Three cases of osteoma cutis occurring in infancy. A brief overview of osteoma cutis and its association with pseudo-pseudohypoparathyroidism.
We report three cases of primary osteoma cutis in children, two of whom (siblings) were associated with Albright's hereditary osteodystrophy (AHO), manifesting as short stature with autosomal dominant inheritance from the father, but no dysmorphic features and no parathyroid hormone (PTH) resistance. Osteoma cutis can manifest as an isolated skin disease, a secondary condition to other skin diseases (such as acne), or in association with several syndromes, including AHO, which in turn may be associated with PTH resistance. The management and prognosis of patients diagnosed with osteoma cutis is determined by whether the skin manifestation has occurred in isolation, in association with a syndrome, or as a secondary skin disease. These three paediatric cases highlight the importance of understanding the aetiology and associations of osteoma cutis in order to appropriately investigate and manage patients who present with this rare skin disease.


MRI findings in parosteal osteosarcoma: correlation with histopathology.
To assess the role of magnetic resonance imaging (MRI), particularly signal intensity changes, in predicting the dedifferentiation of parosteal osteosarcoma, and to evaluate other factors that may affect grading on MRI. MRI of 12 patients with parosteal osteosarcoma diagnosed on plain radiography were reviewed with regard to size, location, extent, soft tissue component, intramedullary invasion, and signal characteristics. The findings are correlated with histopathologic results. By histopathological examination there were 6 Grade I, 3 Grade II, and 3 Grade III tumors. Average size was 11 cm. All cases had a soft tissue component. Intramedullary extension was evident in 3/6 of the Grade I cases, 2/3 of the Grade II cases, and all (3/3) of the Grade III cases. T1-weighted images revealed lesions of marked hypointensity. Signal intensity on T2-weighted images varied with the presence of necrosis and hemorrhage in relation to size, regardless of the grade of the tumor. Contrast-enhanced images revealed enhancement of the solid components; no enhancement was observed in the necrotic or hemorrhagic parts. High and heterogeneous signal on T2-weighted images of Grade I, II, and III tumors is not specific for the dedifferentiated component, due to hemorrhage and necrosis in large masses. Therefore, high signal intensity on T2-weighted images is not always a reliable way to predict the grade of the tumor. Contrast enhanced T1-weighted images can be valuable to show the solid component in the heterogeneous areas on T2-weighted images, and can be useful in guiding the biopsy.


Management of the oral manifestations of senile purpura in an edentulous patient: a case report.
Senile purpura occurs because of a weakness of the vascular supporting tissues mainly caused by aging and is most often seen on the dorsal surface of the hands and the extensor surfaces of the forearms, and has also been observed in the oral mucosa of elderly patients. These red lesions present as sharply margined subcutaneous hemorrhagic spots and are due to trauma, such as damage to the endothelium of small blood vessels, or a coagulation defect. They can also be due to reduced perivascular support, or capillary fragility and permeability, or a combination of all of these factors. Oral manifestation of senile purpura can also be induced by long periods of medication use leading to fragile areas of the mucosa. The presence of senile purpura requires continuous follow-up since drug-induced purpura may cause plaque function alterations. An accurate diagnosis in elderly complete denture wearers can minimize bleeding and prevent possible development of ulcerations under the dentures, especially during the adaptation period to the prosthesis. This case report, presents the care and 3-year follow-up of a 66-year-old woman with complete dentures who presented with the oral manifestations of senile purpura caused by the continued use of several medications.


Implementing Parent-Teen Motivational Interviewing + Behavior Therapy for ADHD in Community Mental Health.
Despite the promise of psychosocial interventions for adolescent Attention Deficit Hyperactivity Disorder (ADHD), there are no studies that examine their implementation in community mental health contexts. In this study, we evaluate the implementation of community-based Supporting Teens' Autonomy Daily (STAND), a parent-teen Motivational Interviewing + Behavior Therapy intervention for adolescents with ADHD. Adolescents with ADHD (N = 225), who were clients at four community mental health agencies, received treatment from 82 therapists. There was double randomization of adolescents and therapists to STAND or Usual Care (UC). Nearly all therapists randomized to STAND completed the training and regularly attended supervision, rating STAND as acceptable and lower burden than UC practices. In the STAND group, MI competence and implementation were lower than in university trials (benchmark range, 19.5% for reflection to question ratio to 83.1% for technical globals). MI integrity in the STAND group was significantly higher than UC across most MITI indices. Content fidelity was adequate in STAND's engagement and skills phases (76.4-85.0%), but not its planning phase (24.4%). Therapists commonly neglected weekly review of goals and home practice and deviated from manualized pace and sequencing of therapy tasks. Learning MI was more challenging for bilingual therapists and therapists with more years of experience. STAND was delivered with higher integrity in earlier sessions and office-based sessions. Discussion identifies future directions for exporting adolescent ADHD interventions to community settings. Patient outcome data for this trial is presented elsewhere. Trial Registration: NCT02694939 www.clinicaltrials.gov .


A Single-Center Study Comparison of Two Different Male-to-Female Penile Skin Inversion Vaginoplasty Techniques and Their 3.5-Year Outcomes.
Vaginoplasty is a crucial part of genital gender-affirming surgery with the number of trans women undergoing this intervention steadily, however, up to date, there is still no standardized vaginoplasty technique. This retrospective single-center study compares single-stage vs two-stage penile skin inversion vaginoplasty techniques and their long-term outcomes. Medical records of 63 consecutive patients who underwent single-stage vaginoplasty, as described by Dr Preecha Tiewtranon, and 62 consecutive patients who underwent 2-stage vaginoplasty were reviewed. The mean postoperative hospital stay was 7 days for patients who underwent single-stage vaginoplasty vs 16 days for patients who underwent 2-stage vaginoplasty. Neovaginal depth proved constant in patients who underwent single-stage vaginoplasty, whereas a loss of more than 30% was observed in patients who underwent 2-stage vaginoplasty during the first postoperative year. Early complications were more common than late-onset complications in both groups. The most common complication in the single-stage group was wound dehiscence (4.8%). There were significantly more complications in 2-stage collective, among which wound dehiscence (33.9%), unsatisfactory cosmetic outcome (25.8%), and urethral stenosis (14.5%) were the most common. In the single-stage cohort, 4 (6.4%) patients needed one revision surgery, whereas 35 (56.5%) patients in the 2-stage cohort necessitated one or more reoperations with up to 10 quaternary revisions. All patients reported to have sensitivity to neoclitoris in the single-stage group, whereas 3 (4.8%) patients in the 2-stage group were deprived of it because of neoclitoral necrosis. Optimizing a vaginoplasty surgical technique and its postoperative protocol. The present retrospective study with a mean follow-up of more than 3.5 years offers the first ever comparison of 2 different PSI vaginoplasty surgical techniques performed in the same center. Significantly lower complication and revision rates, shorter recovery time, and superior esthetic and functional outcomes were observed in the single-stage than in the two-stage penile skin inversion vaginoplasty surgical technique. Fakin RM, Giovanoli P. A Single-Center Study Comparison of Two Different Male-to-Female Penile Skin Inversion Vaginoplasty Techniques and Their 3.5-Year Outcomes. J Sex Med 2021;18:391-399.


Aerodynamic impact of the ventricular folds in computational larynx models.
Ventricular folds (VeFs) act as passive, non-moving structures during normal phonation. According to the literature, VeFs potentially aid the flow-driven oscillations of the vocal folds (VFs) that produce the primary sound of human phonation. In this study, large eddy simulations were performed to analyze this influence in a numerical model with imposed VF motion as measured experimentally from a synthetic silicone vocal fold model. Model configurations with and without VeFs were considered. Furthermore, configurations with rectangular and elliptical glottis shapes were simulated to investigate the effects of three-dimensional glottal jet evolutions. Results showed that VeFs increased flow rate and transglottal pressure difference by a decrease in the pressure level in the ventricles immediately downstream of the VFs. This led to an increase in the glottal flow resistance, increased energy transfer rate between the flow and VFs, and a simultaneous decrease in the laryngeal flow resistance, which shows a higher amount of kinetic energy in the glottal flow. This enhancement was more pronounced in the rectangular glottis and varied with the subglottal pressure and VeF gap size.


[Dactyloscopy in children with retarded psychic development].
To reveal constitutional liability of children with mental retardation (MR), dactiloscopy was performed in 200 children with MR of a cerebral-organic genesis (129 boys and 61 girls), 110 normal children (56 boys and 54 girls) and 95 children with an undifferentiated form of oligophrenia at the stage of debility (68 boys and 27 girls). It was found that mentally retarded children as compared to normal children more frequently had a pattern of the "coil" type, dysplasia of the crest lines, less marked bimanual symmetry of patterns and less pronounced sex differences in the frequency of finger patterns.


Interdependency of EGF and GLP-2 Signaling in Attenuating Mucosal Atrophy in a Mouse Model of Parenteral Nutrition.
Total parenteral nutrition (TPN), a crucial treatment for patients who cannot receive enteral nutrition, is associated with mucosal atrophy, barrier dysfunction, and infectious complications. Glucagon-like peptide-2 (GLP-2) and epidermal growth factor (EGF) improve intestinal epithelial cell (IEC) responses and attenuate mucosal atrophy in several TPN models. However, it remains unclear whether these 2 factors use distinct or overlapping signaling pathways to improve IEC responses. We investigated the interaction of GLP-2 and EGF signaling in a mouse TPN model and in patients deprived of enteral nutrition. Adult C57BL/6J, IEC-Egfrknock out (KO) and IEC-pik3r1KO mice receiving TPN or enteral nutrition were treated with EGF or GLP-2 alone or in combination with reciprocal receptor inhibitors, GLP-2(3-33) or gefitinib. Jejunum was collected and mucosal atrophy and IEC responses were assessed by histologic, gene, and protein expression analyses. In patients undergoing planned looped ileostomies, fed and unfed ileum was analyzed. Enteral nutrient deprivation reduced endogenous EGF and GLP-2 signaling in mice and human beings. In the mouse TPN model, exogenous EGF or GLP-2 attenuated mucosal atrophy and restored IEC proliferation. The beneficial effects of EGF and GLP-2 were decreased upon Gefitinib treatment and in TPN-treated IEC-EgfrKO mice, showing epidermal growth factor-receptor dependency for these IEC responses. By contrast, in TPN-treated IEC-pi3kr1KO mice, the beneficial actions of EGF were lost, although GLP-2 still attenuated mucosal atrophy. Upon enteral nutrient deprivation, exogenous GLP-2 and EGF show strong interdependency for improving IEC responses. Understanding the differential requirements for phosphatidylinositol 3-kinase/phosphoAKT (Ser473) signaling may help improve future therapies to prevent mucosal atrophy.


["Imperial madness" - truth or legend?].
The notion of "imperial madness" was coined in the historical literature and belles-lettres of the 19th century. Around that time up to the first quarter of the 20th century, it was adopted by a few German psychiatrists. Two of them viewed "imperial madness" as ordinary forms of insanity which became excessive only due to reactions of the social environment. Another one, however, classified it as one of "mental borderland states" in between insanity and normality, although he conceived the final stage of the disorder as a paranoid one. In agreement with the historians he postulated that "imperial madness" resulted from unlimited power of predisposed rulers. In recent times the whole concept of "imperial madness" was referred to the realm of legends by historians of antiquity and other historically interested authors. Yet the existence of the phenomenon cannot be denied. Despite its rarity it has played and is still playing an important role with often catastrophic consequences in various cultures all over the world. Therefore, psychiatrists and other physicians as well as clinical psychologists should be acquainted with it. From a modern point of view, it is not a paranoid disorder but rather a syndrome of addiction-like behavioural excesses representing an intensification of a Hybris syndrome as described by Anglo-Saxon psychiatrists. According to the present authors' view, it should be classified nosologically as a chronic adjustment disorder. In this case, the underlying stresses need to be extended to situations of temptation (here: the temptation to abuse almost unlimited power).


Outcomes of therapeutic selective nerve root blocks for whiplash induced cervical radicular pain.
This study was designed to investigate the clinical efficacy of fluoroscopically guided therapeutic cervical selective nerve root blocks (SNRBs) in patients with whiplash induced cervical radicular pain. Study design was restrospective with independent clinical review. Twenty two patients were included. Each patient met specific physical examination criteria and failed to improve clinically after at least four weeks of physical therapy and the use of oral analgesics. Each patient demonstrated a positive response to a fluoroscopically guided diagnostic cervical SNRB. Patients were excluded for radiographic evidence of a focal disc protrusion or foraminal stenosis at the symptomatic level. Therapeutic cervical SNRBs were administered in conjunction with physical therapy. Data collection and analysis were performed by an independent clinical reviewer. Outcome measures included VAS pain scores, work status, medication usage, and Oswestry disability scores. Results showed the patients' symptom duration prior to diagnostic injection averaged 6 months. An average of 2.1 therapeutic injections was administered. Follow up data collection transpired at an average of 33.3 weeks following the final therapeutic injection. Good or excellent results were observed in 14% of patients. In higher functioning individuals a significantly greater (F=.0427) improvement in pain of 48.9% was observed. In these initial findings suggest that fluoroscopically guided therapeutic SNRBs, except possibly for higher functioning individuals, are not effective in the treatment of whiplash induced cervical radicular pain.


Screening in child health: studies of the efficacy and relevance of preventive care practices.
Pediatric screening enables the prevention or early detection of diseases and developmental disturbances in infancy and childhood. Screening is a standard component of pediatric practice in many countries, but its scientific basis is not well known. The scientific justification for pediatric screening beyond the neonatal period is presented on the basis of a selective review of the literature on some aspects of pediatric screening. The level of evidence varies highly among pediatric screening interventions and can be difficult to determine because of confounding variables. Parent counseling is associated with improvements in child-raising competence, accident prevention, and reading behavior. The early detection of abnormalities in a child's motor, linguistic, mental, or social development is possible and often leads to effective early interventions. Cyanotic congenital heart defects can be detected with 63% sensitivity and 99.8% specificity; cerebral palsy can be diagnosed with 33% to 100% sensitivity and 52.3% to 100% specificity (different figures from multiple studies). Physical therapy seems to improve some manifestations of cerebral palsy. Motor development at 90 days is correlated with motor development at 57 months (72% sensitivity, 91% specificity). A developmental quotient above 85 in a two-year-old child is correlated with an intelligence quotient above 85 when the child is 7 years old. There is an increasing amount of scientific evidence in favor of pediatric screening. Nonetheless, further epidemiological studies are needed.


Tumour of the sciatic nerve.
A malignant neurilemmoma of the sciatic nerve is described. The requisites for making this diagnosis are discussed. It is pointed out that such tumours are commonly misdiagnosed as lumbar intervertebral discs and that local examination of the leg along the course of the sciatic nerve should be carried out on every patient complaining of sciatica.


[Endobiliary stenting with laparoscopic assistance--hybrid technology in complicated clinical situation].
The authors suggest an original method of endobiliary stenting with laparoscopic assistance for reduction of obstructive jaundice in patients with non-operative tumors of hepatopancreaduodenal zone in the case of impossibility of performance of percutaneous or endoscopic decompression of the bile ducts. A recanalization of tumor stricture was carried out with the aid of laparoscopic assistance. A self-expandable metal stent with polymeric covering was implanted in the bile ducts. The proposed method was applied in 5 cases. An adequate decompression of the bile ducts was noted in all cases. The patient's condition was good after surgery. There weren't any cases of serious complications or hospital lethality.


Treatment of men with erectile dysfunction with transurethral alprostadil. Medicated Urethral System for Erection (MUSE) Study Group.
Erectile dysfunction in men is common. We evaluated a system by which alprostadil (prostaglandin E1) is delivered transurethrally to treat this disorder. Alprostadil was delivered transurethrally in a double-blind, placebo-controlled study of 1511 men, 27 to 88 years of age, who had chronic erectile dysfunction from various organic causes. The men were first tested in the clinic with up to four doses of the drug (125, 250, 500, and 1000 microg); those who had sufficient responses were randomly assigned to treatment with either the effective dose of alprostadil or placebo for three months at home. During in-clinic testing, 996 men (65.9 percent) had erections sufficient for intercourse. Of these men, 961 reported the results of at least one home treatment; 299 of the 461 treated with alprostadil (64.9 percent) had intercourse successfully at least once, as compared with 93 of the 500 who received placebo (18.6 percent, P<0.001). On average, 7 of 10 alprostadil administrations were followed by intercourse in men responsive to treatment. The efficacy of alprostadil was similar regardless of age or the cause of erectile dysfunction, including vascular disease, diabetes, surgery, and trauma (P<0.001 for all comparisons with placebo). The most common side effect was mild penile pain, which occurred after 10.8 percent of alprostadil treatments, but the pain rarely resulted in refusal to continue in the study. Hypotension occurred in the clinic in 3.3 percent of men receiving alprostadil. Hypotension-related symptoms were uncommon at home. No men had priapism or penile fibrosis. In men with erectile dysfunction, transurethral alprostadil therapy resulted in erections in the clinic and in intercourse at home.


Support for a bipolar affective disorder susceptibility locus on chromosome 12q24.3.
Linkage and association studies of bipolar affective disorder (BAD) point out chromosome 12q24 as a region of interest. To investigate this region further, we conducted an association study of 22 DNA markers within a 1.14 Mb region in a Danish sample of 166 patients with BAD and 311 control individuals. Two-hundred and four Danish patients with schizophrenia were also included in the study. We observed highly significant allelic and genotypic association between BAD and two highly correlated markers. The risk allele of both markers considered separately conferred an odds ratio of 2 to an individual carrying one risk allele and an odds ratio of 4 for individuals carrying both risk alleles assuming an additive genetic model. These findings were supported by the haplotype analysis. In addition, we obtained a replication of four markers associated with BAD in an earlier UK study. The most significantly associated marker was also analyzed in a Scottish case-control sample and was earlier associated with BAD in the UK cohort. The association of that particular marker was strongly associated with BAD in a meta-analysis of the Danish, Scottish and UK sample (P=0.0003). The chromosome region confined by our most distant markers is gene-poor and harbours only a few predicted genes. This study implicates the Slynar locus. We confirmed one annotated Slynar transcript and identified a novel transcript in human brain cDNA. This study confirms 12q24.3 as a region of functional importance in the pathogenesis of BAD and highlights the importance of focused genotyping.


Tracking of muscular strength and power from youth to young adulthood: Longitudinal findings from the Childhood Determinants of Adult Health Study.
Low muscular fitness levels have previously been reported as an independent risk factor for chronic disease outcomes. Muscular fitness tracking, the ability to maintain levels measured at one point in time to another point in time, was assessed from youth to adulthood to provide insight into whether early identification of low muscular fitness in youth is possible. Prospective longitudinal study. Study including 623 participants who had muscular fitness measures in 1985 (aged 9, 12 or 15 years) and again 20 years later in young adulthood. Measures of muscular fitness were strength (right and left grip, leg, shoulder extension and flexion measured by dynamometer, and a combined strength score) and power (standing long jump distance). Strength and power were relatively stable between youth and adulthood; the strongest tracking correlations were observed for the combined strength score (r=0.47, p≤0.001), right grip strength (r=0.43, p≤0.001) and standing long jump (r=0.43, p≤0.001). Youth in the lowest third of muscular fitness had an increased risk of remaining in the lowest third of muscular fitness in adulthood (strength: relative risk (RR)=4.70, 95% confidence interval (CI) (3.19, 6.92); power: RR=4.06 (2.79, 5.90)). Youth with low muscular fitness are at increased risk of maintaining a low muscular fitness level into adulthood. These findings warrant investigation into the long term effects of early interventions that focus on improving low muscular fitness levels in youth which could potentially improve adult muscular fitness and reduce future chronic disease outcomes.


Acute effects of cigarette smoke inhalation on the Syrian hamster lungs.
Syrian golden hamsters were exposed to the smoke from a number of experimental cigarettes which contained differing amounts of nicotine and carbon monoxide. Pulmonary hemorrhages were induced, the number of which were clearly dependent on the nicotine content of the cigarette smoke. Electron microscopy revealed cytoplasmic swelling and ruptured cell membranes in alveolar type 1 cells and endothelial cells.


Targeted delivery of diclofenac sodium via gelatin magnetic microspheres formulated for intra-arterial administration.
In the present work, we have attempted to deliver diclofenac sodium to a target site by intra-arterial injection of gelatin magnetic microspheres and subsequent localization using an external magnet. Drug-loaded magnetic microspheres were prepared by emulsification/cross-linking method, characterized by drug loading, magnetite content, size distribution, optical microscopy, scanning electron microscopy (SEM), Fourier transform infrared (FT-IR) analysis, differential scanning calorimetry (DSC), X-ray diffraction (XRD), absence of glutaraldehyde by gas chromatography, and in vitro release studies. The targeting efficiency and the therapeutic efficacy of microspheres were studied in vivo in rabbits. The microspheres showed drug loading of 9.1, 18.7, 24.9% w/w, magnetite content of 27.8-28.9% w/w with an average size range of 25-30.6 mum, depending upon the drug-polymer ratio. They were spherical in nature as evidenced by optical microscopy and SEM. FT-IR, DSC, and XRD studies revealed the absence of drug-polymer interaction. Gas chromatography confirmed the absence of residual glutaraldehyde. The microspheres were able to prolong the drug release over 24-30 days and the application of sonication during in vitro release study has slightly increased the release rate. After intra-arterial administration of microspheres, 77.7% of injected dose was recovered at the target site which revealed good targeting efficiency. The microspheres effectively reduced joint swelling, but lesser extent than the oral diclofenac sodium in high dose, in antigen induced arthritic rabbits without producing gastric ulceration which was observed in rabbits treated with oral diclofenac sodium.


Effects of a Preventive Mental Health Curriculum Embedded Into a Scholarly Gaming Course on Adolescent Self-Esteem: Prospective Matched Pairs Experiment.
Positive self-esteem predicts happiness and well-being and serves as a protective factor for favorable mental health. Scholarly gaming within the school setting may serve as a channel to deliver a mental health curriculum designed to improve self-esteem. This study aims to evaluate the impact of a scholarly gaming curriculum with and without an embedded preventive mental health curriculum, Mental Health Moments (MHM), on adolescents' self-esteem. The scholarly gaming curriculum and MHM were developed by 3 educators and a school-based health intervention expert. The scholarly gaming curriculum aligned with academic guidelines from the International Society for Technology Education, teaching technology-based career skills and video game business development. The curriculum consisted of 40 lessons, delivered over 14 weeks for a minimum of 120 minutes per week. A total of 83 schools with previous gaming engagement were invited to participate and 34 agreed. Schools were allocated to +MHM or -MHM arms through a matched pairs experimental design. The -MHM group received the scholarly gaming curriculum alone, whereas the +MHM group received the scholarly gaming curriculum plus MHM embedded into 27 lessons. MHM integrated concepts from the PERMA framework in positive psychology as well as the Collaborative for Academic, Social, and Emotional Learning (CASEL) standards in education, which emphasize self-awareness, self-management, social awareness, relationship skills, and responsible decision-making. Participants in the study were students at schools offering scholarly gaming curricula and were enrolled at recruitment sites. Participants completed a baseline and postintervention survey quantifying self-esteem with the Rosenberg Self-Esteem Scale (score range 0-30). A score <15 characterizes low self-esteem. Participants who completed both baseline and postintervention surveys were included in the analysis. Of the 471 participants included in the analysis, 235 received the -MHM intervention, and 236 received the +MHM intervention. Around 74.9% (n=353) of participants were in high school, and most (n=429, 91.1%) reported this was their first year participating in scholarly gaming. Most participants were male (n=387, 82.2%). Only 58% (n=273) reported their race as White. The average self-esteem score at baseline was 17.9 (SD 5.1). Low self-esteem was reported in 22.1% (n=104) of participants. About 57.7% (n=60) of participants with low self-esteem at baseline rated themselves within the average level of self-esteem post intervention. When looking at the two groups, self-esteem scores improved by 8.3% among the +MHM group compared to no change among the -MHM group (P=.002). Subgroup analyses revealed that improvements in self-esteem attributed to the +MHM intervention differed by race, gender, and sexual orientation. Adolescents enrolled in a scholarly gaming curriculum with +MHM had improved self-esteem, shifting some participants from abnormally low self-esteem scores into normal ranges. Adolescent advocates, including health care providers, need to be aware of nontraditional educational instruction to improve students' well-being.


P fimbriation among biochemically inactive strains of Escherichia coli of the group formerly called Alkalescens-Dispar.
Biochemically inactive, non-motile strains of Escherichia coli of the group formerly known as Alkalescens-Dispar (AD) and of known AD serogroups were analysed for biotype, resistotype, type-1 fimbriation, P fimbriation and haemolysin production. All strains of AD serogroups O1 and O2 examined were P-fimbriate and of closely related bio-resistotypes, suggesting that they may be representatives of two E. coli P-fimbriate clones, members of which have not infrequently been isolated from infected urine.


Treatment of celiac disease: from gluten-free diet to novel therapies.
Gluten-free diet (GFD) is the cornerstone treatment for celiac disease (CD). This diet excludes the protein gluten a protein forum in in grains such as wheat, barley, rye and triticale. Gluten causes small intestines inflammation in patients with CD and eating a GFD helps these patients in controlling signs and symptoms and prevent complications. Following a GFD may be frustrating, however, it is important to know that plenty of foods are naturally gluten-free and nowadays is relatively easy to find substitutes for gluten-containing foods. Certain grains, such as oats, are generally safe but can be contaminated with wheat during growing and processing stages of production. For this reason, it is generally recommended avoiding oats unless they are specifically labelled gluten-free. Other products that may contain gluten include food additives, such as malt flavouring, modified food starch and some supplement and/or vitamins that use gluten as a binding agent. Cross-contamination occurs when gluten-free foods come into contact with foods that contain gluten. It can happen during the manufacturing process or if the same equipment is used to make a variety of products. Cross-contamination can also occur at home if foods are prepared on common surfaces or with utensils that have not been cleaned after being used to prepare gluten-containing foods (using a toaster for gluten-free and regular bread). Although safe and effective, the GFD is not ideal: it is expensive, of limited nutritional value, and not readily available in many countries. Consequently, a need exists for novel, non-dietary therapies for celiac disease. Advances in understanding the immunopathogenesis of CD have suggested several types of therapeutic strategies alternative to the GFD. Some of these strategies attempt to decrease the immunogenicity of gluten-containing grains by manipulating the grain itself or by using oral enzymes to break down immunogenic peptides that normally remain intact during digestion. Other strategies focus on preventing the absorption of these peptides, preventing tissue transglutaminase from rendering gluten peptides more immunogenic, or inhibiting their binding to CD-specific antigen-presenting molecules. Strategies that limit T cell migration to the small intestine or that re-establish mucosal homeostasis and tolerance to gluten antigens are also being explored.


Mucormycosis in COVID-19 patients: A cross-sectional study at IGIMS, Patna.
During the second wave of COVID-19, the incidence of mucormycosis has increased more rapidly. The most common causes attributed to the rise of mucormycosis in COVID-19 are uncontrolled diabetes, the excessive use of corticosteroids, and long-term stays in the intensive care unit, organ or bone marrow transplantation, etc. To determine the sociodemographic and associated risk factors, pattern of disease, treatment of mucormycosis and outcome of individual at time of discharge and after three months and six months of follow-up. This cross-sectional study included all treated mucormycosis cases with prior COVID-19 infection. Data collected from medical records using purposive sampling. Survivors followed up at 3 and 6 months after discharge. In our study, we analyzed 161 mucormycosis cases identified through positive RTPCR/Rapid Antigen reports. Among them, 72% were males and 28% were females. Diabetes mellitus was present in 71.4% and hypertension in 29.8% of patients. The case-fatality rate was 6.8% at discharge, increasing to 18.6% after 3 months and 28% after 6 months of follow-up. Statistical analysis was conducted using SPSS version 15. This analysis helped us draw meaningful conclusions from the data, highlighting the impact of comorbidities and time on mucormycosis outcomes. Post-COVID mucormycosis in India was primarily observed in patients with uncontrolled diabetes, immunodeficiency due to other comorbidities, and dysfunctional immune systems.


The dynamics of acute inflammation.
When the body is infected, it mounts an acute inflammatory response to rid itself of the pathogens and restore health. Uncontrolled acute inflammation due to infection is defined clinically as sepsis and can culminate in organ failure and death. We consider a three-dimensional ordinary differential equation model of inflammation consisting of a pathogen, and two inflammatory mediators. The model reproduces the healthy outcome and diverse negative outcomes, depending on initial conditions and parameters. We analyze the various bifurcations between the different outcomes when key parameters are changed and suggest various therapeutic strategies. We suggest that the clinical condition of sepsis can arise from several distinct physiological states, each of which requires a different treatment approach.


Probiotics for the prevention of pediatric antibiotic-associated diarrhea.
Antibiotics alter the microbial balance commonly resulting in antibiotic-associated diarrhea (AAD). Probiotics may prevent AAD via providing gut barrier, restoration of the gut microflora, and other potential mechanisms of action. The primary objectives were to assess the efficacy and safety of probiotics (any specified strain or dose) used for the prevention of AAD in children. MEDLINE, Embase, CENTRAL, CINAHL, and the Web of Science (inception to 28 May 2018) were searched along with registers including the ISRCTN and Clinicaltrials.gov. We also searched the NICE Evidence Services database as well as reference lists from relevant articles. Randomized, parallel, controlled trials in children (0 to 18 years) receiving antibiotics, that compare probiotics to placebo, active alternative prophylaxis, or no treatment and measure the incidence of diarrhea secondary to antibiotic use were considered for inclusion. Study selection, data extraction, and risk of bias assessment were conducted independently by two authors. Dichotomous data (incidence of AAD, adverse events) were combined using a pooled risk ratio (RR) or risk difference (RD), and continuous data (mean duration of diarrhea) as mean difference (MD), along with corresponding 95% confidence interval (95% CI). We calculated the number needed to treat for an additional beneficial outcome (NNTB) where appropriate. For studies reporting on microbiome characteristics using heterogeneous outcomes, we describe the results narratively. The certainty of the evidence was evaluated using GRADE. Thirty-three studies (6352 participants) were included. Probiotics assessed included Bacillus spp., Bifidobacterium spp., Clostridium butyricum, Lactobacilli spp., Lactococcus spp., Leuconostoc cremoris, Saccharomyces spp., orStreptococcus spp., alone or in combination. The risk of bias was determined to be high in 20 studies and low in 13 studies. Complete case (patients who did not complete the studies were not included in the analysis) results from 33 trials reporting on the incidence of diarrhea show a precise benefit from probiotics compared to active, placebo or no treatment control.After 5 days to 12 weeks of follow-up, the incidence of AAD in the probiotic group was 8% (259/3232) compared to 19% (598/3120) in the control group (RR 0.45, 95% CI 0.36 to 0.56; I² = 57%, 6352 participants; NNTB 9, 95% CI 7 to 13; moderate certainty evidence). Nineteen studies had loss to follow-up ranging from 1% to 46%. After making assumptions for those lost, the observed benefit was still statistically significant using an extreme plausible intention-to-treat (ITT) analysis, wherein the incidence of AAD in the probiotic group was 12% (436/3551) compared to 19% (664/3468) in the control group (7019 participants; RR 0.61; 95% CI 0.49 to 0.77; P <0.00001; I² = 70%). An a priori available case subgroup analysis exploring heterogeneity indicated that high dose (≥ 5 billion CFUs per day) is more effective than low probiotic dose (< 5 billion CFUs per day), interaction P value = 0.01. For the high dose studies the incidence of AAD in the probiotic group was 8% (162/2029) compared to 23% (462/2009) in the control group (4038 participants; RR 0.37; 95% CI 0.30 to 0.46; P = 0.06; moderate certainty evidence). For the low dose studies the incidence of AAD in the probiotic group was 8% (97/1155) compared to 13% (133/1059) in the control group (2214 participants; RR 0.68; 95% CI 0.46 to 1.01; P = 0.02). Again, assumptions for loss to follow-up using an extreme plausible ITT analysis was statistically significant. For high dose studies the incidence of AAD in the probiotic group was 13% (278/2218) compared to 23% (503/2207) in control group (4425 participants; RR 0.54; 95% CI 0.42 to 0.70; P <0.00001; I² = 68%; moderate certainty evidence).None of the 24 trials (4415 participants) that reported on adverse events reported any serious adverse events attributable to probiotics. Adverse event rates were low. After 5 days to 4 weeks follow-up, 4% (86/2229) of probiotics participants had an adverse event compared to 6% (121/2186) of control participants (RD 0.00; 95% CI -0.01 to 0.01; P < 0.00001; I² = 75%; low certainty evidence). Common adverse events included rash, nausea, gas, flatulence, abdominal bloating, and constipation.After 10 days to 12 weeks of follow-up, eight studies recorded data on our secondary outcome, the mean duration of diarrhea; with probiotics reducing diarrhea duration by almost one day (MD -0.91; 95% CI -1.38 to -0.44; P <0.00001; low certainty evidence). One study reported on microbiome characteristics, reporting no difference in changes with concurrent antibiotic and probiotic use. The overall evidence suggests a moderate protective effect of probiotics for preventing AAD (NNTB 9, 95% CI 7 to 13). Using five criteria to evaluate the credibility of the subgroup analysis on probiotic dose, the results indicate the subgroup effect based on high dose probiotics (≥ 5 billion CFUs per day) was credible. Based on high-dose probiotics, the NNTB to prevent one case of diarrhea is 6 (95% CI 5 to 9). The overall certainty of the evidence for the primary endpoint, incidence of AAD based on high dose probiotics was moderate due to the minor issues with risk of bias and inconsistency related to a diversity of probiotic agents used. Evidence also suggests that probiotics may moderately reduce the duration of diarrhea, a reduction by almost one day. The benefit of high dose probiotics (e.g. Lactobacillus rhamnosus orSaccharomyces boulardii) needs to be confirmed by a large well-designed multi-centered randomized trial. It is premature to draw firm conclusions about the efficacy and safety of 'other' probiotic agents as an adjunct to antibiotics in children. Adverse event rates were low and no serious adverse events were attributable to probiotics. Although no serious adverse events were observed among inpatient and outpatient children, including small studies conducted in the intensive care unit and in the neonatal unit, observational studies not included in this review have reported serious adverse events in severely debilitated or immuno-compromised children with underlying risk factors including central venous catheter use and disorders associated with bacterial/fungal translocation.


Simultaneous use of bilateral subthalamic nucleus stimulators and an implantable cardiac defibrillator. Case report.
Bilateral electrical stimulation of the subthalamic nucleus is being used with increasing frequency as a treatment for severe Parkinson disease (PD). Implantable cardiac defibrillators improve survival in certain high-risk patients with coronary artery disease and ventricular arrhythmias. Because of concern about possible interaction between these devices, deep brain stimulation (DBS) systems are routinely disconnected before defibrillators are implanted in patients with PD and arrhythmia. The authors report on a patient with bilateral subthalamic stimulators who underwent successful placement of an implantable defibrillator. Testing of the devices over a wide range of settings revealed no interaction. The patient subsequently underwent multiple episodes of cardioversion when the ventricular lead became dislodged. There was no evidence of adverse neurological effects, and interrogation of the DBS devices after cardioversion revealed no changes in stimulus parameters. The outcome in this case indicates that DBS systems may be safely retained in selected patients who require implantable cardiac defibrillators.


Network Viral Load: A Critical Metric for HIV Elimination.
Associations have been observed between an aggregate viral load measure, the community viral load, and new HIV diagnoses. The community viral load aggregates viral loads within chosen geographic areas, restricting inferences about HIV acquisition risk to these areas. We develop a more precise metric, the network viral load (NVL), to measure the composite viral load within a risk network of a HIV-negative individual. We examined the relationship between NVL and HIV infection among young men who have sex with men in Chicago, United States. Networks were generated using respondent-driven sampling. NVL was defined as the prevalence of viremic individuals in one's risk network, characterized as those with a viral load ≥20 k copies per milliliter. Permutation tests were conducted to account for dependency. After controlling for total connections, age, substance use during sex, syphilis diagnosis (previous 12 months), and frequency of condomless anal sex (previous 6 months), we found a positive association between NVL and HIV infection. Compared with a network with all HIV-seronegative members, the odds of HIV infection with an NVL of <10% viremia were 1.85 (95% confidence interval: 1.18 to 2.92) times higher and those with an NVL of ≥10% viremia were 2.73 (95% confidence interval: 1.54 to 4.85) times higher. We found a positive association between NVL and HIV seroprevalence. Although limited in its ability to infer causality, NVL could have substantial public health implications for persons most at risk for HIV infection, given that this novel metric avoids overreliance on individual level behavior or broad community indices.


Application of extended criteria donor grafts in liver transplantation for acute-on-chronic liver failure: A retrospective cohort study.
There is no consensus on the usage of extended criteria donor (ECD) grafts in liver transplantation (LT) for acute-on-chronic liver failure (ACLF) patients. To summarize the experience of using ECD livers in ACLF-LT. A retrospective cohort study was conducted, enrolling patients who underwent LT at the First Affiliated Hospital of Sun Yat-Sen University from January 2015 to November 2021. The patients were divided into ECD and non-ECD groups for analysis. A total of 145 recipients were enrolled in this study, of which ECD and non-ECD recipients accounted for 53.8% and 46.2%, respectively. Donation after cardiac death (DCD) recipients accounted for the minority compared with donation after brain death (DBD) recipients (16.6% vs 83.4%). Neither overall survival nor graft survival significantly differed between ECD and non-ECD and DCD and DBD recipients. ECD grafts were associated with a significantly higher incidence of early allograft dysfunction (EAD) than non-ECD grafts (67.9% vs 41.8%, P = 0.002). Postoperative outcomes between DCD and DBD recipients were comparable (P > 0.05). ECD graft (P = 0.009), anhepatic phase (P = 0.034) and recipient gamma glutamyltransferase (P = 0.016) were independent risk factors for EAD. Recipient preoperative number of extrahepatic organ failures > 2 (P = 0.015) and intraoperative blood loss (P = 0.000) were independent predictors of poor post-LT survival. Although related to a higher risk of EAD, ECD grafts can be safely used in ACLF-LT. The main factors affecting post-LT survival in ACLF patients are their own severe preoperative disease and intraoperative blood loss.


A crosstalk-suppressed dense multi-view light-field display based on real-time light-field pickup and reconstruction.
A crosstalk-suppressed dense multi-view light-field display based on real-time light-field pickup and reconstruction is demonstrated, which is capable of realizing high view density in the horizontal direction with low crosstalk between micro-pitch viewing zones. The micro-pinhole unit array and the vertically-collimated backlight are specially developed and used, instead of refraction-based optical components like lenticular lens, to avoid aberrations and to suppress crosstalk for accurately projecting multiple view perspectives into each eye pupil of the viewer. Additionally, the spatial information entropy is defined and investigated to improve 3D image perception for balancing resolution, which can be generally applicable to better-reconstructed 3D images with the limited number of resolution pixels. To enlarge the viewing angle of 3D images with smooth motion parallax, the novel high-efficient light-field pickup and reconstruction method based on the real-time position of the viewer's pupils is implemented with an eye tracker to scan 750 view perspectives with the correct geometric occlusion in real time at the frame rate of 40 fps. In the experiment, a floating horizontal-parallax 3D light-field image with the view density of 0.75 mm-1 and the micro-pitch crosstalk of less than 7% can be perceived with the clear floating focus depth of 10 cm and the high resolution of 1920 × 1080 in the viewing angle of 70°.


Cloning, DNA sequence, and expression of the Rhodobacter sphaeroides light-harvesting B800-850-alpha and B800-850-beta genes.
Two deoxyoligonucleotide probes were synthesized in accordance with the available amino acid sequence of the B800-850-beta polypeptide from Rhodobacter sphaeroides and were used to isolate a 2.6-kilobase PstI fragment from R. sphaeroides 2.4.1 chromosomal DNA. Identification of the B800-850-beta and B800-850-alpha structural genes, pucB and pucA, was confirmed by DNA sequencing. Northern (RNA) blot analysis, using restriction endonuclease fragments from the cloned genes as probes, revealed a single puc-operon-specific, highly stable transcript of approximately 640 bases present in photosynthetically grown cells. In vitro transcription-translation analysis of the puc operon revealed that the maximum synthesis of the puc operon gene products was achieved when the entire 2.6-kilobase PstI fragment was used as the template, although a 537-base-pair XmaIII fragment was sufficient to direct the synthesis of pucB and pucA fusion product.


A conserved role for kinesin-5 in plant mitosis.
The mitotic spindle of vascular plants is assembled and maintained by processes that remain poorly explored at a molecular level. Here, we report that AtKRP125c, one of four kinesin-5 motor proteins in arabidopsis, decorates microtubules throughout the cell cycle and appears to function in both interphase and mitosis. In a temperature-sensitive mutant, interphase cortical microtubules are disorganized at the restrictive temperature and mitotic spindles are massively disrupted, consistent with a defect in the stabilization of anti-parallel microtubules in the spindle midzone, as previously described in kinesin-5 mutants from animals and yeast. AtKRP125c introduced into mammalian epithelial cells by transfection decorates microtubules throughout the cell cycle but is unable to complement the loss of the endogenous kinesin-5 motor (Eg5). These results are among the first reports of any motor with a major role in anastral spindle structure in plants and demonstrate that the conservation of kinesin-5 motor function throughout eukaryotes extends to vascular plants.


Rapidly progressive asymmetrical weakness in Charcot-Marie-Tooth disease type 4J resembles chronic inflammatory demyelinating polyneuropathy.
Charcot-Marie-Tooth disease type 4J (CMT4J), a rare form of demyelinating CMT, caused by recessive mutations in the phosphoinositide phosphatase FIG4 gene, is characterised by progressive proximal and distal weakness and evidence of chronic denervation in both proximal and distal muscles. We describe a patient with a previous diagnosis of CMT1 who presented with a two year history of rapidly progressive weakness in a single limb, resembling an acquired inflammatory neuropathy. Nerve conduction studies showed an asymmetrical demyelinating neuropathy with conduction block and temporal dispersion. FIG4 sequencing identified a compound heterozygous I41T/K278YfsX5 genotype. CMT4J secondary to FIG4 mutations should be added to the list of inherited neuropathies that need to be considered in suspected cases of inflammatory demyelinating neuropathy, especially if there is a background history of a more slowly progressive neuropathy.


Evidence for biological denitrification inhibition (BDI) by plant secondary metabolites.
Previous studies on the effect of secondary metabolites on the functioning of rhizosphere microbial communities have often focused on aspects of the nitrogen (N) cycle but have overlooked biological denitrification inhibition (BDI), which can affect plant N-nutrition. Here, we investigated the BDI by the compounds of Fallopia spp., an invasive weed shown to be associated with a low potential denitrification of the soil. Fallopia spp. extracts were characterized by chromatographic analysis and were used to test the BDI effects on the metabolic and respiratory activities of denitrifying bacteria, under aerobic and anaerobic (denitrification) conditions. The BDI of Fallopia spp. extracts was tested on a complex soil community by measuring denitrification enzyme activity (DEA), substrate induced respiration (SIR), as well as abundances of denitrifiers and total bacteria. In 15 strains of denitrifying bacteria, extracts led to a greater BDI (92%) than respiration inhibition (50%). Anaerobic metabolic activity reduction was correlated with catechin concentrations and the BDI was dose dependent. In soil, extracts reduced the DEA/SIR ratio without affecting the denitrifiers: total bacteria ratio. We show that secondary metabolite(s) from Fallopia spp. inhibit denitrification. This provides new insight into plant-soil interactions and improves our understanding of a plant's ability to shape microbial soil functioning.


Genome-wide analysis of thyroid function in Australian adolescents highlights SERPINA7 and NCOA3.
Genetic factors underpin the narrow intraindividual variability of thyroid function, although precise contributions of environmental vs genetic factors remain uncertain. We sought to clarify the heritability of thyroid function traits and thyroid peroxidase antibody (TPOAb) positivity and identify single nucleotide polymorphisms (SNPs) contributing to the trait variance. Heritability of thyroid-stimulating hormone (TSH), free T4 (fT4), free T3 (fT3) and TPOAb in a cohort of 2854 euthyroid, dizygous and monozygous twins (age range 11.9-16.9 years) from the Brisbane Longitudinal Twin Study (BLTS) was assessed using structural equation modelling. A genome-wide analysis was conducted on 2832 of these individuals across 7 522 526 SNPs as well as gene-based association analyses. Replication analysis of the association results was performed in the Raine Study (n = 1115) followed by meta-analysis to maximise power for discovery. Heritability of thyroid function parameters in the BLTS was 70.8% (95% CI: 66.7-74.9%) for TSH, 67.5% (59.8-75.3%) for fT4, 59.7% (54.4-65.0%) for fT3 and 48.8% (40.6-56.9%) for TPOAb. The genome-wide association study (GWAS) in the discovery cohort identified a novel association between rs2026401 upstream of NCOA3 and TPOAb. GWAS meta-analysis found associations between TPOAb and rs445219, also near NCOA3, and fT3 and rs12687280 near SERPINA7. Gene-based association analysis highlighted SERPINA7 for fT3 and NPAS3 for fT4. Our findings resolve former contention regarding heritability estimates of thyroid function traits and TPOAb positivity. GWAS and gene-based association analysis identified variants accounting for a component of this heritability.


The postgraduate medical educational climate assessed by the Danish Residency Educational Climate Test (DK-RECT): a validation and cross-sectional observational study.
A good educational climate is essential for delivering high-quality training for medical trainees, professional development, and patient care. The aim of this study was to (1) validate the Dutch Residency Educational Climate Test (D-RECT) in a Danish setting and (2) describe and evaluate the educational climate among medical trainees. D-RECT was adopted in a three-step process: translation of D-RECT into Danish (DK-RECT), psychometric validation, and evaluation of educational climate. Trainees from 31 medical specialties at Copenhagen University Hospital - Rigshospitalet, Denmark were asked to complete an online survey in a cross-sectional study. We performed a forward-backward translation from Dutch to Danish. Confirmatory factor analysis showed that DK-RECT was robust and valid. The reliability analysis showed that only seven trainees from one specialty were needed for a reliable result. With 304 trainees completing DK-RECT, the response rate was 68%. The subsequent analysis indicated a positive overall educational climate, with a median score of 4.0 (interquartile range (IQR): 3.0-5.0) on a five-point Likert scale. Analysis of the subscales showed that the subscale Feedback received the lowest ratings, while Supervision and Peer collaboration were evaluated highest. Psychometric validation of D-RECT in a Danish context demonstrated valid results on the educational climate in specialist training. DK-RECT can be used to evaluate the effectiveness of interventions in the future and can facilitate the conversation on the educational climate.


Chronic disease profiles of subjective memory complaints: a latent class analysis of older people in a rural Malaysian community.
Background: Subjective memory complaints (SMC) are common in the elderly and have been suggested as the first subtle sign of decline which can predict dementia. Cognitive decline is thought to be related to inflammatory processes similarly found in other chronic diseases and conditions such as stroke, heart disease and arthritis. This study aimed to examine the association of SMC with chronic diseases and the profile of these health conditions reported by a group of older adults.Methods: Data from a cross-sectional survey conducted from August 2013 and March 2014 was drawn from 6179 individuals aged 56 years and above. Multivariable logistic regression analyses were used to examine SMC's relationship with individual chronic diseases (asthma, kidney disease, heart disease, stroke, arthritis, hypertension and diabetes) and multimorbidity. Latent class analysis (LCA) was used to identify the profile of health conditions. The effect of SMC was estimated in a multinomial logistic regression as part of the latent class model.Results: SMC was statistically significant in its association with asthma, stroke, heart disease, arthritis and multimorbidity in the fully controlled multivariable logistic regression models. Three health profiles were identified: low comorbidity (n = 4136, low rates in all health conditions), arthritis group (n = 860) and diabetes and hypertension group (n = 1183). SMC was associated with arthritis group (OR = 2.04, 95% CI = 1.51-2.75) and diabetes and hypertension group (OR = 1.22, 95% CI = 1.03-1.46).Conclusion: Adapting a combination of analytical approaches allows a better understanding in the assessment of SMC's relationship with chronic diseases and the patterns of distribution of these health conditions.


Patient-Reported Outcomes and Costs Associated With Revision Surgery for Degenerative Cervical Spine Diseases.
A retrospective review of a prospective database. The aim of this study was to determine cost and outcomes of revision cervical spine surgery. Revision rates for cervical spine surgery are steadily increasing. It is important to counsel patients on expected results following a revision procedure. However, outcomes and cost of these procedures are poorly defined in the literature. Patients undergoing revision cervical spine surgery at a single institution were included between October 2010 and January 2016 in a prospective registry database. Patients were divided into three cohorts depending on their etiology for revision, including recurrent disease, pseudoarthrosis, or adjacent segment disease. Patient-reported outcomes (PROs), including Neck Disability Index (NDI), EuroQol-5D (EQ-5D), modified Japanese Orthopaedic Association (mJOA) score, numeric rating scale-neck pain (NRS-NP), and numeric rating scale-arm pain (NRS-AP), were measured at baseline and 12 months following revision surgery. Mean costs at 12 months following revision surgery were also calculated. Satisfaction was determined by the NASS patient satisfaction index. Variables were compared using Student t test. A total of 115 patients underwent cervical revision surgery for recurrent disease (n = 21), pseudoarthrosis (n = 45), and adjacent segment disease (n = 49). There was significant improvement in all patient-reported outcomes at 12 months following surgery regardless of etiology (P < 0.0001). Total cost of revision surgery ranged between 21,294 ± 8614 and 23,914 ± 15,396 depending on pathology. No significant differences were seen between costs among different revision groups (P = 0.53). Satisfaction was met in 75.5% to 85.7% (P = 0.21) of patients depending on the etiology of the revision need. Complication rates were between 4% and 9%. This is one of the first studies to determine costs and outcome measures in the setting of cervical spine revision surgery. On the basis of our analysis, a majority of patients can expect to receive some benefit by 12 months and are satisfied with their procedure. 4.


Dietary patterns in relation to lipid profiles among Iranian adults.
Introduction: Lipid metabolism is one of the main concerns of cardiovascular disease and atherosclerosis. Little is known about the association between dietary patterns and dyslipidemia. Therefore, the present study aimed to determine such association among Iranian adults. Methods: This cross-sectional study was conducted on 1433 Iranian adults in Isfahan Healthy Heart Program (IHHP). Usual dietary intakes were assessed with the use of a 48 items food frequency questionnaire (FFQ). Factor analysis was used to identify dietary patterns. Three major dietary patterns were identified: western, semi healthy and healthy fat patterns. Results: After adjustment, subjects in the upper quartiles of western dietary pattern were more likely to have high total cholesterol concentrations than those in the first quartile (odds ratio [OR]: 2.07; 95% CI: 1.25-3.42). Individuals with greater adherence to western dietary pattern had greater odds of having high low-density lipoprotein-cholesterol (LDL-C) levels compared with those in the lowest quartiles (2.53; 1.45-4.40). Conclusion: Semi healthy dietary pattern was not associated with cardiovascular disease (CVD) risk factors. Same trend was observed for healthy fat dietary pattern. Significant association was found between western dietary pattern and dyslipidemia among Iranian adults.


Auranofin inactivates phosphofructokinase in human neutrophils, leading to depletion of intracellular ATP and inhibition of superoxide generation and locomotion.
The effects of the oral gold compound auranofin (AF), at concentrations well within the therapeutic range (0.04-1.5 microM), on human neutrophil functions and energy metabolism were investigated in vitro. At the concentrations tested, this agent had minimal effects on neutrophil degranulation and phagocytosis. However, AF caused dose-related inhibition of neutrophil chemotaxis and stimulus-activated generation of superoxide, which was evident at concentrations as low as 0.04 microM. Inhibition of superoxide generation by activated neutrophils increased with the time of preincubation of the cells with AF at 37 degrees. At low concentrations of AF (less than 0.75 microM), early events (within 5 min) involved in the transduction, assembly, and activity of the neutrophil superoxide-generating enzyme NADPH oxidase appeared to be normal, but the cells were unable to sustain the level of oxygen consumption, superoxide production, and NADPH oxidase activity of the corresponding drug-free control cells. On a mechanistic level, coincubation of neutrophils with AF was associated with decreased glycolytic activity and depletion of intracellular ATP, apparently due to drug-mediated, dose-related inactivation of the glycolytic enzyme phosphofructokinase (PFK). Using purified PFK, the triethylphosphine gold (TEPG) moiety of AF, but not AF per se, caused dose-related inactivation of enzyme activity. These data indicate that the potent inhibition of neutrophil migration and reactive oxidant generation observed during treatment of neutrophils with low, therapeutically attainable concentrations of AF is related to TEPG-mediated inactivation of PFK and consequent interference with cellular energy metabolism and functions.


Systematic review of gastrointestinal nematodes of horses from Australia.
Equine gastrointestinal nematodes (GINs) have been the subject of intermittent studies in Australia over the past few decades. However, comprehensive information on the epidemiology of equine GINs, the efficacy of available anthelmintic drugs and the prevalence of anthelmintic resistance (AR) in Australasia is lacking. Herein, we have systematically reviewed existing knowledge on the horse GINs recorded in Australia, and main aspects of their pathogeneses, epidemiology, diagnoses, treatment and control. Six electronic databases were searched for publications on GINs of Australian horses that met our inclusion criteria for the systematic review. Subsets of publications were subjected to review epidemiology, diagnoses, pathogeneses, treatment and control of GINs of horses from Australia. A total of 51 articles published between 1950 to 2018 were included. The main GINs reported in Australian horses were cyathostomins (at least 28 species), Draschia megastoma, Habronema muscae, H. majus, Oxyuris equi, Parascaris equorum, Strongyloides westeri and Trichostrongylus axei across different climatic regions of Queensland, New South Wales, Victoria, and Western Australia. Nematodes are diagnosed based on the traditional McMaster egg counting technique, though molecular markers to characterise common GINs of equines were characterised in 1990s. The use of anthelmintic drugs remains the most widely-used strategy for controlling equine GIN parasites in Australia; however, the threshold of faecal egg count that should trigger treatment in horses, remains controversial. Furthermore, anthelmintic resistance within GIN population of horses is becoming a common problem in Australia. Although GINs infecting Australian horses have been the subject of occasional studies over the past few decades, the effective control of GIN infections is hampered by a generalised lack of knowledge in various disciplines of equine parasitology. Therefore, coordinated and focused research is required to fill our knowledge gaps in these areas to maximise equine health and minimise economic losses associated with the parasitic infections in Australia.


Age and gender differences in adults' descriptions of emotional reactions to interpersonal problems.
This study examines age and gender differences in descriptions of emotional reactions and reports of the intensity and duration of those emotional responses to interpersonal tensions. As part of a larger study, 185 (85 male and 100 female) participants aged 13 to 99 described the last time they were upset with members of their social networks. Participants then described how they felt and rated the intensity and duration of their distress. Participants' reported emotions were grouped by use of theoretically derived categories and empirically derived post hoc categories. Three emotion categories were examined: anger, sadness, and nonspecific negative emotions. Adolescents and young adults were more likely than older adults to describe anger. Adolescents and young adults also reported more intense aversive responses than older adults. Women rated their distress as more intense than men. With the exception of middle-aged and oldest-old adults, women reported that they experienced distress for a longer duration than men. Findings are interpreted in terms of theories regarding age and gender differences in emotion regulation and interpersonal tensions.


Comparative Evaluation of Metal Ions Release from Titanium and Ti-6Al-7Nb into Bio-Fluids.
The study was designed to investigate the effects of pH, chloride ions and nature of some bio-fluids on the amount of metal ions released from titanium and TiAl(6)Nb(7) plates following incubation in actual and simulated bio-fluids over time. The amounts of released metal ions from commercially pure titanium (CpTi) and TiAl(6)Nb(7)of surgical grade on immersion in 20 mL Hank's solution of pH 4.0 or 7.0, Hank's solution of high chloride ions concentration, Whole Blood Serum (WBS) and Phosphate Buffered Saline (PBS) at 37° C were determined over an incubation time of 20 weeks using atomic absorption spectrophotometry. The levels of released metal ions were compared by two-way ANOVA and Duncan's post-hoc tests. The amounts of titanium ions released by the samples were analyzed by Pearson's correlation. TiAl(6)Nb(7) plate showed no release of Ti ions into the test solutions until after 12 weeks of incubation, while Ti ions were released from the CpTi plate from the 1 day immersion time. The release of measurable amount of Al ions from TiAl(6)Nb(7)was after 12 weeks of incubation. The rate of release of Ti and Al ions from the samples increased initially with incubation time and then stabilized due to adsorption-desorption equilibrium. The results showed that variations in pH and chloride ions of the test media has a significant effect on the amounts of Ti ions released, while increase in chloride ions concentration significantly elevates the release of Al ions into the biofluids.


Safety, tolerability, and pharmacokinetics of oral and intravenous administration of GSK1322322, a peptide deformylase inhibitor.
GSK1322322 is the first in a new class of antibiotics that targets peptide deformylase (PDF), an essential bacterial enzyme required for protein maturation. This randomized, double-blind, placebo-controlled, eight-cohort phase I trial enrolled 62 healthy volunteers to assess safety, tolerability, and pharmacokinetic profiles of GSK1322322. GSK1322322 was administered as a single oral or intravenous (IV) dose, escalating from 500 to 3,000 mg or repeat IV doses escalating from 500 to 1,500 mg twice daily. Upon repeat IV administration, GSK1322322 exhibits linear pharmacokinetics over time upon repeat doses as shown by time-invariant pharmacokinetics. A dose-proportional increase in area under concentration-time curve was observed after single or repeat IV dosing, whereas clearance at steady state remained generally unchanged across doses. There was minimal accumulation of GSK1322322 after repeat IV twice-daily administration. After oral tablet doses of GSK1322322 1,000 and 1,500 mg, absolute bioavailability was 69% and 56%, respectively. GSK1322322 administration at single and repeat IV doses and at supratherapeutic single IV doses of 2,000 and 3,000 mg was associated with mild-to-moderate drug-related adverse events. On the basis of the pharmacokinetics and tolerability demonstrated in this study, GSK1322322 has the potential to become the first-in-class PDF inhibitor for clinical use.


Cognitive Function Prediction of Performance During Dual-Tasks Across Adults With and Without Hearing Loss.
Dual-task procedures are commonly implemented to examine cognitive load and listening effort as individual differences in cognition often determine successful listening. However, which methods are most efficacious is unclear. Specifically, standardized, targeted assessment procedures for establishing cognitive function, and age-related changes that might account for changes in dual-task performance have yet to be established. Additional data are needed across aging populations, including middle-aged adults and older adults to establish the trend of performance changes throughout the aging process. Investigations of the relationship between cognitive function and dual-task performance may better inform clinical decisions. The purpose of this study was to investigate if cognitive function predicts dual-task performance across adults with and without hearing loss. Participants were divided into two groups based on age. Group 1: 14 listeners (Female = 11), 30-50 years old, with normal hearing. Group 2: 12 listeners (Female = 9), 60-80 years old, with normal hearing to near-normal hearing, including typical age-related hearing loss. Participants were administered four of the Woodcock-Johnson III cognitive subtests and standard hearing threshold procedures. All participants were tested in each of three experimental conditions, including two perceptual-cognitive dual-tasks: (1) Auditory word recognition + visual processing, (2) Auditory working memory (sentence) + visual processing in noise, and (3) Auditory working memory (word) + visual processing. Results indicated that cognitive function does predict dual-task performance regardless of age and hearing function. Cognitive function may predict dual-task performance during speech-in-noise tasks. Further research investigating the predictive value of related cognitive subtests to listening effort is warranted.


Large scale healthcare facility redevelopment: A scoping review.
Internationally, organisations are undertaking large scale facility redevelopment as a strategy for the transformation of care systems. Redeveloping facilities provides a once in a generation opportunity to transform health service delivery, typically, however, system level changes are poorly understood. To address this gap, our aim was to investigate the empirical knowledge base regarding large scale redevelopment of healthcare facilities. A scoping review was undertaken, guided by the redeveloped health service management (HSM) scoping review framework (HSM-SRF). Across 17 articles, five key concepts were identified, and they form the principles for successful redevelopment. First, establish a strong governance framework integrating diverse expertise and evidence base. Second, engage with internal and external stakeholders to build effectual relationships. Third, consult with end users, including clinicians and patients, to encourage the acceptance of the redevelopment and actively manage stakeholder dynamics, including politics and power undercurrents. Fourth, commit appropriate resources, including time, workforce, technology and finance to ensure redevelopment success. Finally, reimagine workflows through consultation with end users, including staff and consumers, allowing them to conceptualise how the space will be utilised. This scoping review is the first to synthesise the empirical knowledge base of the redevelopment of healthcare facilities.


Identification of Multiple QTL Hotspots in Sockeye Salmon (Oncorhynchus nerka) Using Genotyping-by-Sequencing and a Dense Linkage Map.
Understanding the genetic architecture of phenotypic traits can provide important information about the mechanisms and genomic regions involved in local adaptation and speciation. Here, we used genotyping-by-sequencing and a combination of previously published and newly generated data to construct sex-specific linkage maps for sockeye salmon (Oncorhynchus nerka). We then used the denser female linkage map to conduct quantitative trait locus (QTL) analysis for 4 phenotypic traits in 3 families. The female linkage map consisted of 6322 loci distributed across 29 linkage groups and was 4082 cM long, and the male map contained 2179 loci found on 28 linkage groups and was 2291 cM long. We found 26 QTL: 6 for thermotolerance, 5 for length, 9 for weight, and 6 for condition factor. QTL were distributed nonrandomly across the genome and were often found in hotspots containing multiple QTL for a variety of phenotypic traits. These hotspots may represent adaptively important regions and are excellent candidates for future research. Comparing our results with studies in other salmonids revealed several regions with overlapping QTL for the same phenotypic trait, indicating these regions may be adaptively important across multiple species. Altogether, our study demonstrates the utility of genomic data for investigating the genetic basis of important phenotypic traits. Additionally, the linkage map created here will enable future research on the genetic basis of phenotypic traits in salmon.


Postoperative burden of hospital-acquired Clostridium difficile infection.
OBJECTIVE Clostridium difficile infection (CDI) is a common hospital-acquired infection. Previous reports on the incidence, risk factors, and impact of CDI on resources in the surgical population are limited. In this context, we study CDI across diverse surgical settings. METHODS We prospectively identified patients with laboratory-confirmed postoperative CDI after 40 different general, vascular, or gynecologic surgeries at 52 academic and community hospitals between July 2012 and September 2013. We used multivariable regression models to identify CDI risk factors and to determine the impact of CDI on resource utilization. RESULTS Of 35,363 patients, 179 (0.51%) developed postoperative CDI. The highest rates of CDI occurred after lower-extremity amputation (2.6%), followed by bowel resection or repair (0.9%) and gastric or esophageal operations (0.7%). Gynecologic and endocrine operations had the lowest rates (0.1% and 0%, respectively). By multivariable analyses, older age, chronic immunosuppression, hypoalbuminemia (≤3.5 g/dL), and preoperative sepsis were associated with CDI. Use of prophylactic antibiotics was not independently associated with CDI, neither was sex, body mass index (BMI), surgical priority, weight loss, or comorbid conditions. Three procedure groups had higher odds of postoperative CDI: lower-extremity amputations (adjusted odds ratio [aOR], 3.5; P=.03), gastric or esophageal operations (aOR, 2.1; P=.04), and bowel resection or repair (aOR, 2; P=.04). Postoperative CDI was independently associated with increased length of stay (mean, 13.7 d vs 4.5 d), emergency department presentations (18.9 vs 9.1%) and readmissions (38.9% vs 7.2%, all P<.001). CONCLUSIONS Incidence of postoperative CDI varies by surgical procedure. Postoperative CDI is also associated with higher rates of extended length of stay, emergency room presentations, and readmissions, which places a potentially preventable burden on hospital resources.


Pharmacological targeting of the ephrin receptor kinase signalling by GLPG1790 in vitro and in vivo reverts oncophenotype, induces myogenic differentiation and radiosensitizes embryonal rhabdomyosarcoma cells.
EPH (erythropoietin-producing hepatocellular) receptors are clinically relevant targets in several malignancies. This report describes the effects of GLPG1790, a new potent pan-EPH inhibitor, in human embryonal rhabdomyosarcoma (ERMS) cell lines. EPH-A2 and Ephrin-A1 mRNA expression was quantified by real-time PCR in 14 ERMS tumour samples and in normal skeletal muscle (NSM). GLPG1790 effects were tested in RD and TE671 cell lines, two in vitro models of ERMS, by performing flow cytometry analysis, Western blotting and immunofluorescence experiments. RNA interfering experiments were performed to assess the role of specific EPH receptors. Radiations were delivered using an x-6 MV photon linear accelerator. GLPG1790 (30 mg/kg) in vivo activity alone or in combination with irradiation (2 Gy) was determined in murine xenografts. Our study showed, for the first time, a significant upregulation of EPH-A2 receptor and Ephrin-A1 ligand in ERMS primary biopsies in comparison to NSM. GLPG1790 in vitro induced G1-growth arrest as demonstrated by Rb, Cyclin A and Cyclin B1 decrease, as well as by p21 and p27 increment. GLPG1790 reduced migratory capacity and clonogenic potential of ERMS cells, prevented rhabdosphere formation and downregulated CD133, CXCR4 and Nanog stem cell markers. Drug treatment committed ERMS cells towards skeletal muscle differentiation by inducing a myogenic-like phenotype and increasing MYOD1, Myogenin and MyHC levels. Furthermore, GLPG1790 significantly radiosensitized ERMS cells by impairing the DNA double-strand break repair pathway. Silencing of both EPH-A2 and EPH-B2, two receptors preferentially targeted by GLPG1790, closely matched the effects of the EPH pharmacological inhibition. GLPG1790 and radiation combined treatments reduced tumour mass by 83% in mouse TE671 xenografts. Taken together, our data suggest that altered EPH signalling plays a key role in ERMS development and that its pharmacological inhibition might represent a potential therapeutic strategy to impair stemness and to rescue myogenic program in ERMS cells.


[A wide-ranging project to the best use of S. Niccolo Psychiatric Hospital].
The S. Niccolò Psychiatric Hospital was one of the most important health institutions not only for Siena but for the entire Tuscan district and beyond. It was known to serve all the catchment area for mentally ill patients coming from other cities. At a national level, it is also one of the most beautiful models of hospital architecture of the "village" type, the expression of a late nineteenth-century tendency to perceive mental disorders as illnesses that could be improved and cured through "moral treatment", with work and distraction as the principal therapeutic instruments. The closure of the psychiatric hospital in Siena provided for by the Italian psychiatric reform of 1978 actually took place over an extremely long period of time. It was definitively closed only on 30 September 1999 and was the last psychiatric hospital in Tuscany to cease its activity. Its history, the importance it had for the considerable number of committed patients, the extension of the area of the hospital over 183,574 m2 and its organization in 16 edifices, mean that S. Niccolò is now an architectonic complex of great value and interest but also subject to progressive deterioration. This reality, together with the urgency of salvaging the collections of books from its very rich library and its archives of administrative documents and medical records, has led the author to prepare a wide-ranging and extremely complex project that aims at the best use of S. Niccolò. Thanks to the collaboration of a group of experts from various Faculties of the University of Siena, and beginning with a multidisciplinary study of S. Niccolò's history, the project proceeds to the identification of concrete actions of cultural policy as well.


Resonance-enhanced Multiphoton Ionization Time-of-Flight Mass Spectrometry for Evaluating Emulsion Inversion via Temperature Change.
This study used resonance-enhanced multiphoton ionization time-of-flight mass spectrometry (REMPI-TOFMS) to evaluate the phase inversion that is driven via temperature change. A change in temperature prompts phase inversion in an oil-in-water (O/W) emulsion that uses a nonionic surfactant as an emulsifier. In this study, an O/W emulsion was prepared containing Triton X-100 as an emulsifier. To promote emulsion inversion, we heated only the outlet of a capillary column that was used for sample introduction during REMPI-TOFMS. When the emulsion was continuously measured at 40°C, several intense spikes could be detected on a time profile for the analyte, toluene, constructed by extracting the peak areas from a series of obtained mass spectra. This indicated the presence of toluene droplets in the O/W emulsion. No intense spikes appeared at 80°C, however, which suggested the shrinkage or even disappearance of the oil droplets following phase inversion. Using this technique, an emulsion can be measured without affecting the influence of vaporization even at elevated temperatures, which surely is a serious concern when using other analytical techniques. Therefore, this technique would be quite useful for evaluating the phase inversion of an emulsion at elevated temperatures.


Dissociable Disruptions in Thalamic and Hippocampal Resting-State Functional Connectivity in Youth with 22q11.2 Deletions.
The 22q11.2 deletion syndrome (22q11DS) is a recurrent copy number variant with high penetrance for developmental neuropsychiatric disorders. Study of individuals with 22q11DS therefore may offer key insights into neural mechanisms underlying such complex illnesses. Resting-state functional connectivity MRI studies in idiopathic schizophrenia have consistently revealed disruption of thalamic and hippocampal circuitry. Here, we sought to test whether this circuitry is similarly disrupted in the context of this genetic high-risk condition. To this end, resting-state functional connectivity patterns were assessed in a sample of human youth with 22q11DS (n = 42; 59.5% female) and demographically matched healthy controls (n = 39; 53.8% female). Neuroimaging data were acquired via single-band protocols and analyzed in line with methods provided by the Human Connectome Project. We computed functional relationships between individual-specific anatomically defined thalamic and hippocampal seeds and all gray matter voxels in the brain. Whole-brain Type I error protection was achieved through nonparametric permutation-based methods. The 22q11DS patients displayed dissociable disruptions in thalamic and hippocampal functional connectivity relative to control subjects. Thalamocortical coupling was increased in somatomotor regions and reduced across associative networks. The opposite effect was observed for the hippocampus in regards to somatomotor and associative network connectivity. The thalamic and hippocampal dysconnectivity observed in 22q11DS suggests that high genetic risk for psychiatric illness is linked with disruptions in large-scale corticosubcortical networks underlying higher-order cognitive functions. These effects highlight the translational importance of large-effect copy number variants for informing mechanisms underlying neural disruptions observed in idiopathic developmental neuropsychiatric disorders.SIGNIFICANCE STATEMENT Investigation of neuroimaging biomarkers in highly penetrant genetic syndromes represents a more biologically tractable approach to identify neural circuit disruptions underlying developmental neuropsychiatric conditions. The 22q11.2 deletion syndrome confers particularly high risk for psychotic disorders and is thus an important translational model in which to investigate systems-level mechanisms implicated in idiopathic illness. Here, we show resting-state fMRI evidence of large-scale sensory and executive network disruptions in youth with 22q11DS. In particular, this study provides the first evidence that these networks are disrupted in a dissociable fashion with regard to the functional connectivity of the thalamus and hippocampus, suggesting circuit-level dysfunction.


Selective counting and sizing of single virus particles using fluorescent aptamer-based nanoparticle tracking analysis.
Detection and counting of single virus particles in liquid samples are largely limited to narrow size distribution of viruses and purified formulations. To address these limitations, here we propose a calibration-free method that enables concurrently the selective recognition, counting and sizing of virus particles as demonstrated through the detection of human respiratory syncytial virus (RSV), an enveloped virus with a broad size distribution, in throat swab samples. RSV viruses were selectively labeled through their attachment glycoproteins (G) with fluorescent aptamers, which further enabled their identification, sizing and counting at the single particle level by fluorescent nanoparticle tracking analysis. The proposed approach seems to be generally applicable to virus detection and quantification. Moreover, it could be successfully applied to detect single RSV particles in swab samples of diagnostic relevance. Since the selective recognition is associated with the sizing of each detected particle, this method enables to discriminate viral elements linked to the virus as well as various virus forms and associations.


Optimizing neural networks for medical data sets: A case study on neonatal apnea prediction.
The neonatal period of a child is considered the most crucial phase of its physical development and future health. As per the World Health Organization, India has the highest number of pre-term births [1], with over 3.5 million babies born prematurely, and up to 40% of them are babies with low birth weights, highly prone to a multitude of diseases such as Jaundice, Sepsis, Apnea, and other Metabolic disorders. Apnea is the primary concern for caretakers of neonates in intensive care units. The real-time medical data is known to be noisy and nonlinear and to address the resultant complexity in classification and prediction of diseases; there is a need for optimizing learning models to maximize predictive performance. Our study attempts to optimize neural network architectures to predict the occurrence of apneic episodes in neonates, after the first week of admission to Neonatal Intensive Care Unit (NICU). The primary contribution of this study is the formulation and description of a set of generic steps involved in selecting various model-specific, training and hyper-parametric optimization algorithms, as well as model architectures for optimal predictive performance on complex and noisy medical datasets. The data used for the study being inherently complex and noisy, Kernel Principal Component Analysis (PCA) is used to reduce dataset dimensionality for the analysis such as interpretations and visualization of the dataset. Hyper-parametric and parametric optimization, in different categories, are considered, including learning rate updater algorithms, regularization methods, activation functions, gradient descent algorithms and depth of the network, based on their performance on the validation set, to obtain a holistically optimized neural network, that best model the given complex medical dataset. Deep Neural Network Architectures such as Deep Multilayer Perceptron's, Stacked Auto-encoders and Deep Belief Networks are employed to model the dataset, and their performance is compared to the optimized neural network obtained from the parametric exploration. Further, the results are compared with Support Vector Machine (SVM), K Nearest Neighbor, Decision Tree (DT) and Random Forest (RF) algorithms. The results indicate that the optimized eight layer Multilayer Perceptron (MLP) model, with Adam Decay and Stochastic Gradient Descent (AUC 0.82) can outperform the conventional machine learning models, and perform comparably to the Deep Auto-encoder model (AUC 0.83) in predicting the presence of apnea in neonates. The study shows that an MLP model can undergo significant improvements in predictive performance, by the proposed step-wise optimization. The optimized MLP is proved to be as accurate as deep neural network models such as Deep Belief Networks and Deep Auto-encoders for noisy and nonlinear data sets, and outperform all conventional models like Support Vector Machine (SVM), Decision Tree (DT), K Nearest Neighbor and Random Forest (RF) algorithms. The generic nature of the proposed step-wise optimization provides a framework to optimize neural networks on such complex nonlinear datasets. The investigated models can help neonatologists as a diagnostic tool.


A graph theoretic model to understand the behavioral difference of PPCA among its paralogs towards recognition of DXCA.
Among all the proteins of Periplasmic C type Cytochrome family obtained from cytochrome C7 found in Geobacter sulfurreducens, only the Periplasmic C type Cytochrome A (PPCA) protein can recognize the deoxycholate (DXCA), while its other paralogs do not, as observed from the crystal structures. Though some existing works have used graph-theoretic approaches to realize the 3-D structural properties of proteins, its usage in the rationalisation of the physiochemical behavior of proteins has been very limited. To understand the driving force towards the recognition of DXCA exclusively by PPCA among its paralogs, in this work, we propose two graph theoretic models based on the combinatorial properties, namely, base-pair-type and impact, of the nucleotide bases and the amino acid residues, respectively. Combinatorial analysis of the binding sequences using the proposed base-pair type based graph theoretic model reveals the differential behaviour of PPCA among its other paralogs. Further, to investigate the underlying chemical phenomenon, another graph theoretic model has been developed based on impact. Analysis of the results obtained from impact-based model clearly indicates towards the helix formation of PPCA which is essential for the recognition of DXCA, making PPCA a completely different entity from its paralogs.


Single-vessel access venoarterial extracorporeal membrane oxygenation and impella technique for acute cardiogenic shock complicated by lung congestion.
The combination of the Impella and peripheral venoarterial extracorporeal membrane oxygenation (Ecmella) is a promising treatment for critically ill patients. We report a single access Ecmella approach using the brachiocephalic artery. A 65-year-old woman with acute myocardial infarction involving the left main coronary artery underwent intra-aortic balloon pump and peripheral venoarterial extracorporeal membrane oxygenation (VA-ECMO) placement. Given the progression of pulmonary congestion and lower limb ischaemia, and an axillary artery diameter of 4.9 mm, we decided to perform a single Ecmella approach. A Y-shaped 9-mm Dacron woven graft was anastomosed to the BCA through a reverse T-shaped partial sternotomy. The Impella 5.5 and arterial cannula of VA-ECMO were introduced through each graft. Six days after, VA-ECMO was removed. Sixty-two days after the surgery, the patient received durable left ventricle assist device implantation. In conclusion, haemodynamic support using a single access Ecmella through brachiocephalic artery allows for managing patients with narrow peripheral arteries.


Use and access to medications for type 2 diabetes mellitus in elderly: a population-based household survey.
The objective of this study was to analyze the use and access to medications for type 2 diabetes among older people registered in the family health strategy in Ribeirão Preto, São Paulo. A population-based household survey was undertaken with 338 older adults selected using two-stage cluster sampling. Pharmacotherapy of diabetes and access to medications was investigated using a structured questionnaire administered by means of face-to-face interviews. The number of medicines used to treat diabetes ranged between 1 and 4. Respondents predominantly used only oral antidiabetic agents. The use of metformin and sulfonylureas on their own was reported by 37.9% and 9.8% of respondents, respectively. Frequency of insulin use was greatest in the 80 years and overage group (38.9%). The large majority of respondents (96.4%) had full access to medicines. Means of payment was "free of charge" in 78.1% of the respondents and public pharmacies were the main source of medication (74.8%). The most commonly used oral antidiabetic was metformin, which is consistent with current treatment guidelines. However, the findings show inappropriate medication use among older people, more specifically the use of sulfonylureas on their own. The findings of this study highlight the important role played by the public health service in providing medications for type 2 diabetes.


Magnetic resonance imaging of the adrenal gland in women with late-onset adrenal hyperplasia.
To determine the presence of structural abnormalities of the adrenal in late-onset adrenal hyperplasia, four consecutive patients were studied by MRI before beginning glucocorticoid replacement therapy. Three women were diagnosed as 21-hydroxylase deficient late-onset adrenal hyperplasia by a 17-OHP level greater than 1,000 ng/dL 30 minutes after acute adrenal stimulation, and one patient was diagnosed as 11-hydroxylase deficient late-onset adrenal hyperplasia when her 11-deoxycortisol level was threefold the upper 95th percentile of normal. Two patients with 21-hydroxylase deficient late-onset adrenal hyperplasia had normal adrenal glands on MRI. Another 21-hydroxylase deficient late-onset adrenal hyperplasia patient was noted to have a 2.5 x 3.3-cm left adrenal nodule, which had been documented some 4 years earlier on CT scan and had not changed in size during that interval. This patient was 40 years of age when the diagnosis of late-onset adrenal hyperplasia was established. The patient with 11-hydroxylase deficient late-onset adrenal hyperplasia demonstrated a diffuse enlargement of the left adrenal gland consistent with hyperplasia, with no focal lesions. In conclusion, although patients with late-onset adrenal hyperplasia may often demonstrate nodular or diffuse adrenocortical hyperplasia on MRI, not all patients with endocrinologically evident disease demonstrate such abnormalities, consistent with a lesser degree of ACTH stimulation compared with women with classical congenital adrenal hyperplasia.


Role of huge geometric circular structures in the reproduction of a marine pufferfish.
We report that male pufferfishes (Torquigener sp., Tetraodontidae) constructed large geometric circular structures on the seabed that played an important role in female mate choice. Males dug valleys at various angles in a radial direction, constructing nests surrounded by radially aligned peaks and valleys. Furthermore, they created irregular patterns in the nest comprising fine sand particles. The circular structure not only influences female mate choice but also functions to gather fine sand particles in nests, which are important in female mate choice. Strangely enough, the males never reuse the nest, always constructing a new circular structure at the huge cost of construction. This is because the valleys may not contain sufficient fine sand particles for multiple reproductive cycles.


Occupational exposure to organic solvents and sleep-disordered breathing.
To investigate whether people with occupational exposure to organic solvents have a higher prevalence of obstructive sleep apnea syndrome (OSAS) than the general population and to examine the relationship between snoring and exposure to organic solvents. Consecutive patients, aged 30-64 years, referred during a 3-year period to the sleep laboratory at Avesta Hospital, Sweden, because of suspected OSAS made up the patient groups. Following admission, patients underwent a simplified sleep apnea investigation and were divided into two groups, OSAS (n = 320) and snorers (n = 443). A random sample of 296 men and 289 women aged 30-64 years obtained from a register of all country residents maintained by the county tax authority served as referents (controls). Both patients and referents responded to two questionnaires, including questions about occupation, exposure to organic solvents, and other chemical and physical agents. Men with OSAS or snoring and women with snoring had more often been occupationally exposed to organic solvents than the referents, showing an almost twofold increase in risk for those exposed during whole workdays. For men, the risk of OSAS or snoring increased with increasing exposure. The result indicates that occupational exposure to organic solvents might cause sleep apnea. A new observation is that even snoring could be caused by exposure to organic solvents. It is important to elucidate whether exposure to organic solvents is a cause of OSAS, because such a finding may have important implications for prevention and treatment of sleep disturbances.


Sorption of dodecyltrimethylammonium chloride (DTAC) to agricultural soils.
Quaternary ammonium compounds (QACs) used as cationic surfactants are intensively released into environment to be pollutants receiving more and more concerns. Sorption of dodecyltrimethylammonium chloride (DTAC), one of commonly used alkyl QACs, to five types of agricultural soils at low concentrations (1-50mg/L) was investigated using batch experiments. DTAC sorption followed pseudo-second-order kinetics and reached reaction equilibrium within 120min. Both Freundlich model and Langmuir model fitted well with DTAC isotherm data with the latter better. DTAC sorption was spontaneous and favorable, presenting a physical sorption dominated by ion exchanges. Sorption distribution coefficient and sorption affinity demonstrated that soil clay contents acted as a predominant phase of DTAC sorption. DTAC could display a higher mobility and potential accumulation in crops in the soils with lower clay contents and lower pH values. Sorption of DTAC was heavily affected by ions in solution with anion promotion and cation inhibition.