Effect of Vitamin D Supplementation on Clinical Course and T Helper 17/ T-Regulatory Balance in Peripheral Blood of Patients with Crohn's Disease.
Vitamin D has anti-inflammatory properties and is involved in immune function, making it a potential therapy for Crohn's disease. This study aimed to investigate the effects of vitamin D supplementation on immune function and the clinical efficacy of patients with Crohn's disease. From September 2017 to September 2021, patients with Crohn's disease were recruited and randomly divided into 2 groups: the routine treatment group (n = 52) and the vitamin D supplement group (n = 50). In addition to routine treatment, the vitamin D group received oral calcitriol capsule supplementation, while the routine treatment group did not receive any additional intervention. T helper 17/T-regulatory cell level, inflammatory indicators, and nutritional status were compared between the 2 groups, as well as mucosal healing under endoscopy and the life quality of patients. C-reactive protein was significantly lower in the vitamin D treatment group compared to the routine treatment group (6.08 ± 2.72 vs. 18.91 ± 2.66, P < .05). Compared to the routine treatment group, the ratio of T helper 17/T-regulatory cells was significantly lower in the vitamin D group (0.26 ± 0.12 vs. 0.55 ± 0.11, P < .05). After vitamin D treatment, both of the average Crohn's disease activity index score (from 319.7 ± 72.7 to 179.6 ± 48.5, P < .05) and simple endoscopic score for Crohn's disease score (from 7.9 ± 2.3 to 3.9 ± 0.6, P < .05) were significantly decreased, while the Inflammatory Bowel Disease Questionnaire score was significantly increased (from 137.8 ± 21.2 to 158.1 ± 25.1, P < .05). Vitamin D has the potential to improve the inflammatory status and immune environment of patients with Crohn's disease, which can reduce the level of inflammatory factors and help the recovery of symptoms, thus improving the clinical course and quality of life in Crohn's disease patients.


The role of objectively recorded smartphone usage and personality traits in sleep quality.
The proliferation of smartphones, accompanied by internet facilities, has contributed to a decrease in sleep quality over the last decades. It has been revealed that excessive internet usage impacts the physical and mental health of smartphone users, while personality traits (PT) could play a role in developing internet addictions and preventing their negative effects. The objective of the present study is to assess the role of PT and smartphone usage in sleep quality. The sample comprised 269 participants, 55% females, within the age range of 15-64 years. We objectively collected one-week smartphone apps usage data from the participants. They also responded to demographics and the PT (BFI-10) questionnaires. The usage data of smartphone apps were processed to calculate smartphone usage amounts and sleep variables, including sleep duration, sleep distraction, sleeping time, and wake-up time. The data were analyzed using the correlation coefficient and regression analyses. The results indicated that more smartphone usage was associated with reduced sleep duration, increased sleep distraction, and later bedtime. Furthermore, smartphone users with the conscientiousness trait had a longer sleep duration, earlier sleeping time, less sleep distraction, and earlier wakeablity. Sleep distraction was positively associated with openness. Extraversion and neuroticism were found to be positive predictors of early wakeablity. Neuroticism had a negative association with early wakeablity. Finally, the implications of the study have been discussed. Our study's usage of data that was acquired objectively has strong methodological qualities. The present study is the first to contribute to the literature on the role of PT and objectively measured smartphone usage in the prediction of sleep quality. We found that smartphone use and sleep variables are associated with PT. Other scholars can use our dataset for benchmarking and future comparisons.


Free groin flap for aesthetic and functional donor-site closure of the anterolateral thigh flap.
Better methods for anterolateral thigh flap donor-site reconstruction are desirable in cases when direct closure is impossible. Multiple surgical strategies have been attempted, and each has its shortcomings. The use of a contralateral free groin flap to repair the anterolateral thigh flap donor site is investigated in this report. From October 2015 to February 2016, free groin flaps were harvested on six patients for aesthetic and functional donor-site closure of the anterolateral thigh flap, which could not be directly closed. In these cases, the reverse-flow distal portion of the descending branch of the lateral circumflex femoral artery and vein were used as recipient vessels and anastomosed to the superficial circumflex iliac artery and vein, respectively. One flap had presented a few blisters on the distal margin; the other five flaps fully survived without any complications. Patients were highly satisfied with the aesthetic outcomes of both the anterolateral thigh area and the groin site. Although with theoretical risks of compromised venous blood flow, free groin flaps are an effective strategy for closure of massive anterolateral donor-site defects and can be safely performed with thoughtful planning and meticulous microsurgical techniques.


Cytokinin enhancement of the light induction of nitrate reductase transcript levels in etiolated barley leaves.
To investigate the molecular mechanism of cytokinin regulation of nitrate reductase (NR) activity, the influence of benzyladenine (BA) on the level of NR transcript was studied in etiolated barley leaves using a barley NR cDNA as a probe. Northern blot analyses of the levels of NR poly (A)+ RNA indicate that the amount present is proportional to the concentration of BA (2 x 10(-8) to 2 x 10(-4) M) applied to the leaves. Enhancement of NR mRNA by 2 x 10(-5) M BA was clearly detected after 15 minutes of exposure of the leaves to light. The enhancement is cytokinin-specific and adenine is ineffective. Brief treatment with the protein synthesis inhibitor, cycloheximide, inhibited BA-enhanced NR activity but did not inhibit BA-enhanced NR transcript level, thus the enhancement was independent of concurrent protein synthesis. Nuclear runoff transcription studies showed that the enhancement of NR mRNA was at least partially due to increased transcription rates.


Acute effects of marijuana smoke on complex operant behavior in rhesus monkeys.
The acute behavioral effects of marijuana smoke were assessed in rhesus monkeys using a battery of food-reinforced complex operant tasks that included incremental repeated acquisition (IRA, n = 9), conditioned position responding (CPR, n = 8), progressive ratio (PR, n = 8), delayed matching to sample (DMTS, n = 6), and temporal response differentiation responding (TRD, n = 3). Marijuana or placebo smoke was delivered by a specialized face mask 15-min before sessions at exposure levels of 1, 5, 10, and 15 puffs (35cc/puff) or one cigarette smoked to a butt length of approximately 10 mm (approximately 20 puffs). Marijuana smoke caused significant disruptions of performance in all tests except PR after exposure to 10 or more puffs. Generally, response rates decreased or latencies to respond increased. Performance in the PR test was not consistently affected by marijuana exposure. Accuracy of responding was not altered by marijuana smoke at doses lower than those that decreased response rates in the IRA or CPR tests. In the three animals performing under all five schedules, the relative sensitivities for detecting marijuana behavioral effects were DMTS = TRD greater than IRA = CPR greater than PR. These results suggest that performance under operant schedules that are thought to represent some aspect of time perception, short-term memory, learning, motivation, and position discrimination show differential sensitivity to disruption by marijuana smoke, a finding similar to that noted previously for iv THC administration.


Color Doppler ultrasonography for evaluation of internal mammary artery application in adolescent female patients with right-convex thoracic idiopathic scoliosis.
Prospective comparative study. To establish the use of Color Doppler Ultrasonography to investigate internal mammary artery. Breast asymmetry in female adolescents with right convex idiopathic scoliosis was supposed to be linked with anatomic and functional asymmetry of the internal mammary artery that is the main supplier to the mammary gland. However, no measurements of anatomic and hemodynamic parameters of internal mammary artery have been made to justify or to reject the hypothesis of asymmetric blood flow volume to the breasts and costosternal junction in female adolescent scoliotics. Color Doppler Ultrasonography is a well established noninvasive method to assess vessel anatomy and hemodynamics. Twenty female adolescents with right thoracic scoliosis and 16 comparable female individuals without spine deformity were examined with Color Doppler Ultrasonography to measure at the origin of internal mammary artery lumen diameter, cross sectional area, time average mean flow and flow volume per minute and were compared each other. The reliability of Color Doppler Ultrasonography was high and the intraobserver variability low (ANOVA, P = 0.92-0.94). There was no statistically significant difference in the ultrasonographic parameters of the internal mammary artery between right and left side in each individual as well as between scoliotics and controls. Color Doppler Ultrasonography applied to assess anatomic or hemodynamic blood flow parameters at the origin of internal mammary artery was proven a highly reliable method. Color Doppler Ultrasonography disclosed no side-differences, while there were no differences between scoliotics and controls. Thus, it seems that this study cannot justify previous theories for development of right thoracic scoliosis in female adolescents.


Systems approaches to uncovering the contribution of environment-mediated drug resistance.
Cancer drug response is heavily influenced by the extracellular matrix (ECM) environment. Despite a clear appreciation that the ECM influences cancer drug response and progression, a unified view of how, where, and when environment-mediated drug resistance contributes to cancer progression has not coalesced. Here, we survey some specific ways in which the ECM contributes to cancer resistance with a focus on how materials development can coincide with systems biology approaches to better understand and perturb this contribution. We argue that part of the reason that environment-mediated resistance remains a perplexing problem is our lack of a wholistic view of the entire range of environments and their impacts on cell behavior. We cover a series of recent experimental and computational tools that will aid exploration of ECM reactions space, and how they might be synergistically integrated.


Monitoring of naturally acquired and artificially induced immunity to Amblyomma variegatum and Rhipicephalus appendiculatus ticks under field and laboratory conditions.
The ability of rabbits, goats and cattle to acquire immunity to the ixodid ticks Amblyomma variegatum and Rhipicephalus appendiculatus was studied under laboratory and field conditions. Rabbits were successfully immunized with crude salivary gland extract (SGE) and midgut extract (ME) obtained from flat or partly fed female R. appendiculatus ticks. The lowest numbers of larvae were produced by females fed on rabbits immunized with unfed midgut extract. Similar reductions in larval production could be induced after three infestations of rabbits with adult R. appendiculatus. Also, successive feedings of nymphs of R. appendiculatus on rabbits resulted in significantly reduced engorgement weights. Skin testing with SGE induced delayed-type hypersensitivity reactions, which could be correlated with immunity to R. appendiculatus in rabbits. Moreover, circulating antibodies were detected in rabbits with an ELISA using SGE of R. appendiculatus. Immunity to A. variegatum nymphs could be induced in rabbits by repeated infestations, but this failed in goats. Immunization of goats with midgut extract from adult A. variegatum did not protect against subsequent nymphal challenge, but strong skin reactions were noticed when adults ticks fed on immunized goats. Sodium dodecyl sulfate polyacrylamide gel electrophoresis of SGE and ME from A. variegatum revealed the presence of 48 protein bands in SGE and 29 bands in midgut extract. Western blotting employing serum from a rabbit immune to R. appendiculatus recognized a number of bands in SGE from R. appendiculatus, but also in SGE of A. variegatum. Immunity acquired by cattle to ixodid tick infestations under field conditions was monitored by skin testing with SGE and western blot analysis. In general, cattle with the lowest tick numbers manifested the strongest delayed-type hypersensitivity responses. Finally, western blot analysis employing sera from tick-infested and tick-naive cattle could not be related to actual immune status.


A comparative study on the effects of rIL-4, rIL-2, rIFN-gamma, and rTNF-alpha on specific T-cell non-responsiveness to mycobacterial antigens in lepromatous leprosy patients in vitro.
We have studied lepromatous leprosy (LL) as a human model disease for T-cell non-responsiveness to specific mycobacterial antigens and studied the effect of rIL-4, rIL-2, rIFN-gamma and rTNF-alpha thereon. T-cell non-responsiveness to Mycobacterium bovis bacillus Calmette-Guerin (BCG) or purified protein derivative of M. tuberculosis (PPD) antigens could be overcome in 5 out of 8 non-responder patients by rIL-2 and in 2 out of 8 by rIL-4. The ability of rIL-4 to overcome BCG/PPD non-responsiveness was strongly dose-dependent. When rIL-2 and rIL-4 were added simultaneously, they seemed to synergize in their effect. T-cell non-responsiveness to M. leprae could be overcome only in 2 out of 18 non-responders by rIL-2 but not by rIL-4 alone. The ability of rIL-2 to overcome T-cell non-responsiveness to M. leprae antigens became particularly marked when the recombinant 65-kDa heat shock antigen of M. leprae was used instead of whole bacilli. Exogenously added rIL-4, and to a lesser extent rIL-2, strongly enhanced existing T-cell responses to BCG or M. leprae in the majority (8 out of 11) of responders. These findings may have implications for the in vivo manipulation of the immune response by recombinant lymphokines and vaccines.


Full genotype constellations analysis of unusual DS-1-like G12P[6] and G6P[8] rotavirus strains detected in Brazil, 2019.
Rotavirus A (RVA) is a major cause of acute gastroenteritis (AGE) in children worldwide. We report unusual RVA G12P[6] and G6P[8] strains isolated from fecal samples from Brazilian children hospitalized for AGE. The characterized RVA have genome segments backbone: G12-P[6]/ G6-P[8]-I2-R2-C2-M2-A2-N2-T2-E2-H2 of DS-1-like genogroup. Our study describes the first identification of G6P[8], a DS-1-like genogroup strain. Nucleotide analysis of VP7 and VP4 genes revealed that all G12 Brazilian strains clustered into the sub-lineages IIIB, mostly associated with P[6] lineage I. Additionally, our G6 lineage I strains were closely related to German G6 genotypes, bound with P[8] lineage III, differing from both vaccine strains. The comparative sequence analysis of our strains with vaccine strains revealed amino acid substitutions located in immunodominant regions of VP7 and VP4 proteins. Continuous monitoring of RVA genotypes is essential to evaluate the impact of vaccination on the dynamic nature of RVA evolution.


Packet theory of conditioning and timing.
Packet theory is based on the assumption that the momentary probability of producing a bout or packet of responding is controlled by the conditional expected time function. Bouts of head entry responses of rats into a food cup appear to have the same characteristics across a range of conditions. The conditional expected time function is the mean expected time remaining until the next food delivery as a function of time since an event such as food or stimulus onset. The conditional expected time function encodes mean interval duration as well as the distribution form so that both the mean response rate and form of responding in time can be predicted. Simulations of Packet theory produced accurate quantitative predictions of: (1) the effect of reinforcement density (mean food-food interval) and distribution form on responding; (2) scalar variance in fixed interval responding; (3) CS-US and intertrial interval effects on the strength of conditioning; and (4) the effect of the ratio of cycle:trial time on the strength of conditioning.


Studies on the attachment response of Isthmiophora melis cercariae (Trematoda: Echinostomatidae).
The cercaria of Isthmiophora melis is relatively specific to suitable intermediate hosts, amphibia and fish, as early as the stage of attachment. Attachment responses are maximally stimulated by intact amphibia, whereas isolated frog tissues have a reduced efficiency. Human urine contains attachment triggering substances. Its effectiveness is reduced, when carbonate systems are removed, and may be restored by addition of carbonate. Aqueous solution systems of dissolved CO2 and H2CO3/HCO-3 stimulate attachment responses, especially at pH 6.0-7.5. The attachment response to frog skin surface seems to be triggered by the buffering system, which uses carbonate solution equilibria as important components.


[Cystectomy in superficial bladder tumours. Analysis of criterion include and prediction factors].
Though usually the treatment of a superficial bladder tumour consists in transurethral resection, exceptionally because of several clinical conditions, in this kind of patients a radical cystectomy may be suitable. From june 1986 through december 2001, 127 radical cystectomies were performed. A series of 25 patients with a radical cystectomy performed in superficial bladder tumours were analysed. Indications, anatomo-pathological correlation and clinical evolution with survival curves are analysed. The mean time of follow-up was 47 months. Extensive GIIIpT1 tumours (40%) were the chief indication. The remaining of the series consisted in carcinoma uncontrollable by endoscopy and refractory to chemotherapy. Anatomo-pathological correlation coincided in 48% of patients, existing supra and understaging in 25% and 28% respectively. A period of 54 months was without relapse. Seven patients died during the evolution (28%), and 18 patients are alive without disease. 128,48 months were the mean actuarial survival. GIIIpT1 tumours were the chief indication of our series. The significant percentage of understaging, poor morbidity and good survival curves are emphasized. Because of these results we consider that radical cystectomies are a viable choice for selected patients with superficial vesical tumour.


An unfamiliar social presence reduces facial disgust responses to food stimuli.
Consumers' emotional responses complement sensory and hedonic ratings in the prediction of food choice and consumption behaviour. The challenge with the measurement of consumption emotions is that emotions are highly context dependent. For emotion evaluations to bring greater insight to food research and development, it is essential that the influence of contextual variables on emotion are quantified. The present study contributes to the discussion with an investigation of the effect of an unfamiliar social presence on affective facial responses to visual food stimuli. Seventy participants (52 female and 18 male) viewed food images of varying acceptability either alone, or in the presence of the researcher. Subjective liking ratings were measured using a labelled affective magnitude scale, and facial muscle activity from zygomaticus major (contracted during smiling), corrugator supercilii (contracted during frowning) and levator labii superioris (contracted during nose wrinkling) were measured with an EMG recording system. Controlling for individual differences in facial expressivity and food image acceptability using linear mixed models, it was found that social context did not predict smiling or frowning muscle activity. Social context did predict the intensity of muscle activity indicative of a disgust response, with participants in the observed condition exhibiting less levator activity than participants in the alone condition. Regardless of social context, each muscle was found to have a relationship with subjective liking, with the direction of effects as expected. The results indicate that emotional stimuli and social context both influence food-evoked facial expression and provides support for the utility of facial EMG in measuring food-evoked emotion.


Arsenic sorption and speciation with branch-polyethyleneimine modified carbon nanotubes with detection by atomic fluorescence spectrometry.
Multi-wall carbon nanotubes (MWNTs) are modified with branched cationic polyethyleneimine (BPEI). The MWNTs-BPEI nanocomposites serve as a novel adsorbent and exhibit favorable selectivity toward adsorption of As(V). Appropriate amount of MWNTs-BPEI suspension containing ca. 5 mg of the composites is used to pack a mini-column for on-line solid phase extraction preconcentration of inorganic arsenic in a sequential injection system, following detection by hydride generation atomic fluorescence spectrometry. At pH 5.8, an sorption efficiency of 80% is achieved for As(V) at 10 μg L(-1), resulting in a sorption capacity of 26.18 mg g(-1). Meanwhile, the sorption efficiency for As(III) is <5%. The retained As(V) is readily recovered by 100 μL NH4HCO3 (0.6%, m/v). With a sample volume of 2.0 mL, an enrichment factor of 16.3 for As(V) is obtained along with a detection limit of 14 ng L(-1) within a linear range of 0.05-1.50 μg L(-1). A RSD of 3.6% is derived at 0.5 μg L(-1). Total amount of arsenic is obtained by converting As(III) to As(V) and following the same procedure. The speciation of inorganic arsenic is realized by difference. This procedure is validated by analyzing a certified reference material of human hair (GBW09101), achieving satisfactory agreements between the certified and the obtained values. Speciation of As(V) and As(III) is also performed in snow water and rain water samples.


Granule size informs the characteristics and performance of microalgal-bacterial granular sludge for wastewater treatment.
In this study, four groups of microalgal-bacterial granules with averaged diameters of about 356, 760, 951 and 1,444 µm were used to investigate their characteristics and performance in treating wastewater. A strong correlation between extracellular polymeric substances of microalgal-bacterial granules and the granule size was observed. Moreover, granule size showed a positive effect on the specific organics removal rate, but being negative for ammonium and phosphorus removal. It appeared that granule size could be used as a useful index to reflect the synergistic interactions between microalgae and bacteria in terms of the abundances, distributions and functional species in the microalgal-bacterial granules. This study is expected to offer new insights into the size-dependent performances of microalgal-bacterial granules for wastewater treatment.


Non-Invasive, Focal Disconnection of Brain Circuitry Using Magnetic Resonance-Guided Low-Intensity Focused Ultrasound to Deliver a Neurotoxin.
Disturbances in the function of neuronal circuitry contribute to most neurologic disorders. As knowledge of the brain's connectome continues to improve, a more refined understanding of the role of specific circuits in pathologic states will also evolve. Tools capable of manipulating identified circuits in a targeted and restricted manner will be essential not only to expand our understanding of the functional roles of such circuits, but also to therapeutically disconnect critical pathways contributing to neurologic disease. This study took advantage of the ability of low-intensity focused ultrasound (FUS) to transiently disrupt the blood-brain barrier (BBB) to deliver a neurotoxin with poor BBB permeability (quinolinic acid [QA]) in a guided manner to a target region in the brain parenchyma. Ten male Sprague-Dawley rats were divided into two groups receiving the following treatments: (i) magnetic resonance-guided FUS + microbubbles + saline (n = 5), or (ii) magnetic resonance-guided FUS + microbubbles + QA (n = 5). Systemic administration of QA was well tolerated. However, when QA and microbubbles were systemically administered in conjunction with magnetic resonance-guided FUS, the BBB was disrupted and primary neurons were destroyed in the targeted subregion of the hippocampus in all QA-treated animals. Administration of vehicle (saline) together with microbubbles and FUS also disrupted the BBB but did not produce neuronal injury. These findings indicate the feasibility of non-invasively destroying a targeted region of the brain parenchyma using low-intensity FUS together with systemic administration of microbubbles and a neurotoxin. This approach could be of therapeutic value in various disorders in which disturbances of neural circuitry contribute to neurologic disease.


Benthic ecosystem functioning in the severely contaminated Mar Piccolo of Taranto (Ionian Sea, Italy): focus on heterotrophic pathways.
The benthic ecosystem functioning is a rarely applied holistic approach that integrates the main chemical and biological features of the benthic domain with the key processes responsible for the flux of energy and C through the system. For the first time, such conceptual model, with an emphasis on the heterotrophic pathways, has been applied to the sediments at four stations within one of the most polluted coastal areas in Italy: the Mar Piccolo of Taranto. The functioning of the benthic ecosystem was different according to the investigated site. Nearby the military arsenal, i.e., the main source of organic contaminants and heavy metals, the system seemed inhibited at all the investigated structural and functional levels. Slow microbial processes of C reworking together with very limited densities of benthic fauna suggested a modest transfer of C both into a solid microbial loop and to the higher trophic levels. On the other hand, the ingression of marine water through the "Navigabile" channel seemed to stimulate the organic matter degradation and, consequently, the proliferation of meiofauna and macrofauna. In the innermost part of the basin, the system functioning, to some extent, is less impacted by contaminants and more influenced by mussel farms. The organic matter produced by these bivalves fueled faster C reworking by benthic prokaryotes and enhanced the proliferation of filter feeders.


[A clinical study of a multiregression analysis on the NK activity and related clinical factors in patients with lung cancer].
Using 24 lung cancer patients (20 males and 4 females) who had received radiotherapy, a multivariate analysis has been performed in relation to 19 factors suspected of exerting an effect on natural killer (NK) cell activity. As influencing factors, two factors of the disease, the stage (p less than 0.05) and the leukocyte count (p less than 0.08), were calculated to be significant. In the univariate analysis, the NK activity was found to be significantly low (p less than 0.05) when the leukocyte count was 7,000 or higher. In addition, patients who had died during the course of radiotherapy showed an NK activity which was significantly lower (p less than 0.05) than the activity manifested in both the disease-free patients and the relapsed progressive disease patients. Moreover, the patients with a PS of 40% or less had a significantly lower NK activity than the patients with a PS of 50% or more, though no correlation was found between the NK activity and the disease stage. In the use of this radiotherapy, the NK activity was found to be more strongly influenced by the size of the irradiated field than by the irradiated dose.


Successful management of empyema in a patient with a total artificial heart.
A description of successful management of a patient who developed an empyema as a postoperative complication following the insertion of a CardioWest total artificial heart (TAH) as a bridge to cardiac transplantation is presented. By using traditional methods of management, the patient recovered and went on to transplant.


What we have learned about the predictors of preterm birth.
The Preterm Prediction Study conducted by the Maternal Fetal Medicine Network between 1993 and 1996 studied a large number of risk factors for preterm birth in more than 3,000 women at 10 centers. The goals of the study were to better understand the strength of one risk factor versus another and to explore interactions among the predictors looking for combinations of factors that were more predictive of preterm birth than any single factor used alone. The most potent factors that were associated with spontaneous preterm birth at < 32 weeks were a positive cervical-vaginal fetal fibronectin test (odds ratio, 32.7) and < l0th percentile cervical length (odds ratio, 5.8), and in serum, > 90th percentiles of alpha-fetoprotein (odds ratio, 8.3) and alkaline phosphatase (odds ratio, 6.8), and > 75th percentile of granulocyte colony-stimulating factor (odds ratio, 5.5). Results for spontaneous preterm birth at < 35 weeks were generally similar but not as strong. The overlap among the strongest biologic markers for predicting spontaneous preterm birth was small. This suggests that the use of tests such as maternal alpha-fetoprotein, alkaline phosphatase, and granulocyte colony-stimulating factor as a group or adding their results to fetal fibronectin and cervical length test results may enhance our ability to predict spontaneous preterm birth and that the development of a multiple-marker test for spontaneous preterm birth is feasible.


Colistin and rifampicin compared with colistin alone for the treatment of serious infections due to extensively drug-resistant Acinetobacter baumannii: a multicenter, randomized clinical trial.
Extensively drug-resistant (XDR) Acinetobacter baumannii may cause serious infections in critically ill patients. Colistin often remains the only therapeutic option. Addition of rifampicin to colistin may be synergistic in vitro. In this study, we assessed whether the combination of colistin and rifampicin reduced the mortality of XDR A. baumannii infections compared to colistin alone. This multicenter, parallel, randomized, open-label clinical trial enrolled 210 patients with life-threatening infections due to XDR A. baumannii from intensive care units of 5 tertiary care hospitals. Patients were randomly allocated (1:1) to either colistin alone, 2 MU every 8 hours intravenously, or colistin (as above), plus rifampicin 600 mg every 12 hours intravenously. The primary end point was overall 30-day mortality. Secondary end points were infection-related death, microbiologic eradication, and hospitalization length. Death within 30 days from randomization occurred in 90 (43%) subjects, without difference between treatment arms (P = .95). This was confirmed by multivariable analysis (odds ratio, 0.88 [95% confidence interval, .46-1.69], P = .71). A significant increase of microbiologic eradication rate was observed in the colistin plus rifampicin arm (P = .034). No difference was observed for infection-related death and length of hospitalization. In serious XDR A. baumannii infections, 30-day mortality is not reduced by addition of rifampicin to colistin. These results indicate that, at present, rifampicin should not be routinely combined with colistin in clinical practice. The increased rate of A. baumannii eradication with combination treatment could still imply a clinical benefit. NCT01577862.


Evidence of abnormalities of insulin metabolism in rats with spontaneous hypertension.
Various aspects of insulin metabolism were compared in rats with spontaneous hypertension (SHR) and a suitable control group of similar sized Kyota Wistar (WKY) rats. The results indicated that the total integrated serum insulin response to an oral glucose challenge was significantly greater in the SHR rats, despite the fact that the total integrated serum glucose responses were similar in the two groups. This indirect evidence of resistance to insulin-stimulated glucose disposal was supported by the observation that the ability of similar serum concentrations of exogenous insulin to stimulate glucose disposal was reduced in SHR rats. In addition, the metabolic clearance rate of insulin was lower in the SHR rats. These data indicate that abnormalities in insulin secretion, action, and catabolism exist in rats with spontaneous hypertension. Whether this defect is unique to SHR rats, or common to all forms of experimental hypertension, is an important issue. Equally important is the relationship between the observed changes in insulin metabolism and the elevated blood pressure.


In vitro reconstruction of a tissue-engineered endothelialized bladder from a single porcine biopsy.
Augmentation of the urinary bladder using a tissue-engineered approach with autologous cells is a very promising technique. To prevent risks of necrosis after transplantation, the graft vascularization process could be markedly enhanced by incorporation of autologous endothelial cells in the tissue-engineered organ. The purpose of this study was to develop a separation technique to extract four bladder cell types from the same biopsy, and to prepare an endothelialized reconstructed bladder. Fibroblasts, smooth muscle cells (SMC), urothelial cells (UC) and endothelial cells (EC) were extracted from a small porcine bladder biopsy. The SMC, fibroblasts and EC were seeded on the top of the sponge and cultured for 10 days. Then, the UC were seeded on top of these cells for 15 additional days to produce a three-dimensional bladder wall. The UC and EC extracts from a single porcine biopsy were 97.2+/-0.6% keratin 8/18-positive and 97.7+/-0.3% PECAM-1-positive pure cells, respectively, as assessed by flow cytometry. The SMC could not be dissociated from fibroblasts, and were present as 37+/-0.5% desmin-positive cells. UC differentiated into a urothelium characterized by umbrella cells and a laminin-positive basal membrane. The EC reorganized in the matrix to form PECAM-1-positive capillary-like tubes. This new model of tissue-engineered bladder has the main advantages of being at least 2mm thick, autologous, and able to promote the formation of capillary-like tubes. It could be a promising alternative to the use of gastrointestinal segments to improve bladder capacity.


An integrated approach to unravel a putative crosstalk network in Alzheimer's disease and Parkinson's disease.
Integration of multiple profiling data and construction of functional regulatory networks provide a powerful approach to uncover functional relationships and significant molecular entities from transcriptomic data, highlighting the molecular mechanisms of complex diseases. Despite having an overlap in the neuropathologies of AD and PD, the molecular entities overlapped and mechanisms behind them are less known. Here we used an integrated strategy to analyze miRNA and gene transcriptomic data to understand the role of miRNAs and genes in regulatory activities taking place in cells, and find transcriptomic signatures linking AD and PD. We preprocessed and analyzed publicly available microarray datasets and identified 97 DEGs and 21 DEmiRs that may be involved in the overlapped mechanisms between these two disorders. Among the DEGs, we found HSPA9, PGK1, SDHC, FH, DLD, YWHAZ and ACLY as the major protein-coding genes involved in the crosstalk for AD-PD pathogenesis. Further we integrated these DEGs and DEmiRs with regulatory TFs to construct an overlapped dysregulated network of AD and PD. In the network, miR-27a-3p, miR-148a-3p and miR-15a-5p were found to be the most relevant with maximum interactions, describing their significance in the potential crosstalk. We also looked into the dysregulated biological processes and pathways overlapped in AD and PD. In conclusion, we highlighted the DEGs, DEmiRs, their interactions and related pathways overlapped in AD and PD pathogenesis, also describing a potential crosstalk at molecular level. Besides, our findings can further be used for molecular studies to reveal an assured AD-PD crosstalk.


Costs of diabetes medication among male former elite athletes in later life.
Regular physical activity plays a major role, in both prevention and treatment of type 2 diabetes. Less is known whether vigorous physical activity during young adulthood is associated with costs of diabetes medication in later life. The aim of this study is to evaluate this question. The study population consisted of 1314 former elite-class athletes and 860 matched controls. The former athletes were divided into three groups based on their active career sport: endurance, mixed and power sports. Information on purchases of diabetes medication between 1995 and 2009 was obtained from the drug purchase register of the Finnish Social Insurance Institution. The total cost of diabetes medication per person year was significantly lower among the former endurance (mean 81 € [95% CI 33-151 €]) and mixed group athletes (mean 272 € [95% CI 181-388 €]) compared with the controls (mean 376 € [95% CI 284-485 €]), (p < 0.001 and p = 0.045, respectively). Of the former endurance athletes, 0.4% used insulin, while 5.2% of the controls used insulin (p = 0.018). A career as former endurance, sprint, jumper or team game athlete seems to reduce the costs of diabetes medication in later life.


[Dens invaginatus. Review of the literature and presentation of two clinical cases].
Authors present two cases of dens invaginatus, radicular variety in lateral incisors teeth. They suggest a revision of literature, underlining epidemiological, classifying, clinical and terapeutical aspects of this pathology.


Key tools for turning receivables into cash.
Not sure why your organization has problems turning receivables into cash? Administrators can use the tools described to perform a bill test and examine a statistically significant sample of accounts to identify revenue-cycle operations in need of improvement.


Probing the Arabidopsis flagellin receptor: FLS2-FLS2 association and the contributions of specific domains to signaling function.
Flagellin sensing2 (FLS2) is a transmembrane receptor kinase that activates antimicrobial defense responses upon binding of bacterial flagellin or the flagellin-derived peptide flg22. We find that some Arabidopsis thaliana FLS2 is present in FLS2-FLS2 complexes before and after plant exposure to flg22. flg22 binding capability is not required for FLS2-FLS2 association. Cys pairs flank the extracellular leucine rich repeat (LRR) domain in FLS2 and many other LRR receptors, and we find that the Cys pair N-terminal to the FLS2 LRR is required for normal processing, stability, and function, possibly due to undescribed endoplasmic reticulum quality control mechanisms. By contrast, disruption of the membrane-proximal Cys pair does not block FLS2 function, instead increasing responsiveness to flg22, as indicated by a stronger oxidative burst. There was no evidence for intermolecular FLS2-FLS2 disulfide bridges. Truncated FLS2 containing only the intracellular domain associates with full-length FLS2 and exerts a dominant-negative effect on wild-type FLS2 function that is dependent on expression level but independent of the protein kinase capacity of the truncated protein. FLS2 is insensitive to disruption of multiple N-glycosylation sites, in contrast with the related receptor EF-Tu receptor that can be rendered nonfunctional by disruption of single glycosylation sites. These and additional findings more precisely define the molecular mechanisms of FLS2 receptor function.


Anti-FSH antibodies associate with poor outcome of ovarian stimulation in IVF.
FSH is required for spontaneous folliculogenesis and is widely used in ovarian stimulation in IVF. Previously, increased concentrations of antibodies against FSH (anti-FSH) have been demonstrated in infertile women. This study aimed to: (i) assess the possible association of anti-FSH with an adverse outcome of IVF with regard to clinical parameters characterizing the ovarian reserve; and (ii) compare serum and follicular fluid (FF) anti-FSH concentrations in relation to follicle size and endocrine markers. IVF patients (n = 182) subjected to gonadotrophin-releasing hormone-antagonist protocol were assessed for anti-FSH using enzyme-linked immunosorbent assay. Increased concentrations of serum anti-FSH immunoglobulin (Ig)G and IgA were associated with impaired ovarian stimulation outcome, with cut-off values <1.0 arbitrary units predicting poor ovarian response (<or=3 oocytes) (adjusted odds ratio for IgG = 6.95, P = 0.005 and IgA = 3.60, P = 0.039). FF anti-FSH IgG and IgA were positively associated with serum anti-FSH concentrations and FSH concentration in FF. Additionally, FF anti-FSH IgG increased with follicle growth (linear regression coefficient = 0.02, P = 0.022). Collectively, these data suggest that serum anti-FSH antibodies are associated with poor ovarian response to FSH stimulation in IVF, with anti-FSH IgA and IgG potentially exerting a local FSH antagonizing effect in maturing follicles.


Dipeptide forms of glycine support mouse preimplantation embryo development in vitro and provide protection against high media osmolality.
To examine potential benefits of dipeptide forms of amino acids for embryo culture by determining ability of dipeptide glycine forms to support embryo development, act as osmolytes, and reduce ammonia production. Frozen thawed 1-cell mouse embryos were cultured in media with varying osmolality with glycine and dipeptide forms of glycine and development assessed. Ammonia levels were measured in various media. Dipeptide forms of glycine, alanyl- and glycyl-glycine, can support mouse embryo development in vitro. Additionally, dipeptide glycine can act as an organic osmolyte in developing embryos, permitting blastocyst formation in high osmolality media. Interestingly, as evidenced by decreased embryo development, dipeptides are not as efficient as osmolytes as their constituent individual amino acids. Dipeptide glycine produced less ammonia than glycine. Though dipeptides can provide osmoregulation in preimplantation embryos, efficacy may be lower than individual amino acids. The mechanism by which embryos transport and utilize dipeptide amino acids remains to be identified.


Musical patterns for comparative epigenomics.
Scientific data has been transformed into music in order to raise awareness in the non-scientific community. While the general public is nowadays familiar with the genetic code, there is still a lack of knowledge regarding epigenetic regulation. By making use of the binary nature of the methylome, we here describe a method that transforms methylation patterns into music. The resulting musical pieces show decent complexity and allow the audible recognition between music and underlying methylation state. This approach might therefore facilitate the recognition of complex methylation patterns and increase awareness for epigenetic regulation in the general public.


A well-sampled phylogenetic analysis of the polystichoid ferns (Dryopteridaceae) suggests a complex biogeographical history involving both boreotropical migrations and recent transoceanic dispersals.
Intercontinental disjunctions in ferns have often been considered as the result of long-distance dispersal (LDD) events rather than of vicariance. However, in many leptosporangiate groups, both processes appear to have played a major role in shaping current geographical distribution. In this study, we reconstructed the phylogenetic relationships and inferred the ancestral distribution areas of the polystichoid ferns (Cyrtomium, Phanerophlebia, and Polystichum), to evaluate the relative impact of vicariance and LDD on the biogeography of this group. We used a molecular dataset including 3346 characters from five plastid loci. With 190 accessions our taxon coverage was about three times as large as any previous worldwide sampling. Biogeographical analyses were performed using S-DIVA and S-DEC and divergence times were estimated by integrating fossil and secondary calibrations. The polystichoid ferns are a monophyletic clade that may have originated in East Asia during the Eocene, an age much younger than previously estimated. Three transoceanic disjunctions between East Asia and New World were identified in the Paleogene: one for Phanerophlebia during late Eocene (34Ma, 19-51Ma), and two in Polystichum at the Eocene-Oligocene boundary (30Ma, 18-43Ma; 28Ma, 19-39Ma respectively). During the Neogene, further range expansions took place from Asia to Africa, Hawaii, and the Southwestern Indian Ocean region. Our results indicate that early transfers between the Old and the New World are compatible with a boreotropical migration scenario. After evolving in Asia during the Eocene, the polystichoid ferns reached the New World in independent migrations at the Eocene-Oligocene boundary through the boreotropical belt. However, although less likely, the alternative hypothesis of independent transoceanic dispersals from the Old to the New World cannot be ruled out. Further range expansion during the Neogene was most likely the result of long-distance dispersal (LDD).


Western blotting method (TESAcruzi) as a supplemental test for confirming the presence of anti-Trypanosoma cruzi antibodies in finger prick blood samples from children aged 0-5 years in Brazil.
Some Latin American countries have plans for total control and/or eradication of Chagas disease by the main vector (Triatoma infestans) and by blood transfusion. To achieve this, patients with Chagas disease must be identified. A Western blotting test, TESAcruzi, is described as a supplemental test for diagnosis of Chagas disease using samples collected from children <5 years living in different states of Brazil. Blood samples collected by finger prick on filter paper were sent to the test laboratory by a central laboratory to confirm results obtained previously. Ten percent of negative samples, all doubtful and all positive samples were received. Commercial reagents, IgG indirect immunofluorescence, enzyme immunoassay, and a recently introduced TESAcruzi test were used. From 8788 samples, 163 (1.85%) were reactive by IgG-ELISA and 312 (3.55%) by IgG IIF. From these, 77 (0.87%) were reactive in the TESAcruzi test. The results had high clinical value to identify those truly infected.


Does it get better with age? Women's experience of communication in maternity care.
Communication with maternity care providers is one of the strongest predictors of the perceived quality of maternity care. There is evidence that older mothers experience better communication than younger mothers, but no evidence for why this occurs. To identify differences between younger (<35 years) and older (35+ years) mother's perceived quality of communication and any apparent age-related differences. We analysed cross-sectional data from 2504 first-time mothers in the Having a Baby in Queensland Survey 2012. Binary logistic regression assessed associations between maternal age and perceived optimal communication (information, participation, and connection) from care providers during women's most recent pregnancy and birth. Multivariable logistic regression modelling determined the effect of potential confounders (model of care, mode of birth, maternal age, and risk perceptions) on associations between age and communication quality. After adjustment for confounders, older mothers were more likely to report experiencing optimal information (e.g., not receiving conflicting information) and connection with caregivers (e.g., comfortable asking questions) in both pregnancy and birth. There were no age-related differences in the perception of participation. Model of care and mode of birth were more influential than maternal age in predicting communication perceptions. Women who used midwifery or private obstetric models and had unassisted vaginal births were more likely to perceive optimal communication. Given the benefits of communication on maternity care, redressing these age-related differences should be a focus of future communication training for care providers to ensure that women receive optimal communication, regardless of their age.


Beneficial effects of aloperine on inflammation and oxidative stress by suppressing necroptosis in lipopolysaccharide-induced acute lung injury mouse model.
Alveolar epithelial cell death, inflammation, and oxidative stress are typical features of acute lung injury (ALI). Aloperine (Alo), an alkaloid isolated from Sophora alopecuroides, has been reported to display various biological effects, such as anti-inflammatory, immunoregulatory, and anti-oxidant properties. In this study, we investigated the effects and mechanisms of Alo in treating a lipopolysaccharide (LPS)-induced ALI in a murine model. The effects of Alo in LPS-induced ALI were investigated in C57BL/6 mice. The RIPK1 inhibitor (Nec-1) and the RIPK3 inhibitor (GSK'872) were used to evaluate the relationship of necroptosis, NF-κB activation, and PDC subunits in LPS-treated mouse alveolar epithelial cells (MLE-12). Then the effects of Alo on necroptosis, inflammation, and oxidative stress of LPS-stimulated MLE-12 cells were evaluated. Alo significantly attenuated histopathological lung injuries and reduced lung wet/dry ratio in LPS-induced ALI mice. Alo also remarkedly reduced total protein and neutrophils recruitment in bronchoalveolar lavage fluid of ALI mice. Meanwhile, Alo ameliorated the LPS-induced necroptosis in the lungs of ALI mice. The RIPK3 inhibitor GSK'872, but not the RIPK1 inhibitor Nec-1, reversed LPS-induced p65 phosphorylation and translocation to the nucleus in MLE-12 cells. GSK'872 also reversed the LPS-induced increase in ROS and binding of RIPK3 and PDC subunits in MLE-12 cells. Moreover, Alo down-regulated the levels of p-RIPK1, p-RIPK3, p-MLKL, p-p65, the translocation of p65 to the nucleus, and reduced the expression of IL-6 and IL-8 in LPS-stimulated MLE-12 cells. Alo also inhibited the binding of RIPK3 and PDC-E1α, PDC-E1β, PDC-E2, and PDC-E3 and the ROS production in LPS-treated MLE-12 cells. The present study validated the beneficial effects of Alo on LPS-induced ALI , suggesting Alo may be a new drug candidate against ALI.


Increasing the mass accuracy of high-resolution LC-MS data using background ions: a case study on the LTQ-Orbitrap.
With the advent of a new generation of high-resolution mass spectrometers, the fields of proteomics and metabolomics have gained powerful new tools. In this paper, we demonstrate a novel computational method that improves the mass accuracy of the LTQ-Orbitrap mass spectrometer from an initial +/- 1-2 ppm, obtained by the standard software, to an absolute median of 0.21 ppm (SD 0.21 ppm). With the increased mass accuracy it becomes much easier to match mass chromatograms in replicates and different sample types, even if compounds are detected at very low intensities. The proposed method exploits the ubiquitous presence of background ions in LC-MS profiles for accurate alignment and internal mass calibration, making it applicable for all types of MS equipment. The accuracy of this approach will facilitate many downstream systems biology applications, including mass-based molecule identification, ab initio metabolic network reconstruction, and untargeted metabolomics in general.


Correlating the Bethesda System for Reporting Thyroid Cytopathology with Histology and Extent of Surgery: A Review of 21,746 Patients from Four Endocrine Surgery Registries Across Two Continents.
The Bethesda system for cytopathology (TBSRTC) is a 6-tier diagnostic framework developed to standardize thyroid cytopathology reporting. The aim of this study was to determine the risk of malignancy (ROM) for each Bethesda category. Thyroidectomy-related data from 314 facilities in 22 countries were entered into the following outcome registries: CESQIP (North America), Eurocrine (Europe), SQRTPA (Sweden) and UKRETS (UK). Demographic, cytological, pathologic and extent of surgery data were mapped into one dataset and analyzed. Out of 41,294 thyroidectomy patient entries from January 1, 2015, to June 30, 2017, 21,746 patients underwent both thyroid FNA and surgery. A comparison of cytology and surgical pathology data demonstrated a ROM for Bethesda categories 1 to 6 of 19.2%, 12.7%, 31.9%, 31.4%, 77.8% and 96.0%, respectively. Male patients had a higher rate of malignancy for every Bethesda category. Secondary analysis demonstrated a high ROM in male patients with Bethesda 3 category aged 31-35 years (52.1%, 95% confidence interval (CI) 37.9-66.2%), aged 36-40 years (55.9%, 95% CI 39.2-72.6%) and aged 41-45 years (46.9%, 95% CI 33-60.9%). Patients with Bethesda 5 and 6 scores were more likely to undergo total thyroidectomy (65.9% and 84.6%); for patients with Bethesda scores 2 and 3, a higher percentage of females underwent total thyroidectomy compared to males in spite of a higher ROM for males. These data demonstrate that Bethesda categories 1-4 are associated with a higher ROM compared to the first edition of TBSRTC, especially in male patients, and validate findings from the second edition of TBSRTC.


Estrogen and progesterone play pivotal roles in endothelial progenitor cell proliferation.
It has been previously suggested that angiogenesis occurs during the menstrual cycle. Moreover, a rise in uterine blood flow is largely maintained by vasodilatation and substantial increases in angiogenesis. It is known that estradiol (E2) and progesterone (P4) are involved in angiogenesis. Recently, endothelial progenitor cells (EPCs) were found to be involved in neovascularization; however, their roles in uterine neovascularization have not been well characterized. We hypothesized that E2- or P4-mediated EPC proliferation plays important roles in uterine neovascularization during the menstrual cycle. The number of EPCs in peripheral blood from subjects in the menstrual phase (n=12), follicular phase (n=8), and luteal phase (n=16), was measured using flow cytometry. Peripheral blood mononuclear cells (PBMCs) were cultured for seven days with or without 17beta-estradiol (E2beta) or P4, followed by assessment of EPC proliferation based upon the uptake of acetylated low density lipoprotein (LDL) and lectin. The expression of estrogen receptor (ER) or progesterone receptor (PR) in EPCs was also evaluated using real-time PCR. E2beta and P4 significantly increased the proliferation of EPCs derived from the peripheral blood of subjects in menstrual phase, but not subjects in the luteal phase. In addition, the expression level of ERalpha was markedly higher than ERbeta in EPCs derived from women in menstrual phase. EPC proliferation is induced during the menstrual phase and proliferation can be affected by estrogen through ERalpha activation.


Recent advances in liver sinusoidal endothelial ultrastructure and fine structure immunocytochemistry.
Ultrastructure reports have described that liver sinusoidal endothelial cell (LSEC)s contain a cytoskeletal framework of filamentous actin. Small G protein has emerged as an important regulator of the actin cytoskeleton, and consequently, of cell morphology and motility. We investigated actin filaments in relation to SEF in LSECs using a heavy meromyosin-decorated reaction and thereby elucidated the roles of small G protein and actin cytoskeleton in the morphological and functional alterations of SEF. Caveolin-1 expression has also been found in fenestrations with many characteristics of liver sinusoidal endothelial cells. Currently, fenestral studies and human disease are revealing ways to increase the liver sieve's porosity, which is reduced through pathological mechanisms. Hepatic sinusoidal endothelial dysfunction, which is known to impair endothelium-dependent relaxation in the liver microcirculation, contributes to increased intrahepatic vascular resistance.


Metronidazole need not be combined with an aminoglycoside when used for prophylaxis in elective colorectal surgery.
A prospective randomized controlled study has compared prophylactic intravenous metronidazole alone with the combination of metronidazole and gentamicin in 100 patients having elective colorectal surgery. There was no significant difference in mortality, infection, dehiscence or postoperative stay between the antibiotic groups. Postoperative sepsis was almost entirely due to aerobic organisms but was associated with minimal morbidity. A significantly higher rate of anastomotic dehiscence and postoperative infection was seen where the quality of bowel preparation was judged to be poor.


Recombination and its roles in DNA repair, cellular immortalization and cancer.
Genetic recombination is the creation of new gene combinations in a cell or gamete, which differ from those of progenitor cells or parental gametes. In eukaryotes, recombination may occur at mitosis or meiosis. Mitotic recombination plays an indispensable role in DNA repair, which presumably directed its early evolution; the multiplicity of recombination genes and pathways may be best understood in this context, although they have acquired important additional functions in generating diversity, both somatically (increasing the immune repertoire) and in germ line (facilitating evolution). Chromosomal homologous recombination and HsRad51 recombinase expression are increased in both immortal and preimmortal transformed cells, and may favor the occurrence of multiple oncogenic mutations. Tumorigenesis in vivo is frequently associated with karyotypic instability, locus-specific gene rearrangements, and loss of heterozygosity at tumor suppressor loci - all of which can be recombinationally mediated. Genetic defects which increase the rate of somatic mutation (several of which feature elevated recombination) are associated with early incidence and high risk for a variety of cancers. Moreover, carcinogenic agents appear to quite consistently stimulate homologous recombination. If cells with high recombination arise, either spontaneously or in response to "recombinogens," and predispose to the development of cancer, what selective advantage could favor these cells prior to the occurrence of growth-promoting mutations? We propose that the augmentation of telomere-telomere recombination may provide just such an advantage, to hyper-recombinant cells within a population of telomerase-negative cells nearing their replicative (Hayflick) limit, by extending telomeres in some progeny cells and thus allowing their continued proliferation.


Robotic interval debulking with radical hysterectomy and partial urinary bladder resection for locally advanced carcinosarcoma of the uterus.
•Extensive ureterolysis due to the lateral extent of the tumor with postoperative ureteral stenting.•Partial urinary bladder cystectomy due to clinical concern for invasion followed by two-layer cystorrhapy.•'Port-hopping' for development of the bilateral tunnels of Wertheim with the Vessel Sealer Extend.


Computational investigation of a new ion-pair receptor for calix[4]pyrrole.
Theoretical studies of a new ion-pair receptor, meso-octamethylcalix[4]pyrrole (OMCP), and its interactions with the halide anions F(-), Cl(-), and Br(-) and the cesium halides CsF, CsCl, and CsBr have been performed. Geometries, binding energies, and binding enthalpies were evaluated with the restricted hybrid Becke three-parameter exchange functional (B3LYP) method using the 6-31+G(d) basis set and relativistic effective core potentials. The optimized geometric structures were used to perform natural bond orbital (NBO) analysis. The two typical types of hydrogen bonds, N-H…X(-) and C-H…X(-), were investigated. The results indicate that hydrogen bonding interactions are dominant, and that the halide anions (F(-), Cl(-), and Br(-)) offer lone pair electrons to the σ*(N-H) or σ*(C-H) antibonding orbitals of OMCP. In addition, electrostatic interactions between the lone pair electrons of the halide anion and the LP* orbitals of Cs(+) as well as cation-π interactions between the metal ion and π-orbitals of the pyrrole rings have important roles to play in the Cs(+)•OMCP•X(-) complexes. The current study further demonstrates that this easy-to-make OMCP host compound functions as not only an anion receptor but also an ion-pair receptor.


Thermoregulatory behavior varies with altitude and season in the sceloporine mesquite lizard.
In ectothermic animals, body temperature is the most important factor affecting physiology and behavior. Reptiles depend on environmental temperature to regulate their body temperature, so geographic variation in environmental temperature can affect the biology of these organisms in the short and long term. We may expect physiological and behavioral responses to temperature change to be especially important in ectotherms inhabiting temperate zones, where different seasons present different thermal challenges. High-mountain temperate systems represent a natural laboratory for studies of evolutionary and plastic variation in thermal biology. The aim of the present study is to evaluate operative temperature with biophysical models, active body temperature under field conditions, preferred temperature in a thermal gradient in the laboratory, and thermal indexes in Sceloporus grammicus lizards along an elevational gradient. We measured these traits in three populations at 2500, 3400, and 4100 m elevation at different seasons of the year (spring, summer and autumn). Our results showed that operative temperature varied with season and elevation, with greater variation at middle and high elevations than at low elevations. Body temperature and preferred temperature varied with altitude and season but did not differ between sexes. Thermal quality was lowest in the high-altitude population and in the summer season. Thermoregulatory efficiency was highest in the three populations in the autumn. Our results suggest that thermoregulatory strategies vary with elevation and season, allowing individual lizards to confront annual fluctuations in the thermal environment and conflicting with some previous descriptions of Sceloporus lizards as thermally conservative.


PaPI: pseudo amino acid composition to score human protein-coding variants.
High throughput sequencing technologies are able to identify the whole genomic variation of an individual. Gene-targeted and whole-exome experiments are mainly focused on coding sequence variants related to a single or multiple nucleotides. The analysis of the biological significance of this multitude of genomic variant is challenging and computational demanding. We present PaPI, a new machine-learning approach to classify and score human coding variants by estimating the probability to damage their protein-related function. The novelty of this approach consists in using pseudo amino acid composition through which wild and mutated protein sequences are represented in a discrete model. A machine learning classifier has been trained on a set of known deleterious and benign coding variants with the aim to score unobserved variants by taking into account hidden sequence patterns in human genome potentially leading to diseases. We show how the combination of amphiphilic pseudo amino acid composition, evolutionary conservation and homologous proteins based methods outperforms several prediction algorithms and it is also able to score complex variants such as deletions, insertions and indels. This paper describes a machine-learning approach to predict the deleteriousness of human coding variants. A freely available web application (http://papi.unipv.it) has been developed with the presented method, able to score up to thousands variants in a single run.


Impact of rest breaks on musculoskeletal discomfort of Chikan embroiderers of West Bengal, India: a follow up field study.
This study aimed to determine risk factors that predict musculoskeletal discomfort in Chikan embroiderers of West Bengal, India, and to compare the effect of two rest break schedules to reduce these symptoms. The Nordic musculoskeletal questionnaire was performed on 400 Chikan embroiderers at baseline containing questions on job autonomy, working behavior, and work stress factors. Relative risk was calculated to identify prognostic factors for musculoskeletal discomfort in different body regions. Two groups of workers received two rest break schedules for 4 months and compared in a between-subject design. Outcome variables were scores of Body Part Discomfort (BPD) scale. Chikan embroiderers are afflicted with musculoskeletal discomfort mainly in the lower back, neck/shoulder and wrist/forearm region, which is attributed to their prolonged working timeinvolving hands and wrists, being in a static seating posture. Rigidity in working methods, prolonged working time, inadequate rest break during the working day, dissatisfaction regarding earning, monotonous work, static sitting posture, and repetitive movement of wrist and forearm were the significant predictors of these symptom developments. Rest break schedule 1 with more frequent and shorter breaks had more significant improvement on the severity of these musculoskeletal discomforts. Chikan embroiderers perform a highly dreary occupation and various ergonomics conditions work as predictors for developing musculoskeletal discomforts among them. Design of proper rest break schedule involving shorter and frequent breaks was competent for reducing these discomforts to a certain extent.


Impact of digitalization on clean governance: An analysis of China's experience of 31 provinces from 2019 to 2021.
The goal of deepening institutional reforms was to bring transparency and accountability, address corruption, and establish a clean government (CG) in China. The first step toward this transparency is considered to be the free development and transmission of Open Data (OD). In this regard, China has set up open data centers in provincial governments. Considering that OD can have an impact on CG and bring new ideas for CG construction, ODs of 31 provincial governments have been analyzed through fsQCA3.0 to test these assumptions. To see how much it can contribute to the development of the Technology Organization Environment Framework (TOE). To this end, between 2019 and 2021, 31 provincial government data have been clustered into low, medium, and high corruption case enrollment areas to determine the impact of OD. The study mentioned that improvements in ODs in 31 provinces could strengthen cooperation with the disciplinary inspection department in the fight against corruption. The study, on the other hand, made two assumptions that environmental barriers and internal pressures could affect data's reliability.


Sustainability of energy, water, and environmental systems: a view of recent advances: Special issue dedicated to 2021 conference on sustainable development of energy, water, and environment systems.
This paper presents an overview for the Special Issue (SI) of Clean Technology and Environmental Policy journal (CTEP), and it includes accepted papers from 16th Conferences on Sustainable Development of Energy, Water and Environment Systems (SDEWES) held from October 10-15, 2021, in Dubrovnik, Croatia. Considering CTEPs policy of high-quality research papers, guest editors have invited 35 research articles, presented at the SDEWES 2021 conference. After a vigorous review process, 12 papers have been accepted for publication in this special issue. All 12 accepted papers are briefly presented in this overview together with a wider view that presents research efforts within the SDEWES community published through previous SDEWES special issues.


Lymph node metastases arising from uveal melanoma.
Since the eye lacks lymphatic vessels, uveal melanomas primarily metastasize hematogenously. Here we report the case of a patient with ciliary body ring melanoma who developed lymph node metastases after a fistulating glaucoma operation. A 40-year-old female Caucasian patient presented with unilateral pigment dispersion. Pigment dispersion glaucoma was diagnosed and since the intraocular pressure could not be managed with topical medication, transscleral cyclophotocoagulation and two trabeculectomies had to be performed. Due to enlargement of the pigmented iris mass and cell deposits in the chamber angle, a ciliary body ring melanoma was presumed and the eye enucleated. Histology confirmed the diagnosis of "ciliary body ring melanoma". Six months after enucleation the patient presented multiple metastases including ipsilateral preauricular and submandibular lymph node metastases. The patient died two months later. Lymph node metastases arising from ciliary body melanomas are very rare. Tumor seeding through the trabeculectomy site into the bleb and then via conjunctival lymphatic vessels might be the crucial factor for this pathway of metastases. Therefore, in cases of unilateral pigment dispersion, malignancy should be excluded before fistulating operations are performed.


Calcineurin A gamma and B gene expressions in the whole blood in Japanese patients with schizophrenia.
Calcineurin (CaN) has been regarded as a candidate gene for vulnerability of schizophrenia. Although CaN gene expression has been investigated with postmortem brain specimens or in association studies, little information is available about CaN gene expression levels in peripheral sources. We obtained whole blood samples from 16 patients with schizophrenia and 16 controls, and total RNA was extracted. CaN A gamma and CaN B genes were analyzed by quantitative RT-PCR. In the patient group, expression levels of both genes were correlated with psychopathology, as measured by the Brief Psychiatric Rating Scale (BPRS), and neuroleptic dose. No significant differences in CaN A gamma or CaN B gene expression were observed between patients with schizophrenia and normal controls. Linear regression analysis revealed that the CaN A gamma gene expression level was associated with the BPRS score but not with neuroleptic dose. Neither of the clinical variables was associated with the CaN B gene expression level. The results of this study suggest that the CaN A gamma gene may be an effective predictor of the progression of psychosis. The effect of medications on expression of CaN genes requires further study.


Botany: floral fluorescence effect.
The way flowers appear to insects is crucial for pollination. Here we describe an internal light-filtering effect in the flowers of Mirabilis jalapa, in which the visible fluorescence emitted by one pigment, a yellow betaxanthin, is absorbed by another, a violet betacyanin, to create a contrasting fluorescent pattern on the flower's petals. This finding opens up new possibilities for pollinator perception as fluorescence has not previously been considered as a potential signal in flowers.


Genomic sequence of mouse COL1A1 encoding the collagen propeptides.
The nucleotide sequences of the mouse pro alpha 1(I) gene regions coding for the N- and C-propeptides is reported. The exon-intron structure was highly homologous to human COL1A1 and the deduced amino acid sequences of the N- and C-propeptides showed 67% and 91% identity with the human sequence. This gene sequence information will allow the production of specific gene mutations by site-directed mutagenesis to study the structure and function of these important propeptide domains.


Effect of the intravesical resiniferatoxin instillation evaluated by the ice provocative urodynamic study.
Prospective urodynamic investigation before and after intravesical resiniferatoxin instillation treatment. To evaluate the effectiveness of intravesical resiniferatoxin instillation for the treatment of neurogenic detrusor overactivity (NDO), using conventional and ice provocative urodynamic studies to monitor the activity of the unmyelinated C-fiber. Spinal Cord Injury Unit, Yonsei Rehabilitation Hospital, Seoul, Korea. A measure of 100 ml of resiniferatoxin solution, at a concentration of 100 nM diluted in 10% ethanol, was intravesically instilled into the bladder of 15 spinal cord injury patients with NDO. Conventional and ice provocative urodynamic studies were performed to evaluate the change in the involuntary detrusor activity, reflex volume, maximal bladder capacity, compliance, maximal detrusor pressure and reflex volume ratio 7 days before and 30 days after the instillation. Before the intravesical resiniferatoxin instillation, all patients exhibited NDO in both the conventional and ice provocative urodynamic studies, with a mean reflex volume ratio of 0.45+/-0.22. There was no significant change in the maximal bladder capacity, compliance and maximal detrusor pressure at the follow-up urodynamic study, but the reflex volume ratio was significantly increased (P<0.05) after the intravesical resiniferatoxin instillation. Among the 15 patients, three (20%) showed complete and nine (60%) partial suppression of the unmyelinated C-fiber activities. Intravesical resiniferatoxin instillation was partially controlled by the unmyelinated C-fiber activities, which were estimated by an ice provocative urodynamic study. Therefore, further studies on the optimal dosage and accurate indications for resiniferatoxin instillation are required.


Transfer and expression of the human multiple drug resistance gene as potential human gene therapy.
The human multiple drug resistance (MDR) gene has been used as a model for human gene transfer which could lead to human gene therapy. MDR is a transmembrane protein which pumps a number of toxic substances out of cells including several drugs used in cancer chemotherapy. Normal bone marrow cells express low levels of MDR and are particularly sensitive to the toxic effects of these drugs. There are two general applications of MDR gene therapy: (1) to provide drug-resistance to the marrow of cancer patients receiving chemotherapy, and (2) as a selectable marker which when co-transferred with a non-selectable gene such as the human beta globin gene can be used to enrich the marrow for cells containing both genes. We demonstrate efficient transfer and expression of the human MDR gene in a retroviral vector into live mice and human marrow cells including CD34(+) cells isolated from marrow and containing the bulk of human hematopoietic progenitors. MDR gene transduction corrects the sensitivity of CD34(+) cells to taxol, an MDR drug substrate, and enriches the marrow for MDR-transduced cells. The MDR gene-containing retroviral supernatant used has been shown to be safe and free of replication-competent retrovirus. Because of the safety of the MDR retroviral supernatant, and efficient gene transfer into mouse and human marrow cells, a phase 1 clinical protocol for MDR gene transfer into cancer patients has been approved to evaluate MDR gene transfer and expression in human marrow.


C-reactive protein and angiographic coronary artery disease: independent and additive predictors of risk in subjects with angina.
The objective of this study was to determine the prognostic value of C-reactive protein (CRP) independent of coronary angiographic findings. High sensitivity CRP, a marker of inflammation, predicts risk of cardiovascular events. However, it is uncertain whether it remains predictive once angiographic findings are considered. A total of 2,554 patients with angina but without acute myocardial infarction (MI) were studied angiographically; 1,848 patients had coronary artery disease (CAD) and 706 patients did not. Coronary artery disease was quantified in five ways and combined for a CAD score. C-reactive protein was measured and patients were followed for up to five years for death or MI. C-reactive protein correlated with the extent of CAD, but correlation coefficients were low (0.02 to 0.08). Of angiographic measures, the CAD score best predicted future events (hazard ratio [HR] = 1.8 [1.2 to 2.6], p = 0.004, for CAD score > 4). C-reactive protein > or = 1.0 mg/dl was predictive in both patients without CAD (HR = 2.3 [0.9 to 5.5], p = 0.07) and with CAD (HR = 2.1 [1.5 to 3.1], p = 0.0001). Multivariate adjustment resulted in little change in HR. C-reactive protein retained predictive value within each quintile of CAD score. C-reactive protein and CAD independently and additively contributed to the risk prediction: low CRP and lowest CAD score was associated with lowest risk, and high CRP and highest CAD score was associated with the highest risk, with a 10-fold difference between extremes (2.5% vs. 24%). C-reactive protein correlates with extent of CAD, but the degree of correlation is low. Severity/extent of CAD and CRP are independent and additive predictors of risk. Therapy should target CRP-associated risk as well as angiographically evident stenosis.


Rare genomic characters do not support Coelomata: RGC_CAMs.
Recently there has been a lively debate about a new class of rare genomic characters, RGC_CAMs, and their implications for deep bilaterian phylogeny. Most recently, nine bilaterian species were analyzed along with subsets of six outgroups (Rogozin et al. 2007b), and support for a coelomate clade reported. The authors suggested that our previously reported support for an ecdysozoan clade (Irimia et al. 2007) reflected (i) one outgroup, Nematostella vectensis, being too closely related to bilaterians and (ii) lack of "rigorous statistical analysis." Here, we report further studies of these characters. First, we discuss general issues of outgroup choice. Second, we point out that an argument used by Rogozin et al. against backmutation is not statistically significant. Third, we point out that the statistical method of Rogozin et al. fails to incorporate backmutations, leading to systematic placement of the long-branch taxon as the outgroup. A simple modification of the method yields very different results: 51 of 63 outgroup combinations favor Ecdysozoa, including 51 of 52 with at least eight phylogenetically informative characters, and all 19 with statistically significant signal. These results indicate that the Coelomata signal is a long-branch artifact.


Laser in situ keratomileusis interface deposits.
A clinical investigation was undertaken to determine the origin of a brown interface deposit that developed in 15 eyes after laser in situ keratomileusis (LASIK). The LASIK procedure was evaluated and agents that were thought to be related to these brown deposits in the interface were eliminated sequentially. Eyes were observed after LASIK for presence or absence of the deposit. Twenty-five consecutive LASIK eyes in which a methylcellulose sponge was eliminated as a protector of the hinge developed no similar interface deposits. The use of a dry methylcellulose sponge to protect the hinge may result in unexpected interface deposits after LASIK.


Predicting the Effect of CYP3A Inducers on the Pharmacokinetics of Substrate Drugs Using Physiologically Based Pharmacokinetic (PBPK) Modeling: An Analysis of PBPK Submissions to the US FDA.
We recently published analyses regarding the predictive performance of physiologically based pharmacokinetic (PBPK) models, submitted to the US Food and Drug Administration (FDA), for the effect of cytochrome P450 (CYP) inhibitors on the pharmacokinetics of substrate drugs. We now analyze and summarize the predictive performance of PBPK models for the effect of CYP3A inducers on a substrate's pharmacokinetics. This analysis was based on 11 substrate PBPK models, developed by six sponsors, using a commercial PBPK software, with 13 clinical interaction studies. Four CYP3A inducers were used: rifampicin, rifabutin, carbamazepine, and efavirenz. Sponsors either directly used the software-provided inducer models or verified these models' induction magnitude prior to use. The metric for assessing predictive performance was the R predicted/observed value [R predicted/observed = (predicted mean exposure ratio)/(observed mean exposure ratio)], with the exposure ratio defined as maximum plasma concentration (C max) or area under the plasma concentration-time curve (AUC) with and without an inducer. In 77% (10/13; AUCR) and 83% (10/12; C max R) of the cases, the R predicted/observed values were within 1.25-fold of the observed data. Cases with R predicted/observed values >1.25-fold (>twofold for all three AUCR) were under-predictions as a result of using the PBPK software's default rifampicin model. Improved predictions were observed when the rifampicin model was modified by increasing the induction potency. Based on submissions to the FDA, and similar to our previous findings for CYP inhibition, we observed good agreement between PBPK-predicted and observed effect of CYP3A inducers on substrate pharmacokinetics. Verification of the inducer model appears to be crucial for improved predictive performance.


Mitochondrial dysfunction precedes neurodegeneration in mahogunin (Mgrn1) mutant mice.
Oxidative stress, ubiquitination defects and mitochondrial dysfunction are commonly associated with neurodegeneration. Mice lacking mahogunin ring finger-1 (MGRN1) or attractin (ATRN) develop age-dependent spongiform neurodegeneration through an unknown mechanism. It has been suggested that they act in a common pathway. As MGRN1 is an E3 ubiquitin ligase, proteomic analysis of Mgrn1 mutant and control brains was performed to explore the hypothesis that loss of MGRN1 causes neurodegeneration via accumulation of its substrates. Many mitochondrial proteins were reduced in Mgrn1 mutants. Subsequent assays confirmed significantly reduced mitochondrial complex IV expression and activity as well as increased oxidative stress in mutant brains. Mitochondrial dysfunction was obvious many months before onset of vacuolation, implicating this as a causative factor. Compatible with the hypothesis that ATRN and MGRN1 act in the same pathway, mitochondrial dysfunction and increased oxidative stress were also observed in the brains of Atrn mutants. Our results suggest that the study of Mgrn1 and Atrn mutant mice will provide insight into a causative molecular mechanism common to many neurodegenerative disorders.


Recent development of metal-organic framework nanocomposites for biomedical applications.
Albeit metal-organic framework (MOF) composites have been extensively explored, reducing the size and dimensions of various contents within the composition, to the nanoscale regime, has recently presented unique opportunities for enhanced properties with the formation of MOF-based nanocomposites. Many distinctive strategies have been used to fabricate these nanocomposites such as through the introduction of nanoparticles (NPs) into a MOF precursor solution or vice versa to achieve a core-shell or heterostructure configuration. As such, MOF-based nanocomposites offer seemingly limitless possibilities and promising solutions for the vast range of applications across biomedical disciplines especially for improving in vivo implementation. In this review, we focus on the recent development of MOF-based nanocomposites, outline their classification according to the type of integrations (NPs, coating materials, and different MOF-derived nanocomposites), and direct special attention towards the various approaches and strategies employed to construct these nanocomposites for their prospective utilization in biomedical applications including biomimetic enzymes and photo, chemo, sonodynamic, starvation and hyperthermia therapies. Lastly, our work aims to highlight the exciting potential as well as the challenges of MOF-based nanocomposites to help guide future research as well as to contribute to the progress of MOF-based nanotechnology in biomedicine.


[Long-term results following denervation of the wrist].
This retrospective study examines long-term follow-up results after complete denervation of the wrist. Between 1994 and 2000 a total of 61 complete wrist denervations of 59 patients (median age at operation 46 years) were performed. In 2009 29 patients with 30 complete wrist denervations took part in a follow-up examination after an average of 10 years. The mobility of the wrist and the grip force were examined. Pain and satisfaction with the operation were determined by means of a visual analogue scale (VAS) (0-100). The patients were asked about pain reduction and how long it lasted. Further the DASH and the Mayo Wrist Score were evaluated. Radiographs of the denervated wrist were performed and the degree of the degenerative osteoarthritis was determined according to Knirk and Jupiter. In 7 of the 36 patients examined, a partial or total wrist arthrodesis was performed. These patients were excluded from the study. Pain was improved in 28 of the 30 denervated wrists examined, in 22 the improvement lasted until the follow-up examination, whereas in 6 the pain increased after a median of 90 months. The median pain intensity was 10 at rest and 50 with activity; the satisfaction was 90. The median of the extension/flexion was 81% and the grip force 82% in comparison to the opposite hand. The DASH Score was 25 and the Mayo Wrist Score 73. Complete denervation of the wrist according to Wilhelm is a treatment option for the chronically painful wrist and can lead to good grip force, mobility, sufficient pain reduction and satisfaction in the long term.


Phosphorylation and down-regulation of Bim by muscarinic cholinergic receptor activation via protein kinase C.
Bim is one of the proapoptotic BH3-only homologs of the Bcl-2 family proteins, which interacts with other Bcl-2 family proteins to activate the intrinsic apoptotic pathway. The expression and protein level of Bim are highly regulated in cells at both transcriptional and post-translational levels, and inadequate control of Bim level may largely determine its pro-apoptic activity. In the present study, we reported that carbachol, a muscarinic cholinergic receptor agonist, regulated Bim in human SH-SY5Y neuroblastoma cells. Carbachol rapidly induced an upward gel mobility shift of Bim, which was abolished by protein phosphatase treatment, indicating an increased Bim phosphorylation by carbachol. The effect of carbachol was mimicked by the protein kinase C activator 12-myristate 13-acetate (PMA) and was blocked by the protein kinase C inhibitor rottlerin, suggesting that activation of protein kinase C was required for carbachol-induced phosphorylation of Bim. Prolonged treatment with carbachol and PMA significantly decreased Bim protein levels in total cell lysates and mitrochondria. Carbachol and PMA had no effect in the transcriptional regulation of Bim, whereas the reduction of Bim by both carbachol and PMA was reversed by the proteosome inhibitors, suggesting that carbachol and PMA facilitated the proteosome-dependent Bim degradation. Thus, this study identified the muscarinic receptor-protein kinase C signaling pathway as a regulator of Bim in neuroblastoma cells, and activation of muscarinic receptor and protein kinase C functions to induce Bim phosphorylation, followed by down-regulation of the proapoptotic protein.


Beyond type 2 diabetes, obesity and hypertension: an axis including sleep apnea, left ventricular hypertrophy, endothelial dysfunction, and aortic stiffness among Mexican Americans in Starr County, Texas.
There is an increasing appreciation for a series of less traditional risk factors that should not be ignored when considering type 2 diabetes, obesity, hypertension, and cardiovascular disease. These include aortic stiffness, cardiac structure, impaired endothelial function and obstructive sleep apnea. They are associated to varying degrees with each disease categorization and with each other. It is not clear whether they represent additional complications, concomitants or antecedents of disease. Starr County, Texas, with its predominantly Mexican American population has been shown previously to bear a disproportionate burden of the major disease categories, but little is known about the distribution of these less traditional factors. Type 2 diabetes, obesity and hypertension frequencies were determined through a systematic survey of Starr County conducted from 2002 to 2006. Individuals from this examination and an enriched set with type 2 diabetes were re-examined from 2010 to 2014 including assessment of cardiac structure, sleep apnea, endothelial function and aortic stiffness. Individual and combined frequencies of these inter-related (i.e., axis) conditions were estimated and associations evaluated. Household screening of 5230 individuals aged 20 years and above followed by direct physical assessment of 1610 identified 23.7 % of men and 26.7 % of women with type 2 diabetes, 46.2 and 49.5 % of men and women, respectively with obesity and 32.1 and 32.4 % with hypertension. Evaluation of pulse wave velocity, left ventricular mass, endothelial function and sleep apnea identified 22.3, 12.7, 48.6 and 45.2 % of men as having "at risk" values for each condition, respectively. Corresponding numbers in women were 16.0, 17.9, 23.6 and 28.8 %. Cumulatively, 88 % of the population has one or more of these while 50 % have three or more. The full axis of conditions is high among Mexican Americans in Starr County, Texas. Individual and joint patterns suggest a genesis well before overt disease. Whether they are all mediated by common underlying factors or whether there exist multiple mechanisms remains to be seen.


Prevalence of rifampicin resistant tuberculosis among pulmonary tuberculosis patients In Enugu, Nigeria.
We determined the prevalence of rifampicin resistance in pulmonary tuberculosis patients in Enugu Nigeria. A prospective hospital-based study involving 1300 presumptive multidrug-resistant tuberculosis patients was conducted in Enugu between April 2017 and 31st March, 2019.Participants age ranged from 15 years and older and each submitted one sputum specimens Sputum specimens were analyzed using the Gene Xpert MTB/RIF assay to detect resistance to rifampicin according to manufacturer's protocol. The prevalence of rifampicin resistant tuberculosis was 6.8% (95% CI: 5.5- 8.3). Rifampicin resistance was significantly higher in males (9.0%) than females (4.2%) (P = 0.036< 0.05). Most of the cases were seen in the age group 35-44 years (28.4%). Prevalence of rifampicin resistant tuberculosis was 2.7% in treatment naive (new) patients and 4.1% in patients on anti-tuberculosis therapy (previously treated). The prevalence of rifampicin resistant tuberculosis in Enugu was high. Rifampicin resistance in treatment naive (new) patients was also high. This study therefore highlights that active transmission of Multidrug-resistant tuberculosis among young males could be on-going.


Insulin stimulates postnatal development of renal tubular transport of p-aminohippurate.
The influence of repeated administration of insulin on renal tubular transport of PAH was investigated. There was a stimulating effect in young rats with an immature kidney function. The distinctly higher degree of accumulation in renal cortical slices is in accordance with the enhanced PAH excretion in 10- and 20-day-old animals.


Genetic diversity in maize landraces from indigenous settlements of Northeastern Argentina.
In South America, native maize germplasm has been extensively studied particularly for the Andean region. However, relatively few genetic diversity studies include materials from the eastern region of the continent. Herein we present a genetic diversity characterization of four Popcorn maize landraces, maintained in indigenous settlements, from Northeastern Argentina (NEA). In addition, one Popcorn landrace from Northwestern Argentina (NWA) was incorporated for comparison. We characterized these landraces using ten microsatellite markers. For the whole data set, a total of 65 alleles were found, with an average of 7.22 alleles per locus. The average gene diversity was 0.370. Global fit to Hardy-Weinberg proportions was observed in all landraces. Global estimates of F (ST) revealed a significant differentiation among the populations. Individual Neighbor-joining clustering and Bayesian analyses allowed the recognition of most populations studied. Two main groups were distinguished by the Neighbor-joining clustering of populations. This grouping pattern would be consistent with a hypothesis of successive introductions of Popcorn in South America. The results presented will be useful to design strategies that maximize the utility of maize genetic resources.


Proposal for a uniform designation of zearalenone and its metabolites.
The Fusarium mycotoxin zearalenone is a frequent contaminant of food and feed. Up to now, different abbreviations and counting systems for the numerous positions of this macrocyclic ß-resorcylic acid lactone and its metabolites have been used. As the number of identified fungal and mammalian metabolites of zearalenone is still growing, the lack of a uniform designation makes the literature on these important toxins confusing and complicated. Here, we propose a logical set of abbreviations and a simple counting system, in order to facilitate future research communications on zearalenone and its congeners.


Assessing the efficacy of different upper limb hemiparesis interventions on improving health-related quality of life in stroke patients: a systematic review.
This review aims to assess the efficacy of upper limb interventions on stroke survivors' health-related quality of life (QOL). Published studies were identified following a systematic search of the literature from 10 electronic databases, 3 subject-relevant journals, a Web search via a popular search engine, and reference lists of the included articles. In total, 22 articles met the inclusion criteria and were subjected to data extraction to establish the effectiveness of the intervention on QOL scores. Interventions varied according to their content, including acupuncture treatment, botulinum toxin type A (BTX-A) injections, constraint-induced movement therapy (CIMT), task training, and therapeutic exercise. Studies were required to have at least 1 quantitative outcome QOL measure. Of the 22 studies, 12 reported significant findings within groups and between control groups. Interventions including BTX-A injections, CIMT, exercise programs, baclofen pump, robotic-assisted therapy, electrical stimulation, and acupuncture were reported to significantly improve either overall health-related QOL or certain individual QOL domains, such as strength, hand function, memory, mood, activities of daily living, mobility, social participation, communication, energy, pain, and sleep. The review demonstrates the need for upper limb intervention studies to focus on QOL as a primary outcome measure in addition to the functional outcomes currently used.


Racemization of the amyloidal beta Asp1 residue blocks the acceleration of fibril formation caused by racemization of the Asp23 residue.
Amyloid beta proteins extracted from the amyloid cores of neuritic plaques are considerably racemized at their Asp residues. To assess the impact of D-Asp on amyloid beta(1-42) conformation and on initiation of amyloid fibril formation, we used wild-type amyloid beta(1-42) and analogs in which D-Asp was substituted for L-Asp at residues 1, 7, 23, and all combinations of these residues. Amyloid fibril formation was enhanced by D-Asp23; modulation of Asp chirality at N-terminal position 1 blocked this enhancement and modulation at position 7 augmented it. Knowledge of such chirality modifications may help to develop potent inhibitors of amyloid fibril formation.


"Acquired" lobar emphysema: a complication of respiratory distress in premature infants.
Ten premature infants with respiratory distress developed a type of pulmonary lobar emphysema that is clinically and histologically distinct from interstitial or congenital lobar emphysema. In eight patients emphysema was noted in the right lower lobe, while in two the left upper lobe was affected. Five infants exhibited nonresolution of the emphysema and an inability to be weaned from ventilator support. Lung scans in these five infants showed absent or markedly decreased perfusion of the involved lobe. Lobectomy was necessary. Postoperatively, their respiratory status improved and they were successfully weaned from the ventilator. Five premature infants with identical radiographic emphysematous changes had normal lung scans. These infants did not require lobectomy and were also successfully weaned from the ventilator. Radiographic changes of lobar emphysema in these five infants completely resolved. Pathologic changes in the excised lobes were characteristic of bronchopulmonary dysplasia and obstructive intraalveolar emphysema. The long-term effects of positive pressure ventilation, oxygen, and suctioning techniques directed toward the right lower lobe may play an important role in the etiology of "acquired" lobar emphysema.


Further characterization of the porcine LH subunits precursors in the translation products of pituitary RNAs.
We have shown that the precursors of porcine LH alpha and beta subunits have similar apparent molecular weights (Biochem. Biophys. Res. Comm., 1984, 118, 254). The aim of the present study was to characterize physiochemical features which permit to distinguish these precursors from each other. We report here that these precursors can be clearly distinguished by both their tryptic digests analyzed by one-dimension electrophoresis and their behavior in two-dimension electrophoresis whose first dimension was made in a non equilibrium pH gradient (2D-NEPHGE). The 2D-NEPHGE method developed in this study appears also useful to estimate simultaneously the translation activities of pituitary hormone mRNAs without a previous immunoprecipitation.