TGF-β promotes fibrosis after severe acute kidney injury by enhancing renal macrophage infiltration.
TGF-β signals through a receptor complex composed of 2 type I and 2 type II (TGF-βRII) subunits. We investigated the role of macrophage TGF-β signaling in fibrosis after AKI in mice with selective monocyte/macrophage TGF-βRII deletion (macrophage TGF-βRII-/- mice). Four weeks after injury, renal TGF-β1 expression and fibrosis were higher in WT mice than macrophage TGF-βRII-/- mice, which had decreased renal macrophages. The in vitro chemotactic response to f-Met-Leu-Phe was comparable between bone marrow-derived monocytes (BMMs) from WT and macrophage TGF-βRII-/- mice, but TGF-βRII-/- BMMs did not respond to TGF-β. We then implanted Matrigel plugs suffused with either f-Met-Leu-Phe or TGF-β1 into WT or macrophage TGF-βRII-/- mice. After 6 days, f-Met-Leu-Phe induced similar macrophage infiltration into the Matrigel plugs of WT and macrophage TGF-βRII-/- mice, but TGF-β induced infiltration only in WT mice. We further determined the number of labeled WT or TGF-βRII-/- BMMs infiltrating into WT kidneys 20 days after ischemic injury. There were more labeled WT BMMs than TGF-βRII-/- BMMs. Therefore, macrophage TGF-βRII deletion protects against the development of tubulointerstitial fibrosis following severe ischemic renal injury. Chemoattraction of macrophages to the injured kidney through a TGF-β/TGF-βRII axis is a heretofore undescribed mechanism by which TGF-β can mediate renal fibrosis during progressive renal injury.


[Bioethical dimensions of medical care in the elderly].
This editorial examines the challenges posed by the current epidemiological transition towards ageing of societies, against the background of medical technologies: life-saving, life-sustaining and life-enhancing. Increased life expectancy among the elderly, compression of morbidity in the last year of life, cost containment in health-care delivery and humane treatment are elements of the dilemma facing modern medicine confronted to the aged. Technical success and medicalization of life are doomed to failure if the necessary reflection on what is proper, what is good and what is fair or just is not incorporated into everyday practice. These bioethical dimensions' should be reformulated at the level of the individual professional, the institutional environment and the social milieu. Aside from gloomy predictions about the future, the challenges imposed by treatment of the elderly are seen as invigorating stimuli for the continuous improvement of medical care.


An in vitro model for polymorphonuclear-leukocyte-induced injury to an extracellular matrix. Relative contribution of oxidants and elastase to fibronectin release from amnionic membranes.
Alteration of the extracellular matrix by inflammatory cells is believed to be important in both lung injury and the subsequent restoration of lung architecture. Here we describe the results of the interaction between an acellular human amnionic membrane model and stimulated human polymorphonuclear neutrophils (PMN) in vitro. Polymorphonuclear neutrophil suspensions were placed on one surface of the amnion, and either the chemotactic peptide FMLP or the cell membrane activator phorbol myristate acetate (PMA) was placed on the opposite side of the amnion. Stroma and basement membrane sides of the amnion were separately exposed to the PMN. The PMN suspension was removed and centrifuged, and the supernatant was assayed for superoxide anion (O2-.) and for elastase activity. Injury to the acellular amnion was evaluated by transmission electron microscopy and by measurement of fibronectin (FN) released from the membrane matrix. Although both stimulants cause a concentration-dependent release of O2-., only PMA stimulated elastase release. These effects were similar when either the stroma or the basement membrane side was exposed to PMN. PMA-stimulated cells and supernatants from PMA-stimulated cells caused solubilization of membrane at different incubation times. Electron microscopy confirmed the disruption of the basement membrane of the amnion by PMA-stimulated PMN. Oxidant scavengers (SOD and catalase) did not prevent matrix degradation, and elastase inhibition by a specific chloromethylketone inhibitor diminished FN release on both sides of the amnion by activated PMN supernatants, but only on the basement membrane side by intact PMN. We conclude that in this model, elastase rather than oxygen radicals solubilizes FN from the matrix.


Polymer-based nanoparticles for protein delivery: design, strategies and applications.
Therapeutic proteins have attracted significant attention as they perform vital roles in various biological processes. The delivery of therapeutic proteins to target sites is, however, challenging due to their intrinsic sensitivity to different environmental conditions. Polymeric nanoparticles (NPs) can offer not only physical protection from environmental stimuli but also targeted delivery of such proteins to specific sites. In particular, NPs containing charged polymers are preferred for many applications as they provide gentle protection through electrostatic interactions. Moreover, most organs exhibit a specific pH, and by tuning the extent of the electrostatic interactions and contact duration between the target organ and polymeric NPs, the intracellular uptake of the latter and thus long-term therapeutic efficacy can be optimized. In this article, we will critically discuss the design considerations of charged polymeric NPs, strategies for and routes of protein delivery and how these are influenced depending on the choice of delivery route.


A single centre experience in circumcision of haemophilia patients: Izmir protocol.
Haemophiliacs and their families consider that circumcision is a very important step to become a member of society and it is a social obligation for men in Turkey. Although bleeding risk is high, almost all haemophiliacs would like to be circumcised in Turkish society. The aim of this study was to evaluate our experience in circumcision of haemophilia patients and define efficacy, safety and complication rates of our protocol, called 'Izmir protocol'. In this study, we retrospectively reviewed medical records of 50 patients with haemophilia who underwent circumcision at our hospital according to Izmir protocol between 1996 and 2009. Oral tranexamic acid and fibrin glue were used in all children. One hour before the operation, first dose of factor concentrate was given. After reaching a plasma factor level of around 90-100%, the prepuce was incised circumferentially and excised using Gomco clamp or open technique under general anaesthesia. Intermittent injections of factor concentrate were given every 12 for 48 h. While the first two doses were given at higher amount to achieve or continue plasma factor level at 90-100%, in the last three doses, the aim was to maintain the plasma factor level at 50-60%. Forty-eight hours after the circumcision, patients were discharged. Three patients (6%) showed bleeding complication and all were resolved easily. All had at least one excuse from the protocol (Lower doses of factor concentrates was used in 2, tranexamic acid was not used in 2). Izmir protocol is safe, cheap and easy to carry out.


Synthesis and self-assembling properties of polymerizable organogelators.
In this paper we report the development of a family of polymerizable urea derivatives that are gelators for organic solvents. The design involves amino-acid-based urea derivatives containing methacrylate functional groups. Several of the bis-ureas show excellent gelation properties in a variety of organic solvents at very low concentrations (1.5 mM). The self-assembling properties of these compounds were studied by X-ray powder diffraction, optical microscopy, and electronic microscopy. The molecules self-assemble into fibrous aggregates as indicated by scanning electron microscopy. Depending on the nature of the monomeric unit, the structure of the aggregates ranges from small to large fibers and planar sheets. In polar solvents, the molecules exhibit multilamellar packing modes. The organogels can be polymerized by photoirradiation leading to significant increases in stability as indicated by changes in phase-transition temperature. The morphology of the aggregates was seen to maintain a similar structure both before and after irradiation. This method provides a novel type of polymer with designed self-assembling architecture and also affords to a route to stabilized polymer gels.


Urinary endothellin-1 level in children with pyelonephritis and hydronephrosis.
Hydronephrosis is a common finding in patients with urinary tract infection (UTI). Endothellin-1 (ET-1) is a potent vasoactive peptide that has vasoconstrictive effects. It has been shown that urinary ET-1 increases in urinary obstructions. In this study, we measured the urinary ET-1 level in patients with UTI and hydronephrosis of various causes. In this case-control study, we evaluated the urinary ET-1 level in 45 patients who had UTI and hydronephrosis, serving as a case group, and 45 patients who had UTI without hydronephrosis, serving as a control group. Urinary ET-1 was quantified using enzyme-linked immunosorbent assay and urinary creatinine (Cr) by Jaffe method. To rule out the effect of urinary flow rate, the urinary ET-1 to Cr correlation was considered for analysis of the results. The mean age of the patients in the case and control groups was 36.5 ± 27.2 and 26.2 ± 15.5 months, respectively (P >0.01). The mean urinary ET-1 was 89.6 ± 41.7 pg/dL in the case group and 29.3 ± 26 pg/dL in the control group, P <0.001. The mean urinary ET-1 was 121 ± 55.4 pg/dL in patients who had grade 4 hydronephrosis. We conclude that urinary ET-1 was significantly higher in the obstructed than in non-obstructed cases. Urinary ET-1 could be a useful marker that can be utilized in young children for diagnosis of hydronephrosis, especially obstructive cases.


CIRBP protects H9C2 cells against myocardial ischemia through inhibition of NF-κB pathway.
Myocardial ischemia is a major cause of death and remains a disease with extremely deficient clinical therapies and a major problem worldwide. Cold inducible RNA-binding protein (CIRBP) is reported to be involved in multiple pathological processes, including myocardial ischemia. However, the molecular mechanisms of myocardial ischemia remain elusive. Here, we first overexpressed CIRBP by transfection of pc-CIRBP (pcDNA3.1 containing coding sequenced for CIRBP) and silenced CIRBP by transfection of small interfering RNA targeting CIRBP (siCIRBP). pcDNA3.1 and the negative control of siCIRBP (siNC) were transfected into H9C2 cells to act as controls. We then constructed a cell model of myocardial ischemia through culturing cells in serum-free medium with hypoxia in H9C2 cells. Subsequently, AlamarBlue assay, flow cytometry and western blot analysis were used, respectively, to assess cell viability, reactive oxygen species (ROS) level and apoptosis, and expression levels of IκBα, p65 and Bcl-3. We demonstrated that CIRBP overexpression promoted cell proliferation (P<0.001), inhibited cell apoptosis (P<0.05), reduced ROS level (P<0.001), down-regulated phosphorylated levels of IκBα and p65 (P<0.01 or P<0.001), and up-regulated expression of Bcl-3 (P<0.001) in H9C2 cells with myocardial ischemia. The influence of CIRBP knockdown yielded opposite results. Our study revealed that CIRBP could protect H9C2 cells against myocardial ischemia through inhibition of NF-κB pathway.


Thalamocortical Connectivity and Microstructural Changes in Congenital and Late Blindness.
There is ample evidence that the occipital cortex of congenitally blind individuals processes nonvisual information. It remains a debate whether the cross-modal activation of the occipital cortex is mediated through the modulation of preexisting corticocortical projections or the reorganisation of thalamocortical connectivity. Current knowledge on this topic largely stems from anatomical studies in animal models. The aim of this study was to test whether purported changes in thalamocortical connectivity in blindness can be revealed by tractography based on diffusion-weighted magnetic resonance imaging. To assess the thalamocortical network, we used a clustering method based on the thalamic white matter projections towards predefined cortical regions. Five thalamic clusters were obtained in each group representing their cortical projections. Although we did not find differences in the thalamocortical network between congenitally blind individuals, late blind individuals, and normal sighted controls, diffusion tensor imaging (DTI) indices revealed significant microstructural changes within thalamic clusters of both blind groups. Furthermore, we find a significant decrease in fractional anisotropy (FA) in occipital and temporal thalamocortical projections in both blind groups that were not captured at the network level. This suggests that plastic microstructural changes have taken place, but not in a degree to be reflected in the tractography-based thalamocortical network.


5S rRNA gene deletions cause an unexpectedly high fitness loss in Escherichia coli.
In Escherichia coli, ribosomal RNAs (16S, 23S and 5S) are co-transcribed in a highly regulated manner from seven genomically dispersed operons. Previous studies on the cellular effects of altered levels of two of these rRNAs (16S and 23S) have been useful in better understanding the regulation of rRNA expression. Furthering these studies, we have investigated the effect of 5S rRNA deficiencies on cell fitness through the sequential deletion of 5S rRNA genes. Our findings indicate that the loss of 5S rDNA from multiple genes decreases cell fitness more rapidly than loss of a similar number of 16S and 23S rRNA genes. These results suggest that the cell's innate ability to up-regulate rRNA operons does not compensate for 5S rRNA deficiencies, as was previously shown for 16S and 23S rRNAs. A plasmid-borne 5S rRNA gene is able to compensate for the deleted 5S rRNA genes.


Usefulness of myocardial perfusion SPECT in patients with left bundle branch block and previous myocardial infarction.
The diagnostic value of myocardial perfusion scintigraphy in patients with left bundle branch block (LBBB) and previous acute myocardial infarction has not been evaluated. To determine the utility of single photon emission computed tomography (SPECT) in patients with LBBB and previous acute myocardial infarction. Seventy two consecutive patients with permanent LBBB and previous acute myocardial infarction were studied with stress-rest SPECT using 99mTc compounds. The same stress procedures were followed in all patients: (1) exercise alone when it was sufficient; (2) exercise plus simultaneous administration of dipyridamole if exercise was insufficient. In 26 of 28 patients (93%) who had a Q wave acute myocardial infarct before the development of LBBB, there was concordance between abnormal Q waves and rest SPECT in the localisation of myocardial necrosis (kappa = 0.836; p = 0.0001). In 48 patients who had coronary angiography, the positive predictive value of exercise (+dipyridamole) myocardial SPECT for the diagnosis of left anterior descending coronary artery stenosis was 93%, for left circumflex coronary artery stenosis, 96%, and for right coronary artery stenosis, 89%. Specificity values were 83%, 91%, and 69%, respectively. However, sensitivity (69%, 64%, and 89%) and negative predictive values (48%, 46%, and 82%) were suboptimal. Rest myocardial perfusion SPECT with technetium compounds is useful for localising healed myocardial infarction in patients with LBBB, and exercise (+dipyridamole) SPECT has a high positive predictive value and specificity for the diagnosis of coronary stenosis in these patients.


A multi-omics approach unravels metagenomic and metabolic alterations of a probiotic and synbiotic additive in rainbow trout (Oncorhynchus mykiss).
Animal protein production is increasingly looking towards microbiome-associated services such as the design of new and better probiotic solutions to further improve gut health and production sustainability. Here, we investigate the functional effects of bacteria-based pro- and synbiotic feed additives on microbiome-associated functions in relation to growth performance in the commercially important rainbow trout (Oncorhynchus mykiss). We combine complementary insights from multiple omics datasets from gut content samples, including 16S bacterial profiling, whole metagenomes, and untargeted metabolomics, to investigate bacterial metagenome-assembled genomes (MAGs) and their molecular interactions with host metabolism. Our findings reveal that (I) feed additives changed the microbiome and that rainbow trout reared with feed additives had a significantly reduced relative abundance of the salmonid related Candidatus Mycoplasma salmoninae in both the mid and distal gut content, (II) genome resolved metagenomics revealed that alterations of microbial arginine biosynthesis and terpenoid backbone synthesis pathways were directly associated with the presence of Candidatus Mycoplasma salmoninae, and (III) differences in the composition of intestinal microbiota among feed types were directly associated with significant changes of the metabolomic landscape, including lipids and lipid-like metabolites, amino acids, bile acids, and steroid-related metabolites. Our results demonstrate how the use of multi-omics to investigate complex host-microbiome interactions enable us to better evaluate the functional potential of probiotics compared to studies that only measure overall growth performance or that only characterise the microbial composition in intestinal environments. Video Abstract.


Exclusive enteral nutritional therapy can relieve inflammatory bowel stricture in Crohn's disease.
To examine the efficiency of exclusive enteral nutrition (EEN) in relieving inflammatory bowel stricture in patients with Crohn's disease (CD). Patients with CD usually develop bowel strictures due to transmural edema of intestinal wall, which can potentially be managed with conservative medical treatment. Previous studies showed that EEN therapy could induce clinical remission through its anti-inflammation effect. We achieved a prospective observational study. CD patients with inflammatory bowel stricture were preliminarily differentiated from a fibrous one, and further treated with EEN therapy for 12 weeks. Demographics and clinical variables were recorded. Nutritional (body mass index, albumin, pre-albumin, transferrin, etc.), inflammatory (C-reactive protein, erythrocyte sedimentation rate, white blood cell, etc.), and radiologic parameters (bowel wall thickness, luminal diameter, and luminal cross-sectional area) were evaluated at baseline, week 4, and week 12, respectively. Between May 2012 and January 2013, 65 patients with CD were preliminarily diagnosed with inflammatory bowel stricture and 6 patients were further excluded. Among the remaining 59 cases, 50 patients (84.7%) finished the whole EEN treatment, whereas the other 9 patients (15.3%) gained progressive bowel obstruction resulting in surgery. Intention-to-treat analyses showed that 48 patients (81.4%) achieved symptomatic remission, 35 patients (53.8%) achieved radiologic remission, and 42 patients (64.6%) achieved clinical remission. Among those patients who complete the whole EEN therapy, inflammatory, nutritional, and radiologic parameters improved significantly compared with baseline. Of note, the average luminal cross-sectional area at the site of stricture increased approximately 331% at week 12 (195.7 ± 18.79 vs. 59.09 ± 10.64 mm, P<0.001). EEN therapy can effectively relieve inflammatory bowel stricture in CD, which replenishes roles of enteral nutrition in the treatment of CD. Further studies are expected to investigate the underlying mechanisms of this effect in the future.


Bladder carcinoma. Long-term survival and late recurrence.
The records of 115 patients with bladder carcinoma and five years or longer post-diagnosis survival were surveyed after reclassification of the histologic specimens according to UICC. Late recurrence, 5-10 years after the initial diagnosis, was found in 39 patients (34%). Fourteen patients (12%) had died of bladder carcinoma during the observation period, generally as a consequence of transformation to higher tumour stage. Intercurrent disease, i.e. cardiovascular disorders or a second malignancy, led to 21 intercurrent deaths (18%). Large size and high grade of the primary tumour, but not multiplicity, were significantly associated with poorer long-term prognosis. The study underlines the importance of close long-term follow-up of patients with bladder carcinoma in order to permit early detection and treatment or recurrent tumours.


Refinement and reproducibility of histologic criteria for the assessment of microscopic lesions in patients with gastroesophageal reflux disease: the Esohisto Project.
Standardized criteria for assessing microscopic esophageal lesions are required to test their utility as markers of gastroesophageal reflux disease (GERD). To finalize draft criteria for assessing microscopic esophageal lesions associated with gastroesophageal reflux and to test them for interobserver agreement. An international group of gastrointestinal pathologists was convened to finalize, using a consensus-based approach, draft criteria for recognizing microscopic esophageal lesions. Finalized criteria were retested for interobserver variability by four of the pathologists using 120 digitized esophageal biopsy slides from patients with GERD. The finalized criteria included further clarification on lesion definitions and new guidance on how to select the area for assessing each lesion. This latter refinement was guided by the high interobserver agreement observed when draft criteria were previously applied to biopsies where the assessment area was preselected. When finalized criteria were applied in the current study to digitized biopsies without a preselected assessment area, the pairwise agreement was 73-97% for basal cell hyperplasia, papillary elongation, intraepithelial eosinophil, neutrophil and mononuclear cell numbers, and active/healed erosions, with slightly lower agreement (64%) for dilated intercellular spaces (DIS). When a combined severity score was applied, the level of agreement was 77%. The mean kappa ranged from fair to high (0.26-0.77) for individual lesions and was high for the combined score (0.64). These levels of agreement are comparable with or higher than those for other accepted histologic definitions. Further steps include clinical validation of these criteria by correlating microscopic lesions with clinical variables such as esophageal acid exposure.


[Scientific explanation as a language and its application to psychiatry].
The concept of scientific explanation plays a crucial role in the methodological discussion within psychiatry. This article shows that since scientific explanation employs a language of its own, its syntactic, semantic, and pragmatic dimensions must therefore be analysed with the help of semiotics. The pragmatic dimension is given particular attention because, hitherto, it has been comparatively neglected in the methodological discussion within psychiatry. Furthermore, the concept of explanation is viewed as a problem sui generis and investigated, to begin with, independently of problems such as causality and teleology. By means of the problem of the ambiguity of inductive-statistical explanations, it is shown that scientific explanations which employ statistical laws without taking into consideration the pragmatic concept of the state of knowledge must necessarily come to incomplete and/or contradictory results. The state of knowledge (K) is defined as the set of propositions which are accepted as true by a person (x) at a given time (t). A more precise analysis shows that, within a given state of knowledge, an accepted proposition is generally seen as more or less probable where it can be assigned a value of credibility (B) which lies between 0 and 1. The force of an explanation, in the pragmatic-informative sense, thus consists in the fact that an explanation can increase the credibility value of an explanandum-event (E) through a presentation of particular circumstances (C) and of general laws (T) such that the following holds: BTUC(E) greater than B(E). Depending on the level of the absolute value of BTUC(E), a gradual differentiation is made with respect to the quality of pragmatic-informative explanations. The various types of explanation can be differentiated according to the type of arguments employed in the explanans of a pragmatic-informative explanation; the most important members of this family of explanations are the causal, functional, teleological, and dispositional elements. Finally, the concept of explanation is differentiated from that of understanding, another key concept in psychiatry. In this respect, it is important that the incorporation of pragmatic dimensions into scientific explanation must not be equated with the use of psychological categories; the latter are of importance solely for the concept of understanding. Furthermore, the notion is rejected that in psychiatry a higher value is to be attributed to explanation than to understanding. Rather, both concepts represent different approaches to psychiatric disorders, whereby each employs a language of its own.


Flexible gating between subspaces by a disinhibitory motif: a neural network model of internally guided task switching.
Behavioral flexibility relies on the brain's ability to switch rapidly between multiple tasks, even when the task rule is not explicitly cued but must be inferred through trial and error. The underlying neural circuit mechanism remains poorly understood. We investigated recurrent neural networks (RNNs) trained to perform an analog of the classic Wisconsin Card Sorting Test. The networks consist of two modules responsible for rule representation and sensorimotor mapping, respectively, where each module is comprised of a circuit with excitatory neurons and three major types of inhibitory neurons. We found that rule representation by self-sustained persistent activity across trials, error monitoring and gated sensorimotor mapping emerged from training. Systematic dissection of trained RNNs revealed a detailed circuit mechanism that is consistent across networks trained with different hyperparameters. The networks' dynamical trajectories for different rules reside in separate subspaces of population activity; they become virtually identical and performance was reduced to chance level when dendrite-targeting somatostatin-expressing interneurons were silenced, demonstrating that rule-based gating critically depends on the disinhibitory motif.


Development of a microsphere-based immunoassay for the serological diagnosis of equine trypanosomosis.
Trypanozoon infections in equids are caused by three parasite species in the Trypanozoon subgenus: Trypanosoma equiperdum, T. brucei and T. evansi. They are respectively responsible for infectious diseases dourine, nagana and surra. Due to the threat that Trypanozoon infection represents for international horse trading, accurate diagnostic tests are crucial. Current tests suffer from poor sensitivity and specificity, due in the first case to the transient presence of parasites in the blood and in the second, to antigenic cross-reactivity among Trypanozoon subspecies. This study was designed to develop a microsphere-based immunoassay for diagnosing equine trypanosomosis. We tested beads coated with eight Trypanosoma spp. recombinant antigens: enolase, GM6, PFR1, PFR2, ISG65, VSGat, RoTat1.2 and JN2118HU. Of these, GM6 was identified as the best candidate for the serological diagnosis of Trypanozoon infections in equids. Using a receiver operating characteristic (ROC) analysis on 349 equine sera, anti-GM6 antibodies were detected with an AUC value of 0.994 offering a sensitivity of 97.9% and a specificity of 96.0%. Our findings show that the GM6 antigen is a good target for diagnosing equine trypanosomosis using a microsphere-based immunoassay. This promising assay could be a useful alternative to the official diagnostic tool for equine trypanosomosis.


Two Stacked Coins Mimicking an Esophageal Button Battery: A Case Presentation and Review of the Literature.
As button battery (BB) ingestion has become a popular topic with growing public awareness in recent years, pediatric otolaryngologists maintain a high index of suspicion for this diagnosis. Several recent reports have revealed the possibility for benign objects to masquerade as BBs, such as two coins stacked together or a coin with different metals in concentric rings. A 4-year-old female presented to the ED after unwitnessed ingestion of a foreign body. The child was reportedly seen playing with her sister's coin collection prior to the acute onset of drooling and dysphagia. She was vitally stable and without any shortness of breath, stridor, or wheezing. Plain film X-ray revealed a round, metallic object with a double density on the frontal view and beveled step-off on the lateral view at the level of the thoracic inlet. Due to high radiographic concern for BB ingestion, the patient was taken emergently to the operating room for a rigid esophagoscopy. A metallic object was seen at the thoracic inlet and removed with Magill forceps. The object was found to be two coins stuck together, with a smaller coin in the center of a larger coin mimicking the shape of a BB. The patient was discharged the next day without complication. This case highlights stacked coins as a radiologic masquerade for BBs as well as the emphasis on prompt esophagoscopy for both identification and removal. Radiographic densities alone cannot be relied upon to distinguish BBs from more innocuous objects, and esophagoscopy remains the mainstay of management for pediatric esophageal foreign bodies.


A new probabilistic relaxation scheme.
Let a vector of probabilities be associated with every node of a graph. These probabilities define a random variable representing the possible labels of the node. Probabilities at neighboring nodes are used iteratively to update the probabilities at a given node based on statistical relations among node labels. The results are compared with previous work on probabilistic relaxation labeling, and examples are given from the image segmentation domain. References are also given to applications of the new scheme in text processing.


All-Cause and Cause-Specific Mortality among Patients with Vitiligo: A Nationwide Population-Based Study in Korea.
Vitiligo is a common autoimmune skin disorder; however, there is limited information about risks of mortality among patients with vitiligo. Therefore, we aimed to investigate the mortality in patients with vitiligo. A population-based cohort study was conducted using the data linkage of the National Health Insurance Service database and the National Death Registry. Patients with incident vitiligo were matched with sociodemographic factors-matched controls without vitiligo in a 1:5 ratio. All-cause and cause-specific mortalities were compared between patients with vitiligo and controls. In total, 107,424 patients with incident vitiligo and 537,120 matched controls were included. The mortality rates were 34.8 and 45.3 per 10,000 person-years in patients and controls, respectively. Patients with vitiligo showed a significantly lower risk of mortality (adjusted hazard ratio = 0.75, 95% confidence interval = 0.72-0.78). The cause-specific mortality from infectious diseases, oncologic diseases, hematologic diseases, endocrine diseases, neurologic diseases, cardiovascular diseases, respiratory diseases, and renal/urogenital disease was significantly lower in patients with vitiligo. Patients with vitiligo were associated with a lower risk of mortality, suggesting that vitiligo-associated autoimmunity might contribute to reduced morbidity and mortality.


Preinjury and Postinjury Factors That Predict Sports-Related Concussion and Clinical Recovery Time.
To evaluate the relationship between preinjury risk factors (RFs) and subsequent occurrence of concussion and examine whether preinjury RFs or postinjury assessments predict clinical recovery in collegiate athletes. Risk factors (sex, sport, and self-report history of concussion, migraine, attention-deficit disorder, learning disability, depression, and anxiety) and Sport Concussion Assessment Tool (SCAT), depression/anxiety screenings, and neuropsychological testing were obtained before the season. For athletes who sustained concussion, RFs, postinjury SCAT, neuropsychological assessment, and clinical recovery were assessed. We assessed 1152 athletes (69% male) at baseline and 145 (75% male) after subsequent concussion diagnosis. Only sport type (Wald = 40.29, P = 0.007) and concussion history (Wald = 9.91, P = 0.007) accounted for unique variance in subsequent concussion. Of athletes followed until full recovery, mean days until symptom-free (DUSF) was 9.84 ± 11.11 days (n = 138, median = 5 days, range = 1-86) and mean days until full return to play (DUFRTP) was 20.21 ± 19.17 (n = 98, median = 20.21, range = 4-150). None of the RFs or baseline testing measures were associated with DUSF or DUFRTP (P's > 0.05). After injury, athletes who reported more total symptoms (rs = 0.31, P < 0.001) and higher symptom severity (rs = 0.33, P < 0.001) exhibited longer DUSF. Days until symptom-free correlated with DUFRTP (rs = 0.75, P < 0.001). Among athletes assessed within 2 days after injury, DUSF was associated with Immediate Postconcussion Assessment and Cognitive Test visual motor (rs = -0.31, P = 0.004), reaction time (rs = 0.40, P < 0.001), and symptom score (rs = 0.54, P < 0.001). Only sport type and concussion history predicted subsequent occurrence of concussion, and none of the RFs or baseline measures predicted clinical recovery. Immediate postinjury assessments, including symptom number and severity, and select clinical measures predicted longer clinical recovery.


[Mechanism of decrease in noradrenaline content in the myocardium under the effect of various industrial poisons].
Alteration in content of catecholamines, DOPA and the monoaminooxidase activity (MAO) were observed in rat myocardium under prolonged administration of cobalt (5 mg of the metal per 1 kg of body weight). A correlation was observed between the decrease in noradrenaline content and the MAO activation. In myocardium content of noradrenaline was approximately constant in simultaneous administration of an MAO inhibitor nyalamide (20 mg/kg of body weight) and cobalt within 10 days. In heart muscle the adrenaline concentration did not depend on the MAO activity; content of the amine was increased when the content of noradrenaline decreased and the MAO activity increased.


[Clinical relevance of vertebral fractures].
Existing vertebral fractures are often missed because they are clinically difficult to diagnose, because recognition of the fractures on radiological images is difficult or because the clinical relevance of the diagnosis of vertebral fractures may be underestimated by the treating physician. There is every reason to focus on the diagnosis and treatment of vertebral fractures: they are strong predictors of new vertebral and nonvertebral fractures, they are associated with significant morbidity, and, particularly importantly, effective anti-osteoporotic drugs are available. In the diagnostic work-up, vertebral morphometry in combination with dual energy X-ray absorptiometry (DEXA) can be valuable. The disadvantage of the poorer image quality, particularly in the higher thoracic region, is amply compensated for by the efficiency and diagnostic convenience to the patients and reduced exposure to radiation.


Voltage-Gated Sodium Channels as Insecticide Targets.
Voltage-gated sodium channels are critical for the generation and propagation of action potentials. They are the primary target of several classes of insecticides, including DDT, pyrethroids and sodium channel blocker insecticides (SCBIs). DDT and pyrethroids preferably bind to open sodium channels and stabilize the open state, causing prolonged currents. In contrast, SCBIs block sodium channels by binding to the inactivated state. Many sodium channel mutations are associated with knockdown resistance (kdr) to DDT and pyrethroids in diverse arthropod pests. Functional characterization of kdr mutations together with computational modelling predicts dual pyrethroid receptor sites on sodium channels. In contrast, the molecular determinants of the SCBI receptor site remain largely unknown. In this review, we summarize current knowledge about the molecular mechanisms of action of pyrethroids and SCBIs, and highlight the differences in the molecular interaction of these insecticides with insect versus mammalian sodium channels.


Extracellular Subunit Interactions Control Transitions between Functional States of Acid-sensing Ion Channel 1a.
Acid-sensing ion channels (ASICs) are neuronal, voltage-independent Na(+) channels that are transiently activated by extracellular acidification. They are involved in pain sensation, the expression of fear, and in neurodegeneration after ischemic stroke. Our study investigates the role of extracellular subunit interactions in ASIC1a function. We identified two regions involved in critical intersubunit interactions. First, formation of an engineered disulfide bond between the palm and thumb domains leads to partial channel closure. Second, linking Glu-235 of a finger loop to either one of two different residues of the knuckle of a neighboring subunit opens the channel at physiological pH or disrupts its activity. This suggests that one finger-knuckle disulfide bond (E235C/K393C) sets the channel in an open state, whereas the other (E235C/Y389C) switches the channel to a non-conducting state. Voltage-clamp fluorometry experiments indicate that both the finger loop and the knuckle move away from the β-ball residue Trp-233 during acidification and subsequent desensitization. Together, these observations reveal that ASIC1a opening is accompanied by a distance increase between adjacent thumb and palm domains as well as a movement of Glu-235 relative to the knuckle helix. Our study identifies subunit interactions in the extracellular loop and shows that dynamic changes of these interactions are critical for normal ASIC function.


Hierarchical tree snipping: clustering guided by prior knowledge.
Hierarchical clustering is widely used to cluster genes into groups based on their expression similarity. This method first constructs a tree. Next this tree is partitioned into subtrees by cutting all edges at some level, thereby inducing a clustering. Unfortunately, the resulting clusters often do not exhibit significant functional coherence. To improve the biological significance of the clustering, we develop a new framework of partitioning by snipping--cutting selected edges at variable levels. The snipped edges are selected to induce clusters that are maximally consistent with partially available background knowledge such as functional classifications. Algorithms for two key applications are presented: functional prediction of genes, and discovery of functionally enriched clusters of co-expressed genes. Simulation results and cross-validation tests indicate that the algorithms perform well even when the actual number of clusters differs considerably from the requested number. Performance is improved compared with a previously proposed algorithm. A java package is available at http://www.cs.bgu.ac.il/~dotna/ TreeSnipping


Thrombin-induced exposure and prostacyclin inhibition of the receptor for factor VIII/von Willebrand factor on human platelets.
The receptor for Factor VIII/von Willebrand factor (F. VIIIVWF) is readily available on circulating platelets. We have found that the stimulation of platelets with traces of thrombin at concentrations that are generated physiologically (0.008 U-0.05 U/ml) induced concentration-dependent binding of 125I-labeled F. VIIIVWF in a steady-state system. The binding induced by thrombin was specific because it was inhibited by a 100-fold molar excess of unlabeled F. VIIIVWF factor, by rabbit monospecific antibody against Factor VIII, and was not inhibited by an excess of fibrinogen or fibronectin. Binding induced by thrombin required metabolically active platelets, in contrast to a system with ristocetin that also prompted binding to glutaraldehyde-treated platelets. The thrombin effects on binding of 125I-F. VIIIVWF was not observed when platelets were washed with EDTA-containing buffers; EDTA and EGTA both inhibited thrombin-induced binding. Platelet membrane glycoproteins were required because enzymatic stripping od them from the platelet surface with chymotrypsin reduced binding 2.5-5.0-fold. Prostacyclin, in the concentration range of 1 to 50 nM, had two distinct effects on the receptor for F. VIIIWVF: (a) it prevented exposure of this receptor when added 10 min before thrombin, and (b) it reversed the binding of 125I-F. VIIIVWF to the platelet receptor when added 30 min after thrombin and the ligand, ie., when binding was at equilibrium. The dual effect of prostacyclin on the receptor for F. VIIIVWF was reproduced by dibutyryl cyclic AMP.


Retina S antigen-induced uveitis. The efficacy of cyclosporine and corticosteroids in treatment.
This study compares the efficacy of cyclosporine and corticosteroids in the treatment of retina S antigen-induced uveitis (experimental autoimmune uveitis). Forty guinea pigs were immunized with retina S antigen in complete Freund's adjuvant to induce uveitis. After 16 days, animals were divided into groups that received a two-week course of daily intramuscular injections of cyclosporine, corticosteroids, both drugs, or saline. Eyes were graded by a masked retinal specialist for amount of vitreous cells by biomicroscopy, and after enucleation by a masked ocular pathologist for histologic evidence of inflammation. Clinically and histopathologically, animals treated with cyclosporine, or cyclosporine and corticosteroids, had statistically significant reduction of intraocular inflammation compared with controls. Corticosteroids alone had a less beneficial effect. The combined use of cyclosporine and corticosteroids, at the single dose tested, did not demonstrate synergism.


Trafficking highways to the intercalated disc: new insights unlocking the specificity of connexin 43 localization.
With each heartbeat, billions of cardiomyocytes work in concert to propagate the electrical excitation needed to effectively circulate blood. Regulated expression and timely delivery of connexin proteins to form gap junctions at the specialized cell-cell contact region, known as the intercalated disc, is essential to ventricular cardiomyocyte coupling. We focus this review on several regulatory mechanisms that have been recently found to govern the lifecycle of connexin 43 (Cx43), the short-lived and most abundantly expressed connexin in cardiac ventricular muscle. The Cx43 lifecycle begins with gene expression, followed by oligomerization into hexameric channels, and then cytoskeletal-based transport toward the disc region. Once delivered, hemichannels interact with resident disc proteins and are organized to effect intercellular coupling. We highlight recent studies exploring regulation of Cx43 localization to the intercalated disc, with emphasis on alternatively translated Cx43 isoforms and cytoskeletal transport machinery that together regulate Cx43 gap junction coupling between cardiomyocytes.


MiRNA-10b Reciprocally Stimulates Osteogenesis and Inhibits Adipogenesis Partly through the TGF-β/SMAD2 Signaling Pathway.
As the population ages, the medical and socioeconomic impact of age-related bone disorders will further increase. An imbalance between osteogenesis and adipogenesis of mesenchymal stem cells (MSCs) can lead to various bone and metabolic diseases such as osteoporosis. Thus, understanding the molecular mechanisms underlying MSC osteogenic and adipogenic differentiation is important for the discovery of novel therapeutic paradigms for these diseases. miR-10b has been widely reported in tumorigenesis, cancer invasion and metastasis. However, the effects and potential mechanisms of miR-10b in the regulation of MSC adipogenic and osteogenic differentiation have not been explored. In this study, we found that the expression of miR-10b was positively correlated with bone formation marker genes ALP, RUNX2 and OPN, and negatively correlated with adipogenic markers CEBPα, PPARγ and AP2 in clinical osteoporosis samples. Overexpression of miR-10b enhanced osteogenic differentiation and inhibited adipogenic differentiation of human adipose-derived mesenchymal stem cells (hADSCs) in vitro, whereas downregulation of miR-10b reversed these effects. Furthermore, miR-10b promoted ectopic bone formation in vivo. Target prediction and dual luciferase reporter assays identified SMAD2 as a potential target of miR-10b. Silencing endogenous SMAD2 expression in hADSCs enhanced osteogenesis but repressed adipogenesis. Pathway analysis indicated that miR-10b promotes osteogenic differentiation and bone formation via the TGF-β signaling pathway, while suppressing adipogenic differentiation may be primarily mediated by other pathways. Taken together, our findings imply that miR-10b acts as a critical regulator for balancing osteogenic and adipogenic differentiation of hADSCs by repressing SMAD2 and partly through the TGF-β pathway. Our study suggests that miR-10b is a novel target for controlling bone and metabolic diseases.


Molecular markers for rapidly identifying candidate genes in Chlamydomonas reinhardtii. Ery1 and ery2 encode chloroplast ribosomal proteins.
To take advantage of available expressed sequence tags and genomic sequence, we have developed 64 PCR-based molecular markers in Chlamydomonas reinhardtii that map to the 17 linkage groups. These markers will allow the rapid association of a candidate gene sequence with previously identified mutations. As proof of principle, we have identified the genes encoded by the ERY1 and ERY2 loci. Mendelian mutations that confer resistance to erythromycin define three unlinked nuclear loci in C. reinhardtii. Candidate genes ribosomal protein L4 (RPL4) and L22 (RPL22) are tightly linked to the ERY1 locus and ERY2 locus, respectively. Genomic DNA for RPL4 from wild type and five mutant ery1 alleles was amplified and sequenced and three different point mutations were found. Two different glycine residues (G(102) and G(112)) are replaced by aspartic acid and both are in the unstructured region of RPL4 that lines the peptide exit tunnel of the chloroplast ribosome. The other two alleles change a splice site acceptor site. Genomic DNA for RPL22 from wild type and three mutant ery2 alleles was amplified and sequenced and revealed three different point mutations. Two alleles have premature stop codons and one allele changes a splice site acceptor site.


Exercise and immunity: a review with emphasis on the horse.
Exercise has been recognized as a stress, which can significantly alter the host's immune response and, therefore, its susceptibility to disease. Whereas research in this area has previously focused primarily on human subjects and laboratory animals, it has more recently extended to domestic animals, especially the equine athlete. Despite several studies, defining the relationship among exercise, the immune response, and disease has proven difficult due to a number of factors, including the complexity of the immune system and the variable nature of exercise itself. It now appears that exercise has dual effects on the immune system. Suppressive effects, such as a decline in the ratio of CD4+ to CD8+ cells, diminished lymphocyte function, and a decline in the number and cytolytic activity of natural killer cells have been observed in response to brief high-intensity exercise, prolonged exhaustive exercise, and overtraining. In contrast, moderate training generally has beneficial effects on host defense mechanisms. The mechanisms for regulating the dual effects of exercise are complex, involving a network of neuroendocrine hormones and cytokines.


Widespread presence of histologically occult cytomegalovirus.
Disseminated cytomegalovirus (CMV) has been investigated by in situ hybridization in formalin-fixed paraffin-embedded tissue sections with biotinylated DNA probes. Two cases of disseminated CMV infection were studied at autopsy by this highly specific technique. The presence of CMV in cytomegalic cells is readily shown. In addition, CMV has been detected and localized in many normal-appearing cells. This occult infection occurs in cardiac myocytes, hepatocytes, spleen and lymph node reticular cells, endometrial stromal and glandular cells, and breast stromal cells, as well as in cells in the renal glomerulus, tubule, and interstitium, adrenal cortex and medulla, fallopian tube submucosa, myometrium, and anterior pituitary. Cytomegalovirus infection of endothelial cells has been further documented by immunohistochemical methods utilizing antibody to Factor VIII. These findings suggest that CMV disseminates hematogenously throughout the body, initiating necrotizing foci of infection. The appearance of many diffuse foci suggests that local viral spread occurs via endothelial cell infection. Surprisingly , lymphocyte involvement was not observed.


OSIP1 is a self-assembling DUF3129 protein required to protect fungal cells from toxins and stressors.
Secreted proteins are key players in fungal physiology and cell protection against external stressing agents and antifungals. Oak stress-induced protein 1 (OSIP1) is a fungal-specific protein with unknown function. By using Podospora anserina and Phanerochaete chrysosporium as models, we combined both in vivo functional approaches and biophysical characterization of OSIP1 recombinant protein. The P. anserina OSIP1Δ mutant showed an increased sensitivity to the antifungal caspofungin compared to the wild type. This correlated with the production of a weakened extracellular exopolysaccharide/protein matrix (ECM). Since the recombinant OSIP1 from P. chrysosporium self-assembled as fibers and was capable of gelation, it is likely that OSIP1 is linked to ECM formation that acts as a physical barrier preventing drug toxicity. Moreover, compared to the wild type, the OSIP1Δ mutant was more sensitive to oak extractives including chaotropic phenols and benzenes. It exhibited a strongly modified secretome pattern and an increased production of proteins associated to the cell-wall integrity signalling pathway, when grown on oak sawdust. This demonstrates that OSIP1 has also an important role in fungal resistance to extractive-induced stress.


Red coral extinction risk enhanced by ocean acidification.
The red coral Corallium rubrum is a habitat-forming species with a prominent and structural role in mesophotic habitats, which sustains biodiversity hotspots. This precious coral is threatened by both over-exploitation and temperature driven mass mortality events. We report here that biocalcification, growth rates and polyps' (feeding) activity of Corallium rubrum are significantly reduced at pCO2 scenarios predicted for the end of this century (0.2 pH decrease). Since C. rubrum is a long-living species (>200 years), our results suggest that ocean acidification predicted for 2100 will significantly increases the risk of extinction of present populations. Given the functional role of these corals in the mesophotic zone, we predict that ocean acidification might have cascading effects on the functioning of these habitats worldwide.


Probing magnetic interactions in metal-organic frameworks and coordination polymers microscopically.
Materials with magnetic interactions between their metal centres play a tremendous role in modern technologies and can exhibit unique physical phenomena. In recent years, magnetic metal-organic frameworks and coordination polymers have attracted significant attention because their unique structural flexibility enables them to exhibit multifunctional magnetic properties or unique magnetic states not found in the conventional magnetic materials, such as metal oxides. Techniques that enable the magnetic interactions in these materials to be probed at the atomic scale, long established to be key for developing other magnetic materials, are not well established for studying metal-organic frameworks and coordination polymers. This review focuses on studies where metal-organic frameworks and coordination polymers have been examined using such microscopic probes, with a particular focus on neutron scattering and density-functional theory, the most-well established experimental and computational techniques for understanding magnetic materials in detail. This paper builds on a brief introduction to these techniques to describe how such probes have been applied to a variety of magnetic materials starting with select historical examples before discussing multifunctional, low dimensional and frustrated magnets. This review highlights the information that can be obtained from such microscopic studies, including the strengths and limitations of these techniques. The article then concludes with a brief perspective on the future of this area.


Reduction in the incidence of carbon monoxide exposures in humans undergoing general anesthesia.
Carbon monoxide forms via reaction of isoflurane, enflurane, and desflurane with dried CO2 absorbents. The authors hypothesize that interventions by nonphysician support personnel to decrease absorbent drying will decrease the exposure rate of patients to carbon monoxide from anesthetic breakdown. In the control group, all anesthetizing personnel were made aware of the factors enabling CO generation from anesthetic breakdown, and prevention techniques were left to the anesthetizing personnel. After data collection was complete, the following interventions were initiated to reduce absorbent drying: Anesthesia technicians and housekeeping personnel were instructed to turn off all anesthesia machines after the last case of the day in each room, and the CO2 absorbent was changed each morning if fresh gas was found flowing. Baralyme was used in all phases of this study. Five cases of intraoperative carbon monoxide exposure occurred among 1,085 (0.46%) first cases in the control group. Postintervention, patient carbon monoxide exposures decreased (P < 0.05), with one exposure among 1,961 (0.051%) first cases in the main operating room. Two exposures among 68 (2.9%) first cases occurred in remote locations (P < 0.001) versus main operating room. Predisposing factors for absorbent drying include the prolonged use of anesthesia machines for monitored anesthesia care, inappropriate drying techniques for expiratory flowmeters, understaffing of support personnel, and anesthesia in remote locations. These interventions reduced patient exposure to carbon monoxide. Monitoring for carbon monoxide exposures during general anesthesia may be necessary to recognize and end patient exposures that occur despite preventative measures.


Wavefront shaping improves the transparency of the scattering media: a review.
Wavefront shaping (WFS) can compensate for distortions by optimizing the wavefront of the input light or reversing the transmission matrix of the media. It is a promising field of research. A thorough understanding of principles and developments of WFS is important for optical research. To provide insight into WFS for researchers who deal with scattering in biomedicine, imaging, and optical communication, our study summarizes the basic principles and methods of WFS and reviews recent progress. The basic principles, methods of WFS, and the latest applications of WFS in focusing, imaging, and multimode fiber (MMF) endoscopy are described. The practical challenges and prospects of future development are also discussed. Data-driven learning-based methods are opening up new possibilities for WFS. High-resolution imaging through MMFs can support small-diameter endoscopy in the future. The rapid development of WFS over the past decade has shown that the best solution is not to avoid scattering but to find ways to correct it or even use it. WFS with faster speed, more optical modes, and more modulation degrees of freedom will continue to drive exciting developments in various fields.


Mesenteric panniculitis. Part 1: MDCT--pictorial review.
Mesenteric panniculitis is an uncommon benign inflammatory condition of unknown etiology that involves the adipose tissue of the mesentery and for which an extremely varied terminology has been used, causing considerable confusion. It can be evaluated as a single disease with two pathological subgroups: Mesenteric Panniculitis (MP), representing the very large major subgroup where inflammation and fat necrosis predominate and Retractile Mesenteritis (RM), much rarely found, where fibrosis and retraction predominate. In histo-pathological terms the preferred terminology is sclerosing mesenteritis. We hereby extensively illustrate the characteristic MDCT findings of MP through pictures selected among a collection of cases constituted over a 5-year period. All patients were scanned with 64-row MDCT equipment. We also review the literature and discuss the differential diagnosis. The radiological diagnosis of MP was based on classical CT signs described in the literature and comprising: the presence of a well-defined "mass effect" on neighbouring structures (sign 1) constituted by mesenteric fat tissue of inhomogeneous higher attenuation than adjacent retroperitoneal or mesocolonic fat (sign 2) and containing small soft tissue nodes (sign 3). It may typically be surrounded by a hypoattenuated fatty "halo sign" (sign 4) and an hyperattenuating pseudocapsule may also surround the all entity (sign 5). The last two signs are considered inconstant but very specific. The absence of histological verification constitutes the weakness of our study. The differential diagnosis of MP is extensive and includes all disorders that can affect the mesentery. The most common ones are lymphoma, well-differentiated liposarcoma, peritoneal carcinomatosis, carcinoid tumor, retroperitoneal fibrosis, lipoma, mesenteric desmoid tumor, mesenteric inflammatory pseudotumor, mesenteric fibromatosis and mesenteric edema. PET/CT is proved useful to correctly exclude mesenteric tumoral involvement in patients presenting with typical MR The course of MP is favorable in most cases and progression of MP to retractile mesenteritis not only appears very being rare but finally remains doubtful.


Counterion exchange to achieve reversibly switchable hydrophobicity and oleophobicity on fabrics.
We describe a simple layer-by-layer (LbL) technology and counterion exchange procedure to tune the liquid wettability of commercially available cotton fabrics. A polyelectrolyte multilayer is deposited on the fabric surface by the LbL technology, and counterion exchange is used to control the surface composition and thereby to modulate the solid surface energy. The tunability of the solid surface energy, along with the inherent re-entrant texture of the cotton fabric, results in simultaneously switchable wettability between a nonwetting state and a fully wetted state for water and hexadecane. This switchable hydrophobicity and oleophobicity can be explained within a robustness factor, which is a quantitative criterion for the transition between the two states. The counterion exchange can be confirmed by X-ray photoelectron spectroscopy analysis.


Optimization of mosquito egg production under mass rearing setting: effects of cage volume, blood meal source and adult population density for the malaria vector, Anopheles arabiensis.
Anopheles arabiensis is one of the major malaria vectors that put millions of people in endemic countries at risk. Mass-rearing of this mosquito is crucial for strategies that use sterile insect technique to suppress vector populations. The sterile insect technique (SIT) package for this mosquito species is being developed by the Insect Pest Control Subprogramme of the Joint FAO/IAEA Division of Nuclear Techniques in Food and Agriculture. To improve mass-rearing outcomes for An. arabiensis, the question of whether the egg production by females would be affected by the size of the adult holding cages, the source of the blood meal and the total number of pupae that could be loaded into the cages was addressed and finally the impact of adding additional pupae to the cage daily to maintain adult numbers on egg productivity assessed. Mass production cages of two different volumes, two different sources of blood meal (bovine and porcine) and two different population densities (cages originally loaded with either 15,000 or 20,000 pupae) were tested and evaluated on the basis of eggs produced/cage or per female. Males and females pupae with a ratio of 1:1 were added to the cages at day 1 and 2 of pupation. The emerging adults had constant access to 5% sugar solution and blood fed via the Hemotek membrane feeding system. Eggs were collected either twice a week or daily. A generalized linear model was used to identify factors which gave significantly higher egg production. Neither cage volume nor blood meal source affected egg production per cage or per female. However, increasing population density to 20,000 pupae had a negative effect on eggs produced per cage and per female. Although high density negatively impacted egg production, adding 1000 daily additional pupae compensating for daily mortality resulted in a substantial increase in egg production. Moreover, in all tests the first and the third egg batches collected were significantly higher than others eggs batches. With the equipment and protocols described here and routinely used at the Insect Pest Control Laboratory (IPCL), it was possible to produce up to 120,000 eggs/cage/day. These results demonstrated that 15,000 is the optimal number of pupae to be loaded into the Anopheles Mass production cages. Under this condition, an average of 40 eggs per female was obtained for five gonotrophic cycles. However, an improvement in egg production can be achieved by daily addition, to the original 15,000 pupae, of one thousand pupae a day. Interestingly, feeding females with bovine or porcine blood using both large and small versions of the mass production cage did not affect egg productivity.


Bacillus subtilis EzrA and FtsL synergistically regulate FtsZ ring dynamics during cell division.
Previous work has shown that the Bacillus subtilis EzrA protein directly inhibits FtsZ ring assembly, which is required for normal cell division, and that loss of EzrA results in hyperstabilization of the FtsZ polymer in vivo. Here, it was found that in ezrA-disrupted cells, artificial expression of YneA, which suppresses cell division during the SOS response, and disruption of noc (yyaA), which acts as an effector of nucleoid occlusion, resulted in accumulation of multiple non-constricting FtsZ rings, inhibition of cell division, and synthetic lethality. Overexpression of the essential cell division protein FtsL suppressed the effect of ezrA disruption. FtsL overexpression recovered the delayed FtsZ ring constriction seen in ezrA-disrupted wild-type cells. Conversely, the absence of EzrA caused lethality in cells producing a lower amount of FtsL than wild-type cells. It has previously been reported that FtsL is recruited to the division site during the later stages of cell division, although its exact role is currently unknown. The results of this study suggest that FtsL and EzrA synergistically regulate the FtsZ ring constriction in B. subtilis. Interestingly, FtsL overexpression also suppressed the cell division inhibition due to YneA expression or Noc inactivation in ezrA-disrupted cells.


The Genomic Regions That Contain Ochratoxin A Biosynthetic Genes Widely Differ in Aspergillus Section Circumdati Species.
Aspergillus section Circumdati includes 27 species, some of which are considered ochratoxin A (OTA) producers. However, there is considerable controversy about their potential OTA synthesis ability. In this work, the complete genomes of 13 species of Aspergillus section Circumdati were analyzed in order to study the cluster of OTA biosynthetic genes and the region was compared to those previously reported in A. steynii and A. westerdijkiae. The results obtained reveal that the genomes of some species in this section, including A. affinis, A. cretensis, A. elegans, A. muricatus, A. pulvericola, A. roseoglobulosus, and A. subramanianii, contain a potentially functional OTA biosynthetic cluster. Therefore, they might be able to synthesize the toxin. On the contrary, A. melleus, A. ochraceus, A. ostianus, A. persii, A. sclerotiorum, A. sesamicola, and A. westlandensis contain a truncated version of the cluster that lacks many of the genes involved in OTA biosynthesis, which might be related to their inability to produce OTA. The gain/loss pattern is different in all species, which suggests that the genetic evolution of this region might be due to independent events.


Ventilating tubes in the middle ear. Long-term observations.
This follow-up study is of the same patients we studied in 1976. Then we thought the results were unsatisfactory in 20.9% of the ears treated with ventilating tubes. The hearing losses varied from 25 to 60 dB and chronic otitis media developed in 7.7% of the cases. We think the results of treatment with ventilating tubes in chronic serous otitis media are not good enough. This study shows that there has been an increase in the number of patients with permanent hearing loss and chronic otitis media than in the first study.


Hydration status and fluid and sodium balance in elite Canadian junior women's soccer players in a cool environment.
Dehydration can impair mental and on-field performance in soccer athletes; however, there is little data available from the female adolescent player. There is a lack of research investigating fluid and electrolyte losses in cool temperatures. Therefore, the purpose of this study was to investigate the pretraining hydration status, fluid balance, and sweat sodium loss in 34 female Canadian junior elite soccer athletes (mean age ± SD, 15.7 ± 0.7 years) in a cool environment. Data were collected during two 90 min on-field training sessions (9.8 ± 3.3 °C, 63% ± 12% relative humidity). Prepractice urine specific gravity (USG), sweat loss (pre- and post-training body mass), and sweat sodium concentration (regional sweat patch method) were measured at each session. Paired t tests were used to identify significant differences between training sessions and Pearson's product moment correlation analysis was used to assess any relationships between selected variables (p ≤ 0.05). We found that 45% of players presented to practice in a hypohydrated state (USG > 1.020). Mean percent body mass loss was 0.84% ± 0.07% and sweat loss was 0.69 ± 0.54 L. Although available during each training session, fluid intake was low (63.6% of players consumed <250 mL). Mean sweat sodium concentration was 48 ± 12 mmol·L⁻¹. Despite low sweat and moderate sodium losses, players did not drink enough to avoid mild fluid and sodium deficits during training. The findings from this study highlights the individual variations that occur in hydration management in athletes and thus the need for personalized hydration guidelines.


Efficacy and Prognostic Analysis of 315 Stage I-IVa Esophageal Cancer Patients Treated with Simultaneous Integrated Boost-Intensity-Modulated Radiation Therapy.
Use of simulated integrated boost-intensity-modulated radiation therapy (SIB-IMRT) is rarely reported in the treatment of esophageal cancer. This study was performed to observe the curative effect and prognostic factors associated with concurrent chemoradiotherapy for esophageal cancer using modern radiotherapy (RT) techniques. In total, 315 patients with esophageal squamous cell carcinoma who received SIB-IMRT between 2015 and 2018 were included in this retrospective study. Median doses were planning target volume (PTV) 5400 cGy, 30 times (180cGy/fraction); planning gross tumor volume (PGTV) 6000 cGy, 30 times (200 cGy/fraction), once a day and 5 times a week. The entire period of RT was 6 weeks. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and adverse reactions were observed. Univariate analysis was performed, and factors with P<0.15 were included in multivariate analysis. Cox regression analysis was used for multivariate prognostic analysis. P<0.05 was considered statistically significant. The incidence of adverse reactions under single chemotherapy concurrent chemoradiotherapy (sCCRT) and double chemotherapy concurrent chemoradiotherapy (dCCRT) was analyzed. Two-year, 3-year OS and PFS of the entire group were 49.5%, 40.2% and 40.3%, 34.0%, and the median survival time was 23.5 months. Univariate and multivariate analyses showed that T-stage (P=0.049), N-stage (P=0.024), clinical stage (P=0.041), short-term efficacy (P<0.001), and use of concurrent chemotherapy (P<0.001) were the influencing factors for OS. ORR was 87.6%. Adverse reactions were significantly increased with increasing chemotherapy dose. The adverse reactions of SIB-IMRT in esophageal cancer can be tolerated. T-stage, N-stage, clinical stage, short-term curative effect, and concurrent chemotherapy are the prognostic factors affecting survival. Because it has lower toxicity and is as effective as dCCRT, sCCRT should be considered in the management of esophageal cancer.


[The impact of the intravenous He-Ne laser therapy on the antioxidant system in patient with stable exertion angina and postinfarct cardiosclerosis].
The authors' study show that intravenous He-Ne laser therapy (HNLT) in patients with stable angina of effort (functional class II-III) and postinfarction cardiosclerosis irrespective of ejection fraction increased plasma katalase and red cell vitamin A concentrations. HNLT aroused vitamin E concentration in red cells in anginal patients with intact ejection fraction whereas in those with reduced ejection fraction it elevated blood peroxidase, plasma vitamin A and E concentrations. For patients with postinfarction cardiosclerosis there were, respectively, higher levels of blood peroxidase, plasmic vitamin A, red cell vitamin E, plasmic SH-groups and blood peroxidase, plasmic vitamins A and E.


Variation among internet based calculators in predicting spontaneous resolution of vesicoureteral reflux.
An increasing number of parents and practitioners use the Internet for health related purposes, and an increasing number of models are available on the Internet for predicting spontaneous resolution rates for children with vesicoureteral reflux. We sought to determine whether currently available Internet based calculators for vesicoureteral reflux resolution produce systematically different results. Following a systematic Internet search we identified 3 Internet based calculators of spontaneous resolution rates for children with vesicoureteral reflux, of which 2 were academic affiliated and 1 was industry affiliated. We generated a random cohort of 100 hypothetical patients with a wide range of clinical characteristics and entered the data on each patient into each calculator. We then compared the results from the calculators in terms of mean predicted resolution probability and number of cases deemed likely to resolve at various cutoff probabilities. Mean predicted resolution probabilities were 41% and 36% (range 31% to 41%) for the 2 academic affiliated calculators and 33% for the industry affiliated calculator (p = 0.02). For some patients the calculators produced markedly different probabilities of spontaneous resolution, in some instances ranging from 24% to 89% for the same patient. At thresholds greater than 5%, 10% and 25% probability of spontaneous resolution the calculators differed significantly regarding whether cases would resolve (all p <0.0001). Predicted probabilities of spontaneous resolution of vesicoureteral reflux differ significantly among Internet based calculators. For certain patients, particularly those with a lower probability of spontaneous resolution, these differences can significantly influence clinical decision making.


Health care technology in Canada (with special reference to Quebec).
In Canada, all citizens are insured for health services. Health care is a provincial responsibility. The federal role is limited to health care financing, health protection including regulation of pharmaceuticals, and environmental health. The health care system represents a balance among government direction, consumer choice, and provider autonomy. Canada has largely controlled the costs of health care by funding and management mechanisms, the most important of which is the global budget formula used to fund hospitals. This paper discusses the Canadian health care system, with particular emphasis on the province of Quebec. In 1988, the provincial government of Quebec established the first Canadian body dedicated to technology assessment. Since then, a national coordinating office and several other provincial bodies have developed. The work of these and other evaluation efforts has had a growing influence on technology management decisions, particularly those dealing with procurement of capital-intensive technologies. Expanding this influence into the realm of technology use, especially for low-cost, high-volume technologies, remains a challenge.


Fetal Intracardiac Transfusions in Hydropic Fetuses with Severe Anemia.
Fetal anemia can have significant perinatal morbidity and mortality, particularly with onset prior to 20 weeks of gestation. We detail a case-cohort study (n = 8) of all women who underwent fetal in-utero, intracardiac transfusion prior to 24 weeks of gestation (7 women before 20 + 1 weeks), between March 2004 and September 2014, in a supraregional Fetal Medicine Center in the United Kingdom, comprising 2.2% of all transfusions performed during this period. All the fetuses were hydropic, with high maternal BMI, and had severe anemia as an indicator for transfusion. It was an attempt to perform intravascular transfusion when other common routes of fetal vascular access had failed. There were 2 intrauterine deaths (25%), both of which were associated with in-utero transfusion and fulminant parvovirus B19 infection. The perinatal survival rate was 75% (6/8). Fetal in-utero, intravascular transfusion by the intracardiac route may be used to correct severe early-onset anemia. It is particularly useful when technical issues of fetal size, early gestation (<20 weeks), maternal adiposity, and hydrops fetalis make umbilical cord or intrahepatic vein puncture technically difficult. Survival rates appear comparable to other series of pregnancies where in-utero transfusion is performed at early gestation.


Ex vivo lung perfusion prior to transplantation: an overview of current clinical practice worldwide.
Lung transplantation is a lifesaving treatment in numerous forms of end-stage lung disease but organ shortage remains nowadays his biggest issue. Ex vivo lung perfusion (EVLP) has recently emerged as a solution to this problem and begins to be accepted is clinical practice. In this review, we will focus on his experience worldwide. We would like to describe the technique and the criteria used to select the donors and the transplantable lungs. We will also browse the acceptance rate described in literature as well as numerous other aspects of this new tool.


Nascent pre-mRNA transcripts are associated with nuclear regions enriched in splicing factors.
We have used in situ hybridization and immunocytochemistry to compare the nuclear localization of a specific nascent pre-mRNA and the essential non-snRNP splicing factor SC-35. Nascent c-fos transcripts were detected in serum-induced mouse fibroblasts by in situ hybridization with genomic c-fos probes. Prior to serum induction no c-fos RNA is detected, but these transcripts localize to two dots in the interphase nucleus after induction. The time course of appearance of the dots correlates with the previously determined time course of transcriptional activation of the gene. Upon further analysis by confocal laser scanning microscopy, we have determined that the dots extend through the depth of the nucleus, forming paths. By using high-voltage electron microscopy, we have found that the c-fos path extends out and comes into direct contact with the nuclear envelope. We have also compared the localization of c-fos transcripts with the speckled nuclear regions that are enriched in snRNPs and the non-snRNP splicing factor SC-35. Direct observations of three-dimensional rotations have revealed a close association between the c-fos transcripts and the nuclear speckles. This study demonstrates a direct link between specific nascent RNA transcripts and nuclear speckles that are enriched in pre-mRNA splicing factors.


NSAIDs in combination therapy for the treatment of chronic pseudophakic cystoid macular edema.
The purpose of this study was to evaluate the addition of topical nonsteroidal antiinflammatory drugs (NSAIDs) to intravitreal corticosteroid and antivascular endothelial growth factor injections for the treatment of chronic cystoid macular edema. Thirty-nine patients with chronic pseudophakic cystoid macular edema completed a single-center, randomized, investigator-masked study. All patients were treated with an intravitreal triamcinolone and bevacizumab injection at study entry; the bevacizumab injection was repeated at 1 month. To evaluate the effect of adding an NSAID, patients were randomized to treatment with 1 of 4 topical NSAIDs (diclofenac 0.1%, ketorolac 0.4%, nepafenac 0.1%, and bromfenac 0.09%) or placebo for 16 weeks. At Weeks 12 and 16, both the nepafenac and bromfenac groups showed a significant reduction in retinal thickness compared with that in placebo (nepafenac, P = 0.0048, bromfenac, P = 0.0113). A difference, however, between these 2 NSAID groups was observed in that only the nepafenac group was able to maintain the demonstrated retinal thickness decrease at Weeks 12 and 16. The nepafenac group also experienced a significant improvement in visual acuity at Weeks 12 (P = 0.0084) and 16 (P = 0.0233). The addition of NSAIDs did not produce an increase in mean intraocular pressure over the course of therapy. Although NSAID therapy seems to potentiate the improvements produced by corticosteroids and antivascular endothelial growth factor therapy for chronic pseudophakic cystoid macular edema, only nepafenac- and bromfenac-treated eyes showed reduced retinal thickness at 12 weeks and 16 weeks. Furthermore, nepafenac produced a sustained improvement in visual acuity.


Acute respiratory distress syndrome and COVID-19 in a child with systemic lupus erythematosus.
We report a case of COVID-19 in a pediatric patient with systemic lupus erythematosus (SLE), who presented with respiratory distress marked by increased work of breathing and low oxygen saturation. Lab tests confirmed COVID-19, and showed lymphocytopenia and elevated markers of inflammation and coagulopathy. Chest X-ray showed bilateral mid-lung opacities, and the patient required intubation early in his disease course. Imaging and clinical findings were consistent with acute respiratory distress syndrome (ARDS) with inflammation. The patient was treated with different combinations of antivirals (hydroxychloroquine and remdesivir), cytokine inhibitors (anakinra and tocilizumab), glucocorticoids (hydrocortisone and methylprednisolone), and an anticoagulant (enoxaparin). Inflammatory markers decreased before clinical improvement in lung aeration. This case highlights the potential for pediatric patients with SLE to present with COVID-19 similar to the clinical presentation described in adults.


The two faces of FBW7 in cancer drug resistance.
Chemotherapy is an important therapeutic approach for cancer treatment. However, drug resistance is an obstacle that often impairs the successful use of chemotherapies. Therefore, overcoming drug resistance would lead to better therapeutic outcomes for cancer patients. Recently, studies by our own and other groups have demonstrated that there is an intimate correlation between the loss of the F-box and WD repeat domain-containing 7 (FBW7) tumor suppressor and the incurring drug resistance. While loss of FBW7 sensitizes cancer cells to certain drugs, FBW7-/- cells are more resistant to other types of chemotherapies. FBW7 exerts its tumor suppressor function by promoting the degradation of various oncoproteins that regulate many cellular processes, including cell cycle progression, cellular metabolism, differentiation, and apoptosis. Since loss of the FBW7 tumor suppressor is linked to drug resistance, FBW7 may represent a novel therapeutic target to increase drug sensitivity of cancer cells to conventional chemotherapeutics. This paper thus focuses on the new functional aspects of FBW7 in drug resistance.


Purged versus non-purged peripheral blood stem-cell transplantation for high-risk neuroblastoma (COG A3973): a randomised phase 3 trial.
Myeloablative chemoradiotherapy and immunomagnetically purged autologous bone marrow transplantation has been shown to improve outcome for patients with high-risk neuroblastoma. Currently, peripheral blood stem cells (PBSC) are infused after myeloablative therapy, but the effect of purging is unknown. We did a randomised study of tumour-selective PBSC purging in stem-cell transplantation for patients with high-risk neuroblastoma. Between March 16, 2001, and Feb 24, 2006, children and young adults (<30 years) with high-risk neuroblastoma were randomly assigned at diagnosis by a web-based system (in a 1:1 ratio) to receive either non-purged or immunomagnetically purged PBSC. Randomisation was done in blocks stratified by International Neuroblastoma Staging System stage, age, MYCN status, and International Neuroblastoma Pathology classification. Patients and treating physicians were not masked to treatment assignment. All patients were treated with six cycles of induction chemotherapy, myeloablative consolidation, and radiation therapy to the primary tumour site plus meta-iodobenzylguanidine avid metastases present before myeloablative therapy, followed by oral isotretinoin. PBSC collection was done after two induction cycles. For purging, PBSC were mixed with carbonyl iron and phagocytic cells removed with samarium cobalt magnets. Remaining cells were mixed with immunomagnetic beads prepared with five monoclonal antibodies targeting neuroblastoma cell surface antigens and attached cells were removed using samarium cobalt magnets. Patients underwent autologous stem-cell transplantation with PBSC as randomly assigned after six cycles of induction therapy. The primary endpoint was event-free survival and was analysed by intention-to-treat. The trial is registered with ClinicalTrials.gov, number NCT00004188. 495 patients were enrolled, of whom 486 were randomly assigned to treatment: 243 patients to receive non-purged PBSC and 243 to received purged PBSC. PBSC were collected from 229 patients from the purged group and 236 patients from the non-purged group, and 180 patients from the purged group and 192 from the non-purged group received transplant. 5-year event-free survival was 40% (95% CI 33-46) in the purged group versus 36% (30-42) in the non-purged group (p=0·77); 5-year overall survival was 50% (95% CI 43-56) in the purged group compared with 51% (44-57) in the non-purged group (p=0·81). Toxic deaths occurred in 15 patients during induction (eight in the purged group and seven in the non-purged group) and 12 during consolidation (eight in the purged group and four in the non-purged group). The most common adverse event reported was grade 3 or worse stomatitis during both induction (87 of 242 patients in the purged group and 93 of 243 patients in the non-purged group) and consolidation (131 of 177 in the purged group vs 145 of 191 in the non-purged group). Serious adverse events during induction were grade 3 or higher decreased cardiac function (four of 242 in the purged group and five of 243 in the non-purged group) and elevated creatinine (five of 242 in the purged group and six of 243 non-purged group) and during consolidation were sinusoidal obstructive syndrome (12 of 177 in the purged group and 17 of 191 in the non-purged group), acute vascular leak (11 of 177 in the purged group and nine of 191 in the non-purged group), and decreased cardiac function (one of 177 in the purged group and four of 191 in the non-purged group). Immunomagnetic purging of PBSC for autologous stem-cell transplantation did not improve outcome, perhaps because of incomplete purging or residual tumour in patients. Non-purged PBSC are acceptable for support of myeloablative therapy of high-risk neuroblastoma.


Characterization of the Serralysin-Like Gene of 'Candidatus Liberibacter solanacearum' Associated with Potato Zebra Chip Disease.
The nonculturable bacterium 'Candidatus Liberibacter solanacearum' is the causative agent of zebra chip disease in potato. Computational analysis of the 'Ca. L. solanacearum' genome revealed a serralysin-like gene based on conserved domains characteristic of genes encoding metalloprotease enzymes similar to serralysin. Serralysin and other serralysin family metalloprotease are typically characterized as virulence factors and are secreted by the type I secretion system (T1SS). The 'Ca. L. solanacearum' serralysin-like gene is located next to and divergently transcribed from genes encoding a T1SS. Based on its relationship to the T1SS and the role of other serralysin family proteases in circumventing host antimicrobial defenses, it was speculated that a functional 'Ca. L. solanacearum' serralysin-like protease could be a potent virulence factor. Gene expression analysis showed that, from weeks 2 to 6, the expression of the 'Ca. L. solanacearum' serralysin-like gene was at least twofold higher than week 1, indicating that gene expression stays high as the disease progresses. A previously constructed serralysin-deficient mutant of Serratia liquefaciens FK01, an endophyte associated with insects, as well as an Escherichia coli lacking serralysin production were used as surrogates for expression analysis of the 'Ca. L. solanacearum' serralysin-like gene. The LsoA and LsoB proteins were expressed as both intact proteins and chimeric S. liquefaciens-'Ca. L. solanacearum' serralysin-like proteins to facilitate secretion in the S. liquefaciens surrogate and as intact proteins or as a truncated LsoB protein containing just the putative catalytic domains in the E. coli surrogate. None of the 'Ca. L. solanacearum' protein constructs expressed in either surrogate demonstrated proteolytic activity in skim milk or zymogram assays, or in colorimetric assays using purified protein, suggesting that the 'Ca. L. solanacearum' serralysin-like gene does not encode a functional protease, or at least not in our surrogate systems.


The hepatitis A virus polyprotein expressed by a recombinant vaccinia virus undergoes proteolytic processing and assembly into viruslike particles.
Hepatitis A virus (HAV) contains a single-stranded, plus-sense RNA genome with a single long open reading frame encoding a polyprotein of approximately 250 kDa. Viral structural proteins are generated by posttranslational proteolytic processing of this polyprotein. We constructed recombinant vaccinia viruses which expressed the HAV polyprotein (rV-ORF) and the P1 structural region (rV-P1). rV-ORF-infected cell lysates demonstrated that the polyprotein was cleaved into immunoreactive 29- and 33-kDa proteins which comigrated with HAV capsid proteins VP0 and VP1. The rV-P1 construct produced a 90-kDa protein which showed no evidence of posttranslational processing. Solid-phase radioimmunoassays with human polyclonal anti-HAV sera and with murine or human neutralizing monoclonal anti-HAV antibodies recognized the rV-ORF-infected cell lysates. Sucrose density gradients of rV-ORF-infected cell lysates contained peaks of HAV antigen with sedimentation coefficients of approximately 70S and 15S, similar to those of HAV empty capsids and pentamers. Immune electron microscopy also demonstrated the presence of viruslike particles in rV-ORF-infected cell lysates. Thus, the HAV polyprotein expressed by a recombinant vaccinia virus demonstrated posttranslational processing into mature capsid proteins which assembled into antigenic viruslike particles.


Electronic Characterization of Glycolaldehyde: Experimental and Theoretical Insights from the Core- and Valence-Level Spectroscopy.
The core-level electron excitation and ionization spectra of glycolaldehyde have been investigated by photoabsorption and photoemission spectroscopy at both carbon and oxygen K-edges; the valence ionization spectra were also recorded by photoelectron spectroscopy in the UV-vis region. The spectra are interpreted by means of ab initio calculations based on the equation-of-motion coupled cluster singles and doubles (EOM-CCSD) and coupled cluster singles, doubles, and perturbative are in good agreement with the experimental results, and many of the observed features are assigned. The photoabsorption spectra are not only dominated by transitions from core-level orbitals to unoccupied π and σ orbitals but also show structures due to Rydberg transitions.


A Heart Image Segmentation Method Based on Position Attention Mechanism and Inverted Pyramid.
In the realm of modern medicine, medical imaging stands as an irreplaceable pillar for accurate diagnostics. The significance of precise segmentation in medical images cannot be overstated, especially considering the variability introduced by different practitioners. With the escalating volume of medical imaging data, the demand for automated and efficient segmentation methods has become imperative. This study introduces an innovative approach to heart image segmentation, embedding a multi-scale feature and attention mechanism within an inverted pyramid framework. Recognizing the intricacies of extracting contextual information from low-resolution medical images, our method adopts an inverted pyramid architecture. Through training with multi-scale images and integrating prediction outcomes, we enhance the network's contextual understanding. Acknowledging the consistent patterns in the relative positions of organs, we introduce an attention module enriched with positional encoding information. This module empowers the network to capture essential positional cues, thereby elevating segmentation accuracy. Our research resides at the intersection of medical imaging and sensor technology, emphasizing the foundational role of sensors in medical image analysis. The integration of sensor-generated data showcases the symbiotic relationship between sensor technology and advanced machine learning techniques. Evaluation on two heart datasets substantiates the superior performance of our approach. Metrics such as the Dice coefficient, Jaccard coefficient, recall, and F-measure demonstrate the method's efficacy compared to state-of-the-art techniques. In conclusion, our proposed heart image segmentation method addresses the challenges posed by diverse medical images, offering a promising solution for efficiently processing 2D/3D sensor data in contemporary medical imaging.


Self-reported occupational blood exposure among paramedics in Poland: a pilot study.
Introduction. Paramedics are at risk of occupational blood exposure, increased by the immediacy of provided treatment. However, the issue has not been acknowledged to date by any research in Europe. Methods. This research aimed at assessing occupational blood exposure among paramedics in Poland. Respondents represented 21 Polish medical institutions. Their participation was voluntary and anonymous. Paramedics were provided with a self-directed job-specific questionnaire adapted to Polish conditions from an original US version. Results. 118 paramedics participated in the study from institutions constituting the National Emergency Medical System in Poland; including ambulance crews, Helicopter Emergency Medical Services and emergency department employees. Occupational exposure was reported by 18.64% of respondents and the main route of exposure was needlestick events. Conclusions. There is a further need to improve education among paramedics concerning the threat of being infected with blood-borne pathogens through all existing routes. Our findings point to the problem as being hidden and considered a shameful issue.


The multiple roles of the unfolded protein response regulator IRE1α in cancer.
Cancer is associated with a number of conditions such as hypoxia, nutrient deprivation, cellular redox, and pH changes that result in accumulation of unfolded or misfolded proteins in the endoplasmic reticulum (ER) and trigger a stress response known as the unfolded protein response (UPR). The UPR is a conserved cellular survival mechanism mediated by the ER transmembrane proteins activating transcription factor 6, protein kinase-like endoplasmic reticulum kinase, and inositol-requiring enzyme 1α (IRE1α) that act to resolve ER stress and promote cell survival. IRE1α is a kinase/endoribonuclease (RNase) with multiple activities including unconventional splicing of the messenger RNA (mRNA) for the transcription factor X-Box Binding Protein 1 (XBP1), degradation of other mRNAs in a process called regulated IRE1α-dependent decay (RIDD) and activation of a pathway leading to c-Jun N-terminal kinase phosphorylation. Each of these outputs plays a role in the adaptive and cell death responses to ER stress. Many studies indicate an important role for XBP1 and RIDD functions in cancer and new studies suggest that these two functions of the IRE1α RNase can have opposing functions in the early and later stages of cancer pathogenesis. Finally, as more is learned about the context-dependent role of IRE1α in cancer development, specific small molecule inhibitors and activators of IRE1α could play an important role in counteracting the protective shield provided by ER stress signaling in cancer cells.


The clonogenic growth of cells derived from bladder barbotage in patients with transitional cell carcinoma of the bladder: a preliminary report.
Tumor cells obtained from bladder washings in 41 patients with transitional cell carcinoma of the bladder and 15 control subjects were analyzed for their ability to produce cluster and/or colony formation in a tumor stem cell assay. In vitro cell growth was correlated with the presence of tumor at the time of bladder washing, tumor grade and treatment status. Of 34 bladder washings from patients with biopsy-proved transitional cell carcinoma 88 per cent produced cluster and/or colony formation. Specimens from patients not currently receiving intravesical chemotherapy at the time of bladder barbotage produced colonies in 54 per cent of the cases, compared to 25 per cent from patients receiving therapeutic or maintenance therapy. Higher grade tumors produced more viable cells at bladder barbotage but clonal growth rates were independent of histologic grade. We conclude that bladder barbotage may serve as a source of cells for chemotherapeutic drug testing in patients with transitional cell carcinoma of the bladder. Bladder washings also may be useful as a source of tumor cells for monitoring the in vivo growth potential of bladder cancer in the tumor stem cell assay.


[Creutzfeldt-Jakob disease in France. Value of familial forms. Is there a gene controlling the length of the incubation period?].
An extensive search for patients who died of Creutzfeld-Jakob disease in France between 1968 and 1982 resulted in the discovery of 327 cases, 233 of which were histologically proven and 29 transmitted to animals; 17 patients belonged to 6 families. Further investigations among members of these 6 families yielded 21 additional cases, i.e. a total of 38 familial cases. Studies among sibships suggested an autosomal dominant pattern of transmission but did not exclude lateral contamination infancy. The patients' age at death was 10 to 15 years lower than that of the total of French cases and seemed to be a characteristic of each individual family. This suggests that, as in scrapie, a gene may control the length of the incubation period.


[Surgical treatment of a patient with retrosternal thyroid goiter].
The term thyroid goiter is accepted worldwide, while the terms "substernal", "retrosternal" or "intrathoracic" are not clearly agreed on. The tendency to enlarge and to compress adjacent anatomical structures and the chance of malignancy impose the surgical excision as the principal treatment option. We present our experience on the management of substernal goiter and through this, a rapid review of the literature. The last seventeen years we treated 94 patients with substernal goiter. The mean age was 57 years and the male - female ratio was 1:5. All patients had preoperatory assessment with chest X ray, ultrasound and CT scan of the neck. We performed a total thyroidectomy through cervical access in 96.7% of cases and in 3.2% through sternotomic access. We found 95.7% cases of anterior and 4.3% cases of posterior goiters, with only one ectopic goiter. Pathologic examination reveal 72.3% colloidocystic goiters, 18% adenomas, 7.4% carcinomas and 2.3% cases of thyroiditis. The most important postoperatory complications were: 2 cases of persistent hypoparathyroidism, 3 cases of recurrent damage and 2 cases of chylothorax. No deaths were observed. It is necessary a scientific agreement on the definition of substernal goiter, in order to uniform epidemiological and clinical data. Preoperative assessment is based on chest X ray, ultrasound and CT scan of the neck. Cervicotomic access represents the most frequent approach and total thyroidectomy is the procedure recommended. Postoperative complications are almost the same as for cervical goiters and mortality is nowadays extremely low.