A simple simulation model of dispersal of animals among units of discrete habitats.
A simple simulation model of dispersal of animals among units of discrete habitats has been constructed. This model outputs the numbers of animals reaching each of twenty-five "habitats" at preselected loci in a grid under a variety of operating conditions. These conditions consist of variables controlling directionality, velocity and mortality during dispersal. The relationship between numbers of animals reaching a particular site and the distance of that site from the starting point was investigated. Similarly, the effects of directionality (as determined by the variance of the normal distribution used to assign directions of movement), mortality and velocity on the overall rate of success were studied. A negative exponential-type drop off in numbers of animals reaching a site was predicted with increasing distance from the starting point. The relationship between percent success, directionality and rate of mortality was predicted to be curvilinear; the percentage declining with decreased directionality and increased mortality. A positive linear relationship was indicated between the spatial displacement per iteration used and percent success.Wherever possible the assumptions and predictions of the model are compared with available data. The assumptions concerning initial and subsequent directions of movement were found to be borne out by the data examined as were the results showing the relationship between numbers at each site and distance from starting point. The other results of the simulations were more difficult to compare with available data and some of these remain to be tested.The advantages and disadvantages of the model and the prospects for its expansion are discussed. It is concluded that the model is simplistic but that this gives it a generality and versatility which make it a useful tool for further thinking and investigation on the process of dispersal.


Accuracy of caregivers' recall of hospital admissions: implications for research.
To determine the accuracy of caregivers' recall of hospital admissions in early childhood. Prospective cohort study of babies born at risk of neonatal hypoglycaemia at Waikato Hospital, New Zealand, a regional public hospital and sole provider of acute inpatient care to over 100,000 children. Caregivers' recall of children's hospital admissions up to 4.5 years was compared with medical records. Accuracy of recall was related to neonatal and socio-demographic characteristics. Of 267 children, 179 (67%) visited hospital and 106 (40%) were admitted at least once. The most frequent reasons for admission were for respiratory (29%) and gastrointestinal (18%) problems. Of 106 children admitted to hospital, 27 (25%) caregivers did not recall the admission and only 37 (35%) accurately recalled the number of admissions. The accuracy of recall was lower for gastrointestinal (38%) and surgical (40%) problems, while recall of respiratory (64%) and ear, nose and throat (60%) admissions was more accurate. Low socio-economic status and multiple admissions were associated with less accurate recall of number of admissions. Caregivers do not accurately report hospital admissions. Questionnaire data about use of hospital facilities should be interpreted cautiously and may not be sufficiently accurate for use in research studies.


SsATG8 and SsNBR1 mediated-autophagy is required for fungal development, proteasomal stress response and virulence in Sclerotinia sclerotiorum.
Autophagy plays vital roles in the interaction between the necrotrophic fungal pathogen Sclerotinia sclerotiorum and its hosts. However, so far, only little is known about the impacts of autophagy machinery in S. sclerotiorum per se on the fungal morphogenesis and pathogenesis. Here, through functional genomic approaches, we showed that SsATG8, one of the core components of the autophagy machinery, and its interactor SsNBR1, an autophagy cargo receptor, are important for vegetative growth, sclerotial formation, oxalic acid (OA) production, compound appressoria development, and virulence of S. sclerotiorum. Complementation assays with chimeric fusion constructs revealed that both LDS [AIM (ATG8 interacting motif) / LIR (LC3-interacting region) docking site] and UDS [UIM (ubiquitin-interacting motif) docking site] sites of the SsATG8 are required for its functions in autophagy and pathogenesis. Importantly, ΔSsatg8 and ΔSsnbr1 mutants showed enhanced sensitivity to the exogenous treatment with the proteasome inhibitors bortezomib and carfilzomib, and ΔSsnbr1 mutant had decreased expression of SsATG8 under the proteasomal stress conditions, suggesting that a cross-talk exists between ubiquitin-proteasome and selective autophagy pathways, which enables downstream protein degradation to proceed properly during diverse biological processes. Collectively, our data indicate that SsATG8- and SsNBR1-mediated autophagy is crucial for S. sclerotiorum development, proteasomal stress response and virulence.


Diagnostic Tests for Latent Tuberculosis Infection.
Diagnosing latent tuberculosis (TB) infection (LTBI) is important globally for TB prevention. LTBI diagnosis requires a positive test for infection and negative evaluation for active disease. Current tests measure an immunologic response and include the tuberculin skin test (TST) and interferon-gamma release assays (IGRAs), T-SPOT.TB and QuantiFERON. The IGRAs are preferred in bacille Calmette-Guérin-vaccinated populations. The TST is still used when cost or logistical advantages over the IGRAs exist. Both TST and IGRAs have low positive predictive values. Tests that differentiate the TB spectrum and better predict future TB risk are needed.


New patch-based strategy for COVID-19 automatic identification using chest x-ray images.
The development of a robust model for automatic identification of COVID-19 based on chest x-rays has been a widely addressed topic over the last couple of years; however, the scarcity of good quality images sets, and their limited size, have proven to be an important obstacle to obtain reliable models. In fact, models proposed so far have suffered from over-fitting erroneous features instead of learning lung features, a phenomenon known as shortcut learning. In this research, a new image classification methodology is proposed that attempts to mitigate this problem. To this end, annotation by expert radiologists of a set of images was performed. The lung region was then segmented and a new classification strategy based on a patch partitioning that improves the resolution of the convolution neural network is proposed. In addition, a set of native images, used as an external evaluation set, is released. The best results were obtained for the 6-patch splitting variant with 0.887 accuracy, 0.85 recall and 0.848 F1score on the external validation set. The results show that the proposed new strategy maintains similar values between internal and external validation, which gives our model generalization power, making it available for use in hospital settings. The online version contains supplementary material available at 10.1007/s12553-022-00704-4.


Electrophysiological identification of superior vena cava: Novel insight into slow conduction or conduction block.
It has not been clarified how to identify the electrophysiological junction between right atrium (RA) and superior vena cava (SVC). The aim of this study was to identify the electrophysiological RA-SVC junction according to slow conduction or conduction bock and to examine the electrophysiological SVC isolation procedure. Seventy-three consecutive atrial fibrillation patients who underwent SVC mapping using a CARTO 3 system were enrolled in this study. Slow conduction or conduction block between the RA and SVC was identified by adjusting the lower threshold criteria of the early meets late function and was described as a white line. The SVC isolation was performed along the white line and with pacing maneuvers to confirm direct SVC capture. Activation mapping (1296 ± 631 points) was obtained in 66 patients (90%) in 4.6 ± 1.8 min. Slow conduction or conduction block was observed in all patients. The threshold for detecting slow conduction or conduction block was 24 ± 8 ms. The location of the electrophysiological RA-SVC junction was higher in the anterior portion (anterior-septal, anterior, and anterior-lateral) than in the posterior portion (posterior-septal, posterior, and posterior-lateral) (-2.3 ± 6.2 mm vs. 7.1 ± 6.3 mm, p < .001). The SVC isolation at the electrophysiological RA-SVC junction was successful in all patients without any injury to the sinus node function. Asymptomatic phrenic nerve injury was observed in three patients (4.5%). In all patients, the electrophysiological RA-SVC junction determined by slow conduction or conduction block was identified and the electrophysiological SVC isolation was performed successfully and safely.


Pro-inflammatory potential of ultrafine particles in mono- and co-cultures of primary cardiac cells.
Inhalation of particulate air pollution has been associated with increased risks for cardiovascular mortality and morbidity, but the underlying mechanisms are still under discussion. One possible pathway may be that inhaled particles cross the air-blood barrier and interact directly with cardiac tissue. The aim of the present study was to examine the pro-inflammatory potential of particles in cardiac cells. Mono- and co-cultures of primary adult male Wistar (Han) rat cardiomyocytes (CMs) and cardiofibroblasts (CFs) were exposed to increasing concentrations of ultrafine (<100nm) carbon black particles (Printex 90). Expression and release of cytokines (IL-6, IL-1beta and TNF-alpha) were measured by using quantitative real-time PCR and ELISA, respectively. Cytotoxicity was estimated by measuring cellular release of lactate dehydrogenase (LDH). A particle concentration-dependent increase in IL-6 release was observed in both CM mono- and co-cultures (EC(50) approximately 57microg/ml). Furthermore, IL-6 levels detected in both control and particle-exposed co-cultures were synergistically increased compared to mono-cultures (10-19-fold, dependent on the exposure). Experiments with contact and non-contact co-cultures indicate that direct cellular contact is of key importance for the enhanced release of IL-6 in co-cultures. An apparent particle-induced release of IL-1beta was only detected in co-cultures. The release of TNF-alpha was low and did not seem notably influenced by particle exposure. Treatment with an IL-1 receptor antagonist apparently eliminated the particle-induced release of IL-6. In conclusion, ultrafine particles have a pro-inflammatory potential in primary cardiac cells. Furthermore, IL-1 seems critical in triggering particle-induced release of IL-6. These pro-inflammatory responses may be elicited when particles are translocated into the pulmonary circulation upon inhalation or administered intravascularly during medical procedures.


Attenuation of hepatic fibrosis by p-Coumaric acid via modulation of NLRP3 inflammasome activation in C57BL/6 mice.
A prolonged high-fat and high-sucrose (HFHS) diet induces hepatic inflammation and mediates hepatic stellate cell (HSC) activation, which result in hepatic fibrosis. Aberrant activation of the innate immune system components, such as the NOD-like receptor protein 3 (NLRP3) inflammasome, has been implicated in HSC activation and hepatic fibrosis. We have previously shown that p-coumaric acid (PCA)-enriched peanut sprout extracts exert anti-inflammatory effects. However, it is unknown whether PCA reduces hepatic fibrosis by modulating innate immunity and HSC activation. To test this hypothesis, C57BL/6 male mice were randomly assigned to three groups and fed low-fat (LF) diet (11% calories from fat), high-fat (HF) diet (60% calories from fat, 0.2% cholesterol) with sucrose drink (20% sucrose, HFHS), or HFHS diet with PCA treatment (HFHS+PCA, 50 mg/kg body weight, intraperitoneally) for 13 weeks. The results showed that PCA treatment (1) partly improved systemic insulin sensitivity without altering adiposity, (2) attenuated hepatic signaling pathways associated with NLRP3 inflammasome activation, including toll-like receptor 4 (TLR4)/nuclear factor kappa B (NFκB), and endoplasmic reticulum/oxidative stress, and (3) reduced circulating interleukin (IL)-1β levels. More importantly, PCA ameliorated hepatic fibrosis compared to that in the HFHS group, and the anti-fibrogenic effects of PCA were confirmed in vitro in transforming growth factor β (TGFβ) treated-LX-2 HSCs. The role of PCA in decreased NLRP3 activation and caspase-1 cleavage was recapitulated in primary bone marrow‒derived macrophages. These findings indicate that PCA contributes to the prevention of HFHS diet‒mediated liver fibrosis, partly by attenuating the activation of the NLRP3 inflammasome.


Molecular Detection of Leishmania in Wild Caught Sand Flies of Larroussius Subgenus in Iran: Combined Use of Internal and External Morphological Characters as a Mean to Differentiate Morphologically Similar Females.
Phlebotomine sand flies are the primary vectors of leishmaniasis; visceral form of disease is transmitted mainly by species belonging to Larroussius and Adlerius subgenus. Species identification of some females in Larroussius subgenus is not easy due to the high similarity. Accurate species identification enables control operations to target only main vectors and increase understanding of ecological needs, bionomic characteristics, and behavioral traits. The purpose of current study was to use two approaches based on internal and external morphological characters to identify the wild caught of female specimens belonged to Larroussius subgenus and investigate Leishmania infection. Totally, 128 specimens belonging to Larroussius' subgenus were collected from a VL focus in northwestern Iran, species differentiation was done by two approaches proposed in literature: (1) characters of pharyngeal armature, number of Spermathecal segment, length of spermathecal neck, palpal and ascoid formulae; (2) blindly on the basis of the shape of the base of spermathecal duct. Their potential infection to Leishmania was investigated by kDNA-Nested-PCR. The results of species identification were consistent based on two methods. Among three identified species, Phlebotomus perfiliewi was found to be the dominant species, followed by Ph. neglectus and Ph. tobbi. Two specimens of Ph. perfiliewi were found to be infected by Leishmania infantum, which emphasizes the role of this species in VL transmission in study area. It is suggested that combination of the characters used here be considered for species identification of female of Larroussius subgenus to take advantage of maximum characters, especially where species present sympatrically.


Exploring the experience of reflective writing among Taiwanese undergraduate nursing students: A qualitative study.
Reflective learning plays an important role in students' professional and personal development. However, some nursing curricula provide insufficient opportunity for students to understand how to reflect and what reflection is. The study aimed to explore baccalaureate nursing students' experiences of reflective writing. The study used a hermeneutic phenomenological approach. Through purposive sampling, 15 participants were recruited for individual in-depth face-to-face interviews which were conducted after they had completed the course 'Application of Emergency Nursing'. Interviews were semi-structured and audio-recorded. Additional data were obtained from 20 documents on consulting faculty for reflective writing. Data analysis was undertaken through a hermeneutic phenomenological framework based on van Manen's approach. Participants reported that reflective writing had helped them to optimise their personal and professional development. Four themes emerged from the analysis: recording a personal story, presenting a process of events, confronting challenges, and strengthening personal characteristics. Students were satisfied with their learning achievements and growth and felt they had become better through reflective writing. The results demonstrated that: reflective writing needs to be elaborated objectively and carefully; continuing self-dialogue can reveal the true meaning of an incident; students learned strategies to apply in future situations.


Evaluation of PEETER V1.0 urine sensors for measuring individual urination behavior of dairy cows.
Due to environmental concerns around N leaching and NO2 emissions from intensive pastoral dairying systems, there has been an increase in research focused on mitigation strategies and on-animal technologies to evaluate urination behavior of grazing dairy cows. Nitrogen leaching and NO2 emissions are associated with urine nitrogen loading onto pasture, which is a function of urine nitrogen concentration and urine volume per urination event. The PEETER V1.0 urine sensor (Lincoln University, Christchurch, New Zealand) is a promising on-animal measurement technology; however, it has yet to be validated in vivo. The objective of this work was to validate the PEETER V1.0 urine sensor's estimations of individual urination events (i.e., urine volume). We fitted 15 Holstein-Friesian × Jersey lactating dairy cows (506 ± 35 kg of live weight, body condition score of 3.75 ± 0.25, and 150.4 ± 20.7 d in milk) with individual PEETER V1.0 sensors and placed them in metabolism crates for 72 h. Every urination event (n = 480) was collected manually and compared with the urine volume estimated by the PEETER V1.0 sensor to determine precision and accuracy using Lin's concordance correlation coefficient (CCC). The CCC is calculated as a function of the Pearson's correlation (precision) and bias correction factor (Cb; Cb = 1 is perfect), and it demonstrates how far the values of the 2 methods are from perfect agreement (accuracy; i.e., a 45° line). The mean urination event volume (mean ± standard deviation) was 2.7 ± 0.94 and 2.6 ± 0.92 L for the actual and PEETER V1.0 sensor, respectively. The PEETER V1.0 sensor showed excellent precision (r = 0.90) with near-perfect accuracy (Cb = 1.00), and the CCC value was high (CCC = 0.90), indicating excellent agreement. Based on these results, the PEETER V1.0 urine sensor provides estimates that are precise and accurate. We conclude that the PEETER V1.0 sensor can be used to evaluate urination behavior of grazing dairy cows.


Acute kidney injury in infants with congenital diaphragmatic hernia.
To assess the incidence of acute kidney injury (AKI) in infants with congenital diaphragmatic hernia (CDH), including those who had fetoscopic endoluminal tracheal occlusion (FETO), and the effect of AKI on mortality and length of stay. Ten-year retrospective review of infants admitted with CDH to a tertiary perinatal centre. Ninety-four infants with median gestational age of 38+1 weeks were included. Fifty-nine (62.8%) infants had AKI. Compared to infants without AKI, infants with AKI, had a similar incidence of mortality (p = 0.989). In survivors, AKI was not independently associated with a longer adjusted median length of stay [23 versus 15 days (p = 0.194)]. FETO was associated with an increased risk of AKI (p = 0.005), but neither the mortality nor length of stay of FETO infants who had AKI was increased. AKI was present in the majority of infants with CDH and most common in those who had undergone FETO.


Prey size-distributions and size-specific foraging success of Ambystoma larvae.
We examined how prey size-distributions influence size-specific foraing rate and food gain, i.e., food intake scaled to metabolic demands, in Jefferson's and small-mouth salamander larvae. Ambystoma jeffersonianum larvae sampled on 17 dates from a farm pond whose fauna was dominated by macrozooplankton and chironomid larvae were rarely gape-limited, and total volume of food in the stomach (VS) showed only a slight tendency to increase with larval size. Although 15 of 17 correlation coefficients of VS with larval size were positive, only 1 of 17 correlations were statistically significant, and body size explained only 8% of the overall variation in VS. Correlation coefficients of food gain and body size were positive in 9 cases and negative in 8, but only 3 were statistically significant.In contrast, Ambystoma texanum larvae in 42 samples taken from five sites dominated by macrozooplankton as well as relatively large isopods and amphipods were almost always gape-limited, and VS tended to increase markedly with larval size. 40 of 42 correlation coefficients of VS and larval size were positive, and 19 correlations were statistically significant. Body size in turn explained about 35% of the overall variation in VS. Correlation coefficients of food gain and larval size were positive in 32 of 42 samples, and 9 of 10 significant correlations were positive.When food is limiting and prey selection is not limited by gape, smaller larvae may grow as fast or in some cases faster than larger larvae because they are nearly as effective foragers, but have lower metabolic demands. Larger larvae may in turn grow faster than smaller larvae in environments which support a broad size spectrum of prey, particularly when gape limitations are highly disproportionate among size classes. The growth rate of larvae in one size class relative to another depends primarily on the extent to which increased foraging rate compensates for higher energy demands as body size increases. Size-specific foraging rate may in turn be strongly influenced by the prey size-distribution within a habitat. These relationships suggest that relative size is not always a good a priori predictor of exploitative competitive ability.


A survey of cats and dogs for fleas: with particular reference to their role as intermediate hosts of Dipylidium caninum.
Three species of fleas, viz. Ctenocephalides felis, Ctenocephalides canis, and Pulex irritans were found in an examination of 81 cats and 48 dogs in Wellington. C. felis was the most prevalent flea in cats, and C. canis predominated in dogs. It is speculated that C. felis, and its primary host the cat, may assume greater medical and veterinary significance than C. canis. In an examination of 1578 fleas for cysticercoids of the dog tapeworm, Dipylidium caninum, all were found negative. These results do not necessarily reflect the availability of cysticercoids in the environment, and the reasons for this are discussed.


Oral decontamination with colistin plus neomycin in solid organ transplant recipients colonized by multidrug-resistant Enterobacterales: a multicentre, randomized, controlled, open-label, parallel-group clinical trial.
To evaluate the efficacy of oral colistin-neomycin in preventing multidrug-resistant Enterobacterales (MDR-E) infections in solid organ transplant (SOT) recipients. Multicentre, open-label, parallel-group, controlled trial with balanced (1:1) randomization in five transplant units. SOT recipients were screened for MDR-E intestinal colonization (extended-spectrum β-lactamase or carbapenemase producing) before transplantation and +7 and + 14 days after transplantation and assigned 1:1 to receive treatment with colistin sulfate plus neomycin sulfate for 14 days (decolonization treatment (DT) group) or no treatment (no decolonization treatment (NDT) group). The primary outcome was diagnosis of an MDR-E infection. Safety outcomes were appearance of adverse effects, mainly diarrhoea, rash, nausea and vomiting. Patients were monitored weekly until 30 days after treatment. Intention-to-treat analysis was performed. MDR-E rectal colonization was assessed in 768 SOT recipients; 105 colonized patients were included in the clinical trial, 53 receiving DT and 52 NDT. No significant decrease in the risk of infection by MDR-E was observed in the DT group (9.4%, 5/53) compared to the NDT group (13.5%, 7/52) (relative risk 0.70; 95% confidence interval 0.24-2.08; p 0.517). Four patients (5.6%), three (5.6%) in the DT group and one (1.9%) in the NDT group, developed colistin resistance. Twelve patients (22.7%) in the DT group had diarrhoea, eight related to treatment (15.0%); one patient (1.8%) developed skin rash and another (1.8%) nausea and vomiting. Two patients (3.8%) in the NDT group developed diarrhoea. DT does not reduce MDR-E infections in SOT. Colistin resistance and adverse effects such as diarrhoea are a potential issue that must be taken seriously.


Eruptive lingual papillitis with household transmission: a prospective clinical study.
Eruptive lingual papillitis with household transmission (ELP) is an acute stomatitis of unknown cause occurring in children, with possible spread to one or several members of the family. To verify clinical features and search for clinical characteristics of ELP. A prospective case series, including an analysis of epidemiological and clinical factors, was conducted within private paediatric practices in collaboration with a dermatology department at the University Hospital of Nice, France. Thirty-eight children (21 girls and 17 boys) with clinical criteria of ELP referred from 1 February 2000 to 31 January 2002 were included in the study. Mean age at diagnosis was 3 years and 6 months. Thirty-three children attended day nursery or school. The seasonal distribution of observed cases showed a peak of incidence in spring. The eruption started abruptly. Fever was found in 15 (39%) cases. Difficulties in feeding were observed in all cases; intense salivation in 23 (61%) cases. The glossitis was characterized by inflammatory hypertrophy of the fungiform papillae on the tip and dorsolateral part of the tongue. Enlarged submaxillary or cervical lymph nodes were noted in 16 (42%) cases. Angular cheilitis was observed in four (11%) children. Spontaneous regression of the stomatitis occurred between the second and 15 days of clinical evolution. Mean duration was 7.3 days. Transmission to one or several members of the family was noted in 20 (53%) cases. Recurrence of symptoms was observed in five (13%) children. This study confirms some clinical characteristics of ELP: localized lesions of the fungiform papillae on the tip and dorsolateral part of the tongue, high frequency of intrafamilial transmission, and possibility of recurrence. This study also showed unsuspected clinical data such as possible occurrence of fever and angular cheilitis. ELP resembles an entity termed 'transient lingual papillitis' or commonly 'lie bumps'. The origin of this eruption remains unknown, but the transmission data could suggest a possible infectious origin.


Reduction of alloxan by microsomal electron transport proteins.
Alloxan behaves as a substrate for NADH:ferricytochrome b5 oxidoreductase (EC 18.104.22.168). The apparent Km for alloxan was 10 mM in liver microsomes and 20 mM with the enzyme prepared by lysosomal digestion. The apparent Km for NADH was the same with microsomes and the isolated enzyme (30 microM). The maximum turnover rate was calculated as 426 moles electrons/min X mole enzyme. Cytochrome b5 was shown to reduce alloxan nonenzymatically.


Vulnerability and resilience to pandemic-related stress among U.S. women pregnant at the start of the COVID-19 pandemic.
Women pregnant during the COVID-19 pandemic are experiencing moderate to high levels of emotional distress, which has previously been shown to be attributable to two types of pandemic-related pregnancy stress: stress associated with feeling unprepared for birth due to the pandemic (Preparedness Stress) and stress related to fears of perinatal COVID-19 infection (Perinatal Infection Stress). Given the well-documented harms associated with elevated prenatal stress and the critical importance of developing appropriately targeted interventions, we investigated factors predictive of pandemic-related pregnancy stress. Between April 25 and May 15, 2020, 4,451 pregnant women in the U.S. were recruited via social media to complete an online questionnaire that included sociodemographic, medical, and COVID-19 situational factors, as well as the Pandemic-Related Pregnancy Stress Scale (PREPS). Binary logistic regression was used to calculate odds ratios for high stress. Nearly 30% of participants reported high Preparedness Stress; a similar proportion reported high Perinatal Infection Stress. Abuse history, chronic illness, income loss due to the pandemic, perceived risk of having had COVID-19, alterations to prenatal appointments, high-risk pregnancy, and being a woman of color were associated with greater levels of one or both types of stress. Access to outdoor space, older age, and engagement in healthy behaviors were protective against stress. Practices that may alleviate pandemic-related stress such as minimizing disruptions to prenatal care, ensuring access to outdoor space, and motivating engagement in health behaviors are of vital importance. Particular attention is needed for more vulnerable populations including women of color, women with a history of abuse, and those with high-risk pregnancy. Research focused on the short and longer-term impact of pandemic-related pregnancy stress on maternal mental and physical health, perinatal outcomes, and child development is critical to identify these effects and marshal appropriate resources to reduce them.


Prolonged cultivation of rat uterine cells with preserved estrogen responsiveness.
A rat uterine cell culture was prepared as an experimental system for investigation of mechanisms of steroid hormone actions. Cells frequently supplemented with fresh medium were successfully cultured for 4 weeks through 2 successive passages. Studies of estrogen responsiveness in the primary culture as well as in it's first subculture were performed by a small scale uptake assay for determination of specific steroid binding. Scatchard analysis of specific ovarian hormone binding confirmed that cultured uterine cells preserve both estradiol and progesterone receptors. Characteristics of specific [3H]estradiol binding detected in cells of the first subculture were comparable to those obtained in the initial primary culture. The number of specific estradiol binding sites was diminished to one third of the initial values only in cells of the second subculture, 22 days after isolation of cells from tissue. In the primary culture and in it's first subculture the cells responded to estradiol with a 2-3-fold increase in progesterone receptor level. The subcellular distribution of steroid receptors was also studied; estradiol receptor complexes were detected predominantly in the nuclei whereas progesterone receptors were nearly equally distributed between nuclei and cytosol.


Genetic polymorphisms of xeroderma pigmentosum group D gene Asp312Asn and Lys751Gln and susceptibility to prostate cancer: a systematic review and meta-analysis.
Many studies have reported the role of xeroderma pigmentosum group D (XPD) with prostate cancer risk, but the results remained controversial. To derive a more precise estimation of the relationship, a meta-analysis was performed. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to assess the association between XPD Asp312Asn and Lys751Gln polymorphisms and prostate cancer risk. A total of 8 studies including 2620 cases and 3225 controls described Asp312Asn genotypes, among which 10 articles involving 3230 cases and 3582 controls described Lys751Gln genotypes and were also involved in this meta-analysis. When all the eligible studies were pooled into this meta-analysis, a significant association between prostate cancer risk and XPD Asp312Asn polymorphism was found. For Asp312Asn polymorphism, in the stratified analysis by ethnicity and source of controls, prostate cancer risk was observed in co-dominant, dominant and recessive models, while no evidence of any associations of XPD Lys751Gln polymorphism with prostate cancer was found in the overall or subgroup analyses. Our meta-analysis supports that the XPD Asp312Asn polymorphism contributed to the risk of prostate cancer from currently available evidence. However, a study with a larger sample size is needed to further evaluate gene-environment interaction on XPD Asp312Asn and Lys751Gln polymorphisms and prostate cancer risk.


Vaginal misoprostol for cervical priming prior to diagnostic hysteroscopy--efficacy, safety and patient satisfaction: a randomized controlled trial.
To evaluate the effectiveness and safety of vaginal misoprostol for cervical priming prior to diagnostic hysteroscopy and to assess impact on pain scores and patient satisfaction. One hundred women undergoing hysteroscopy were randomly allocated into two groups. The study group (n = 50) received 400 microg of misoprostol vaginally (self administered) 4-6 h prior to hysteroscopy while the control group (n = 50) did not receive any cervical priming. Primary outcome measured was need for cervical dilatation, analgesia or sedation. Secondary outcomes were pain scores, patient satisfaction and side effects. There was no significant difference in the need for cervical dilatation, analgesia or sedation in the two groups (P = 0.25, 0.64 and 0.5, respectively). In addition, there was no difference in subjective patient satisfaction (P = 0.70). However, those in the control group recorded a higher pain score (median +/- SD = 5 +/- 1.8) when compared to those who received misoprostol (median +/- SD = 4.5 +/- 2, P = 0.03). Only two women (4%) had bleeding per vaginum and one (2%) had a slight fever attributable to misoprostol. Vaginal misoprostol prior to diagnostic hysteroscopy did not facilitate cervical dilatation. It did effect a reduction in pain scores, but there was no difference in patient satisfaction, need for analgesia or sedation. No significant side effects were reported.


Intraocular injections of tetrodotoxin reduce transiently expressed acetylcholinesterase activity in developing rat visual cortex.
Geniculo-recipient layers of primary visual cortex in the rat display a transient pattern of acetylcholinesterase (AChE) activity during the second postnatal week of life. Previous work has demonstrated that neonatal enucleations markedly reduce the transient AChE activity in visual cortex. The present studies were undertaken to determine the effects of reduced afferent neural activity on expression of the transient pattern of AChE activity. Rat pups received intraocular injections of tetrodotoxin (TTX) on postnatal days (PND) 3, 5, 7, 9 and 11 and were sacrificed on PND 12. Some animals were enucleated on PND 3. Brain sections were processed for AChE histochemistry and analyzed by optical densitometry. These experiments show that uniocular injections result in a markedly decreased level of AChE activity in layer IV of the medial part of cortical area 17 contralateral to the injected eye. The degree of reduction of AChE activity from repeated TTX injections was similar to the degree of reduction following enucleation on PND 3. Binocular injections of TTX result in a reduction of AChE activity in layer IV throughout cortical area 17, similar to the effects of binocular enucleation on PND 3. Experiments combining injection of horseradish peroxidase along with TTX on PND 11 demonstrate that retinal ganglion cells of TTX injected eyes are still capable of anterograde axonal transport. These data demonstrate that normal innervation and afferent activity are necessary for the transient expression of AChE activity by geniculocortical neurons.


The diagnostic potential of oxidative stress biomarkers for preeclampsia: systematic review and meta-analysis.
Preeclampsia is a multifactorial cardiovascular disorder of pregnancy. If left untreated, it can lead to severe maternal and fetal outcomes. Hence, timely diagnosis and management of preeclampsia are extremely important. Biomarkers of oxidative stress are associated with the pathogenesis of preeclampsia and therefore could be indicative of evolving preeclampsia and utilized for timely diagnosis. In this study, we conducted a systematic review and meta-analysis to determine the most reliable oxidative stress biomarkers in preeclampsia, based on their diagnostic sensitivities and specificities as well as their positive and negative predictive values. A systematic search using PubMed, ScienceDirect, ResearchGate, and PLOS databases (1900 to March 2021) identified nine relevant studies including a total of 343 women with preeclampsia and 354 normotensive controls. Ischemia-modified albumin (IMA), uric acid (UA), and malondialdehyde (MDA) were associated with 3.38 (95% CI 2.23, 4.53), 3.05 (95% CI 2.39, 3.71), and 2.37 (95% CI 1.03, 3.70) odds ratios for preeclampsia diagnosis, respectively. The IMA showed the most promising diagnostic potential with the positive predictive ratio (PPV) of 0.852 (95% CI 0.728, 0.929) and negative predictive ratio (NPV) of 0.811 (95% CI 0.683, 0.890) for preeclampsia. Minor between-study heterogeneity was reported for these biomarkers (Higgins' I2 = 0-15.879%). This systematic review and meta-analysis identified IMA, UA, and MDA as the most promising oxidative stress biomarkers associated with established preeclampsia. IMA as a biomarker of tissue damage exhibited the best diagnostic test accuracy. Thus, these oxidative stress biomarkers should be further explored in larger cohorts for preeclampsia diagnosis.


Cutaneous plasmablastic lymphoma.
Plasmablastic lymphoma is a variant of diffuse large B-cell lymphoma occurring in immunocompromised individuals. Multiple organ sites may be involved; however, cutaneous involvement has been rarely reported in the medical literature. To date, there have been only 7 reports of cutaneous plasmablastic lymphoma without systemic involvement. We report a case of isolated cutaneous plasmablastic lymphoma occurring in an HIV-positive man with more than 10 years of follow-up.


Applying Experiential Learning to Career Development Training for Biomedical Graduate Students and Postdocs: Perspectives on Program Development and Design.
Experiential learning is an effective educational tool across many academic disciplines, including career development. Nine different institutions bridged by the National Institutes of Health Broadening Experiences in Scientific Training Consortium compared their experiments in rethinking and expanding training of predoctoral graduate students and postdoctoral scholars in the biomedical sciences to include experiential learning opportunities. In this article, we provide an overview of the four types of experiential learning approaches our institutions offer and compare the learning objectives and evaluation strategies employed for each type. We also discuss key factors for shaping experiential learning activities on an institutional level. The framework we provide can help organizations determine which form of experiential learning for career training might best suit their institutions and goals and aid in the successful design and delivery of such training.


Optimizing a readout protocol for low dose retrospective OSL-dosimetry using household salt.
The authors' aim has been to find a single aliquot regenerative dose (SAR) protocol that accurately recovers an unknown absorbed dose in the region between 1-250 mGy in household salt. The main investigation has been conducted on a specific mine salt (>98.5% NaCl) intended for household use, using optical stimulation by blue LED (λ = 462 nm). The most accurate dose recovery for this brand of salt is found to be achieved when using Peak Signal Summing (PSS) of the OSL-decay and a preheat temperature of 200°C after the test dose. A SAR protocol for the household salt with preset values of regenerative doses (R1--R5) and a test dose (TED) of 17 mGy is also suggested here. Under laboratory conditions, the suggested protocol recovers unknown absorbed doses in this particular brand within 5% (2 SD) in the dose range between 1-250 mGy. This is a very promising result for low dose applications of household salt as a retrospective dosimeter after a nuclear or radiological event.


As loud as a construction site: Noise levels in the emergency department.
The Emergency Department (ED), while being an integral part of healthcare systems, frequently experiences noise levels surpassing the World Health Organization's recommended thresholds. These excessive noise levels could considerably compromise the safety and wellbeing of both patients and staff. To evaluate noise levels throughout the ED environment, this study utilized dosimeters to measure noise levels over a 24-hour period in six distinct locations, including the ED Waiting Room and Treatment areas. The study found that noise exceeded the WHO recommendations in all six areas of the ED for the entire 24-hour period. Peak noise levels were recorded up to 102.8 dB, which is as loud as noise levels at a construction site. The ED Waiting Room exhibited high peak and average noise levels, indicating the urgent need for quality improvement efforts. These findings align with the results of previous research, thereby suggesting that noise levels in the ED have remained problematic for more than a decade. The findings of this study underscore the importance of addressing excessive noise levels in the ED to create a safe and therapeutic hospital environment for both patients and staff. Healthcare organizations must implement proactive measures to address excessive noise levels in the ED.


ZRC3308 Monoclonal Antibody Cocktail Shows Protective Efficacy in Syrian Hamsters against SARS-CoV-2 Infection.
We have developed a monoclonal antibody (mAb) cocktail (ZRC-3308) comprising of ZRC3308-A7 and ZRC3308-B10 in the ratio 1:1 for COVID-19 treatment. The mAbs were designed to have reduced immune effector functions and increased circulation half-life. mAbs showed good binding affinities to non-competing epitopes on RBD of SARS-CoV-2 spike protein and were found neutralizing SARS-CoV-2 variants B.1, B.1.1.7, B.1.351, B.1.617.2, and B.1.617.2 AY.1 in vitro. The mAb cocktail demonstrated effective prophylactic and therapeutic activity against SARS-CoV-2 infection in Syrian hamsters. The antibody cocktail appears to be a promising candidate for prophylactic use and for therapy in early COVID-19 cases that have not progressed to severe disease.


Brain 18F-FDG PET analysis via interval-valued reconstruction: proof of concept for Alzheimer's disease diagnosis.
We propose an innovative approach for 18F-FDG PET analysis based on an interval-valued reconstruction of 18F-FDG brain distribution. Its diagnostic performance for Alzheimer's disease (AD) diagnosis with comparison to a validated post-processing software was assessed. Brain 18F-FDG PET data from 26 subjects were acquired in a clinical routine setting. Raw data were reconstructed using an interval-valued version of the ML-EM algorithm called NIBEM that stands for Non-Additive interval-based expectation maximization. Subject classification was obtained via interval-based statistical comparison (intersection ratio, IR) between cortical regions of interest (ROI) including parietal, temporal, and temporo-mesial cortices and a reference region, the sub-cortical grey nuclei, known not to be affected by AD. In parallel, PET images were post-processed using a validated automated software based on the computation of ROI normalized uptake ratios standard deviation (SUVr SD) with reference to a healthy control database (Siemens Scenium). Clinical diagnosis made during follow-up was considered as the gold-standard for patient classification (16 healthy controls and 10 AD patients). Both methods provided cortical ROI indices that were significantly different between controls and AD patients. The area under the ROC curve for control/AD classification was statistically identical (0.96 for NIBEM IR and 0.95 for Scenium SUVr SD). At the optimal threshold, the sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were, respectively, 100%, 88%, 92%, 83%, and 100% for both Scenium SUVr SD and NIBEM IR methods. This preliminary study shows that interval-valued reconstruction allows self-consistent analysis of brain 18F-FDG PET data, yielding diagnostic performances that seem promising with respect to those of a commercial post-processing software based on SUVr SD analysis.


The In-Gap Electronic State Spectrum of Methylammonium Lead Iodide Single-Crystal Perovskites.
The density of trap states within the bandgap of methylammonium lead iodide single crystals is investigated. Defect states close to both the conduction and valence bands are probed. Additionally, a comprehensive electronic characterization of crystals is carried out, including measurements of the electron and hole mobility, and the energy landscape (band diagram) at the surface.


Association Between (18)F-FDG Avidity and the BRAF Mutation in Papillary Thyroid Carcinoma.
The BRAF mutation, a potential prognostic factor in papillary thyroid carcinoma (PTC), is associated with a high expression of the glucose transporter gene. We investigated which clinicopathologic factors, including BRAF mutation status, influence (18)F-fluoro-2-deoxyglucose ((18)F-FDG) avidity. We retrospectively reviewed 55 patients who underwent BRAF analysis from biopsy-confirmed PTC and (18)F-FDG positron emission tomography/computed tomography within 6 months before undergoing thyroid surgery from September 2008 to August 2014. Tumors were considered to be (18)F-FDG avid if the uptake was greater than that of the liver. (18)F-FDG uptake of PTCs was also analyzed semiquantitatively using SUVmax. The association between (18)F-FDG avidity and clinicopathologic variables (age, tumor size, perithyroidal extension, cervical lymph node status, and BRAF mutation status) was investigated. Twenty-nine (52.7 %) of 55 patients had (18)F-FDG-avid PTCs. PTCs with the BRAF mutation showed higher (18)F-FDG avidity (24/38, 63.2 %) than those without (5/17, 29.4 %). The BRAF mutation (p = 0.025) and tumor size (p = 0.003) were significantly associated with (18)F-FDG avidity in univariate analysis, and the BRAF mutation status remained significant after adjusting for tumor size in multivariate analysis (p = 0.015). In the subgroup of tumor size ≥ 1 cm, the BRAF mutation was the only factor significantly associated with (18)F-FDG avidity (p = 0.021). The mean SUVmax of PTCs with the BRAF mutation was significantly higher than that of those without (4.89 ± 6.12 vs. 1.96 ± 1.10, p = 0.039). The BRAF mutation must be one of the most important factors influencing (18)F-FDG avidity in PTCs, especially in those with a tumor size ≥ 1 cm.


Syrian women's perceptions and experiences of ultrasound screening in pregnancy: implications for antenatal policy.
Ultrasound scanning is firmly embedded in antenatal maternity care around the world. This paper reports on a qualitative study carried out in 2003 of 30 Syrian women's perceptions and experiences of routine ultrasound in pregnancy. It was part of a larger study of the experiences of pregnancy and childbirth of 500 women from Damascus and its suburbs who had recently given birth to healthy newborns. The women had had multiple scans during pregnancy and accepted its use uncritically nearly all the time. The scans gave them reassurance that the baby was healthy, the pregnancy was progressing well and allowed them to learn the sex of the baby. The women also reacted positively to the antenatal educational messages that were conveyed using scans. However, we found the excessive use of this technology worrying. We believe private doctors, who attend 80% of pregnant women, use ultrasound primarily to attract women to their clinics and increase their income. We recommend that maternity care in Syria should be better regulated; that women and their doctors should be made aware of the essential components of antenatal care; that notional guidelines for antenatol care should be developed and that Syrian women should be empowered to ask questions about pregnancy and childbirth and the care they receive.


Overexpression of CD7 in classical Hodgkin lymphoma-infiltrating T lymphocytes.
Diagnosis of Hodgkin lymphoma (HL) is sometimes complicated by the scarcity of neoplastic cells in a reactive inflammatory background. Immunophenotyping by flow cytometry (FC) has not played a significant role in HL diagnosis because of its consistent failure to identify these neoplastic cells. However, HL-infiltrating T cells have been shown to play a role in HL pathogenesis. This study characterizes the FC immunophenotype of these T lymphocytes to determine whether they can be used to assist in the diagnosis of HL. Cell suspensions from 76 lymph nodes involved by HL and 156 lymph nodes with reactive lymphadenopathy (LAD) were analyzed by flow cytometry to assess the expression of T-cell antigens. The CD4:CD8 ratio and CD7 expression in both CD4(+) and CD8(+) T cells are increased in HL compared with reactive lymph nodes and there are significant differences between these features in different subtypes of HL. However, only the expression of CD7 in CD4(+) T cells distinguishes between HL and reactive LAD. This is especially true for classical HL in younger patients. Using a CD7 mean fluorescence intensity (MFI) cutoff value generated by this data, 37/47 FNA specimens were correctly diagnosed. There are significant differences in the immunophenotypes of HL-infiltrating T cells. Of these, the CD7 expression in CD4(+) T cells discriminates between HL and reactive LAD, suggesting that this could be a useful and practical adjunctive tool in the diagnosis of HL. It may also further our understanding of the pathophysiology of this disease.


No panacea? Tai Chi enhances motoric but not executive functioning in a normal aging population.
Tai Chi Chuan (TCC) is a promising intervention against age-related decline. Though previous studies have shown benefits in motoric and cognitive domains, it is unclear how these effects are functionally related. Therefore, a randomized controlled trial was conducted in an aging population (53-85). Two measures of motor functioning - motor speed and functional balance - and three cognitive control measures - shifting, updating and inhibition - were included. The TCC condition consisted of an online 10 week 20 lessons video program of increasing level and control condition of educational videos of similar length and frequency. All analyses were done with Bayesian statistics. Counter to expectation no differences were found in cognition between TCC and control pre-to-posttest. However, there was extreme evidence for TCC benefits on functional balance and moderate evidence for increased motoric speed. After weighing the evidence and limitations of the intervention we conclude that TCC does not enhance cognitive control.


Electrolysis-sulfate-reducing up-flow sludge bed-biological contact oxidation reactor for Norfloxacin removal from wastewater with high sulfate content.
This study investigated the treatment of 100-mg/L Norfloxacin (NOR) wastewater containing high concentrations of sulfate through a combination of electrolysis, sulfate-reducing up-flow sludge bed (SRUSB), and biological contact oxidation reactor (BCOR) treatments. Results revealed that after 62 h, the reaction system had processed over 97% of the NOR. Additionally, electrolysis with sodium sulfate as the electrolyte transformed 87.8% of the NOR but only 33.5% of the total organic carbon (TOC). In the SRUSB, the TOC and SO42- contents were simultaneously reduced by 87.4% and 95.6%, respectively, providing a stable environment to the BCOR. In the BCOR, 36.3% and 85.9% of the NOR and TOC were degraded. High-performance liquid chromatography-tandem mass spectrometry analysis identified three possible degradation pathways under the attack of -OH during electrolysis, including defluorination, piperazinyl ring transformation, and quinolone ring transformation. Furthermore, the Illumina HiSeq sequencing results demonstrated that the sulfate-reducing bacteria (represented by Desulfobacter and Desulfobulbus) in the SRUSB and the sulfate-oxidizing bacteria (mainly consisting of Gammaproteobacteria and Alphaproteobacteria) in the BCOR played important roles in carbon chain oxidation and benzene ring opening and thoroughly degraded the electrolysis products. Thus, this method effectively overcomes the incomplete degradation and low removal efficiency issues associated with single electrolysis or biological methods in traditional processes.


HDL-cholesterol and the incidence of lung cancer in the Atherosclerosis Risk in Communities (ARIC) study.
This study examined prospectively the association of baseline plasma HDL-cholesterol levels with incidence of lung cancer in 14,547 members of the Atherosclerosis Risk in Communities (ARIC) cohort. There were 259 cases of incident lung cancer identified during follow-up from 1987 through 2000. Results of this study indicated a relatively weak inverse association of HDL-cholesterol with lung cancer that was dependent on smoking status. The hazard ratio of lung cancer incidence in relation to low HDL-cholesterol, adjusted for race, gender, exercise, alcohol consumption, body mass index, triglycerides, age, and cigarette pack-years of smoking, was 1.45 (95% confidence interval 1.10, 1.92). This association was observed among former smokers (hazard ratio: 1.77, 95% confidence interval 1.05, 2.97), but not current smokers. The number of cases among never smokers in this study was too small (n=13) for meaningful interpretation of effect estimates. Excluding cases occurring within 5 years of baseline did not appreciably change the point estimates, suggesting lack of reverse causality. The modest association of low plasma HDL-cholesterol with greater incident lung cancer observed in this study is in agreement with existing case-control studies.


UHPLC-MS/MS-GNPS based phytochemical investigation of Dryopteris ramosa (Hope) C. Chr. and evaluation of cytotoxicity against liver and prostate cancer cell lines.
Dryopteris ramosa (family; Dryopteridaceae) has been reported for its medicinal importance in cancer, gastrointestinal disorders, and infections. The present study aimed to investigate the detailed phytochemical profile of D. ramosa and its cytotoxic potential using various cancer cell lines. The phytochemical profile of D. ramosa methanolic extract and its fractions were established by employing UHPLC-MS/MS and Global Natural Product Social (GNPS) molecular networking. Moreover, the cytotoxic activity of extract and fractions was evaluated against human liver (HepG-2) and prostate cancer (PC-3) cells using MTT assay. Overall, 18 compounds including flavonoids, flavonoid O-glycosides, isoflavone di-C-glycoside, flavanol, flavanone, rotenoid, phloroglucinol derivative, coumarin derivative, benzofuranone, abietic acid, and phenolic acid were observed as the major phytochemical bioactive constituents in the extract and fractions of D. ramosa. In MTT assay, chloroform fraction showed highest anti-proliferative activity against liver cancer cells (IC50 = 53.49 μg/mL) followed by n-hexane fraction (IC50 = 55.36 μg/mL), D. ramosa extract (IC50 = 85.67 μg/mL) and ethyl acetate (IC50 = 125.00 μg/mL) fraction. However, n-hexane and chloroform fractions presented maximum cytotoxic effect against prostate cancer cells with respective IC50 values of 214.53 and 281.47 μg/mL. Moreover, all the tested samples showed negligible toxicity against non-cancer (BHK-21) cells. The results indicated that D. ramosa is rich in flavonoids, phloroglucinol derivative, and phenolic acids and showed positive results in cytotoxic studies, especially against liver cancer. Therefore, it can be considered safe for the development of anticancer drugs, especially against liver cancer.


A systematic overview of rare disease patient registries: challenges in design, quality management, and maintenance.
Patient registries serve to overcome the research limitations inherent in the study of rare diseases, where patient numbers are typically small. Despite the value of real-world data collected through registries, adequate design and maintenance are integral to data quality. We aimed to describe an overview of the challenges in design, quality management, and maintenance of rare disease registries.A systematic search of English articles was conducted in PubMed, Ovid Medline/Embase, and Cochrane Library. Search terms included "rare diseases, patient registries, common data elements, quality, hospital information systems, and datasets". Inclusion criteria were any manuscript type focused upon rare disease patient registries describing design, quality monitoring or maintenance. Biobanks and drug surveillances were excluded.A total of 37 articles, published between 2001 and 2021, met the inclusion criteria. Patient registries covered a wide range of disease areas and covered multiple geographical locations, with a predisposition for Europe. Most articles were methodological reports and described the design and setup of a registry. Most registries recruited clinical patients (92%) with informed consent (81%) and protected the collected data (76%). Whilst the majority (57%) collected patient-reported outcome measures, only few (38%) consulted PAGs during the registry design process. Few reports described details regarding quality management (51%) and maintenance (46%).Rare disease patient registries are valuable for research and evaluation of clinical care, and an increasing number have emerged. However, registries need to be continuously evaluated for data quality and long-term sustainability to remain relevant for future use.


Normalized cDNA libraries from a porcine model of orthopedic implant-associated infection.
Staphylococcal infections that result from an alteration in a patient's immune response at the surgical site are a major problem in procedures that incorporate biomaterials in trauma surgery and joint replacement. Diagnosis of infection based on pathogen detection is difficult and exacerbated by increasing numbers of partially or totally resistant strains of nosocomial pathogens, particularly Staphylococcus aureus. Expression profiling of a host's cellular immune response could facilitate the identification of the pathways involved in pathogen recognition and eradication and could lead to more rational design of drugs and therapies. To this end, we constructed and characterized ten individually tagged and directionally cloned cDNA libraries from peripheral blood cells (PBC), spleen (Sp), thymus (Th), lymph node (LN), and bone marrow (BM) from immunologically naive and challenged pigs as part of an implant-associated orthopedic model of deep infection. Three of these libraries were normalized at C(0)(t) values 5, 10, 20, and 30. The libraries comprise more than 20 million primary transformants with an average insert length >1.4 kb. Cluster analysis of 7620 ESTs revealed 1029 clusters containing an average of 3.6 sequences and 3846 singletons. Gene discovery is estimated to be approximately 64%. Searches of public databases resulted in 49.3% annotated porcine sequences, of which 22.2% had significant homologies to ESTs from a variety of species, and 28.5% were without a significant match in any public database. We also identified 9.1% ESTs as involved in host cell and organism defense and 11.5% related to cell signaling and communication. These sequences, together with the 28.5% appearing as novel, are of specific interest to the infectious disease process.


Copper-Mediated Aerobic Oxidative Synthesis of 3-Bromo-imidazo[1,2-a]pyridines with Pyridines and Enamides.
A conversion of pyridines and enamides for the synthesis of 3-bromo-imidazo[1,2-a]pyridines was developed by copper-mediated aerobic oxidative coupling in a one-pot manner. This procedure tolerates various functional groups and affords a series of 3-bromo-imidazo[1,2-a]pyridines under mild conditions.


Production and preliminary characterization of monoclonal antibodies to rat plasma fibronectin.
We have produced several monoclonal antibodies which appear to be directed against different antigenic determinants of rat plasma fibronectin. Fibronectin was purified from rat plasma by affinity chromatography on gelatin-Sepharose and arginine-Sepharose columns. Mice were immunized and hybridomas were prepared by fusing spleen cells with Sp2/0-Ag14 myeloma cells using poly(ethylene glycol). Three hybridomas (RFN1, RFN2 and RFN3) were selected for characterization. All are IgG molecules, one is IgG2a, one IgG2b and one IgG1. Titers of ascites fluids produced using these hybridomas range from 102 400 to greater than 409 600. The antibodies cross-reacted to different degrees with human fibronectin. Rat fibronectin was radioactively labeled and cleaved using human polymorphonuclear leukocyte elastase. Four major peptides, Mr approx. 160 000, 140 000, 60 000 and 30 000 were produced. Each of the hybridoma antibodies immunoprecipitated different elastase peptides. RFN1 precipitated the Mr 160 000 peptide, RFN2 precipitated the Mr 160 000 and the Mr 140 000 peptide and RFN3 precipitated the Mr 60 000 peptide as well as low molecular weight material migrating at the buffer front. These antibodies will be useful in studies of structure/function relationships of rat fibronectin.


Polymerase chain reaction and partial sequencing of a British isolate (T637) of feline immunodeficiency virus.
We have used the polymerase chain reaction (PCR) and direct sequencing of the amplified products to obtain information of the molecular nature of an FIV isolate, T637. Cats experimentally infected with T637 have progressed to clinical immunodeficiency disease. The 5' long terminal repeat (LTR), most of the genes coding for internal proteins (GAG) and surface proteins (ENV), and part of the polymerase (POL) gene have been sequenced. The LTR of T637 has 92% nucleic acid identity with the prototype strain, FIV-Petaluma and the Glasgow isolate, FIV-14, 89% with a Swiss isolate, FIVZ2, and 95% with the PPR isolate. Both GAG and POL genes of T637 share extensive homology with Petaluma and PPR. In the ENV gene, T637 has 91% nucleic acid homology with Petaluma and 86% with PPR, and an overall amino acid homology of between 81-87%. For the surface (SU) region of the ENV gene product, T637 has 89% amino acid homology with Petaluma and FIVZ2 and 86% with PPR.


[Efficiency of prognostic scores for the assessment of patients with severe influenza pneumonias].
To compare the efficiency of some prognostic scores in patients with severe influenza pneumonias. The study was performed on a cohort of 75 cases of 2009 AH1N1 influenza associated pneumonias. Clinical and laboratory features at admission were used to calculate retrospectively the following prognostic scores: SCAP (Severe Community Acquired Pneumonia), CAP-PIRO (Community Acquired Pneumonia--Predisposition Infection Reaction, Organ failure), SMRT-CO (Systolic blood pressure, Multilobar infiltrates, Respiration rate, Tachycardia, Confusion, Oxygen), IDSA/ATS (Infectious Diseases Society of America/American Thoracic Society). The scores were used to assess two different outcomes--death and need for invasive mechanical ventilation (IMV). The performance of the prognostic tools were assessed using the area under receiver operating characteristic (AUC), and the sensitivity and specificity for identifying high risk patients for severe course of pneumonia. IMV was applied in 29 (38.7%) of studied cases, in 15 (20%) the diseases had a fatal outcome. Despite the fact that all scores had a very good discriminatory power in predicting both outcomes (AUC > 0,8), some of them have a very low sensitivity, in classes corresponding to sever pneumonias, in predicting mortality (IDSA/ATS-0%; 95% CI, 0-21.8%), as well as the need for IMV (IDSA/ATS-0%; 95% CI, 0-11.9%); SCAP-58.6% (95% CI, 38.9-76.5%); CAP-PIRO-58,6% (95% CI, 38.9-76.5%). The CAP-PIRO and SMRT-CO scores were found to have the best performances to predict death from influenza associated severe pneumonias and the last, also in predicting the need for IVM. Other analyzed scores underestimate the risk of occurrence of both assessed outcomes.


The effectiveness of neural mobilizations in the treatment of musculoskeletal conditions: a systematic review protocol.
The objective of this review is to identify the effectiveness of neural mobilization techniques in various neuro-musculoskeletal conditions. Outcomes will be analyzed in terms of subgroups such as low back pain, cervico-brachial pain and carpal tunnel syndrome. Musculoskeletal disorders were ranked as the second largest contributor to disability worldwide in a study on the global burden of disease. Low back pain and neck pain contributed to 70% of disability in this comprehensive population-based study. Low back pain and neck pain are multifactorial, with heterogeneous populations. It has been proposed that targeting subgroups of patients may result in better treatment outcomes. Neck pain associated with upper limb pain is prevalent. These patients are more disabled than patients with neck pain alone. Similarly, low back pain with leg pain is a common phenomenon and is acknowledged as a predictor for chronicity.Neuropathic pain is often associated with musculoskeletal complaints including low back pain, whiplash associated disorders (WAD) and acute or chronic radiculopathy, and can be a feature of syndromes such as cervico-brachial pain syndrome. According to the International Association for the Study of Pain, neuropathic pain can be described as "pain caused by a lesion or disease of the somatosensory nervous system." Leg pain associated with back pain can be caused by central sensitization, denervation, nerve sensitization or somatically referred pain. In patients with WAD, neck pain is the most common symptom, but upper limb pain, weakness, paraesthesia and anesthesia are often present. Other conditions in which neural tissue is thought to contribute to the clinical picture are, for instance, lateral epicondalalgia and carpal tunnel syndrome.Management strategies for back pain and neck pain are often multimodal. However, the evidence for effective treatment of nerve related pain is lacking. Neural mobilizations are often used to affect the neural structures in conditions with signs of neural involvement or neural mechano-sensitivity. Neural mobilizations are defined as interventions aimed at affecting the neural structures or surrounding tissue (interface) directly or indirectly through manual techniques or exercise. Neural mobilizations have been studied in various populations such as low back pain, carpal tunnel syndrome, lateral epicondalalgia and cervico-brachial pain. Neural mobilization techniques studied include cervical lateral glides for cervico-brachial pain, nerve gliding exercises for the treatment of carpal tunnel syndrome, cervical lateral glides for lateral epicondalalgia and the slump as a neural mobilization technique in the treatment of low back pain. No specialized equipment is needed in the performance of neural mobilization techniques, which contributes to its popularity.Neural mobilization is said to affect the axoplasmic flow, movement of the nerve and its connective tissue and the circulation of the nerve by alteration of the pressure in the nervous system and dispersion of intraneural oedema. Neural mobilization decreases the excitability of dorsal horn cells. Neural mobilizations can be performed in various ways using passive movement, manual mobilization of the nerve or interface, and exercise. The aim of neural mobilization is to restore the mechanical and neurophysiological function of the nerve.Only one systematic review on the effectiveness of neural mobilizations could be identified in the literature. Since this review, several more studies have been published on this subject. The authors hypothesize that a review of the more recent literature (2008-2014) may confirm positive support for the use of neural mobilizations for neuro-musculoskeletal complaints as previously seen by Ellis and Hing. This review aims to include a meta-analysis and subgrouping of conditions which will be an extension of the previous review by Ellis and Hing. The outcomes of this systematic review may be used to inform clinical practice and the development of best practice guidelines.


Haplotype analysis of SNAP-25 suggests a role in the aetiology of ADHD.
Several lines of evidence suggest a role for SNAP-25 (synaptosomal-associated protein of 25 kDa) in the genetic aetiology of ADHD. Most notable is the coloboma mouse mutant, which displays spontaneous hyperactivity and is hemizygous for a deletion spanning this gene. We have screened the SNAP-25 gene using denaturing high-performance liquid chromatography and sequencing, and genotyped six polymorphic single-nucleotide polymorphisms and two microsatellites in a clinically ascertained sample of 188 probands. Several markers were found to show association with ADHD, both individually and in combination with other markers to form multimarker haplotypes. Analyses of transmission by parental sex suggested that the association of SNAP-25 with ADHD is largely due to transmission of alleles from paternal chromosomes to affected probands, suggesting that this locus may be subject to genomic imprinting. Overall our data provide some evidence for a role of this gene in ADHD, although the precise causal functional variant is yet to be ascertained.


Granulocyte colony-stimulating factor partially repairs the damage provoked by Trypanosoma cruzi in murine myocardium.
The hallmark of Trypanosoma cruzi infection is cardiomyopathy that leads to end-stage heart failure. We investigated whether G-CSF, known to induce heart tissue repair by bone marrow stem cell mobilization, ameliorates T. cruzi-induced myocarditis. T. cruzi-infected C3H/He mice were treated with G-CSF and monitored for parasite burden, BMSC mobilization, cytokine profile and cardiac remodeling. G-CSF increased the expression of CXCR4, CD34, and c-Kit, indicating mobilization and migration of BMSC, some of which differentiated to cardiomyocytes as evidenced by increased levels of GATA4(+)/MEF2C(+) cells and desmin expression in chagasic hearts. G-CSF enhanced a mixed cytokine response (IL-10+TGF-β>IFN-γ+TNF-α>IL-4) associated with increased heart inflammation and no beneficial effect on parasite control. Further, G-CSF controlled T. cruzi-induced extracellular-matrix alterations of collagens (Col I and Col llI), hydroxyproline, and glycosaminoglycan contents and promoted compensatory cardiac remodeling; however, these responses were not sufficient to control T. cruzi-induced cardiomyocyte atrophy. Benznidazole treatment prior to G-CSF resulted in the control of parasitism and parasite-induced inflammation, and subsequently, G-CSF was effective in executing the tissue repair, as evidenced by extracellular-matrix homeostasis and normalization of cardiomyocyte size in chagasic hearts. G-CSF treatment after T. cruzi infection enhanced migration and homing of BMSC, some of which differentiated to cardiomyocytes. Yet, G-CSF promoted a mixed (Treg>Th1>Th2) immune response that contributed to persistent inflammation and limited improvement in cardiac homeostasis. Combinatorial therapy (BZ → G-CSF) was beneficial in arresting inflammatory processes and tissue damage in chagasic hearts.


Direct connections between the central nucleus of the amygdala and the nucleus of the solitary tract: an electrophysiological study in the rat.
Reciprocal connections between the central nucleus of the amygdala (CNA) and the nucleus of the solitary tract (NST) have been implied from anatomical studies in the rat and physiological studies in other species. Our work supports this conclusion in that microstimulation of the NST caused both antidromic and orthodromic activation of neurons in the CNA. The distribution of CNA neurons activated by NST stimulation suggests that the dorsomedial portion of the CNA provides input to the dorsal medulla while the ventrolateral CNA receives input from the NST.


[Comparative biochemical and histological studies of the effect of magnesium and profound hypothermia on the preservation of the isolated perfused rat liver (author's transl)].
In order to determine, if magnesium aspartate has the same favorable effect on the liver as on the arrested heart, the isolated rat liver preperfused with isotonique Mg-aspartate or saline solution 15 minutes and stored 1 hour at 36 degrees C or 12 hours at 36 degrees C has been reperfused 150 minutes at 37 degrees C. During the storage the concentrations of ATP and ADP decrease significantly whereas AMP, lactate and beta-hydroxybutyrate increase remarkably, accompanied by a pronounced breakdown of glycogen. Upon reperfusion a de novo synthesis of ATP and ADP is resumed. Lactate, beta-hydroxybutyrate and AMP approach normal values whereas a resynthesis of glycogen is missing. A focal distribution of well preserved and disintegrated hepatocytes is being observed and seems rather to be due microcirculatory disorders. No conclusive evidence of a protective Mg-effect as observed in induced cardiac arrest has been obtained. Several concentrations of Mg-aspartate should be studied, in order to elucidate the different acting mechanism of Mg++ on the two organs.


The development of neurosurgical techniques: the postoperative notes and sketches of Dr. Harvey Cushing.
In the early development of American neurosurgical techniques, Harvey Cushing is often considered the founding father. As an accomplished artist and prolific writer his original operative sketches and detailed notes at the Peter Bent Brigham Hospital (1912-1932) are now being explored as early documentation of this pioneering surgeon's development of a field. We present four brain tumor cases with his unpublished sketches and direct quotations to illustrate both the trials and tribulations of those times and Cushing's innate surgical genius.


Current concepts of bone grafting in trauma surgery.
Bone graft in trauma surgery is commonly used in managing bone defects, non-union, fracture related infections, arthrodesis or to provide structural support in fractures. A variety of bone grafts are made available to the treating physician, which includes autograft, allograft and bone graft substitutes. The future of bone grafting in trauma surgery is exciting with the incorporation of technological advancement such as gene therapy, 3D-printing and tissue engineering. Regardless, there are still limitations to what we understand regarding current bone grafting techniques with conflicting literature on their clinical utility and indication. The aim of this review article therefore is to take a step back and critically evaluate the current concepts of bone grafting in trauma surgery, with special emphasis made on reviewing the types of bone graft, biology of bone graft incorporation and indication for its use in various clinical scenarios.


Nano-Mechanical Characterization of Ataxia Telangiectasia Cells Treated with Dexamethasone.
Ataxia telangiectasia is a rare genetic disease and no therapy is currently available. Glucocorticoid analogues have been shown to improve the neurological symptoms of treated patients. In the present study ataxia telangiectasia and wild type cells were used as a cellular model and treated with dexamethasone. The cells were subsequently investigated for membrane and whole cell mechanical properties by atomic force microscopy. In addition, cytoskeleton protein dynamics and nuclear shapes were assayed by fluorescence microscopy, while western blots were used to assess actin and tubulin content. At the macro level, dexamethasone directly modified the cell shape, Young's modulus and cytoskeleton protein dynamics. At the nano level, the roughness of the cell surface and the local nano-mechanical proprieties were found to be affected by Dexa. Our results show that ataxia telangiectasia and wild type cells are affected by Dexa, although there are dissimilarities in some macro-level and nano-level features between the tested cell lines. The Young's modulus of the cells appears to depend mainly on nuclear shape, with a slight contribution from the tested cytoskeleton proteins. The current study proposes that dexamethasone influences ataxia telangiectasia cell membranes contents, cell components and cell shape.


Sleep movements of leaves: In defense of Darwin's interpretation.
On the basis of extensive but indirect evidence, Darwin proposed that an important function of daily leaf movements is to minimize radiative heat loss to the night sky and thereby protect the leaves from nocturnal chilling, an interpretation which has currently fallen into disrepute. Measurements made on flowering bean seedlings demonstrate that consistent orientation-dependent differences in nighttime leaf temperature do indeed arise even on warm nights, as Darwin had concluded, but the observed differences tended to be quite small (usually less than 1°C). Nevertheless, experiments in which growth of bean seedlings was measured, while nighttime orientation of the primary leaves was mechanically constrained, demonstrate that leaf growth can be significantly retarded when nocturnal orientation of the leaves is horizontal. This reduction in growth rate, apparently mediated by very modest temperature effects, is consistent with Darwin's speculation about the "injurious" consequences of nocturnal leaf chilling under nonfreezing conditions.


Comparison of intravenous versus topical tranexamic acid in primary total hip and knee arthroplasty: An updated meta-analysis.
The appropriate route for administering tranexamic acid in primary total hip (THA) and knee arthroplasty (TKA) remains controversial. The purpose of this meta-analysis was to compare the efficacy and safety of topical or intravenous tranexamic acid. PubMed, EMBASE, and the Cochrane Library databases were systematically searched for randomized controlled trials (RCTs) comparing topical and intravenous tranexamic acid following primary THA or TKA. Primary outcomes were transfusion frequency and maximum drop in hemoglobin. Other parameters included total blood loss (TBL), hidden blood loss, drainage volume, hemoglobin level on postoperative day 1 (POD 1), deep vein thrombosis (DVT), pulmonary embolism (PE), wound complications and other adverse events. Data were analyzed using Rev Man 5.2. A total of 18 RCTs involving TKA and 4 RCTs involving THA, corresponding to approximately 2260 patients, were included in the meta-analysis. No significant difference between topical and intravenous tranexamic acid was found in transfusion requirement (RR 1.14, 95%CI 0.87 to 1.50, p=0.35). The maximum drop in hemoglobin was significantly smaller in the intravenous group than in the topical group (MD 0.33g/dL, 95%CI 0.07 to 0.58, p=0.01); similar results were observed for the subset of studies involving THA (MD 0.49g/dL, 95%CI 0.28 to 0.70, p<0.001) and the subset involving TKA (MD 0.30g/dL, 95%CI 0.02 to 0.59, p=0.04). The topical and intravenous groups did not differ significantly in TBL, drainage volume, hemoglobin level on POD 1, DVT, PE, wound complications or other adverse events. The available evidence indicates similar transfusion requirements and safety for topical and intravenous tranexamic acid in THA and TKA. However, intravenous injection seems to be associated with a smaller maximum drop in hemoglobin.


Serological analysis of cell surface antigens in choriocarcinoma cell lines.
Major histocompatibility complex (MHC) antigens as well as blood group related antigens were investigated in four newly established gestational choriocarcinoma cell lines (NaUCC-1, -2, -3, and -4) using protein A and immune adherence assays. Antibodies to both monomorphic determinants of HLA class I antigens and beta 2 microglobulin reacted with all of the choriocarcinoma cell lines at levels equal to or much greater than SCH, which was teratoid choriocarcinoma cell line. Antibodies to polymorphic determinants not only of the patient's HLA type, but also of the husband's type, reacted to NaUCC-1 and -2. These results indicated that all four newly established choriocarcinoma cell lines express class I HLA antigens. However, we could not demonstrate expression of class II antigens. No expression of blood group A and B antigens could be established, and binding of antibody to Rho(D) antigens was only positive in the NaUCC-1 cell line. These results suggest that some choriocarcinoma cell lines actually express alloantigens and that choriocarcinomas have the character of transplanted tumors that have activities to induce transplantation immunity of the patients.


High-Resolution, High b-Value Computed Diffusion-Weighted Imaging Improves Detection of Pancreatic Ductal Adenocarcinoma.
Our purpose was to investigate the potential of high-resolution, high b-value computed DWI (cDWI) in pancreatic ductal adenocarcinoma (PDAC) detection. We retrospectively enrolled 44 patients with confirmed PDAC. Respiratory-triggered, diffusion-weighted, single-shot echo-planar imaging (ss-EPI) with both conventional (i.e., full field-of-view, 3 × 3 × 4 mm voxel size, b = 0, 50, 300, 600 s/mm2) and high-resolution (i.e., reduced field-of-view, 2.5 × 2.5 × 3 mm voxel size, b = 0, 50, 300, 600, 1000 s/mm2) imaging was performed for suspected PDAC. cDWI datasets at b = 1000 s/mm2 were generated for the conventional and high-resolution datasets. Three radiologists were asked to subjectively rate (on a Likert scale of 1-4) the following metrics: image quality, lesion detection and delineation, and lesion-to-pancreas intensity relation. Furthermore, the following quantitative image parameters were assessed: apparent signal-to-noise ratio (aSNR), contrast-to-noise ratio (aCNR), and lesion-to-pancreas contrast ratio (CR). High-resolution, high b-value computed DWI (r-cDWI1000) enabled significant improvement in lesion detection and a higher incidence of a high lesion-to-pancreas intensity relation (type 1, clear hyperintense) compared to conventional high b-value computed and high-resolution high b-value acquired DWI (f-cDWI1000 and r-aDWI1000, respectively). Image quality was rated inferior in the r-cDWI1000 datasets compared to r-aDWI1000. Furthermore, the aCNR and CR were higher in the r-cDWI1000 datasets than in f-cDWI1000 and r-aDWI1000. High-resolution, high b-value computed DWI provides significantly better visualization of PDAC compared to the conventional high b-value computed and high-resolution high b-value images acquired by DWI.


Inflammation in chronic heart failure.
To summarize findings regarding the association of inflammatory processes with chronic heart failure (HF). We conducted PubMed/MEDLINE searches (1966-January 2008) of primary literature using the following key words: ACE inhibitors, allopurinol, angiotensin-receptor antagonists, cardiomyopathy, chemokines, cytokines, diuretics, heart failure, inflammation, interleukins, HMG-CoA reductase inhibitors, immunotherapy, medications used in heart failure, thalidomide, tumor necrosis factor, and uric acid. All articles that appeared to be relevant were read; of 305 articles examined, 87 were selected for discussion. Articles were selected if they were written in English and focused on any of the key words or appeared to have substantial content addressing inflammation in HF. Cytokines, uric acid, and other inflammatory mediators are associated with physiologic effects that are also prominent features of HF (eg, reduced contractility and cardiac output, endothelial dysfunction, hypercoagulability, autonomic dysfunction as evidenced by reduced resting heart rate variability, insulin resistance). With the exception of elevated tumor necrosis factor-alpha as a cause of insulin resistance, it is not clear whether elevated inflammatory mediators directly cause HF signs and symptoms or whether they are incidental markers. Awareness of these associations has occurred relatively recently; there have been few clinical studies of efforts to directly modify inflammatory mediators. Most currently accepted drug therapies of HF reduce concentrations of circulating cytokines, but the significance of these findings awaits directed study. Loss of myocardial function, autonomic dysfunction, and glucose intolerance are interrelated and linked by underlying chronic low-grade inflammation. Drug therapy with statins, pentoxifylline, and perhaps urate-lowering agents, in addition to current therapies, holds promise for treatment of HF.


Insulin sensitivity, and β-cell function in relation to hemoglobin A1C.
The A1C diagnostic criterion for identifying individuals at increased risk for diabetes, introduced by the American Diabetes Association in 2010, was not defined on the basis of the principal pathophysiological abnormalities responsible for the development and progression of type 2 diabetes; we therefore wished to gain a deeper insight into the metabolic abnormalities characterizing the group of at risk individuals with an A1C value of 5.7-6.4%. As many as 338 non-diabetic offspring of type 2 diabetic patients were consecutively recruited. Insulin secretion was assessed using both indexes derived from oral glucose tolerance test (OGTT), and intravenous glucose tolerance test (IVGTT). Insulin sensitivity was measured by hyperinsulinemic euglycemic clamp. As compared with subjects with A1C <5.7%, individuals with A1C of 5.7-6.4% exhibited lower insulin sensitivity after adjusting for age, gender and body mass index (BMI). Insulin secretion estimated from the OGTT, did not differ between the two groups. By contrast, as compared with subjects with A1C <5.7%, the acute insulin response (AIR) during an IVGTT and both IVGTT-derived and OGTT-derived disposition indexes were reduced in individuals with A1C of 5.7-6.4% after adjusting for age, gender and BMI. As A1C increased to ≥ 5.7%, a sharp decrease in insulin sensitivity and β-cell function, measured as disposition index, was observed. Caucasian individuals with A1C ≥ 5.7% exhibit both core pathophysiological defects of type 2 diabetes i.e. insulin resistance and β-cell dysfunction.


Effects of lignite fly ash particulates and soluble components on the interferon system.
Induction of interferon by influenza virus was depressed by approximately 50% when mammalian (LLC-MK2) cell monolayers were pretreated with lignite fly ash. The presence of fly ash, however, did not impair the ability of exogenous interferon to confer antiviral cellular resistance. Influenza virus multiplication in cell monolayers pretreated with fly ash attained a twofold higher level of growth than that noted in normal cell monolayers. This was related to suppression of viral interferon induction by fly ash. Whereas aqueous extracts of fly ash had no adverse effect on interferon induction, extractions of fly ash by either polar or nonpolar solvents, by horse serum with or without EDTA (a metal chelator), and fractionation of serum extracts yielded corresponding compounds, most likely organic and inorganic, that were antagonistic to viral interferon induction. Residual fly ash particulates after extraction by horse serum with EDTA were still capable of inhibiting viral induction of interferon. These findings indicate that several soluble components inherent to lignite fly ash and the particulate matrix per se may modify, independently or in concert, cellular defense behavior. Neither polar, nonpolar, nor horse serum extracts of lignite fly ash, however, showed mutagenic activity as determined by the Salmonella histidine reversion assay. Removal of cell-membrane-bound sialic acid (N-acetylneuraminic acid) by neuraminidase or pretreatment of lignite fly ash with sialic acid abolished the adverse activity of fly ash on viral interferon induction. This suggests that the interaction of cell-membrane-bound sialic acid residue with fly ash particulates may be involved in the altered state of cellular behavior described in response to viral induction of interferon.


Factors that influence resignations of radiographers employed by tertiary hospitals in the KwaZulu-Natal province, South Africa.
The shortage of staff in Kwa-Zulu Natal (KZN) public hospitals is evident and poses a challenge to retain radiographers. Therefore, there is need to identify the factors that influence resignations of radiographers. The aim of this study was to explore the factors that influence resignations of radiographers employed by tertiary hospitals in KZN province. The study was guided by a descriptive quantitative research method. The data was collected in the form of questionnaires. A letter of information describing the details of the study was provided to the participants. All consenting participants were requested to provide a written consent prior to completing the questionnaire. The questionnaire was completed, collected and analysed. The statistical analysis test was conducted using SPSS statistic V25. A response rate of 66.35% was received with 78.3% (n=108) female and 21.7% (n=30) male. The result suggested that participants unanimously agree that resignation of radiographers is precipitated by factors such as poor working conditions, unhygienic working environment and uncompetitive salaries. The result also suggested that moving from their current career in radiography to another career is precipitated by factors such as high stress level and long working hours. The factors identified were further analysed and results showed that the participant's personal reasons for moving from their jobs are co-related with environmental reasons. The most influential factor was stress and remuneration.


A phenylalanine ammonia-lyase gene from parsley: structure, regulation and identification of elicitor and light responsive cis-acting elements.
We demonstrate that phenylalanine ammonia-lyase (PAL) in parsley (Petroselinum crispum) is encoded by a small family of at least four genes. The levels of mRNA from three identified PAL genes increase considerably upon treatment of cultured parsley cells with UV light or fungal elicitor and upon wounding of parsley leaves or roots. In cultured cells these changes were shown to involve transcriptional activation. We present the first primary structure of a plant PAL gene (parsley PAL-1) and the deduced amino acid sequence of the enzyme. Inducible in vivo footprints in the PAL-1 promoter define two nucleotide sequences, within the motifs CTCCAACAAACCCCTTC and ATTCTCACCTACCA, involved in the responses to both UV irradiation and elicitor application. These motifs are conserved at similar positions in several elicitor or light-responsive genes from different species. In two cases they are found within short regions known to confer elicitor or UV-light inducibility. The conserved motifs in the parsley 4-coumarate:CoA ligase gene, which is coordinately regulated with PAL, also display UV-light inducible in vivo footprints. Taken together, our findings suggest a general role of these putative cis-acting elements in the responses of plants to such stresses.


Tamoxifen-loaded nanoparticles based on a novel mixture of biodegradable polyesters: characterization and in vitro evaluation as sustained release systems.
Nanoparticles (NP) from mixtures of two poly(D,L-lactide-co-caprolactone) (PLC) copolymers, PLC 40/60 and PLC 86/14, with poly(D,L-lactide) (PDLLA) and PCL were prepared: PLC 40/60-PCL (25:75), PLC 86/14-PCL (75:25) and PLC 86/14-PLA (75:25). Tamoxifen was loaded with encapsulation efficiency between 65% and 75% (29.9-36.3 µg TMX/ mg NP). All selected systems showed spherical shape and nano-scale size. TMX-loaded NPs were in the range of 293-352 nm. TMX release from NP took place with different profiles depending on polymeric composition of the particles. After 60 days, 59.81% and 82.65% of the loaded drug was released. The cytotoxicity of unloaded NP in MCF7 and HeLa cells was very low. Cell uptake of NP took place in both cell types by unspecific internalization in a time dependent process. The administration of 6 and 10 µm TMX by TMX-loaded NP was effective on both cellular types, mainly in MCF7 cells.


Congenital mucinous eccrine nevus in a 5-month-old girl with frequent intertriginous dermatitis.
We present a 5-month-old girl with one localized plaque in a bandlike distribution on the left wrist since birth. Localized hyperhidrosis was also noted. Histopathologic examination of the lesion showed typical findings of mucinous eccrine nevus. Our report may serve to alert dermatologists to consider this entity in congenital lesions.


Early Signs of End-Organ Damage in Retinal Arterioles in Patients with Type 2 Diabetes Compared to Hypertensive Patients.
Eutrophic and hypertrophic remodeling are major vascular hallmarks for hypertension and diabetes-associated microvascular end-organ damage in peripheral arterioles. The aim of this study is to compare retinal arterioles of diabetic, hypertensive, and healthy individuals. Retinal parameters were assessed in 99 patients with T2DM, 158 hypertensive, and 149 healthy individuals. WT and CA of retinal arterioles (80-140 μm) were measured noninvasively and in vivo by scanning laser Doppler flowmetry (Heidelberg Engineering, Germany). After adjustment for values differing between the groups (age, BMI, gender, HDL cholesterol and serum creatinine, systolic office BP), patients with T2DM showed no significant difference in WT (14.2 ± 3), and CA (4199 ± 1107) in comparison with hypertensive patients (WT = 13.3 ± 4, p = 0.18, CA = 3862 ± 1546, p = 0.10) and healthy individuals (WT = 13.1 ± 3, p = 0.55, CA = 3864 ± 1216, p = 0.86). However, the subgroup of patients with diabetes duration of more than 60 months showed greater WT (14.9 ± 4, p = 0.04) and CA (4557 ± 1137, p = 0.02) than the hypertensive group and greater WT (p = 0.04) and CA (p = 0.03) than the healthy group, which is consistent with hypertrophic remodeling. In the early stage of T2DM no hypertrophic remodeling was seen in retinal arterioles. However, hypertrophic remodeling was found in diabetic patients with more than 60 months duration of disease.


Adenosine A₁ and A₂A receptor-mediated modulation of acetylcholine release in the mice neuromuscular junction.
Immunocytochemistry shows that purinergic receptors (P1Rs) type A1 and A2A (A1 R and A2 A R, respectively) are present in the nerve endings at the P6 and P30 Levator auris longus (LAL) mouse neuromuscular junctions (NMJs). As described elsewhere, 25 μm adenosine reduces (50%) acetylcholine release in high Mg(2+) or d-tubocurarine paralysed muscle. We hypothesize that in more preserved neurotransmission machinery conditions (blocking the voltage-dependent sodium channel of the muscle cells with μ-conotoxin GIIIB) the physiological role of the P1Rs in the NMJ must be better observed. We found that the presence of a non-selective P1R agonist (adenosine) or antagonist (8-SPT) or selective modulators of A1 R or A2 A R subtypes (CCPA and DPCPX, or CGS-21680 and SCH-58261, respectively) does not result in any changes in the evoked release. However, P1Rs seem to be involved in spontaneous release (miniature endplate potentials MEPPs) because MEPP frequency is increased by non-selective block but decreased by non-selective stimulation, with A1 Rs playing the main role. We assayed the role of P1Rs in presynaptic short-term plasticity during imposed synaptic activity (40 Hz for 2 min of supramaximal stimuli). Depression is reduced by micromolar adenosine but increased by blocking P1Rs with 8-SPT. Synaptic depression is not affected by the presence of selective A1 R and A2 A R modulators, which suggests that both receptors need to collaborate. Thus, A1 R and A2 A R might have no real effect on neuromuscular transmission in resting conditions. However, these receptors can conserve resources by limiting spontaneous quantal leak of acetylcholine and may protect synaptic function by reducing the magnitude of depression during repetitive activity.


Life-threatening hyperkalemia following partial pancreatectomy for neonatal hyperinsulinism.
To alert readers to the possibility of rebound hyperkalemia following pancreatic resection for neonatal hyperinsulinism. Case report. Intensive care unit of tertiary pediatric hospital. A term neonate with severe hyperinsulinism complicated by hypokalemia, fluid overload, and necrotizing enterocolitis. Preoperative management consisted of glucose 20.8 mg/kg/min, diazoxide 15 mg/kg/day, octreotide 27 mug/kg/day, and potassium (>10 mmol/kg/day) to maintain normoglycemia and normokalemia. The large glucose requirement, administered as 20% glucose, contributed to congestive heart failure, which was treated with frusemide. Attempts to feed enterally were abandoned because of necrotizing enterocolitis. Partial colectomy and subtotal pancreatectomy were performed on day 20. Serum potassium rose rapidly within 2 hrs of surgery to reach 12.3 mmol/L, causing ventricular tachycardia (240 beats/min) on electrocardiogram. There was no evidence of renal failure or adrenal insufficiency. Management consisted of insulin 0.1 units/kg intravenously, 10% calcium gluconate 0.1 mmol/kg intravenously, sodium bicarbonate 3 mmol/kg intravenously, frusemide 2 mg/kg intravenously, and resonium 0.6 g/kg per rectum with good outcome. This report highlights the rapid electrolyte shifts possible after sudden cessation of hormones regulating Na/K-ATPase activity.


The atherogenic risk of antihypertensive therapy.
The past 20 years have demonstrated the unqualified success of antihypertensive therapy in reducing morbidity and mortality from cardiovascular and cerebrovascular disease. Evidence mounts, however, that certain antihypertensive agents may, themselves, have an adverse effect on the development and progression of cardiovascular disease. The dramatic reductions in the incidence of cerebrovascular events and congestive heart failure among patients receiving antihypertensive therapy have not been paralleled by similar reductions in cardiac morbidity or mortality. Several lines of evidence now point to the possibility that adverse metabolic changes are induced by certain antihypertensive drugs. These changes may offset, negate, or even reverse the potential benefit afforded by successful blood pressure control.


Brain natriuretic peptide (BNP) in differential diagnosis of dyspnea.
The differentiation of congestive heart failure from pulmonary cause of dyspnea is of extreme importance in patients presenting with acute shortness of breath. It seems that the use of B-type natriuretic peptide (BNP) can speed up the diagnostic process significantly. 79 patients (46 men - 58.2%, average 71.9, range 43-92; 33 women - 41.8%, average 75.5, range 51-93). In each of them we measured BNP concentrations by means of rapid fluorescent immunoassay. We divided the patients according to BNP results into two groups: BNP positive and BNP negative. There were 28 BNP negative patients -35.40% (13 men, 15 women). BNP positive patients (51) were divided into NYHA I-IV groups in accordance with BNP results. The rapid, highly sensitive and specific measurement of BNP concentrations in the patients with dyspnea can significantly help to differentiate the cardiac and pulmonary causes of dyspnea (Tab. 1, Fig. 1, Ref. 24).