortality associated with minimum BG < 40, 40 to 54 and 55 to 69 mg/dL compared to patients with minimum BG 80 to 109 mg/dL was 3.55 (3.02 to 4.17), 2.70 (2.31 to 3.14) and 2.18 (1.87 to 2.53), respectively (all P < 0.0001). The RR of mortality associated with any hypoglycemia < 70 mg/dL was 3.28 (2.78 to 3.87) (P < 0.0001), 1.30 (1.12 to 1.50) (P = 0.0005) and 2.11 (1.62 to 2.74) (P < 0.0001) for the ST, NL and GL cohorts, respectively. Multivariate regression analysis demonstrated that minimum BG < 70 mg/dL, 40 to 69 mg/dL and < 40 mg/dL were independently associated with increased risk of mortality for the entire cohort of 6,240 patients (odds ratio (OR) (95% confidence interval (CI)) 1.78 (1.39 to 2.27) P < 0.0001), 1.29 (1.11 to 1.51) P = 0.0011 and 1.87 (1.46 to 2.40) P < 0.0001) respectively. Mild hypoglycemia was associated with a significantly increased risk of mortality in an international cohort of critically ill patients. Efforts to reduce the occurrence of hypoglycemia in critically ill patients may reduce mortality.


Damage of the basilar membrane by acoustic stimulation.
Sound exposures of more than 130 dB lead to typical tears in the basilar membrane in the area of maximal damage. The position, size, and number of these tears are evaluated.


[Cholecystectomy by celioscopy: indications and safety of the method. Apropos of a consecutive series of 300 patients].
We performed a laparoscopic cholecystectomy in 300 patients with gallstone disease complicated or not. The rate success was 97%, however involved the pathology might be. Indeed, 15% of the patients had an acute cholecystitis (10% catarrhalis, 5% empyema). Twenty-four patients with common bile duct stones had a complete endoscopic management of the biliary disease: endoscopic sphincterotomy and laparoscopic cholecystectomy. Operative mortality was absent and overall morbidity was 3.7%, exclusively minor.


Extracellular vesicle-encapsulated miR-21-5p in seminal plasma prevents sperm capacitation via Vinculin inhibition.
To penetrate the zona pellucida before sperm-egg binding, sperm must undergo highly time-controlled capacitation and acrosome reaction in the female reproductive tract. Our previous study demonstrated that miR-21-5p is the most abundant miRNA in boar seminal plasma (SP)-derived extracellular vesicles (EVs) and can target Vinculin (VCL) gene, which may participate in boar sperm capacitation. Thus, this study aims to explore the potential role of miR-21-5p from SP-derived EVs in preventing sperm capacitation and its underlying mechanism. We observed that sperm could incorporate miR-21-5p from SP-derived EVs. The roles of SP-derived EVs miR-21-5p in sperm capacitation were then determined using gain- and loss-of-function analyses. In addition, the expression levels of miR-21-5p, VCL, and VCL protein in liquid-preserved boar sperm following transfection were determined using RT-qPCR and Western blotting. Our results revealed that miR-21-5p overexpression inhibited sperm capacitation and acrosome reaction. Similarly, miR-21-5p expression was significantly lower (P < 0.05) in capacitated sperm than un-capacitated sperm. However, the protein level of VCL was also significantly lower (P < 0.05) in capacitated sperm than un-capacitated sperm. Furthermore, immunofluorescence analysis showed that VCL protein mainly located in sperm head and sperm capacitation was inhibited after treating with VCL protein inhibitor (Chrysin). In conclusion, our study provides reasonable evidence that miR-21-5p expression in SP-derived EVs could prevent sperm capacitation via VCL inhibition.


Information theoretic perspective on genome clustering.
Shannon's information theoretic perspective of communication helps one to understand the storage and processing of information in one-dimensional sequences. An information theoretic analysis of 937 available completely sequenced prokaryotic genomes and 238 eukaryotic chromosomes is presented. Information content (Id) values were used to cluster these chromosomes. Chargaff's second parity rule i.e compositional self-complementarity, an empirical fact is observed in all the genomes, except for the proteobacteria Candidatus Hodgkinia cicadicola. High information content, arising out of biased base composition in all the 14 chromosomes of Plasmodium falciparum is found among two other genomes of prokaryotes viz. Buchnera aphidicola str. Cc (Cinara cedri) and Candidatus Carsonella ruddii PV. Despite size and compositional variations, both prokaryotic and eukaryotic genomes do not deviate significantly from an equiprobable and random situation. Eukaryotic chromosomes of an organism tend to have similar informational restraints as seen when a simple distance based method is used to cluster them. In eukaryotes, in certain cases, Id values are also similar for the two arms (p and q arm) of the chromosomes. The results of this current study confirm that the information content can provide insights into the clustering of genomes and the evolution of messaging strategies of the genomes. An efficient and robust Perl CGI standalone tool is created based on this information theory algorithm for the analysis of the whole genomes and is made available at https://github.com/AlagurajVeluchamy/InformationTheory.


Modulation of electrical activity and cyclic nucleotide metabolism in molluscan nervous system by a peptide-containing nervous system extract.
A peptide-containing extract (PE) from Helix nervous system modifies the endogenous bursting pattern of electrical activity in Helix neurone F-1. This effect is similar to that induced in neuron F-1 by certain phosphodiesterase inhibitors and cAMP derivatives. The PE, and the vertebrate peptide hormones vasopressin and oxytocin, also cause an accumulation of cAMP in Helix ganglia in vitro. The factor in the PE which causes the cAMP accumulation is destroyed by Pronase, is lost on dialysis, and is stable to boiling. In all these respects it is identical to the factor which causes the change in neuronal electrical activity. The PE also stimulates adenylate cyclase activity in a crude membrane fraction prepared from Helix ganglion homogenates. This stimulation is abolished by prior dialysis of the PE, or pretreatment of the PE with pepsin, but is not affected by boiling of the PE. Pepsin-treated PE has no effect on electrical activity in neuron F-1. The adenylate cyclase-stimulating activity of the PE, like the factor which modifies neurone F-1 electrical activity, elutes in the void volume of a Sephadex G-10 column. The included volume of this column contains a factor which inhibits PE modification of neuronal electrical activity, and also inhibits both basal and PE-stimulated adenylate cyclase activity. The data are consistent with the possibility that cAMP mediates the effects of the PE on electrical activity in molluscan neurones.


Block copolymer micelles for the encapsulation and delivery of amphotericin B.
To assess the effect of fatty acid substitution of a micelle-forming poly(ethylene oxide)-block-poly(N-hexyl stearate-L-aspartamide) (PEO-b-PHSA) on the encapsulation, hemolytic properties and antifungal activity of amphotericin B (AmB). PEO-b-PHSA with three levels of stearic acid substitution were synthesized and used to encapsulate AmB by a solvent evaporation method. Size exclusion chromatography and UV spectroscopy were used to confirm and measure levels of encapsulated AmB. The hemolytic activity of encapsulated AmB toward human red blood cells and its minimum inhibitory concentration against Candida albicans, Aspergillus fumigatus and Cryptococcus neoformans were obtained and compared to AmB alone. An increase in the level of stearic acid substitution on PEO-b-PHSA improved the encapsulation of AmB while reducing its hemolytic activity. PEO-b-PHSA micelles having 50% and 70% stearic acid substitution (mol fatty acid: mol reacted and unreacted hydroxyls) were completely non-hemolytic at 22 microg/ml. At 11% stearic acid substitution, AmB caused 50% hemolysis at 1 microg/ml. AmB in PEO-b-PHSA micelles was as effective as AmB alone against pathogenic fungi. PEO-b-PHSA micelles with a high level of stearic acid side chain substitution can effectively solubilize AmB, reduce its hemolytic activity yet retain its potent antifungal effects.


The neuro-radiological examination of endocrine disorders of central origin in the child (precocious puberty, hypopituitarism).
The neuro-radiological findings in 38 cases of precocious puberty of central origin and 9 cases of hypopituitarism (craniopharyngiomas excepted), are reported. The radiological examination consisted of plain films of the skull and pneumo-encephalography. In the 9 cases with hypopituitarism radiological examination was normal in 4 and localised but quite diverse anomalies were discovered in 5. Out of 38 patients presenting with isosexual precocious puberty, 29 were female and 9 male. Out of the 29 girls, neuro-radiological examination was normal in 20 and showed a hypothalamic anomaly in 9. Out of the 9 boys, 8 had a hypothalamic anomaly, and only one examination was normal. In precocious puberty we found 1 ectopic pinealoma and 2 gliomas of the chiasma. In these three cases the clinical context and radiological examination made the diagnosis obvious. Masses were discovered in 7 (3 spongioblastomas and 4 heterotopias). In 2 cases (spongioblastomas) neurological symptoms were present and made an operation mandatory. In 5 cases (1 spongioblastoma, 4 heterotopias) precocious puberty was an isolated finding. It was not possible to make, on a clinical or radiological bases, a distinction between spongioblastoma and heterotopia. As time has passed the role of surgery has changed. Formerly, surgery aimed at excision of the lesion, but with advances in medical treatment surgical intervention is now directed towards biopsy and the histological study of lesions which may be treated by radiotherapy.


Storage and preservation of blood and urine for trace element analysis. A review.
In any well-defined study, a sample preservation and storage scheme compatible with the information or analyte sought should be incorporated. This article emphasizes the need for preservation and storage of biological fluids collected for trace element determination; cites the major factors, such as container material, container pretreatment, storage time, storage temperature, and contamination of the laboratory environment affecting preservation; presents a historical account of the available literature studies on the preservation and storage of trace metals in whole blood, plasma, serum, and urine; and makes recommendations on the most effective storage and preservation methods.


Towards a better understanding of the relationships between the structure and antitumor activity of Gastrodia elata polysaccharides by asymmetrical flow field-flow fractionation.
To better understand the structure-function relationship of Gastrodia elata polysaccharides (PGEs), PGEs were extracted by ultrasound-assisted extraction method and the effects of extraction time on the structure and conformation of PGEs were evaluated by asymmetrical flow field-flow fractionation (AF4) coupled online with multiangle light scattering (MALS) and differential refractive index (dRI) detectors (AF4-MALS-dRI). Besides separation, AF4-MALS-dRI can provide more information about PGEs, such as size and molecular weight (Mw) distributions, apparent density, and conformation. The effects of PGEs on the proliferation, apoptosis, and cell cycle of MCF-7 cells were investigated. The cell activity assay indicated that the PGEs can inhibit the growth of MCF-7 cells by inducing late apoptosis. The results indicated that PGEs with a spherical conformation and compact structure seem to be beneficial to inducing MCF-7 cells late apoptosis. Moreover, results demonstrated that the information obtained by AF4-MALS-dRI is valuable for better understanding of the relationship of structure-activity of PGEs.


Risk factors for rebleeding in Crohn's disease patients with acute severe lower gastrointestinal bleeding: With special reference to the role of anti-tumor necrosis factor therapy.
Acute severe lower gastrointestinal bleeding (LGIB) in patients with Crohn's disease (CD) is uncommon; however, it is a potentially life-threatening complication, and its recurrence is common. We thus aimed to identify the predictors for rebleeding in CD patients with acute severe LGIB and particularly focused on whether anti-tumor necrosis factor (TNF) therapy lowers the risk of rebleeding compared with conventional medical therapy (CMT) or surgery. The risk of rebleeding was analyzed in 131 CD patients with acute severe LGIB. Patients were classified into the CMT group (n = 99), anti-TNF therapy group (n = 22), and surgery group (n = 10). No patients in the surgery group received anti-TNF therapy. During the median follow-up of 98 months after the first episode of acute severe LGIB, rebleeding occurred in 50.5%, 18.2%, and 30.0% of the CMT group, anti-TNF therapy group, and surgery group, respectively (P = 0.015). The cumulative risks of rebleeding at 1 and 10 years were 20.0% and 64.7% in the CMT group, 13.6% and 18.4% in the anti-TNF therapy group, and 0% and 40.7% in the surgery group, respectively (P = 0.020). Multivariable Cox regression analysis showed that anti-TNF therapy was associated with a lower risk of rebleeding compared with CMT (hazard ratio, 0.303; 95% confidence interval, 0.108-0.849; P = 0.023). In CD patients with acute severe LGIB, anti-TNF therapy may reduce the risk of rebleeding compared with CMT. Although surgery is considered effective in preventing early rebleeding, concomitant anti-TNF therapy may be helpful in further lowering the long-term risk of rebleeding.


A systematic review of predicted pathogenic PALB2 variants: an analysis of mutational overlap between epithelial cancers.
Partner and localiser of BRCA2 forms part of a macromolecular complex with BRCA1 and BRCA2, which is critical for the repair of double-strand DNA breaks by homologous DNA recombination. Germline loss-of-function variants in the PALB2 gene may confer an increased lifetime risk of breast, pancreatic, ovarian and other cancers. However, the complete spectrum of predicted pathogenic PALB2 variants associated with each tissue type of cancer remains unknown. A systematic review is performed with the aim of cataloguing predicted pathogenic PALB2 variants in breast, ovary and pancreas cancers. All catalogued predicted pathogenic variants are analysed to assess for overlap and mutational "hotspots" within gene exons. Our results showed that 911 (92.5%) cases were described in breast cancer patients, 49 (5.0%) cases were described in ovarian cancer patients, and 24 (2.4%) cases were described in pancreatic cancer patients. The top five most frequently reported predicted pathogenic PALB2 variants were c.509_510delGA, c.3113G > A, c.1592delT, c.172_175delTTGT, and c.1240C > T, accounting for 57.3% of all cases. Breast and pancreatic cancers share five variants while breast and ovarian cancers share 12 variants. Breast, ovarian and pancreatic cancers share eight common variants. Exons with the highest mutation rates were exons 2 (6.7%), 1 (6.3%) and 3 (5.8%). This systematic review provides a quantitative catalogue of predicted pathogenic PALB2 variants described in cancers. This comprehensive analysis of the PALB2 mutational spectrum represents a useful resource for clinicians overseeing PALB2-related cancer surveillance and provides a valuable resource for future PALB2-specific research.


Two cases of Actinomyces pyogenes infection in humans.
Few confirmed human cases of Actinomyces pyogenes infection have been reported partly because of inadequate identification of this bacterium. In this study, two new cases are reported with emphasis on the characteristics which are relevant for identification of the isolates. A review of previously reported cases is presented.


Inflammatory myofibroblastic tumor with predominant anaplastic lymphoma kinase-positive cells lacking a myofibroblastic phenotype.
Inflammatory myofibroblastic tumor (IMT), synonymously referred to as inflammatory pseudotumor, is a distinctive mesenchymal lesion composed of spindle cells displaying morphological features of myofibroblasts admixed with considerable numbers of inflammatory cells. Recent genetic and molecular studies have shown that a subset of IMT is characterized by the expression of altered anaplastic lymphoma kinase (ALK) protein mostly resulting from rearrangements of the ALK gene such as TPM3-ALK, TPM4-ALK and CLTC-ALK fusion genes. We analyzed the ALK status in nine cases of IMT arising in various anatomical locations. Six cases showed immunohistochemical expression of the ALK protein, and two ALK-positive lesions examined by reverse transcription-polymerase chain reaction and a subsequent sequencing analysis harbored the TPM4-ALK fusion gene. Of note, the majority of ALK-positive tumor cells in four of the six lesions lacked the coexpression of myogenic markers including alpha-smooth muscle actin, a cytoskeletal protein indicating myofibroblastic differentiation, whereas a substantial number of tumor cells in the remaining two cases coexpressed ALK and alpha-smooth muscle actin and/or desmin. In an ultrastructural study of the lesion with predominant ALK-positive/actin-negative cells, spindle cells failed to demonstrate features of myofibroblasts such as intracytoplasmic bundles of thin filaments and dense bodies. The current findings suggest that ALK-positive cells in IMT are not always myofibroblastic but might be immature primitive mesenchymal cells.


Interleukin (IL)-2 and IL-12 responses to Chlamydia trachomatis infection in adolescents.
Chlamydia trachomatis infects epithelial cells at the mucosal surface. While in vitro and animal studies have shown changes in mucosal T(H)1-associated cytokines in the presence of C. trachomatis infection and with its progression to the upper genital tract or clearance, in vivo cytokine responses to chlamydial infection in humans are not well understood. Using a quantitative enzyme-linked immunosorbent assay (ELISA), we examined the endocervical production of two T(H)1-associated cytokines, i.e. interleukin (IL)-2 and IL-12, in relation to C. trachomatis infection in adolescents. At a randomly selected visit for 396 females, median endocervical IL-2 levels were significantly lower (190 versus 283 pg/ml, P = 0.02) and median IL-12 levels significantly higher (307 versus 132 pg/ml, P < 0.001) in subjects testing positive versus negative for C. trachomatis. These divergent T(H)1-associated cytokine responses were: (1) confirmed in paired analyses of 96 individuals before and after infection within 6-month intervals, (2) reversible in 97 patients who cleared infection during consecutive visits, (3) not attributable to sociodemographic factors or other genital infections and (4) independent of common genetic variants at the IL2 and IL12B loci associated previously with differential gene expression. From these findings we infer that increased IL-12 and decreased IL-2, observed commonly during mucosal inflammation, are important features of mucosal immune defence against C. trachomatis infection.


[Changes of masticatory muscles after occlusal recovery in rats with unilateral chew].
To study the effect of occlusal recovery on masticatory muscles in rats with unilateral chew. 40 white rats were divided into two experimental groups and two control groups. The right upper and lower posterior teeth of all the rats were ground to the gingival level without occlusal contact. The rats of the first experimental and control group were killed 10 weeks late,those of the second groups were killed 16 weeks late. The pathological changes of masticatory muscles were studied. SPSS 10.0 software package was used for statistical analysis. There was significant correlation between the first experimental group and control group in the damage of masticatory muscles (Chi(2)=40, P<0.01). However,there was no significant correlation between the second experimental group and control group in the damage of masticatory muscles (Chi(2)=3.66, P>0.05). Early occlusal recovery can rehabilitate the damage of masticatory muscles in rats with unilateral chew.


Localization of three types of arginine vasotocin receptors in the brain and pituitary of the newt Cynops pyrrhogaster.
The distribution of three types of arginine vasotocin (AVT) receptors in the brain and pituitary of the newt Cynops pyrrhogaster, namely, the V1a-, V2-, and V3/V1b-type receptors, was studied by means of in situ hybridization and immunohistochemistry. mRNA signals and immunoreactive cells for the V1a-type receptor were observed in the telencephalon (mitral layer of the olfactory bulb, dorsal and medial pallium, lateral and medial amygdala, bed nucleus of the decussation of the fasciculus telencephali, bed nucleus of the stria terminalis), diencephalon (anterior preoptic area, magnocellular preoptic nucleus, suprachiasmatic nucleus, ventral thalamus, dorsal and ventral hypothalamic nucleus), mesencephalon (tegmentum, interpeduncular nucleus), and medulla oblongata (median reticular formation, nucleus motorius tegmenti). Cells expressing the V2-type receptor were found in the telencephalon (medial pallium, lateral and medial amygdala, bed nucleus of the decussation of the fasciculus telencephali), and mesencephalon (tegmentum trigemini and facialis). In the paraphysis (possibly the main site of cerebrospinal fluid production), only V2-type receptor mRNA signal and immunoreactivity were detected. V3/V1b-type receptor mRNA was expressed in the diencephalon (dorsal hypothalamic nucleus, nucleus tuberculi posterioris), mesencephalon (tegmentum, interpeduncular nucleus), and medulla oblongata (raphe nucleus), whereas V3/V1b-type-receptor-like immunoreactivity was scarcely detectable in the entire brain. The V3/V1b-type receptor was predominantly expressed in the anterior pituitary. V3/V1b-type receptor and proopiomelanocortin mRNAs were co-localized in the distal lobe of the pituitary. This is the first report of the distribution of three types of AVT receptor in the brain and pituitary of non-mammalian vertebrates.


Metabolic Modulation of Intracellular Ammonia via Intravesical Instillation of Nanoporter-Encased Hydrogel Eradicates Bladder Carcinoma.
Tumor protein 53 (TP53) mutation in bladder carcinoma (BC), upregulates the transcription of carbamoyl phosphate synthetase 1 (CPS1), to reduce intracellular ammonia toxicity. To leverage ammonia combating BC, here, an intravesically perfusable nanoporter-encased hydrogel system is reported. A biomimetic fusogenic liposomalized nanoporter (FLNP) that is decorated with urea transporter-B (UT-B) is first synthesized with protonated chitosan oligosaccharide for bladder tumor-targeted co-delivery of urease and small interfering RNA targeting CPS1 (siCPS1). Mussel-inspired hydrogel featured with dual functions of bio-adhesion and injectability is then fabricated as the reservoir for intravesical immobilization of FLNP. It is found that FLNP-mediated UT-B immobilization dramatically induces urea transportation into tumor cells, and co-delivery of urease and siCPS1 significantly boosts ammonia accumulation in tumor inducing cell apoptosis. Treatment with hybrid system exhibits superior anti-tumor effect in orthotopic bladder tumor mouse model and patient-derived xenograft model, respectively. Combined with high-protein diet, the production of urinary urea increases, leading to an augmented intracellular deposition of ammonia in BC cells, and ultimately an enhanced tumor inhibition. Together, the work establishes that cascade modulation of ammonia in tumor cells could induce tumor apoptosis and may be a practical strategy for eradication of TP53-mutated bladder cancer.


Calcitonin gene-related peptide promotes transient radiocalcium uptake into chick bone in vivo.
We have examined the in vivo effects in chicks of intravenously injected chicken (c-) and rat (r-) calcitonin gene-related peptides (CGRP) on uptake into bone of a simultaneously administered 45Ca label. Both peptides caused transient (10 min) increases in 45Ca uptake into a variety of bone types. In dose-response experiments at 10 min, CGRP doses of 0.26-1.04 nmol/100 g body wt were found to give maximal responses. These were well developed in chicks fasted for 22 h but absent in those which were continuously fed. This contrasts with the hypercalcaemic effect of CGRP which is apparent in fed rather than fasted chicks.


Allergic contact dermatitis to phenol-formaldehyde resin at a single tertiary dermatology centre.
Phenol-formaldehyde resin 2 (PFR2) has been shown to be a useful marker of contact allergy (CA) to various phenol-formaldehyde resins. These compounds are used in several industries as solids, powders, or semisolid resins, and are known to be sensitizing agents. The aims were to investigate contact allergy to PFR2 in a single tertiary dermatology centre, to examine associated simultaneous allergic reactions, and to identify cases of allergic contact dermatitis (ACD) to PFR2. A retrospective study was performed of patients patch tested to PFR2 between 1 January 2003 and 17 June 2020. In all, 337 of 7922 patients were tested to PFR2 and 16 (4.7%) reacted. Of those 16 individuals, six (37.5%) had a relevant reaction (1.8% of total). Simultaneous allergic reactions were noted to colophonium in eight (50.0%) patients, Myroxylon pereirae in five (31.3%), and fragrance mix I (FMI) of three cases (18.8%). Contact allergy to PFR2, even in a selected population of patients, is uncommon. However, patients exposed to plastics and glues, or who work with wood products should be routinely patch tested to a plastics and glues series containing PFR2. We recommend that all centres include PFR2 in their plastics and glues series.


Localized in vivo 1H spectroscopy of human skeletal muscle: normal and pathologic findings.
To obtain high signal to noise ratio in small volume elements (8 cm3), in vivo 1H NMR spectroscopy of normal and diseased human skeletal muscle was performed using a double spin-echo localization method on a 1.5-T whole body system. High resolved spectra of normal calf muscle show the well known resonances of lipids (methyl, methylene, olefinic, and other fatty acid resonances), creatine/phosphocreatine, choline/carnitine, taurine, and histidine with good intraindividual reproducibility. Pronounced intraindividual differences in the lipid range were found between different upper thigh muscle groups. On pathologic conditions like myopathy, myositis or irradiation damage the spectral lipid content was increased. Three months after local irradiation of the medial vastus muscle (50 Gy), the localized 1H NMR spectrum showed a complete loss of the choline and creatine signals. In a case of M. Behçet with muscular involvement the relative reduction of the choline signal may provide an insight in the pathobiochemistry. The results of our investigations in nine healthy volunteers and three patients are presented in detail including relaxation times of the metabolites.


ADCK2 Knockdown Affects the Migration of Melanoma Cells via MYL6.
ADCK2 is a member of the AarF domain-containing kinase family, which consists of five members, and has been shown to play a role in CoQ metabolism. However, ADCKs have also been connected to cancer cell survival, proliferation and motility. In this study, we investigated the role of ADCK2 in melanoma. The effect of ADCK2 on melanoma cell motility was evaluated by a scratch assay and a transwell invasion assay upon siRNA-mediated knockdown or stable overexpression of ADCK2. We found that high levels of intratumoral ADCK2 and MYL6 are associated with a higher survival rate in melanoma patients. Knocking down ADCK2 resulted in enhanced cell migration of melanoma cells. Moreover, ADCK2-knockdown cells adopted a more dedifferentiated phenotype. A gene expression array revealed that the expression of ADCK2 correlated with the expressions of MYL6 and RAB2A. Knocking down MYL6 in ADCK2-overexpressing cells could abrogate the effect of ADCK2 overexpression and thus confirm the functional connection between ADCK2 and MYL6. ADCK2 affects melanoma cell motility, most probably via MYL6. Our results allow the conclusion that ADCK2 could act as a tumor suppressor in melanoma.


Evaluation of groundwater quality in central Saudi Arabia using hydrogeochemical characteristics and pollution indices.
The groundwater quality and heavy metal (HM) contamination were evaluated in palm farms, central Saudi Arabia, using pollution indices, irrigation quality parameters, and multivariate statistical analyses. Thirty groundwater samples were collected in October 2020 for major anions, cations, and HMs analyses and interpretation. The results showed that the average concentrations of total dissolved solids (TDS), Ca+, Na+, K+, Cl-, SO42-, and F- were greater than the permissible limits of the WHO standards for drinking water. The groundwater facies types were Ca-Na-SO4-Cl (23 samples), Ca-Cl-SO4, (4 samples), and Ca-SO4-Cl type (3 samples). The groundwater quality index indicated that 15 groundwater samples were of good quality and 15 were of poor quality, whereas the metal index and heavy metal pollution index indicated that all samples were categorized as slightly affected and with low pollution, respectively. The variation is attributed to the increasing average concentrations of some ions and decreasing HMs. The dissolution/precipitation of silicates, gypsum, and carbonates and soil leaching were the natural factors affecting groundwater chemistry, whereas higher PO43-, NO3-, F-, Pb, and Zn values in some samples may be attributed to human activities from the extensive use of fertilizers and pesticides on the investigated farms.


The anti-allergic and anti-inflammatory effects of Benjakul extract (a Thai traditional medicine), its constituent plants and its some pure constituents using in vitro experiments.
Benjakul (BJK), a Thai traditional medicine preparation, has long been used for balanced health, controlled abnormal of element in the body, carminative, and relief of flatulence. It is composed of five plants: Piper interruptum Opiz., Piper longum L., Piper sarmentosum Roxb., Plumbago indica L., and Zingiber officinale Roscoe. The ethanolic extracts of BJK, its five individual plants, and pure constituents of BJK were investigated for their anti-allergic activity using immunoglobulin E (IgE)-sensitized β-hexosaminidase in the rat basophilic leukemia-2H3 (RBL-2H3) cells and anti-inflammatory activity using lipopolysaccharide (LPS)-induced nitric oxide (NO) and tumor necrosis factor-alpha (TNF-α) in the murine macrophage (RAW 264.7) cells. The ethanolic extracts of BJK showed anti-allergic activity (IC50=12.69μg/ml) and exhibited potent NO inhibitory effect (IC50=16.60μg/ml), but inactive on TNF-α release. Moreover, 6-shogaol and plumbagin, two pure compounds from BJK, showed higher anti-allergic activity than the ethanolic BJK extract with IC50 values of 0.28 and 4.03μg/ml, respectively. These compounds were significantly higher than chlorpheniramine (CPM), standard drug, with IC50 value of 17.98μg/ml. Determination of the anti-inflammatory activity by measuring the inhibition of NO production presented that plumbagin and 6-shogaol exhibited higher than crude BJK extract with IC50 values of 0.002 and 0.92μg/ml, respectively. In particular, plumbagin also showed higher anti-inflammatory than prednisolone, positive control, with IC50 value of 0.59μg/ml. 6-Shogaol also showed inhibitory effect on TNF-α release (IC50=9.16μg/ml). These preliminary results may provide some scientific support for the use of BJK for the anti-allergic treatment and inflammatory disorders through the inhibition of NO production.


A randomized, controlled clinical trial of plasma exchange with albumin replacement for Alzheimer's disease: Primary results of the AMBAR Study.
This phase 2b/3 trial examined the effects of plasma exchange (PE) in patients with mild-to-moderate Alzheimer's disease (AD). Three hundred forty-seven patients (496 screened) were randomized (1:1:1:1) into three PE treatment arms with different doses of albumin and intravenous immunoglobulin replacement (6-week period of weekly conventional PE followed by a 12-month period of monthly low-volume PE), and placebo (sham). PE-treated patients performed significantly better than placebo for the co-primary endpoints: change from baseline of Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL; P = .03; 52% less decline) with a trend for Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog; P = .06; 66% less decline) scores at month 14. Moderate-AD patients (baseline Mini-Mental State Examination [MMSE] 18-21) scored better on ADCS-ADL (P = .002) and ADAS-Cog (P = .05), 61% less decline both. There were no changes in mild-AD patients (MMSE 22-26). PE-treated patients scored better on the Clinical Dementia Rating Sum of Boxes (CDR-sb) (P = .002; 71% less decline) and Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) (P < .0001; 100% less decline) scales. This trial suggests that PE with albumin replacement could slow cognitive and functional decline in AD, although further studies are warranted.


Reversible Fetal Tracheal Occlusion in Mice: A Novel Minimal Invasive Technique.
There is a certain need for reversible, cheap, and reproducible animal models for understanding the impact of tracheal occlusion (TO) in the congenital diaphragmatic hernia and pathophysiology. We aimed to present an easy, reversible, and minimally invasive murine TO model with optimized time points for introduction and removal of TO. Time-mated C57BL/6 mice underwent laparotomy at embryonic day 16.5 (E16.5) with transuterine TO performed on two fetuses in each uterine horn. In the TO group, the fetuses were harvested at E18.5 without suture removal; the suture was released at E17.5 in the TO-R group, and all fetuses were harvested at E18.5. The lungs of the fetuses were compared by morphometric and histologic analysis. Successful TO was confirmed in 34 of 37 fetuses. Twenty-nine of them survived to E18.5 (90.6%), six of the fetuses had a spontaneous vaginal delivery. Fetal weights were comparable, but there was significant difference in lung weights and lung-to-body weight ratios (0.020 ± 0.006 [control] versus 0.026 ± 0.002 [TO] versus 0.023 ± 0.005 [TO-R]; P = 0.013). DNA/protein and DNA/lung weight ratios were elevated, whereas protein/lung weight ratio was lower in TO compared with the control group. Reversal of fetal transuterine TO at E17.5, which was put at E16.5 in mice, is feasible with comparable outcomes to other current animal models with certain advantages and potential to translate the studies to the human.


Detection of mycobacterial DNA from sputum of patients with cystic fibrosis.
Patients with cystic fibrosis (CF) are at high risk from atypical mycobacterial infections. There have been few attempts to delineate the intensity of mycobacterial infection in CF patients in Ireland. To examine the incidence of mycobacterial DNA in an archived collection of genomic DNA extracted from the sputa of CF patients within the Northern Ireland population. One hundred and eighty-two CF patients (66 adults and 116 children) were examined for the presence of mycobacterial DNA in their sputum by a genus specific PCR assay based on 16S rRNA, followed by direct automated sequencing of the PCR amplicons. One of 116 (0.9%) children and 2 of 66 adults were positive. Sequence identity revealed Mycobacterium xenopi in the paediatric patient and M. xenopi and M. chelonei in the two adult patients. False-positive results occurred in 11 patients (four adults), mainly due to Corynebacterium spp. There was a low prevalence of Mycobacterium spp in the CF patient population. All PCR positive results should be confirmed by direct automated sequencing and an alternative specific assay employed. Enhanced molecular screening will contribute in understanding their role as opportunistic pathogens in patients with worsening lung function.


Multivariate multi-scale weighted permutation entropy analysis of EEG complexity for Alzheimer's disease.
The complexity change of brain activity in Alzheimer's disease (AD) is an interesting topic for clinical purpose. To investigate the dynamical complexity of brain activity in AD, a multivariate multi-scale weighted permutation entropy (MMSWPE) method is proposed to measure the complexity of electroencephalograph (EEG) obtained in AD patients. MMSWPE combines the weighted permutation entropy and the multivariate multi-scale method. It is able to quantify not only the characteristics of different brain regions and multiple time scales but also the amplitude information contained in the multichannel EEG signals simultaneously. The effectiveness of the proposed method is verified by both the simulated chaotic signals and EEG recordings of AD patients. The simulation results from the Lorenz system indicate that MMSWPE has the ability to distinguish the multivariate signals with different complexity. In addition, the EEG analysis results show that in contrast with the normal group, the significantly decreased complexity of AD patients is distributed in the temporal and occipitoparietal regions for the theta and the alpha bands, and also distributed from the right frontal to the left occipitoparietal region for the theta, the alpha and the beta bands at each time scale, which may be attributed to the brain dysfunction. Therefore, it suggests that the MMSWPE method may be a promising method to reveal dynamic changes in AD.


Knowledge, Attitude and Perception of HIV/Aids Among Antenatal Women and its Correlation with their Socio-Demographic Profile: Study from a Tertiary Care Centre of Northern India.
To evaluate the knowledge, attitude and perception of HIV/AIDS among antenatal women and to correlate them with their socio-demographic profile. We conducted this study on 400 pregnant women attending the antenatal clinic of our hospital for the first time irrespective of their period of gestation, age and parity. All the participants were interviewed with the help of a predesigned questionnaire which included their socio-demographic details and questions to assess their knowledge and attitude toward HIV/AIDS. Data were analyzed using SPSS version 22 and expressed in the form of percentage, frequency distribution, mean, standard deviation and p value. Antenatal women of the study population were having unsatisfactory knowledge about HIV/AIDS and prevention of MTCT. 26% women were totally unaware of any entity like HIV. 44% participants did not know the most common way of spread of HIV. Only half of the subjects knew the correct preventive measures for HIV/AIDS. 54% knew about MTCT, but only 24% knew about its transmission through breast milk. Knowledge and attitude was found to be significantly improving with socioeconomic status. Indian antenatal women have poor awareness and wrong perception about HIV/AIDS and its mother to child transmission (MTCT). Targeted educational interventions can be formulated to increase awareness among antenatal women about prevention of vertical transmission of HIV.


Arachidonic acid metabolites in a nephroblastoma associated with paraneoplastic hypercalcemia.
Blood concentration of PGE2, F2a, 6 keto PGF1a (6kF1a), TxB2 and 13, 14 dehydro 15 keto PGE2 (13, 14 OH 15 k E2) were measured in renal artery and vein of a patient with a PGs producing nephroblastoma. The tumor tissue produced PGs in the following order: PGF2a greater than PGE2 greater than TxB2 greater than 6kF1a greater than 13, 14 OH 15 k E2. However, renal artery concentration of the substances were as follows: 13, 14 OH 15 k E2 greater than TxB2 greater than 6kF1a greater than PGF2a greater than PGE2. Since arterial concentration is critical to postulating a calcium mobilizing effect on bone tissue, PGE2 arterial level seems to be too low to exert a pathogenetic role on hypercalcemia, at least in the patient reported here.


IRE1α-XBP1 but not PERK inhibition exerts anti-tumor activity in osteosarcoma.
Osteosarcoma (OS) is the most common primary malignant bone tumor. However, the therapeutic results of the advanced cases at the first visit were still extremely poor. Therefore, more effective therapeutic options based on molecular profiling of OS are needed. In this study, we investigated the functions of endoplasmic reticulum (ER) stress activities in OS and elucidated whether ER stress inhibitors could exert antitumor effects. The expression of 84 key genes associated with unfolded protein response (UPR) was assessed in four OS cells (143B, MG63, U2OS and KHOS) by RT2 Profiler PCR Arrays. Based on results, we performed both siRNA and inhibitor assays focusing on IRE1α-XBP1 and PERK pathways. All OS cell lines showed resistance to PERK inhibitors. Furthermore, ATF4 and EIF2A inhibition by siRNA did not affect the survival of OS cell lines. On the other hand, IRE1α-XBP1 inhibition by toyocamycin suppressed OS cell growth (IC50: < 0.075 μM) and cell viability was suppressed in all OS cell lines by silencing XBP1 expression. The expression of XBP1s and XBP1u in OS cell lines and OS surgical samples were confirmed using qPCR. In MG63 and U2OS, toyocamycin decreased the expression level of XBP1s induced by tunicamycin. On the other hand, in 143B and KHOS, stimulation by toyocamycin did not clearly change the expression level of XBP1s induced by tunicamycin. However, morphological apoptotic changes and caspase activation were observed in these two cell lines. Inhibition of the IRE1α-XBP1s pathway is expected to be a promising new target for OS.


Novel Catechin-Tiopronin Conjugates Derived from Grape Seed Proanthocyanidin Degradation: Process Optimization, High-Speed Counter-Current Chromatography Preparation, as Well as Antibacterial Activity.
Tiopronin, as a novel thiol-containing nucleophile, was introduced for depolymerizing polymeric proanthocyanidins from grape seed into catechins and three new proanthocyanidin-tiopronin degradation products: (+)-catechin-4β-S-tiopronin methyl ester (CT), (-)-epicatechin-4β-S-tiopronin methyl ester (ECT), and (-)-epicatechin gallate-4β-S-tiopronin methyl ester (ECGT). A Box-Behnken design was employed to optimize degradation conditions based on single-factor experiments to obtain target products. Each of the new degradation compounds was isolated by the high-speed counter-current chromatography combined with semipreparative high performance liquid chromatography in large amounts, and then, their structures were identified by 1H NMR, 13C NMR, 2D-NMR, as well as mass spectrometry analysis. The absolute configurations were further confirmed by comparison between the calculated electronic circular dichroism and experimental spectra. Further evaluation of antibacterial activities of these compounds showed that CT and ECT possessed more inhibiting capacity against Staphylococcus aureus and Escherichia coli than parent compound catechin and epicatechin. However, ECGT has no bacteriostatic capacity against these two bacteria.