Structural genomics of highly conserved microbial genes of unknown function in search of new antibacterial targets.
With more than 100 antibacterial drugs at our disposal in the 1980's, the problem of bacterial infection was considered solved. Today, however, most hospital infections are insensitive to several classes of antibacterial drugs, and deadly strains of Staphylococcus aureus resistant to vancomycin--the last resort antibiotic--have recently begin to appear. Other life-threatening microbes, such as Enterococcus faecalis and Mycobacterium tuberculosis are already able to resist every available antibiotic. There is thus an urgent, and continuous need for new, preferably large-spectrum, antibacterial molecules, ideally targeting new biochemical pathways. Here we report on the progress of our structural genomics program aiming at the discovery of new antibacterial gene targets among evolutionary conserved genes of uncharacterized function. A series of bioinformatic and comparative genomics analyses were used to identify a set of 221 candidate genes common to Gram-positive and Gram-negative bacteria. These genes were split between two laboratories. They are now submitted to a systematic 3-D structure determination protocol including cloning, protein expression and purification, crystallization, X-ray diffraction, structure interpretation, and function prediction. We describe here our strategies for the 111 genes processed in our laboratory. Bioinformatics is used at most stages of the production process and out of 111 genes processed--and 17 months into the project--108 have been successfully cloned, 103 have exhibited detectable expression, 84 have led to the production of soluble protein, 46 have been purified, 12 have led to usable crystals, and 7 structures have been determined.


Enhancement of hydrophobic interactions and hydrogen bond strength by cooperativity: synthesis, modeling, and molecular dynamics simulations of a congeneric series of thrombin inhibitors.
Accurately predicting the binding affinity of ligands to their receptors by computational methods is one of the major challenges in structure-based drug design. One of the potentially significant errors in these predictions is the common assumption that the ligand binding affinity contributions of noncovalent interactions are additive. Herein we present data obtained from two separate series of thrombin inhibitors containing hydrophobic side chains of increasing size that bind in the S3 pocket and with, or without, an adjacent amine that engages in a hydrogen bond with Gly 216. The first series of inhibitors has a m-chlorobenzyl moiety binding in the S1 pocket, and the second has a benzamidine moiety. When the adjacent hydrogen bond is present, the enhanced binding affinity per A(2) of hydrophobic contact surface in the S3 pocket improves by 75% and 59%, respectively, over the inhibitors lacking this hydrogen bond. This improvement of the binding affinity per A(2) demonstrates cooperativity between the hydrophobic interaction and the hydrogen bond.


Identifying Risk Factors for Healthcare-Associated Infections Caused by Carbapenem-Resistant Acinetobacter baumannii in a Neonatal Intensive Care Unit.
Acinetobacter baumannii is a causative pathogen of various healthcare-associated infections (HAIs) and is particularly prevalent in high-risk hospital settings. This study aimed to determine risk factors associated with HAIs caused by carbapenem-resistant A. baumannii (CRAB) in a neonatal intensive care unit (NICU). This prospective study was performed between January 2013 and June 2014 among NICU patients at the Mansoura University Children's Hospital, Mansoura, Egypt. Neonates who developed HAIs due to CRAB were assigned to a case group, while those infected with carbapenem-sensitive A. baumannii (CSAB) were assigned to a control group. Among the 124 neonates who developed A. baumannii-caused HAIs during the study period, 91 (73.4%) were caused by CRAB and 33 (26.6%) were caused by CSAB. Prematurity, premature rupture of the membranes (PROM), a previous stay in another hospital, prolonged NICU stay, the presence of invasive devices, previous exposure to carbapenems or aminoglycosides and prolonged antibiotic therapy before infection were significantly associated with CRAB-caused HAIs. A multivariate logistic regression analysis identified prematurity (adjusted odds ratio [aOR] = 25.3; P <0.01), mechanical ventilation (aOR = 18.9; P <0.01) and the previous use of carbapenems (aOR = 124.7; P <0.01) or aminoglycosides (aOR = 22.6; P = 0.04) to be independent risk factors for CRAB infections. Various risk factors were significantly associated with CRAB-caused HAIs among the studied NICU patients.


Nine cases of chronic hand and foot eczema treated with baricitinib.
Chronic hand and foot eczema (CHFE) is a common inflammatory disorder that generally lasts for over 3 months. If it is intractable to topical agents, systemic immunomodulators can be considered; however, they are not suitable for long-term management because of their adverse effects. Baricitinib is an oral Janus kinase inhibitor that has been approved for the treatment of moderate-to-severe atopic dermatitis. However, its effect on CHFE has rarely been described. Herein, we report nine cases of recalcitrant CHFE that were treated with baricitinib after an inadequate response to low-dose ciclosporin. All patients had more than moderate improvement within 2-8 weeks without serious adverse effects.


Neural mechanisms for selectively tuning in to the target speaker in a naturalistic noisy situation.
The neural mechanism for selectively tuning in to a target speaker while tuning out the others in a multi-speaker situation (i.e., the cocktail-party effect) remains elusive. Here we addressed this issue by measuring brain activity simultaneously from a listener and from multiple speakers while they were involved in naturalistic conversations. Results consistently show selectively enhanced interpersonal neural synchronization (INS) between the listener and the attended speaker at left temporal-parietal junction, compared with that between the listener and the unattended speaker across different multi-speaker situations. Moreover, INS increases significantly prior to the occurrence of verbal responses, and even when the listener's brain activity precedes that of the speaker. The INS increase is independent of brain-to-speech synchronization in both the anatomical location and frequency range. These findings suggest that INS underlies the selective process in a multi-speaker situation through neural predictions at the content level but not the sensory level of speech.


Sodium-glucose cotransporter 2 inhibition in non-diabetic kidney disease.
Sodium-glucose cotransporter 2 (SGLT2) inhibitors have proven cardiorenal protection in patients with diabetes and chronic kidney disease (CKD) as seen in cardiovascular outcome trials (CVOTs) and CREDENCE. In this review, we aim to discuss the mechanisms of kidney protection with SGLT2 inhibition as well as review the results of multiple translational studies and clinical trials of SGLT2 inhibition in the nondiabetic kidney disease (non-DKD) population. The application of SGLT2 inhibitors as dedicated kidney-protective agents continues to evolve with the publication of the dapagliflozin in patients with chronic kidney disease (DAPA CKD) trial, which extends their cardiorenal protection to patients with nondiabetic CKD. This trial was preceded by CREDENCE, a dedicated kidney outcome study in participants with DKD that demonstrated a 30% reduction in the risk of the composite kidney outcome. From a physiological perspective, mechanistic benefits of SGLT2 inhibitors are independent of their glucose-lowering effects as demonstrated in preclinical studies and post hoc analyses of dedicated CVOTs in participants with type 2 diabetes. From a clinical perspective, there is a growing body of evidence for kidney protection in nondiabetes mellitus patients. There exists strong rationale for SGLT2 inhibition to be incorporated into standard of care for appropriate groups of patients with nondiabetic kidney disease.


Inactivation of mammalian target of rapamycin (mTOR) by rapamycin in a murine model of lipopolysaccharide-induced acute lung injury.
The mammalian target of rapamycin (mTOR) pathway, a key cellular signaling pathway associated with various cellular functions, has distinct roles in the inflammatory process. In this study, the mTOR inhibitor rapamycin (Rapa) was used to test whether inhibition of mTOR activation attenuates lipopolysaccharide (LPS)-induced acute lung injury (ALI) in a murine model. Mice pretreated with Rapa or vehicle were given LPS intratracheally. Local cell numbers and inflammatory cytokines present in the bronchoalveolar lavage fluid (BAL), wet-to-dry weight ratio, histopathology of the lungs, and survival were evaluated. The phosphorylation of S6, a major downstream target of mTOR, had a 3-fold increase in lung tissue after LPS stimulation, but the increase was blocked by Rapa. Rapa reduced the levels of TNF-α (LPS vs. LPS + Rapa, (1672.74 ± 193.73) vs. (539.17 ± 140.48) pg/ml, respectively; P < 0.01) and IL-6 (LPS vs. LPS + Rapa: (7790.88 ± 1170.54) vs. (1968.57 ± 474.62) pg/ml, respectively; P < 0.01) in the BAL fluid. However, Rapa had limited effects on the overall severity of ALI, as determined by the wet-to-dry weight ratio of the lungs, number of neutrophils in the BAL fluid, and changes in histopathology. In addition, Rapa failed to reduce mortality in the LPS-induced ALI model. We confirmed that mTOR was activated during LPS-induced ALI and strongly inhibited by Rapa. Although Rapa reduced the levels of the mediators of inflammation, the overall severity and survival of the ALI murine model were unchanged.


Recovering Wind-Induced Plant Motion in Dense Field Environments via Deep Learning and Multiple Object Tracking.
Understanding the relationships between local environmental conditions and plant structure and function is critical for both fundamental science and for improving the performance of crops in field settings. Wind-induced plant motion is important in most agricultural systems, yet the complexity of the field environment means that it remained understudied. Despite the ready availability of image sequences showing plant motion, the cultivation of crop plants in dense field stands makes it difficult to detect features and characterize their general movement traits. Here, we present a robust method for characterizing motion in field-grown wheat plants (Triticum aestivum) from time-ordered sequences of red, green, and blue images. A series of crops and augmentations was applied to a dataset of 290 collected and annotated images of ear tips to increase variation and resolution when training a convolutional neural network. This approach enables wheat ears to be detected in the field without the need for camera calibration or a fixed imaging position. Videos of wheat plants moving in the wind were also collected and split into their component frames. Ear tips were detected using the trained network, then tracked between frames using a probabilistic tracking algorithm to approximate movement. These data can be used to characterize key movement traits, such as periodicity, and obtain more detailed static plant properties to assess plant structure and function in the field. Automated data extraction may be possible for informing lodging models, breeding programs, and linking movement properties to canopy light distributions and dynamic light fluctuation.


Advances in general surgery 50 years ago.
In 1971, some of the new advances that were set to change the field of general surgery included theories about the development of peptic ulcers, new treatments for varicose veins and pioneering work in the introduction of day case surgery.


Detailed cadaveric analysis of perivesical lymph nodes in cystectomy specimens.
Perivesical lymph nodes were added to the 8th edition of American Joint Committee on Cancer (AJCC) staging for bladder cancer. Currently, these nodes are inconsistently evaluated at the time of radical cystectomy. The objective of this study was to provide a detailed anatomic evaluation of perivesical lymph nodes. A radical cystectomy was performed on six un-embalmed cadavers with wide resection of perivesical tissue and meticulous care to separate the pelvic sidewall lymph nodes (e.g. obturator, external iliac) from the bladder and perivesical en-bloc specimen. Perivesical tissue dissection in 2 mm slices was performed with a board-certified pathologist. Lymph node size and location were recorded. Gross tissue resembling lymph nodes were identified in the perivesical tissue in 50% (3/6) of the specimens, with a total of six grossly identified lymph nodes. The mean size was 7.5 mm (2-16 mm). On histologic analysis, 4 of 6 (66%) putative gross lymph nodes had confirmed lymphoid tissue. The mean distance of the lymph nodes from bladder wall was 9 mm (3-15 mm). Eight anatomic locations for perivesical nodes were developed: urachal, anterior bladder wall, posterior peritoneum, bladder neck, bilateral pedicle, bilateral lateral bladder wall. This cadaveric study with meticulous dissection of the perivesical space confirms that perivesical lymph nodes are a distinct entity and separate from other lymph nodes in the true pelvis. Perivesical lymph nodes are not present in all subjects and pathologic evaluation is more difficult owing to the surrounding fat. We herein propose perivesical regions for evaluation which can serve as a foundation for future studies and anatomic grossing techniques.


Identification of potential plasma markers for hepatitis B virus-related chronic hepatitis and liver fibrosis/cirrhosis.
The aim of this study was to identify potential plasma biomarkers for hepatitis B virus (HBV)-related liver diseases. High-throughput transcriptome sequencing analysis was performed on five patients with chronic hepatitis B (CHB), five patients with HBV-associated liver fibrosis/liver cirrhosis (LF/LC), and four healthy participants. By short time-series expression miner and functional analysis, aquaporin 1 (AQP1), dystroglycan 1 (DAG1), and hemoglobin subunit beta (HBB) were identified as potential biomarkers. Immunohistochemical analysis revealed that the expression levels of AQP1, DAG1, and HBB were upregulated in the three groups. Subsequent enzyme-linked immunosorbent assay tests on the training cohort (n = 150) indicated that the plasma levels of AQP1 and DAG1 were highest in LF/LC patients, followed by those in CHB patients, and the lowest in healthy controls. APAD model, a diagnostic panel incorporating age, platelet, AQP1, and DAG1 levels, exhibited the strongest stratification ability to distinguish LF/LC patients from CHB patients, and to differentiate CHB patients from healthy controls. Furthermore, the diagnostic accuracies of the biomarkers and APAD model were verified in an independent cohort consisting of 230 participants. In conclusion, both AQP1 and DAG1 have good diagnostic values and APAD model greatly enhances the diagnostic accuracy for HBV-related hepatic diseases.


Pharmacological and non-surgical renal protective strategies for cardiac surgery patients undergoing cardiopulmonary bypass: a systematic review.
Post-operative acute kidney injury after cardiopulmonary bypass (AKI-CPB) for cardiac surgery is a frequent complication. It may require renal replacement therapy (RRT), which is associated with an increased morbidity and mortality. This review explores the efficacy of proposed pharmacological and non-surgical renal protective strategies. A comprehensive literature search was done using Ovid MEDLINE, Embase and Scopus databases. Keywords included were cardiopulmonary bypass, cardiac surgery, coronary artery bypass, renal protection and renal preservation. Eligible articles consisted of all studies on patients who had undergone cardiac surgery via CPB with an outcome of AKI and/or RRT reported. All studies underwent a quality check via the risk of bias tool. The three most researched interventions (based on number of randomized controlled trials and total patients analysed) and their renal outcomes were then analysed with Review Manager Software. Eighty-eight articles were extracted. A total of 26 management strategies for renal protection following CPB were identified. N-acetylcysteine (NAC), remote ischaemic preconditioning (RIPC) and the use of volatile anaesthetic agents (VAAs) were further analysed. NAC, RIPC and VAA had no statistically significant benefit in reducing either AKI-CPB or the need for RRT following CPB. NAC, RIPC and VAA were found to have no statistical significant benefit in reducing either AKI-CPB or the need for RRT following CPB. There remains clinical uncertainty with all currently proposed pharmacological and non-surgical renal protective strategies for CPB. Future research in this area should analyse the effects of combined interventions or specifically focus on 'at-risk' patients.


Tebentafusp: T Cell Redirection for the Treatment of Metastatic Uveal Melanoma.
Metastatic disease from uveal melanoma occurs in almost 50% of patients suffering from this ocular tumour, with median survival from development of symptoms being around 1 year. In contrast to cutaneous melanoma, kinase inhibitors and immune checkpoint inhibitors are usually ineffective in patients with metastatic uveal melanoma. Tebentafusp is a novel form of immunotherapy based on the immune-mobilising monoclonal T cell receptor against cancer (ImmTAC) platform, which comprises a soluble T cell receptor that is fused to an anti-CD3 single-chain variable fragment. The T cell receptor domain of tebentafusp targets cells present a human leukocyte antigen-A*02:01 complexed with a peptide derived from the melanoma-associated antigen gp100, which is expressed strongly by melanoma cells, weakly by normal melanocytes and minimally by other tissues. The anti-CD3 domain recruits CD3+ T cells (and, indirectly, other immune cells), redirecting these to the melanoma cells. The most common adverse events with tebentafusp are manageable and usually transient. Early survival data in patients with metastatic uveal melanoma are promising when considered alongside historical data. Based on these encouraging results, a randomised study comparing tebentafusp to investigator's choice of therapy in metastatic uveal melanoma is ongoing.


Horizontal natural product transfer: A potential source of alkaloidal contaminants in phytopharmaceuticals.
It was recently shown that nicotine and pyrrolizidine alkaloids that leach out from decomposing plant material (donor plants) are subsequently taken up by the roots of acceptor plants and translocated into their leaves. Furthermore, it is well established that plant roots take up xenobiotics, generally by simple diffusion, and that this passive import depends on the physico-chemical properties of the substances. Based on the well-known uptake of xenobiotics, we assumed that in analogy, the uptake of alkaloids, which are leached out from plant material (donor plants) represents a quite general feature of plant biology. Using barley as a model plant, we analyzed the uptake of alkaloids by applying them to Hordeum vulgare seedlings. Based on HPLC analyses, the presence of the particular alkaloids in the acceptor plants was determined. We demonstrated that numerous alkaloids of different structural types are able to diffuse through biomembranes and are taken up by acceptor plants. In contrast, an uptake of quaternary alkaloids, with a permanent positive charge, could not be detected. As most alkaloidal plants generally die back afield, and the corresponding natural products are leached out into the soil. Our findings have substantial relevance for all plant-derived commodities, especially for the production of phytopharmaceuticals and the related safety issues. Moreover, the evidence that plants are inherently able to take up alkaloids from the soil, which are derived from other plants, will alter our appraisal of plant-plant interactions. In this context, the classical definition of xenobiotics, which are considered as "non-natural" substances, might be also extended by including natural products leached out into the soil.


The role of brachytherapy in treatment of stage I esophageal cancer: A systematic review.
Despite advancements in the early detection of esophageal cancer, optimal radiotherapy methods for treatment of early disease have not yet been determined. Moreover, the benefit of intraluminal brachytherapy on local control or survival remains controversial. We performed a systematic review to establish the role of brachytherapy as boost therapy in stage I esophageal squamous cell carcinoma, and to evaluate associated survival outcomes. A systematic search of three bibliographic databases from January 1950 to January 2019 was conducted. All studies investigating brachytherapy for curative intent were included and palliative treatment was excluded. Primary outcomes included overall survival and disease-free survival (DFS). Secondary outcomes included loco-regional control (LRC) and toxicity grades and/or complications. Two reviewers independently abstracted data and evaluated study quality using grading of recommendations assessment, development, and evaluation, pooled results were presented through risk ratios. A total of 12 retrospective studies met inclusion criteria. The overall quality of evidence yielded a Grade 1C rating (strong recommendation, low quality evidence). Of 525 included patients, 325 patients received both external beam radiation (EBRT), and brachytherapy, 132 underwent EBRT only, and 68 received brachytherapy with and/or without chemoradiation. For patient group treated with EBRT and brachytherapy, 5-year mortality, DFS and LRC were: 43% (27-59%), 63% (49-76%) and 72% (63-80%) respectively. Rates of complications reported included 82.1% Grade 1 esophagitis for a combined external beam radiation and brachytherapy cohort, 12.3% ulcerations, and 3.3% fistulae. Brachytherapy as a combined modality is encouraging, given its relative safety and effectiveness. Further prospective analysis using higher quality evidence is warranted to evaluate oncologic outcomes and survival advantage.


Liponeurocytoma of the left lateral ventricle--case report and review of the literature.
The reported liponeurocytoma of the left lateral ventricle in a 35-year-old man represents the fifth recorded case of a supratentorial intraventricular liponeurocytoma. In this location, liponeurocytomas are very exceptional, whereas it is the typical site for classic central neurocytomas. Conversely, neurocytomas of the cerebellum are predominantly liponeurocytomas with until now more than 25 reported cases. Thus, cerebellar liponeurocytoma is the most frequent neuroepithelial CNS tumor with adipose-like cells followed by ependymomas with a lipid component and supratentorial intraventricular liponeurocytoma. Adipose-like cells in neurocytomas may originate by lipidization of tumor cells, metaplastic transformation of neuroectodermal cells into fat cells or by true adipocytic differentiation. The present case showed also focal glial differentiation with GFAP-positivity of some tumor cells as often seen in cerebellar liponeurocytomas but much rarer in central neurocytomas. Pathogenetic and nosologic implications of supratentorial intraventricular liponeurocytomas are discussed. Future WHO tumor classification should consider that liponeurocytomas are not restricted to the cerebellum. Reports on cerebellar liponeurocytomas with a less favorable clinical course suggest a WHO grade II for liponeurocytomas.


Posttraumatic cholesteatoma complicated by a facial paralysis: a case report.
The posttraumatic cholesteatoma is a rare complication of different types of the temporal bone damage. Its diagnosis is often done after several years of evolution, sometimes even at the stage of complications. A case of posttraumatic cholesteatoma is presented that was revealed by a facial nerve paralysis 23 years after a crash of the external auditory canal underlining the importance of the otoscopic and radiological regular monitoring of the patients with a traumatism of the temporal bone.


High fidelity case-based simulation debriefing: everything you need to know.
In this 30-minute talk, the authors take an in-depth look at how to debrief high-fidelity case-based simulation sessions, including discussion on debriefing theory, goals, approaches, and structure, as well as ways to create a supportive and safe learning environment, resulting in successful small group learning and self-reflection. Emphasis is placed on the "debriefing with good judgment" approach. Video clips of sample debriefing attempts, highlighting the "dos and don'ts" of simulation debriefing, are included. The goal of this talk is to provide you with the necessary tools and information to develop a successful and effective debriefing approach. There is a bibliography and a quick reference guide in Data Supplements S1 and S2 (available as supporting information in the online version of this paper).


Arthrodesis of the shoulder.
Shoulder arthrodesis is an end-stage salvage option for the failing, painful joint that cannot undergo or has failed reconstruction. It is indicated for irreversible and nonreconstructible massive rotator cuff tears and deltoid muscle denervation as well as for detachment of the deltoid from its origin. Rarely, arthrodesis is done to stabilize the glenohumeral joint after many failed attempts at shoulder reconstruction. Arthrodesis for failed prosthetic arthroplasty or tumor resection presents additional challenges because of the associated bone loss on the humeral and/or glenoid side of the joint. Primary arthrodesis requires rigid internal plate fixation and both an extra- and an intra-articular site of fusion. Depending on bone volume and quality needed, the patient may require bracing for 8 to 10 weeks, autogenous or allograft bone grafting, or a vascularized fibular bone graft to reconstruct the bone deficiency, along with prolonged spica cast immobilization. The optimal position for arthrodesis is 20 degrees of forward flexion, 20 degrees of abduction, and 40 degrees of internal rotation, with modifications based on patient body size or other patient-specific factors. Bone fusion is attained in nearly all patients, with marked pain reduction and improved function. Postoperatively, the patient should be able to lift the arm to near shoulder height and to reach the top of the head, the mouth, the ipsilateral back pocket, and the groin. Complications include nonunion, malposition, pain associated with prominent hardware, and periarticular fractures.


Detecting communities using asymptotical surprise.
Nodes in real-world networks are repeatedly observed to form dense clusters, often referred to as communities. Methods to detect these groups of nodes usually maximize an objective function, which implicitly contains the definition of a community. We here analyze a recently proposed measure called surprise, which assesses the quality of the partition of a network into communities. In its current form, the formulation of surprise is rather difficult to analyze. We here therefore develop an accurate asymptotic approximation. This allows for the development of an efficient algorithm for optimizing surprise. Incidentally, this leads to a straightforward extension of surprise to weighted graphs. Additionally, the approximation makes it possible to analyze surprise more closely and compare it to other methods, especially modularity. We show that surprise is (nearly) unaffected by the well-known resolution limit, a particular problem for modularity. However, surprise may tend to overestimate the number of communities, whereas they may be underestimated by modularity. In short, surprise works well in the limit of many small communities, whereas modularity works better in the limit of few large communities. In this sense, surprise is more discriminative than modularity and may find communities where modularity fails to discern any structure.


Dual Model Medical Invoices Recognition.
Hospitals need to invest a lot of manpower to manually input the contents of medical invoices (nearly 300,000,000 medical invoices a year) into the medical system. In order to help the hospital save money and stabilize work efficiency, this paper designed a system to complete the complicated work using a Gaussian blur and smoothing-convolutional neural network combined with a recurrent neural network (GBS-CR) method. Gaussian blur and smoothing (GBS) is a novel preprocessing method that can fix the breakpoint font in medical invoices. The combination of convolutional neural network (CNN) and recurrent neural network (RNN) was used to raise the recognition rate of the breakpoint font in medical invoices. RNN was designed to be the semantic revision module. In the aspect of image preprocessing, Gaussian blur and smoothing were used to fix the breakpoint font. In the period of making the self-built dataset, a certain proportion of the breakpoint font (the font of breakpoint is 3, the original font is 7) was added, in this paper, so as to optimize the Alexnet-Adam-CNN (AA-CNN) model, which is more suitable for the recognition of the breakpoint font than the traditional CNN model. In terms of the identification methods, we not only adopted the optimized AA-CNN for identification, but also combined RNN to carry out the semantic revisions of the identified results of CNN, meanwhile further improving the recognition rate of the medical invoices. The experimental results show that compared with the state-of-art invoice recognition method, the method presented in this paper has an average increase of 10 to 15 percentage points in recognition rate.


Funding, disease area, and internal validity of hepatobiliary randomized clinical trials.
The aim of this study was to assess whether funding and the disease area are related to the internal validity of hepatobiliary randomized clinical trials. We gathered data on funding, disease area, methodological quality (randomization and double blinding), and sample size from 616 hepatobiliary randomized clinical trials published from 1985 to 1996 in 12 MEDLINE indexed journals. The internal validity (methodological quality and sample size) of trials funded by profit or nonprofit organizations was not significantly different. Compared with these trials, trials without funding were significantly less likely to report adequate generation of the allocation sequence (55% vs 41%, p = 0.001) and to be double blind (42% vs 25%, p < 0.001), but the proportion with adequate allocation concealment and the sample size were not significantly different. The trials covered 12 disease areas. The proportion of funded trials did not differ significantly in different disease areas. The disease area was significantly associated with the proportion of trials with adequate generation of the allocation sequence (p < 0.001), allocation concealment (p = 0.003), and double blinding (p < 0.001) as well as the sample size (p < 0.001). This association was not explained by the proportion of trials with funding. External funding was significantly associated with adequate methodological quality, but not with the sample size. Irrespective of funding, the disease area was significantly associated with the methodological quality and sample size. Accordingly, external funding and the disease area are significant predictors of the internal validity of hepatobiliary randomized clinical trials.


Fate of carbon tetrachloride during phytoremediation with poplar under controlled field conditions.
The fate of carbon tetrachloride (CT) during phytoremediation with poplar was assessed by examining the transpiration of CT from leaves, diffusion from soil, tree trunks, and surface roots, and accumulation of chloride ion in soil and plant tissues. Feedwater containing 12-15 mg/L CT was added to the field test beds planted with poplar, and over 99% of the CT was removed. No significant amount of CT was transpired or diffused into the air, and no significant amount of CT-chlorine accumulated in the tree tissues. Chloride ion accumulated in the soil accounted for all of the CT-chlorine removed. When soils from the root zones were compared to unvegetated soils, microbial mineralization of CT was not enhanced in soils from the root zones as compared to unvegetated soils. Thus, we conclude that uptake and dechlorination of CT by plant tissues is likely the primary mechanism for phytoremediation by poplar.


Grass pollen immunotherapy inhibits seasonal increases in basophils and eosinophils in the nasal epithelium.
Symptoms of allergic rhinitis are accompanied by infiltration of the nasal mucosa with inflammatory cells, predominantly eosinophils and metachromatic cells (basophils and mast cells). Specific immunotherapy (IT) reduces mucosal eosinophilia and numbers of metachromatic cells in the epithelium. A specific marker distinguishing basophils from mast cells was recently developed. The basophil-specific monoclonal antibody 2D7 was used to determine the influence of subcutaneous IT on numbers of nasal mucosal basophils compared with the effects of IT on neutrophils, eosinophils and mast cells. During a randomized, placebo-controlled trial of grass pollen IT in 44 adults with severe summer hay fever, nasal biopsies were taken at baseline, out of the pollen season, and at the peak of the pollen season following 2 years treatment. Biopsies were processed for immunohistochemistry for basophils (2D7+), mast cells (AA1+), eosinophils (MBP+) and neutrophils (neutrophil elastase+). In placebo-treated (PL) patients there were significant seasonal increases in basophils (P < 0.01), mast cells (P < 0.05) and eosinophils (P = 0.002) in the nasal submucosa. In IT-treated patients significant increases in 2D7+ cells (P < 0.01) and eosinophils (P = 0.01) but not AA1+ cells (P = 0.9) were observed. These differences were significant between groups for eosinophils (P < 0.05). In the epithelium there were seasonal increases in AA1+ cells and eosinophils in both groups (PL: P < 0.01, IT: P < 0.05 for both). The between-group difference was significant for eosinophils (P = 0.05). Basophils were observed in the epithelium of six out of 17 in the placebo group and one out of 20 in the IT group (P = 0.03). Neutrophil numbers remained constant in both epithelium and submucosa. Successful grass pollen immunotherapy was associated with inhibition of seasonal increases in basophils and eosinophils, but not mast cells or neutrophils within the nasal epithelium. Immunotherapy may act, at least in part, by reducing seasonal recruitment of basophils and eosinophils into the epithelium.


Nucleotide sequence and biochemical characterization of the metJ gene from Salmonella typhimurium LT2.
The nucleotide sequence of the Salmonella typhimurium metJ gene is presented along with the sequence of the promoter region for the closely linked metB gene. The two genes are transcribed in opposite directions, with transcription initiating from a single promoter for metB, and from two apparent promoters for metJ. RNA polymerase binding sites for metJ and metB, determined by in vitro protection studies, lie adjacent to each other and may overlap. The two metJ promoters, PJ1 and PJ2, are separated by approximately 65 base pairs. Binding of RNA polymerase in vitro could only be observed for PJ1, even though transcripts are initiated from both promoters in vivo. The metJ gene codes for a polypeptide of 105 amino acids with a calculated Mr of 12,110. The translation start site was determined by N-terminal amino acid sequence analysis of a metJ-lacZ fusion protein.


[Necessity of physical activities restriction after lumbar diskectomy].
Necessity of physical activities restriction after lumbar discectomy have been described in the literature. The aim of this study was to determine if early rehabilitation could favorably influence the prognosis of military patients who had undergone lumbar disk surgery. We performed a retrospective study involving patients who have had lumbar disk surgery, and had undergone physical rehabilitation program. A clinical evaluation, an assessment of pain and a functional assessment by the Arabic version amended self-questionnaire Oswestry have been made for these patients before and after a rehabilitation program started since the 40th postoperative day. We have collected 50 cases: 40 men and 10 women of average age 30 years. All these patients have been improved after surgery with no radiculalgies, but with persistence lumbar pain syndrome. After rehabilitation program, we noted a reduction of 42.85% of pain and functional improvement with a reduction in the average score of Oswestry index of 61.18%. The average work incapacity was 4 months. A workstation adaptation was indicated for all patients. Intensive rehabilitation program started early after lumbar disk surgery can improve the functionality of patients operated, and allows early return to professional activities with reduction of the healthcare cost.


To reappraise or not to reappraise? Emotion regulation choice and cognitive energetics.
Research shows that cognitive reappraisal is an effective emotion regulation (ER) strategy that often has clear benefits. Yet, surprisingly, recent findings demonstrate that people use cognitive reappraisal less frequently than might be expected (Suri, Whittaker, & Gross, 2015). We employ cognitive energetics theory (CET) to explain this puzzling behavior. CET posits that the likelihood of launching any cognitive process is a function of two opposing forces: the driving force (i.e., the motivation to launch the process) and the restraining force (i.e., task difficulty). We thus hypothesized that people choose to use cognitive reappraisal relatively rarely because of the difficulty of implementing it. We also postulated that the decision to reappraise (or not) does not simply depend on stimuli emotional intensity because the latter is associated with both the driving and the restraining forces. In support of our hypotheses, we found that when the images' emotional intensity posed difficulty for reappraisal (i.e., highly intense images), reducing this difficulty by asking participants to merely predict others' (Study 1) or their own choices (Study 2) increased reappraisal choice. Finally, in Study 3, we show that a relatively easy to implement reappraisal strategy was chosen more often than the more difficult one for high (but not low) intensity images. These findings illustrate the relevance of a CET-based motivational analysis to emotion regulation choice. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Dental injuries with kick-scooters in 6- to 12-year-old children.
The objective of this study was to investigate the occurrence of injuries, especially dental trauma, in scooter-related accidents. In addition, children's habits of wearing protective gear were assessed. The study was conducted in primary schools in three neighboring towns near Basel, Switzerland, using anonymous multiple-choice questionnaires completed by parents of schoolchildren. A total of 953 scooter riders were included in the study. The average age was 9.1 years (range 6-12 years). Of riders, 58.3% wore no protective gear, 39.6% wore a helmet, and 2% wore other protective equipment. Twenty-nine percentage of the children have sustained an accident while riding the scooter, of those injuries, 41.4% affected the lower extremities, 37.0% the upper extremities, 21.6% the head, and 11.2% dental injuries; 20.3% of accidents required medical treatment. Parents, teachers, and doctors should be aware of the dangers involved in scooter riding. Educational measures, especially concerning use of protective gear, should be implemented to reduce the number and severity of injuries caused by this popular recreational activity.


Ecological physiology of Pereskia guamacho, a cactus with leaves.
The specialized physiology of leafless, stem-succulent cacti is relatively well understood. This is not true, however, for Pereskia (Cactaceae), the 17 species of leafy trees and shrubs that represent the earliest diverging lineages of the cacti. Here we report on the water relations and photosynthesis of Pereskia guamacho, a small tree of the semiarid scrubland of Venezuela's Caribbean coast. Sapwood-specific xylem conductivity (Ksp) is low when compared to other vessel-bearing trees of tropical dry systems, but leaf-specific xylem conductivity is relatively high due to the high Huber value afforded by P. guamacho's short shoot architecture. P. guamacho xylem is not particularly vulnerable to drought-induced cavitation, especially considering the high leaf water potentials maintained year round. This is confirmed by the lack of significant variation exhibited in Ksp between wet and dry seasons. In the rainy season, P. guamacho exhibited C3-like patterns of stomatal conductance, but during a prolonged drought we documented nocturnal stomatal opening with a concomitant accumulation of titratable acid in leaves. This suggests that P. guamacho can perform drought-induced crassulacean acid metabolism (CAM photosynthesis), although delta 13C values imply that most carbon is assimilated via the C3 pathway. P. guamacho leaves display very low stomatal densities, and maximum stomatal conductance is low whether stomata open during the day or night. We conclude that leaf performance is not limited by stem hydraulic capacity in this species, and that water use is conservative and tightly regulated at the leaf level.


The Impact of Workplace Violence on Headache and Sleep Problems in Nurses.
Workplace violence (WV) is a significant occupational hazard for nurses. Previous studies have shown that WV has a reciprocal relationship with occupational stress. Headaches and sleep problems are early neuropsychological signs of distress. This cross-sectional study aims to ascertain the frequency of physical or verbal assaults on nurses and to study the association of WV with headaches and sleep problems. During their regular medical examination in the workplace, 550 nurses and nursing assistants (105 males, 19.1%; mean age 48.02 ± 9.98 years) were asked to fill in a standardized questionnaire containing the Violent Incident Form (VIF) concerning the episodes of violence experienced, the Headache Impact Test (HIT-6) regarding headaches, and the Pittsburgh Sleep Quality Inventory (PSQI) on sleep quality. Occupational stress was measured using the Effort/Reward Imbalance questionnaire (ERI). Physical and non-physical violence experienced in the previous year was reported by 7.5% and 17.5% of workers, respectively. In the univariate logistic regression models, the workers who experienced violence had an increased risk of headaches and sleep problems. After adjusting for sex, age, job type, and ERI, the relationship between physical violence and headaches remained significant (adjusted odds ratio aOR = 2.25; confidence interval CI95% = 1.11; 4.57). All forms of WV were significantly associated with poor sleep in a multivariate logistic regression model adjusted for sex, age, job type, and ERI (aOR = 2.35 CI95% = 1.44; 3.85). WV was also associated with the impact of headaches and with sleep quality. WV prevention may reduce the frequency of lasting psychoneurological symptoms, such as headaches and poor sleep quality, that interfere with the ability to work.


Boryl-metal bonds facilitate cobalt/nickel-catalyzed olefin hydrogenation.
New approaches toward the generation of late first-row metal catalysts that efficiently facilitate two-electron reductive transformations (e.g., hydrogenation) more typical of noble-metal catalysts is an important goal. Herein we describe the synthesis of a structurally unusual S = 1 bimetallic Co complex, [((Cy)PBP)CoH]2 (1), supported by bis(phosphino)boryl and bis(phosphino)hydridoborane ligands. This complex reacts reversibly with a second equivalent of H2 (1 atm) and serves as an olefin hydrogenation catalyst under mild conditions (room temperature, 1 atm H2). A bimetallic Co species is invoked in the rate-determining step of the catalysis according to kinetic studies. A structurally related Ni(I)Ni(I) dimer, [((Ph)PBP)Ni]2 (3), has also been prepared. Like Co catalyst 1, Ni complex 3 displays reversible reactivity toward H2, affording the bimetallic complex [((Ph)PBHP)NiH]2 (4). This reversible behavior is unprecedented for Ni(I) species and is attributed to the presence of a boryl-Ni bond. Lastly, a series of monomeric ((tBu)PBP)NiX complexes (X = Cl (5), OTf (6), H (7), OC(H)O (8)) have been prepared. The complex ((tBu)PBP)NiH (7) shows enhanced catalytic olefin hydrogenation activity when directly compared with its isoelectronic/isostructural analogues where the boryl unit is substituted by a phenyl or amine donor, a phenomenon that we posit is related to the strong trans influence exerted by the boryl ligand.


Tremor in Multiple Sclerosis-An Overview and Future Perspectives.
Tremor is an important and common symptom in patients with multiple sclerosis (MS). It constituted one of the three core features of MS triad described by Charcot in the last century. Tremor could have a drastic impact on patients' quality of life. This paper provides an overview of tremor in MS and future perspectives with a particular emphasis on its epidemiology (prevalence: 25-58%), clinical characteristics (i.e., large amplitude 2.5-7 Hz predominantly postural or intention tremor vs. exaggerated physiological tremor vs. pseudo-rhythmic activity arising from cerebellar dysfunction vs. psychogenic tremor), pathophysiological mechanisms (potential implication of cerebellum, cerebello-thalamo-cortical pathways, basal ganglia, and brainstem), assessment modalities (e.g., tremor rating scales, Stewart-Holmes maneuver, visual tracking, digitized spirography and accelerometric techniques, accelerometry-electromyography coupling), and therapeutic options (i.e., including pharmacological agents, botulinum toxin A injections; deep brain stimulation or thalamotomy reserved for severe, disabling, or pharmaco-resistant tremors). Some suggestions are provided to help overcome the unmet needs and guide future therapeutic and diagnostic studies in this complex disorder.


Complement System and Age-Related Macular Degeneration: Implications of Gene-Environment Interaction for Preventive and Personalized Medicine.
Age-related macular degeneration (AMD) is the most common cause of visual loss in developed countries, with a significant economic and social burden on public health. Although genome-wide and gene-candidate studies have been enabled to identify genetic variants in the complement system associated with AMD pathogenesis, the effect of gene-environment interaction is still under debate. In this review we provide an overview of the role of complement system and its genetic variants in AMD, summarizing the consequences of the interaction between genetic and environmental risk factors on AMD onset, progression, and therapeutic response. Finally, we discuss the perspectives of current evidence in the field of genomics driven personalized medicine and public health.


[Prevention of deep venous thrombosis in obstetrico-gynecologic surgery. Our experience with defibrotide].
Defibrotide, a new anti-thrombotic and profibrinolytic agent, has been experimented in the prophylaxis of thromboembolic disease in 99 women subjected to obstetrico-gynaecological operations. The drug's effectiveness, lack of changes in the clotting set-up and good tolerance were demonstrated. In conclusion, it is hoped that the good results obtained will promote more regular use of this drug in the prophylaxis of deep venous thrombosis in obstetrico-gynaecological surgery.


Amlodipine-induced linear IgA disease.
A 58-year-old woman presented with a 3-week history of a pruritic rash, which had started a week after commencing treatment with amlodipine. On physical examination, large, well-demarcated erythematous plaques, surrounded by small clusters of clear vesicles, were seen on the patient's torso. Subepidermal blisters with neutrophils and eosinophils were seen in a skin biopsy, and direct immunofluorescence showed deposition of IgA along the basement membrane, in keeping with a diagnosis of linear IgA dermatosis (LAD). Amlodipine was discontinued, and the patient was started on prednisolone 30 mg, supplemented shortly afterwards by dapsone, which resulted in prompt resolution of the rash. Only a few cases of drug-induced LAD have been reported, mostly in association with vancomycin. To our knowledge, this is the first reported case precipitated by amlodipine.


[Biosynthesis of α-lipoic acid in Gluconobacter oxydans increases the production of vitamin C by one-step fermentation].
In a one-step fermentation system of vitamin C production with Gluconobacter oxydans and Ketogulonicigenium vulgare, a functional module of α-lipoic acid biosynthesis was constructed in G. oxydans. The engineered G. oxydans was co-cultured with K. vulgare to enhance the growth and 2-keto-L-gulonic acid (2-KGA) production of K. vulgare. This one-step fermentation system alleviated the growth inhibition during the mono-culture of K. vulgare and strengthened the interaction between the two bacteria. Moreover, the yield of vitamin C precursor (2-KGA) increased to 73.34 g/L (the control group was 59.09 g/L), and the conversion of D-sorbitol to 2-KGA increased to 86.0%. This study provides a new idea for further optimizing the one-step fermentation system of vitamin C production.


Antagonistic Activity of Fungal Strains against Fusarium Crown Rot.
The crown rot of wheat is a destructive soil-borne pathogen that severely reduces the yield and quality of wheat. This study aimed to screen and identify the antagonistic strains against Fusarium pseudograminearum (Fp), which is the dominant pathogen associated with the crown rot of wheat in China, and evaluate their biosynthetic potential. The antagonistic strains were screened via a dual-culture antagonism assay, and then identified by combining the morphological characteristics and internal transcribed spacer gene sequencing. The polyketide synthases (PKS-I and PKS-II) and non-ribosomal peptide synthetase (NRPS) genes in the antagonistic strains were detected via specific amplification of chromosomal DNA. Eleven out of 157 fungal strains, including six strains with matrix competition and five strains with antibiosis, were obtained. The eleven antagonistic strains belonged to the following four genera: Alternaria, Botryosphaeria, Phoma and Talaromyces. The inhibition rate of six strains with matrix competition was greater than 50%, with B. dothidea S2-22 demonstrating the highest at 80.3%. The width of the inhibition zone of T. trachyspermus R-17 among the five strains with antibiosis was the widest at 11 mm. Among the eleven antagonistic strains, three strains of A. alternata and the strain P. moricola only contained the PKS-II gene, the strain A. tenuissima contained PKS-I and PKS-II genes, three strains of B. dothidea contained PKS-II and NRPS genes, while three strains of T. trachyspermus did not contain any genes. These results demonstrated potential strains for the biocontrol of the crown rot of wheat. In particular, T. trachyspermus R-17 can be investigated further as a promising agent, and the active substances secreted by antagonistic strains may be synthesized by other pathways.


Molecular operation of metals into the function and state of photosystem II.
Action sites of different metals in the electron transport reactions of Photosystem II (PS II) evaluated by delayed fluorescence in the ms range (ms DF) and pigment-pigment, pigment-protein and protein-protein interaction states by electrophoretic measurements are presented. The main targets for the metals action were shown to be:(i) Cd(2+), Ni(2+), Co(2+)-Y(z) or CaMn(4)-cluster on the donor site with dependence on pH;(ii) Ni(2+), Co(2+), Zn(2+), Al(3+), Mn(2+) between Q(A) and Q(B) on the acceptor site; effect of Al(3+) and Mn(2+) is observed only in acidic pH. Investigated metals bring about monomerization of oligomeric and dimeric chlorophyll-protein complexes (CPC) and destabilization of protein-protein interactions. Molecular mechanisms of metals interference with the structure of PS II are discussed.


Ferroelectric Tuning of ZnO Ultraviolet Photodetectors.
The ferroelectric field effect transistor (Fe-FET) is considered to be one of the most important low-power and high-performance devices. It is promising to combine a ferroelectric field effect with a photodetector to improve the photodetection performance. This study proposes a strategy for ZnO ultraviolet (UV) photodetectors regulated by a ferroelectric gate. The ZnO nanowire (NW) UV photodetector was tuned by a 2D CuInP2S6 (CIPS) ferroelectric gate, which decreased the dark current and enhanced the responsivity and detectivity to 2.40 × 104 A/W and 7.17 × 1011 Jones, respectively. This strategy was also applied to a ZnO film UV photodetector that was tuned by a P(VDF-TrFE) ferroelectric gate. Lower power consumption and higher performance can be enabled by ferroelectric tuning of ZnO ultraviolet photodetectors, providing new inspiration for the fabrication of high-performance photodetectors.


Burkholderia stabilis outbreak associated with contaminated commercially-available washing gloves, Switzerland, May 2015 to August 2016.
We describe an outbreak of Burkholderia stabilis associated with contaminated washing gloves, a commercially available Class I medical device. Triggered by an increase in Burkholderia cepacia complex (BCC) bacteremias and the detection of BCC in unopened packages of washing gloves, an ad hoc national outbreak committee comprising representatives of a public health organisation, a regulatory agency, and an expert association convened and commissioned an outbreak investigation. The investigation included retrospective case finding across Switzerland and whole genome sequencing (WGS) of isolates from cases and gloves. The investigation revealed that BCC were detected in clinical samples of 46 cases aged 17 to 91 years (33% females) from nine institutions between May 2015 and August 2016. Twenty-two isolates from case patients and 16 from washing gloves underwent WGS. All available outbreak isolates clustered within a span of < 19 differing alleles, while 13 unrelated clinical isolates differed by > 1,500 alleles. This BCC outbreak was rapidly identified, communicated, investigated and halted by an ad hoc collaboration of multiple stakeholders. WGS served as useful tool for confirming the source of the outbreak. This outbreak also highlights current regulatory limitations regarding Class I medical devices and the usefulness of a nationally coordinated outbreak response.


[Research progress on potential liver toxic components in traditional Chinese medicine].
In recent years, the proportion of traditional Chinese medicine in scientific research and its clinical use increased gradually. The research result also becomes more and more valuable, but in the process of using traditional Chinese medicine, it also needs to pay more attention. With the gradual deepening of the toxicity of traditional Chinese medicine, some traditional Chinese medicines have also been found to have the potential toxicity, with the exception of some traditional toxicity Chinese medicine. Traditional Chinese medicine in the growth, processing, processing, transportation and other aspects of pollution or deterioration will also cause the side effects to the body. Clinical practice should be based on the theory of traditional Chinese medicine to guide rational drug use and follow the symptomatic medication, the principle of proper compatibility. The constitution of the patients are different, except for a few varieties of traditional Chinese medicines are natural herbs with hepatotoxicity, liver toxicity of most of the traditional Chinese medicine has idiosyncratic features. The liver plays an important role in drug metabolism. It is easy to be damaged by drugs. Therefore, the study of traditional Chinese medicine potential liver toxicity and its toxic components has become one of the basic areas of traditional Chinese medicine research. Based on the review of the literatures, this paper summarizes the clinical classification of liver toxicity, the pathogenesis of target cell injury, and systematically summarizes the mechanism of liver toxicity and toxic mechanism of traditional Chinese medicine. This paper provided ideas for the study of potential liver toxicity of traditional Chinese medicine and protection for clinical safety of traditional Chinese medicine.


Benefit of hemoperfusion in acute theophylline intoxication.
Charcoal and resin hemoperfusion or hemodialysis can accelerate theophylline elimination. Their benefit in the treatment of poisoned patients has been accepted on the basis of case reports. We reviewed the treatment of 26 patients with acute theophylline intoxication to determine how much of an effect hemoperfusion or hemodialysis had on the hospital course and outcome of the overdose. Eighteen patients received supportive care and eight patients hemoperfusion (HP) or hemodialysis (HD). The HP/HD patients had more severe theophylline intoxication on the basis of admission and peak theophylline levels, degree of hypotension and occurrence of arrhythmias. During HP/HD, theophylline concentrations decreased, heart rate slowed, blood pressure increased and evidence of central nervous system effects diminished. Despite the severe intoxication in the HP/HD groups, duration of clinical toxicity was shorter (13.5 +/- 7.1 vs. 21.6 +/- 14.1 hr) than in the control group. Seizures occurred in patients in both groups, but there was higher mortality or neurological morbidity in the supportive care (3/4) than in the HP/HD (1/5) group. Our study provides evidence that HP/HD can reduce the duration of clinical intoxication and probably reduces mortality and morbidity in patients with severe theophylline intoxication.


The clinical impact of growth differentiation factor-15 in heart disease: A 2019 update.
Growth differentiation factor-15 (GDF-15), also known as macrophage inhibitory cytokine-1 (MIC-1) or non-steroidal anti-inflammatory drug-activated gene (NAG-1) has been identified as a biomarker of response to treatment and prognosis in cardiovascular diseases. GDF-15 is a member of the transforming growth factor-β superfamily and is involved in several pathological conditions such as inflammation, cancer, cardiovascular, pulmonary and renal diseases. Cardiac myocytes produce and secrete GDF-15 in response to oxidative stress, stimulation with angiotensin II or proinflammatory cytokines, ischemia, and mechanical stretch. Other cellular sources of GDF-15 production are macrophages, vascular smooth muscle cells, endothelial cells, and adipocytes, which secrete GDF-15 in response to oxidative or metabolic stress or stimulation of proinflammatory cytokines. GDF-15 is induced in hypertrophic and dilated cardiomyopathy after volume overload, ischemia, and heart failure. GDF-15 can be used as a marker of prognosis in patients with cardiovascular disorders, in combination with conventional prognostic factors, such as N-terminal pro B-type natriuretic peptide (NT-proBNP) and high-sensitivity troponin T (hs-TnT).


Fungal Endophytes and Their Role in Agricultural Plant Protection against Pests and Pathogens.
Virtually all examined plant species harbour fungal endophytes which asymptomatically infect or colonize living plant tissues, including leaves, branches, stems and roots. Endophyte-host interactions are complex and span the mutualist-pathogen continuum. Notably, mutualist endophytes can confer increased fitness to their host plants compared with uncolonized plants, which has attracted interest in their potential application in integrated plant health management strategies. In this review, we report on the many benefits that fungal endophytes provide to agricultural plants against common non-insect pests such as fungi, bacteria, nematodes, viruses, and mites. We report endophytic modes of action against the aforementioned pests and describe why this broad group of fungi is vitally important to current and future agricultural practices. We also list an extensive number of plant-friendly endophytes and detail where they are most commonly found or applied in different studies. This review acts as a general resource for understanding endophytes as they relate to potential large-scale agricultural applications.


[Species sensitive distribution for aquatic biota exposed to triazophos].
The increasing pollution of organophosphorus pesticides (OP) in water have been of concerns. Taking the widely used triazophos as the object, a species sensitivity distribution (SSD) model was developed using a log-logistic distribution based on the median effective concentrations (EC50) of triazophos to aquatic species at various trophic levels, and then the model was tested and evaluated using probability plots and good-of-fit tests. The results showed that the SSD for aquatic biota exposed to triazophos was well fitted by a log-logistic distribution, which was totally determined by the two parameters, alpha = -0.4788 and beta = 0.7546, with standard error 0.2381 and 0.1078 respectively. Based on the SSD model, the hazardous concentration for 5% of the species (HC5) and the criteria maximum concentration (CMC) of triazophos were 1.992 x 10(-3) mg/L and 9.96 x 10(-4) mg/L, respectively. Through comparing the HC5 and CMC with the safe concentration for single-species, it could be found that environmental quality criteria derived from the SSD model was more strict, and closed to the real ecological environment. In addition, according to the reported data, the potentially affected fraction (PAF) of species exposed to triazophos in the Laizhou Bay (Bohai Sea, China) area was 0.36% predicted by the SSD model, and the corresponding risk might not be significant.


A study on clinicodemographic profile, severity, and outcome of Covid-19 in hospitalized vaccinated individuals at tertiary care centre.
To evaluate the demographic profile, clinical severity, and outcome of Covid-19 infection in hospitalised vaccinated individuals. An observational, cross-sectional study was conducted among Covid-19 infected hospitalised patients. Clinicodemographic profile, severity, and outcome of Covid-19 infection among the vaccinated group (VG) were recorded. These patients were also compared with unvaccinated group (UVG) with Covid-19 infection admitted during the study period. Cox proportional hazards models was used to estimate hazard ratios for mortality risk in both groups. Out of 580 participants, 48.2% were vaccinated with either one (71%) or two doses (28.9%). In both, VG and UVG, majority 55.8% belonged to 51-75 years. Males were predominant with 62.9% in both VG and UVGs. Day of illness at admission from symptom onset (DOI), progression of disease, ICU stay, oxygen requirement, mortality was significantly higher in UVG than in VG (p < 0.05). Steroid duration (p < 0.001) and anti-coagulation time (p < 0.001) were significantly higher in UVG than in VG. D dimer levels were significantly higher in UVG than in VG (p < 0.05). Increased age, (p < 0.0004), severity of disease, (p < 0.0052), increased oxygen requirement (p < 0.001), elevated C-reactive protein levels (Moderate: P < 0.0013; Severe P < 0.0082), and elevated IL-6 levels (p < 0.001) were the significant determinants of Covid-19-related mortality in both VG and UVGs. Vaccinated individuals have shown milder severity, had reduced hospital stay and better outcomes as compared to unvaccinated individuals suggesting a potential vaccine efficacy against Covid-19.


[Therapeutic relevance of the classification of gastritis].
The histological gastritis classification according to the Sydney system is a standardisation of different classification systems used so far. It is based on the principles of etiology, topography and course of the disease, as well as morphological changes of the gastric mucosa in gastritis. Histological examination represents the practical gold standard of Helicobacter pylori detection and can be used on routinely formaldehyde-fixed biopsy material and hematoxylin-eosin stained slides. Histology is therefore also of practical diagnostic value for the control of the eradication therapy of Helicobacter pylori. The sensitivity of histological Helicobacter detection is on average higher than that of other methods including microbiology. Nevertheless, additional bacterial cultures are useful in cases of therapy resistant Helicobacter pylori infections. For routine diagnosis histological Helicobacter pylori detection is often combined with the so-called rapid urease test, which can be used in the endoscopy outpatient department, frequently offering an interim diagnosis of Helicobacter pylori infection. Furthermore, histological examination enables not only exact gastritis classification with Helicobacter pylori detection, but also the diagnosis of precancerous lesions and gastric carcinomas, as well as primary gastric lymphomas. Biopsy material for histological examination can be taken during the routinely necessary gastroscopic examination of patients with gastric symptoms without much additional burden.


Computational study of the conformational space of methyl 2,4-diacetyl-beta-D-xylopyranoside: 4C1 and 1C4 chairs, skew-boats (2SO, 1S3), and B3,O boat forms.
Ring and substituent rotamer conformations of methyl 2,4-diacetyl-beta-D-xylopyranoside, for which experimental results are controversial, were studied in the gas phase and in solvents of different polarity (CCl4, CHCl3, DMSO, and H2O) by B3LYP density functional theory. The 1C4 chair is the most stable ring form in the gas phase, followed by 4C1 and 2S0. Solvents of increasing polarity shift the equilibrium toward the 4C1 chair. Homodesmotic reaction energies show that the 1C4 and 2SO forms are stabilized by hydrogen bonding and anomeric effects and that steric repulsion is smallest in the 4C1 chair and largest in skew-boats.


Differential expression of melanoma-associated antigens and molecules involved in antigen processing and presentation in three cell lines established from a single patient.
Tumour cells are able to evade the immune system by using several 'escape mechanisms'. Downregulation of molecules involved in the processing and presentation of self-antigens has been reported. However, these adaptations have not been compared in metastases in different anatomical locations but derived from a single patient. We investigated three melanoma cell lines--MJT1 from the parietal lobe of the brain, MJT3 from the cerebellum and MJT5 from the left side of the neck--established from biopsies excised from a 45 year old female patient. Although human leukocyte antigen (HLA) class I was detected in all three cell lines by flow cytometry using an anti-HLA monomorphic antibody, further serological analysis demonstrated HLA B38 loss in all three cell lines, HLA B7 downregulation in MJT5 (skin metastases) and B7 loss in MJT3 and MJT1 (brain metastases) compared with the HLA type of the patient's normal autologous lymphocytes. Interferon-gamma (IFNgamma) treatment increased the expression of HLA class I and transporters associated with antigen processing 1 (TAP1) in all three cell lines. De novo HLA class II molecule expression was observed after IFNgamma treatment in MJT3 and MJT5. Western blot and reverse transcription-polymerase chain reaction results revealed heterogeneity of melanoma-associated antigen (MAA) expression in the cell lines: MJT3 cells expressed higher levels of MAAs than the other two cell lines. In conclusion, this study has demonstrated that three metastatic lesions from a single patient can have differential expression of molecules involved in antigen processing (TAP1) and presentation (HLA I and II), but that expression of these molecules is modulated by IFNgamma to a similar degree in all cell lines. In contrast, the downregulation of expression of specific MAAs between the three cell lines was unaffected by the addition of IFNgamma.


Systemic bis-phosphinic acid derivative restores chloride transport in Cystic Fibrosis mice.
Mutations in the Cystic Fibrosis Transmembrane Conductance Regulator gene (CFTR) are responsible for Cystic Fibrosis (CF). The most common CF-causing mutation is the deletion of the 508th amino-acid of CFTR (F508del), leading to dysregulation of the epithelial fluid transport in the airway's epithelium and the production of a thickened mucus favoring chronic bacterial colonization, sustained inflammation and ultimately respiratory failure. c407 is a bis-phosphinic acid derivative which corrects CFTR dysfunction in epithelial cells carrying the F508del mutation. This study aimed to investigate c407 in vivo activity in the F508del Cftrtm1Eur murine model of CF. Using nasal potential difference measurement, we showed that in vivo administration of c407 by topical, short-term intraperitoneal and long-term subcutaneous route significantly increased the CFTR dependent chloride (Cl-) conductance in F508del Cftrtm1Eur mice. This functional improvement was correlated with a relocalization of F508del-cftr to the apical membrane in nasal epithelial cells. Importantly, c407 long-term administration was well tolerated and in vitro ADME toxicologic studies did not evidence any obvious issue. Our data provide the first in vivo preclinical evidence of c407 efficacy and absence of toxicity after systemic administration for the treatment of Cystic Fibrosis.


Impact of the publication of the Italian guidelines for bronchiolitis on the management of hospitalized children in Pisa, Italy.
Bronchiolitis represents one of the major causes of hospitalization and mortality in children younger than 1 year, but its management continues to be heterogenous both in those who are hospitalized and in those who are not. To assess the impact of the publication of the Italian guidelines on bronchiolitis in October 2014, we analyzed data from children aged ≤12 months admitted for bronchiolitis at the University Hospital of Pisa from January 2010 to December 2019, dividing them into two groups based on whether admission was either preceding (Group 1) or following (Group 2) the publication of the guidelines. 346 patients (mean age 4.1 ± 2.8 months, 55% males) were admitted in the study period; 43.3%, 49.4%, and 7.3% of patients had mild, moderate or severe bronchiolitis, respectively. The mean length of hospital stay was 6.7 ± 2.9 days; 90.5% of the patients underwent nasal swab and 200 patients tested positive for RSV (in mono or coinfection with other viruses). We found no difference in RSV prevalence and severity distribution between the two groups, while we observed a significant reduction in the use of both chest X-rays (66.9% vs. 34.8%, p < 0.001), blood testing (93.4% vs. 58.2%, p < 0.001) and inhaled or systemic corticosteroids (93.1% vs. 47.8%, p < 0.001) in Group 2. No significant reduction in the use of antibiotics and of inhaled β2 agonists was found. Our data suggest that the publication of the Italian guidelines for bronchiolitis has contributed to improving the management of patients admitted for bronchiolitis in our Unit.


Alteration of fibroblast phenotype by asbestos-induced autoantibodies.
Pulmonary fibrosis is a relentlessly progressive disease for which the etiology can be idiopathic or associated with environmental or occupational exposures. There is not a clear explanation for the chronic and progressive nature of the disease, leaving treatment and prevention options limited. However, there is increasing evidence of an autoimmune component, since fibrotic diseases are often accompanied by production of autoantibodies. Because exposure to silicates such as silica and asbestos can lead to both autoantibodies and pulmonary/pleural fibrosis, these exposures provide an excellent tool for examining the relationship between these outcomes. This study explored the possibility that autoantibodies induced by asbestos exposure in mice would affect fibroblast phenotype. L929 fibroblasts and primary lung fibroblasts were treated with serum IgG from asbestos- or saline-treated mice, and tested for binding using cell-based ELISA, and for phenotypic changes using immunofluorescence, laser scanning cytometry and Sirius Red collagen assay. Autoantibodies in the serum of C57Bl/6 mice exposed to asbestos (but not sera from untreated mice) bound to mouse fibroblasts. The autoantibodies induced differentiation to a myofibroblast phenotype, as demonstrated by increased expression of smooth muscle α-actin (SMA), which was lost when the serum was cleared of IgG. Cells treated with purified IgG of exposed mice produced excess collagen. Using ELISA, we tested serum antibody binding to DNA topoisomerase (Topo) I, vimentin, TGFβ-R, and PDGF-Rα. Antibodies to DNA Topo I and to PDGF-Rα were detected, both of which have been shown by others to be able to affect fibroblast phenotype. The anti-fibroblast antibodies (AFA) also induced STAT-1 activation, implicating the PDGF-R pathway as part of the response to AFA binding. These data support the hypothesis that asbestos induces AFA that modify fibroblast phenotype, and suggest a mechanism whereby autoantibodies may mediate some of the fibrotic manifestations of asbestos exposure.


Cartilage surface charge. A possible determinant in aging and osteoarthritic processes.
Polycationic labels such as cationized ferritin and colloidal iron were used to evaluate the surface negative charges over the mandibular condyles of ICR mice. The effects of neuraminidase, hyaluronidase, pronase, and collagenase on the binding of cationized ferritin and colloidal iron particles to the condylar articular surface were also studied. The results of this study clearly indicate that the surface area of the cartilaginous condyle is negatively charged and that its composition consists mainly of a collagenous material embedded within a proteinaceous matrix. With age, a substantial decrease in the density of negative charges took place along the surface area and, in particular, in the context of sialic acid residues. It is, therefore, possible that the reduction in cartilage surface charge might be associated with the onset of osteoarthritic changes commonly seen in aging humans and experimental animals.


Congenital Growth Hormone Deficiency - A Review with a Focus on Neuroimaging.
Growth hormone deficiency is an important cause of short stature in childhood. It is characterised by low growth velocity in childhood and is diagnosed by stimulation testing. Individuals with growth hormone deficiency may have other pituitary hormone deficits in addition to growth hormone deficiency. When multiple pituitary hormone deficiencies are present, abnormal pituitary anatomy, as visualised on magnetic resonance imaging (MRI), is a frequent finding. The classic triad (ectopic posterior pituitary, hypoplastic or aplastic anterior pituitary and absent/thin pituitary stalk) or variants of the classic triad are commonly seen in these patients. Volumetric sequencing allows all three planes of visualisation to be reconstructed in post-processing, allowing the radiologist to more fully evaluate pituitary anatomy. The normal dimensions of the pituitary gland vary by age and precise definitions of what constitutes a hypoplastic gland are not clearly defined in the medical literature. Having an experienced neuroradiologist interpret the MRI in patients with pituitary dysfunction is very important.


Intramolecular hydrogen bonds in canonical 2'-deoxyribonucleotides: an atoms in molecules study.
The molecular structure and relative stability of different conformers of isolated canonical 2'-deoxyribonucleotides thymidine-5'-phosphate (pdT), 2-deoxycytidine-5'-phosphate (pdC), 2-deoxyadenosine-5'-phosphate (pdA), and 2'-deoxyguanosine-5'-phosphate (pdG) were calculated using the B3LYP/6-31++G(d,p) level of theory. The results of the calculations reveal that, for all nucleotides except pdG, conformers with a syn orientation of the base do not correspond to a minimum on the potential energy surface. In the case of pdA and pdC, conformers with an orthogonal orientation of the nucleobase are located instead, north/syn conformers. These conformers as well as syn conformers of pdG are stabilized by intramolecular N-H...O hydrogen bonds. Analysis of the electron density distribution within the atoms in molecules theory reveals the presence of numerous C-H...O hydrogen bonds in the nucleotides. However, a more detailed consideration of the properties of these bonds demonstrates that many of them should be considered as strong attractive electrostatic interactions rather than true hydrogen bonds. True hydrogen bonds are represented mainly by C6/ C8-H...O5'/O-P in anti conformers and the N-H...O-P bonds in syn conformers. It is demonstrated that the values of ellipticity of the electron density at the bond critical point (BCP) and the distance between BCP and ring critical point are the most reliable indicators for determining the true intramolecular hydrogen bonds.


Step by step: microsurgical training method combining two nonliving animal models.
The learning of microsurgical techniques and the maintenance of microsurgical skills have been traditionally based on the use of living animals, mainly laboratory rats. This method although extremely valuable can be economically demanding both for the surgeon and the sponsoring institution; it also requires special training facilities that may not always be available or accessible. Furthermore ethical concerns can limit the use of living animals for training purposes. Alternative training methods, such as inert tubes and gloves have not gained popularity among surgeons since they do not offer an experience similar to that of a clinical situation. Non-living animal models include the use of chicken thighs and wings; they offer a practice experience that resembles a clinical situation to a considerable extent. This type of training is relatively cheap and easily available. The microscope and instruments required can be acquired over the internet, and the chicken pieces can be bought at the local supermarket. This approach allows a motivated trainee to rehearse different types of surgical techniques several times at a reasonable expense, helping to develop or maintain his surgical expertise if more complex facilities are not available. On the current manuscript we describe how to setup a small practice station, how to dissect the specimens, and how to practice both with the chicken thighs and with the chicken wings in a progressive fashion. This approach takes advantage on the versatility of the chicken thigh model and the small size of the chicken wing Brachial artery.


To assess the determinants of family planning uptake among women of reproductive age in rural settings, Morogoro Region, Tanzania. Protocol for a cross-sectional study.
Maternal health outcomes in Tanzania had continued to be of great concern. According the Tanzania Demographic and Health surveys, maternal mortality is still unacceptable higher. Effective use of family planning is reported to prevent maternal deaths by more than 30%. However, the prevalence of family planning uptake is still lower especially in rural areas of this country despite the fact that family planning services are provided freely and at a subsidized cost in all public and private health care facilities respectively. The broad objective is to assess the determinants of family planning uptake among women of reproductive age in rural settings, Morogoro Region, Tanzania. This study will be a cross-sectional study that will be conducted in rural areas of Morogoro Region. Study population will be women of reproductive age. Qualitative and quantitative approaches will be used to collect the data. Sampling techniques will involve stratification of urban and rural wards, simple and systematic random sampling for selection wards and households respectively and kish selection table for the selection one participant from a household. Purposive sampling will be applied to get participants for qualitative data. Data collection will be done by using semi-structured questionnaire and interview guide. Frequencies, percentages, chi-square test and logistic regression will be used to analyze the quantitative data whereas codes and themes formation will be used to analyze the qualitative data.


Symptomatic and functional recovery in depression in later life.
Functional limitations give an indication of the total impact of diseases, such as depression, on individuals health and recovery. This study examines the change in several domains of functioning over 2 years in older persons depressed at baseline (non-remitted group and remitted group after 2 years) and in a non-depressed comparison group. Data were used from a cohort study (Netherlands Study of Depression in Older persons [NESDO]) consisting of depressed older persons ≥ 60 years (N = 378) and a non-depressed comparison group (N = 132) with 2 years of follow-up (attrition rate 24%). Functional limitations (outcome) were assessed with the World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0) questionnaire every 6 months. Total scores and domain scores were used. Depression was classified according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria at baseline and at 2-year follow-up. Severity of depression (predictor) was assessed with the Inventory of Depressive Symptomatology (IDS) at 6-month intervals. Linear mixed models showed that the level of functional limitations differed between the three groups during 2 years of follow-up. The non-remitted group had the highest level of functional limitations during 2 years, followed by the remitted group. Stable low levels of functional limitations were found for the non-depressed group. Remission from depression was accompanied by improvements in functioning, however, compared to the non-depressed comparison group significant functional limitations remained. Higher severity of depression appeared as risk factor for a declining course of functioning, especially the social aspects of functioning. Participants that were more severely depressed and more functionally impaired at baseline had higher attrition rates than the participants that were included in the analytical sample. This study showed that depression in later life has long-term debilitating effects on functioning, enduring even after remission from depression. This implies that depression treatment in later life should aim broader than just symptomatic recovery, but also include functional recovery.


An unusual cause of constipation presenting to the emergency department.
A case report of a 16-year-old girl who presented to the emergency department with constipation and recurrent urinary tract infections is examined. She gave a history of persistent coccygeal pain stemming from a fall on a trampoline 1 year ago. On examination, she was found to have an abdominal mass arising from the pelvis and paraesthesia of S1-S5 dermatomes in the right leg. An abdominal radiograph showed bony erosion of the sacrum. Magnetic resonance scanning revealed a mass arising from the sacrum and subsequent biopsy diagnosed the tumour as Ewing's sarcoma.


[Middle ear schwannoma--case report].
Schwannoma is one of the common benign middle ear space tumors. The tumors may present with facial nerve paresis or palsy, otologic symptoms and/or parotid mass middle ear schwannomas may originate from the nerves of the tympanic caviti or by extensions from outside the middle ear space. Schwannomas of the facial nerve can occur along any segment, but they frequently involve the geniculate ganglion and extend proximally or distally from there. MRI and CT imaging characteristics are similar to those of vestibular schwannomas. We present the clinical and radiologic features of a middle-space schwannoma originating from facial nerve. The patient underwent middle ear exploration and mastoidectomy. The tumor was of facial nerve origin and was separated from middle ear. The pathologic diagnosis was schwannoma.


[An intervention comparison of dental hygienist visits and leaflet mailing for improvement of oral health scores in village residents].
This study was undertaken to clarify to what extentintervention by dental hygienist visits and leaflet mailing, once or three times a year, increased the dental health scores of Tobishima Village residents in a 3 year period. The oral health status and oral health score (the Oral Salutogenic Score) of 786 residents were examined in May, 2004. Of the total, 446 people had oral health scores equal to or less than 15. They were divided into three groups at random, receiving: dental hygienist visits (visit group); leaflet mailing three times a year (three times mail group); and leaflet mailing only once a year (single mail group). Oral health status and scores were examined a second time by dentists in May, 2007 and average increases of scores over 3 years were calculated for each of the three groups. The Mann-Whitney test and cost-effectiveness analysis were employed for comparisons. The average increase in oral health score was 46.2 +/- 8.1% for the visit group, 31.2 +/- 4.4% for the three times mail group and 25.0+/-5.2% single mail group over 3 years. The visit group value was significantly higher than the single mail group (P<0.05). Of the resi-dents who had an oral health score equal to or less than 15 points, increase of their oral health score those who received a dental hygienist visit had a higher than the groups who were sent leaflets. With the latter, the greater frequency of leaflet distribution was more effective for increasing the oral health score. It was concluded that visits by dental hygienists are more effective than mailing of leaflets. In addition, mailing 2 or 3 times a year is more effective than once a year.


Physical activity and psychological distress amongst Vietnamese living in the Mekong Delta.
Regular physical activity may be an important contributor to psychological well-being. This link has not been explored in ethnically distinct, low- and middle-income countries (LMIC), especially in countries affected by war. This study aimed to examine the relationship between physical activity and levels of psychological distress in an epidemiological cross-representative sample of Vietnamese living in the Mekong Delta region of Vietnam. The sample was drawn from an urban (Cn Th City) and a rural (H u Giang) region, using a multi-stage probabilistic cluster sampling frame. The measures applied included the Composite International Diagnostic Interview (CIDI 2.0) yielding 12-month prevalence rates of common mental disorders, including anxiety, mood and substance use disorders; the Phan Vietnamese Psychiatric Scale (PVPS), a culturally specific self-report measure; and the Harvard Trauma Questionnaire. The Global Physical Activity Questionnaire (GPAQ version 1) was used to measure activity. Analyses were conducted using SAS software v.9.1.3. The population was assigned to three (high, moderate and low) physical activity levels. Analyses included chi-square tests and univariable and multivariable logistic models. Physical activity was greater in males, the middle-aged group (30-54 years), those who were married, the rural population, less educated individuals and those who were employed. High physical activity was significantly associated with low levels of psychological distress (indexed by a combination of CIDI and PVPS cases identified) when controlling for socio-demographic factors and number of medical conditions). Membership of the lowest of the three physical activity groups was associated with a psychological distress odds ratio of 2.19 (95% CI 1.28-3.75). The results remained consistent when analyses were undertaken separately for males and females. Low levels of physical activity appear to be associated with greater psychological distress in the Mekong Delta of Vietnam. The association remained after adjusting for the influence of socio-demographic characteristics, exposure to past trauma, urban-rural residency and the presence of self-reported physical disorders. These data provide a foundation for exploring the role of physical activity as an adjunct to conventional interventions for common mental disorders in resource-poor LMIC countries.


Cognitive dysfunction in schizophrenia followed up over 5 years, and its longitudinal relationship to the emergence of tardive dyskinesia.
In this study, 51 chronic schizophrenic in-patients were evaluated for a range of demographic, clinical and medication variables, and followed up over five years. There was no significant overall change in cognitive function in this patient group as a whole, suggesting the absence of active disease at this stage of the illness. The only correlate of individual instances of cognitive deterioration over the study period was the emergence of new cases of tardive buccal-lingual-masticatory but not of limb-truncal dyskinesia, and the greater severity of such movement disorder. A positive family history was also identified prospectively as a predictor of the emergence of tardive dyskinesia in chronic schizophrenia.


Preserved heart rate variability identifies low-risk patients with nonischemic dilated cardiomyopathy: results from the DEFINITE trial.
The recent expansion of indications for prophylactic implantable cardioverter-defibrillator (ICD) placement in subjects with nonischemic dilated cardiomyopathy has raised concerns about the cost-effectiveness of this therapy. The purpose of this study was to identify low-risk patients with nonischemic dilated cardiomyopathy who may not require prophylactic ICD placement. This was a prospective study of 274 participants in the Defibrillators in Non-Ischemic Cardiomyopathy Treatment Evaluation (DEFINITE) trial, a randomized controlled trial that evaluated the role of prophylactic ICD placement in patients with nonischemic dilated cardiomyopathy. The patients underwent 24-hour Holter recording for analysis of heart rate variability (HRV). The primary HRV variable was the standard deviation of normal R-R intervals (SDNN). Patients with atrial fibrillation and frequent ventricular ectopy (>25% of beats) were excluded from HRV analysis (23% of patients). SDNN was categorized in tertiles, and Kaplan-Meier analysis was performed to compare survival in the three tertiles and excluded patients. The study population was 73% male, with a mean age of 59 +/- 12 years and mean left ventricular ejection fraction of 21% +/- 6%. After 3-year follow-up, significant differences in mortality rates were observed: SDNN >113 ms: 0 (0%), SDNN 81-113 ms: 5 (7%), SDNN <81 ms: 7 (10%), excluded patients: 11 (17%) (P = .03). There were no deaths in the tertile with SDNN >113 ms regardless of treatment assignment (ICD vs control). Patients with nonischemic dilated cardiomyopathy and preserved HRV have an excellent prognosis and may not benefit from prophylactic ICD placement. Patients with severely depressed HRV and patients who are excluded from HRV analysis because of atrial fibrillation and frequent ventricular ectopy have the highest mortality.


Nosology and etiology of a spirit disorder (vimbuza) in Malawi.
In this study the traditional and transitional nosology and etiology of the spirit disorder vimbuza was investigated by interviewing patients (n = 116) who were suffering from that condition. The illness concept was compared with western psychiatric classifications. As a result, 23 symptom descriptions were identified, 13 can be referred to as conversion or dissociation disorder and 7 to depressive neurosis. The remaining 3 symptom descriptions refer to an acute delusional or confusional state. Comparing the traditional and transitional symptom descriptions on the head and heart, a shift from the heart to the head becomes evident in the transitional or urban Malawian. The transitional etiology is the same as the traditional etiology, only that the transitional person more often refers to 'Too much thinking' and 'natural' than to 'bad ancestral spirits' and 'witchcraft'.


A survey of women's experiences of vaginal loss from 24 hours to three months after childbirth (the BLiPP study).
To describe the range of normal vaginal loss as reported by women from 24 hours after delivery until three months postnatally. Two health districts in the south of England. A prospective survey of women's experiences and expectations of the duration, amount and colour of vaginal loss after childbirth. The term vaginal loss includes all types of fluid loss from the vagina following childbirth. Five hundred and twenty-four women were recruited to the survey in 1995. Vaginal loss, as reported by the women, was considerably more varied in duration, amount and colour than descriptions in current midwifery textbooks. The median number of days reported for the duration of vaginal loss was 21 days and the interdecile range (10th to 90th percentile) was 10-42 days. For colour of lochia, women overall reported their vaginal loss to be more predominantly red/brown in colour and the traditional descriptions of the timing and colour phases of lochia rubra, serosa and alba are not supported by the majority of the women's experiences. Primiparous women were significantly more likely to report feelings of surprise or shock about their experiences of vaginal blood loss after the birth (odds ratio 4 [95% Confidence Interval 2-9]). Seven primiparous women (2%) were unaware that they would have a blood loss at all after the birth. The findings from this survey have been used to develop information leaflets for women and health professionals about vaginal loss following childbirth. These leaflets include descriptions of normal ranges for the colour, amount and duration of vaginal loss in the first three months after childbirth.


Antagonist selective modulation of adenosine A1 and A3 receptor pharmacology by the food dye Brilliant Black BN: evidence for allosteric interactions.
Allosteric binding sites on the adenosine receptor family represent potential therapeutic targets for a number of conditions involving metabolic stress. This study has identified Brilliant Black BN as a novel allosteric modulator of the adenosine A(1) and A(3) receptors. In addition to being a food dye and pharmaceutical excipient, Brilliant Black BN is commonly used within calcium mobilization assays to quench extracellular fluorescence. Brilliant Black BN (5-500 microM) had no significant effect on the calcium mobilization stimulated by the nonselective adenosine receptor agonist 5'-(N-ethylcarboxamido)adenosine in Chinese hamster ovary cells stably transfected with the human adenosine A(1) or A(3) receptor. Likewise, calcium mobilization and radioligand binding assays found that Brilliant Black BN (5-500 microM) did not significantly influence the antagonism mediated by 8-cyclopentyl-1,3-dipropylxanthine (100 nM) at the A(1) receptor. In contrast, the affinity of N-[9-chloro-2-(2-furanyl)[1,2,4]-triazolo[1,5-c]quinazolin-5-yl]benzene acetamide (MRS1220) at the A(3) receptor and xanthine amine congener (XAC) and XAC-X-BY630 at the A(1) and A(3) receptors was significantly decreased in the presence of 500 muM Brilliant Black BN. A reduction in XAC potency at the A(1) and A(3) receptor was achieved within 1 min of Brilliant Black BN addition, despite receptors having been pre-equilibrated with antagonist. Dissociation kinetics of the fluorescent XAC derivative, XAC-X-BY630, revealed that the decrease in affinity is probably due to a significant increase in dissociation rate of the antagonist in the presence of Brilliant Black BN. Taken together, these results suggest that Brilliant Black BN can act allosterically to modify ligand affinity at A(1) and A(3) receptors.


Leadership and the quality of care.
The importance of good leadership is becoming increasingly apparent within health care. This paper reviews evidence which shows that it has effects, not only on financial management, but on the quality of care provided. Some theories of leadership are discussed, primarily in terms of how different types of leaders might affect quality in different ways, including the effects that they might have on the stress or wellbeing of their staff which, in turn, is related to the quality of care produced. Finally, the conflicts shown in terms of leadership within the context of health care are discussed, leading to the conclusion that development programmes must be specially tailored to address the complexities of this arena.


Control of systemic iron homeostasis by the hemojuvelin-hepcidin axis.
Systemic iron homeostasis is maintained by the coordinate regulation of iron absorption in the duodenum, iron recycling of senescent erythrocytes in macrophages, and mobilization of storage iron in the liver. These processes are controlled by hepcidin, a key iron regulatory hormone. Hepcidin is a 25-amino acid peptide secreted predominantly from hepatocytes. It downregulates ferroportin, the only known iron exporter, and therefore inhibits iron efflux from duodenal enterocytes, macrophages, and hepatocytes into the circulation. Hepcidin expression is regulated positively by body iron load. Although the underlying mechanism of iron-regulated hepcidin expression has not been fully elucidated, several proteins have been identified that participate in this process. Among them, hemojuvelin (HJV) plays a particularly important role. HJV undergoes complicated post-translational processing in an iron-dependent manner, and it interacts with multiple proteins that are essential for iron homeostasis. In this review, I focus on the recent findings that elucidate the role of HJV and its interacting partners in the modulation of hepatic hepcidin expression.