SARS-CoV-2 breakthrough infections after COVID-19 vaccination in patients with inflammatory bowel disease: a systematic review and meta-analysis.
Patients with inflammatory bowel disease (IBD) have an attenuated serologic response to COVID-19 vaccination. It is unclear whether an impaired immune response in vaccinated IBD patients impacts the susceptibility to SARS-CoV-2 infection and occurrence of severe COVID-19. To evaluate SARS-CoV-2 breakthrough infection rates and the disease course of COVID-19 in vaccinated IBD patients. A systematic literature search and meta-analysis was performed. The search was performed in Embase, Medline, Web of Science Core Collection, Cochrane Central Register of Controlled Trials and CINAHIL. The articles were independently screened and selected by two reviewers. A random-effects model was used to calculate the pooled relative risk for breakthrough infections in vaccinated IBD patients and controls. A total of 16 studies were included, with study periods ranging from January 2020 to October 2021 and follow-up time from 3 weeks to 6 months. The breakthrough infection rates range from 0 to 37.4% in vaccinated IBD patients. The disease course of COVID-19 was generally mild, with low hospitalization and mortality rates (0-8.7% and 0-4.3%, respectively). Vaccinated IBD patients had a significantly lower relative risk of breakthrough infection rate compared to unvaccinated controls (risk ratio: 0.07, 95% CI: 0.03-0.18). No difference was observed between IBD patients and non-IBD controls, and between partially and fully vaccinated IBD patients. The impact of immunosuppressive therapy on breakthrough infection rates differs between studies. Most studies showed no impact from immunosuppressive treatment, anti-tumour necrosis factor alpha or corticosteroids and other biologics; one study reported higher rates for patients treated with infliximab versus vedolizumab. Vaccination is effective to prevent COVID-19 infections in patients with IBD. Breakthrough infections do occur, but the disease course is generally mild. Available data seem to suggest a declining trend of breakthrough infections during calendar time. The protocol was published in the PROSPERO database (CRD42021292853).


VivosX, a disulfide crosslinking method to capture site-specific, protein-protein interactions in yeast and human cells.
VivosX is an in vivo disulfide crosslinking approach that utilizes a pair of strategically positioned cysteines on two proteins to probe physical interactions within cells. Histone H2A.Z, which often replaces one or both copies of H2A in nucleosomes downstream of promoters, was used to validate VivosX. Disulfide crosslinks between cysteine-modified H2A.Z and/or H2A histones within nucleosomes were induced using a membrane-permeable oxidant. VivosX detected different combinations of H2A.Z and H2A within nucleosomes in yeast cells. This assay correctly reported the change in global H2A.Z occupancy previously observed when the deposition and eviction pathways of H2A.Z were perturbed. Homotypic H2A.Z/H2A.Z (ZZ) nucleosomes accumulated when assembly of the transcription preinitiation complex was blocked, revealing that the transcription machinery preferentially disassembles ZZ nucleosomes. VivosX works in human cells and distinguishes ZZ nucleosomes with one or two ubiquitin moieties, demonstrating that it can be used to detect protein-protein interactions inside cells from different species.


Exercise-induced changes in pulmonary function of healthy, elite long-distance runners in cold air and pollen season exercise challenge tests.
Exercise-induced changes in postexercise pulmonary function have not been studied in healthy elite athletes in normal training conditions. Twelve healthy elite runners volunteered. They showed normal resting spirometry and bronchial responsiveness to histamine, and were non-atopic. They performed free running exercise challenge tests (ECT) at subzero temperature and immediately after highest birch pollen season. The mean maximal postexercise changes in FEV(1), PEF, FVC, and FEV(1)/FVC did not differ between the cold air and pollen season ECTs. Compared with pre-exercise values, FEV(1)increased significantly at 10 min (p = 0.028) and 20 min (p = 0.033) postexercise in the cold air ECT, as well as at 10 min (p = 0.024) and 20 min (p = 0.010) postexercise in the pollen season ECT. The mean (SEM) maximal postexercise change in FEV(1) was mostly small + 2.6 (0.6)% in the winter and + 2.7 (0.9)% in the pollen season. In contrast, significant decreases in PEF, compared with baseline, were found at 10 min (p = 0.071) and 20 min (p = 0.0029) postexercise in the cold air ECT, as well as at 10 min (p = 0.060) and 20 min (p = 0.010) postexercise in the pollen season ECT (p = 0.0076). The mean (SEM) maximal postexercise fall in PEF was 5.9 (1.0)% in the winter and 6.0 (1.8)% in the pollen season. Heavy exercise challenge tests in extreme conditions increased FEV(1) post-exercise, while PEF decreased as compared with pre-exercise values. Thus, even small postexercise falls in FEV(1) may be considered as deviate exercise responses in elite athletes.


Usefulness of one-arm motorized gait device for chronic hemiplegic stroke survivors.
After stroke, gait training is a key component of rehabilitation, and most individuals use a variety of walking aids depending on their physical condition and environment. This study aimed to investigate the potential effect of a one-arm motorized gait device for gait assist of chronic hemiplegic stroke survivors through comparison with traditional gait devices (parallel bar and hemi-walker). This study was conducted on 14 chronic hemiplegic stroke survivors. The participants were asked to walk under three conditions using different gait devices, and their gait parameters during walking were collected and analyzed. The first condition involved walking on parallel bars; second condition, walking using hemi-walkers; and third condition, walking using one-arm motorized gait devices. With the use of a gait analysis system, the spatio-temporal gait parameters in each condition were collected, such as gait velocity, cadence, step length, stride length, single support time, and double support time. In the results by repeated-measures ANOVA or the Friedman test, a significant difference was found in the gait parameters among all three conditions (p< 0.05). The post-hoc test showed a significant change in the spatio-temporal gait parameters (especially, velocity, cadence and affected side single and double support time) when one-arm motorized gait device were used compared with parallel bars and hemi-walkers (p< 0.05). The results of this study suggest that one-arm motorized gait devices developed for hemiplegic stroke survivors may be more effective potentially than parallel bars and hemi-walkers in gait assistance of chronic hemiplegic stroke survivors.


Population Approaches Targeting Metabolic Syndrome Focusing on Japanese Trials.
The clinical importance of assessment of metabolic syndrome lies in the selection of individuals with multiple risk factors based on visceral fat accumulation, and helping them to reduce visceral fat. Behavioral modification by population approach is important, which adds support to the personal approach. The complexity of visceral fat accumulation requires multicomponent and multilevel intervention. Preparation of food and physical environments could be useful strategies for city planners. Furthermore, actions on various frameworks, including organizational, community, and policy levels, have been recently reported. There are universal public health screening programs and post-screening health educational systems in Japan, and diseases management programs in Germany. Understanding one's own health status is important for motivation for lifestyle modification. The U.S. Preventive Services Task Force recommends that primary care practitioners screen all adults for obesity and offer behavioral interventions and intensive counseling. Established evidence-based guidelines for behavioral counseling are needed within the primary care setting.


Lung reactions during poultry handling related to dust and bacterial endotoxin levels.
Airborne dust and endotoxin levels on poultry farms, were determined for various working processes known to involve a heavy exposure. Forty-seven workers at different sites were studied by questionnaires for work-related symptoms. Lung function measurements were made before and after work. Dust levels exceeded the standard for organic dust, and endotoxin levels exceeded those known to cause respiratory and other symptoms. The average decrease in FEV1 over the working day(s) ranged from 0.07-0.19 litres. Upper airway irritation was present in one third of the workers, and about 10% complained of chest tightness. The effect may have been due to the high amounts of dust causing a general respiratory irritation as well as to the endotoxin.


Potential Fluctuations at Low Temperatures in Mesoscopic-Scale SmTiO3/SrTiO3/SmTiO3 Quantum Well Structures.
Heterointerfaces of SrTiO3 with other transition metal oxides make up an intriguing family of systems with a bounty of coexisting and competing physical orders. Some examples, such as LaAlO3/SrTiO3, support a high carrier density electron gas at the interface whose electronic properties are determined by a combination of lattice distortions, spin-orbit coupling, defects, and various regimes of magnetic and charge ordering. Here, we study electronic transport in mesoscale devices made with heterostructures of SrTiO3 sandwiched between layers of SmTiO3, in which the transport properties can be tuned from a regime of Fermi-liquid like resistivity (ρ ∝ T2) to a non-Fermi liquid (ρ ∝ T5/3) by controlling the SrTiO3 thickness. In mesoscale devices at low temperatures, we find unexpected voltage fluctuations that grow in magnitude as T is decreased below 20 K, are suppressed with increasing contact electrode size, and are independent of the drive current and contact spacing distance. Magnetoresistance fluctuations are also observed, which are reminiscent of universal conductance fluctuations but not entirely consistent with their conventional properties. Candidate explanations are considered, and a mechanism is suggested based on mesoscopic temporal fluctuations of the Seebeck coefficient. An improved understanding of charge transport in these model systems, especially their quantum coherent properties, may lead to insights into the nature of transport in strongly correlated materials that deviate from Fermi liquid theory.


Transcriptional signature of islet neogenesis-associated protein peptide-treated rat pancreatic islets reveals induction of novel long non-coding RNAs.
Diabetes mellitus is characterized by chronic hyperglycemia with loss of β-cell function and mass. An attractive therapeutic approach to treat patients with diabetes in a non-invasive way is to harness the innate regenerative potential of the pancreas. The Islet Neogenesis-Associated Protein pentadecapeptide (INGAP-PP) has been shown to induce β-cell regeneration and improve their function in rodents. To investigate its possible mechanism of action, we report here the global transcriptional effects induced by the short-term INGAP-PP in vitro treatment of adult rat pancreatic islets. Rat pancreatic islets were cultured in vitro in the presence of INGAP-PP for 4 days, and RNA-seq was generated from triplicate treated and control islet samples. We performed a de novo rat gene annotation based on the alignment of RNA-seq reads. The list of INGAP-PP-regulated genes was integrated with epigenomic data. Using the new gene annotation generated in this work, we quantified RNA-seq data profiled in INS-1 cells treated with IL1β, IL1β+Calcipotriol (a vitamin D agonist) or vehicle, and single-cell RNA-seq data profiled in rat pancreatic islets. We found 1,669 differentially expressed genes by INGAP-PP treatment, including dozens of previously unannotated rat transcripts. Genes differentially expressed by the INGAP-PP treatment included a subset of upregulated transcripts that are associated with vitamin D receptor activation. Supported by epigenomic and single-cell RNA-seq data, we identified 9 previously unannotated long noncoding RNAs (lncRNAs) upregulated by INGAP-PP, some of which are also differentially regulated by IL1β and vitamin D in β-cells. These include Ri-lnc1, which is enriched in mature β-cells. Our results reveal the transcriptional program that could explain the enhancement of INGAP-PP-mediated physiological effects on β-cell mass and function. We identified novel lncRNAs that are induced by INGAP-PP in rat islets, some of which are selectively expressed in pancreatic β-cells and downregulated by IL1β treatment of INS-1 cells. Our results suggest a relevant function for Ri-lnc1 in β-cells. These findings are expected to provide the basis for a deeper understanding of islet translational results from rodents to humans, with the ultimate goal of designing new therapies for people with diabetes.


Roth spots in pyridoxine dependent epilepsy.
Pyridoxine dependent epilepsy (PDE) is a rare metabolic defect in the degradation of lysine. The authors report a patient with metabolic and DNA confirmed PDE, on the fifth day of life ophthalmoscopy showed bilateral multiple white centred retinal haemorrhages, so called Roth spots. Roth spots are non-specific haemorrhagic signs that occur in a variety of conditions of acute systemic insults in homeostasis - most often infections- which relate to retinal capillary damage and the ensuing reparative process. No biochemical or microbiological signs of infection were present in blood and liquor. MRI of the brain showed an abnormal diffusion signal with increased apparent diffusion coefficient and little blood around the tentorium. The knowledge of the pathogenesis of PDE is still limited. The presence of Roth spots is suggestive for a pathogenic mechanism of vasogenic damage in PDE.


Hybrid Acid/Base Electrolytic Cell for Hydrogen Generation and Methanol Conversion Implemented by Bifunctional Ni/MoN Nanorod Electrocatalyst.
Combining the methanol oxidation reaction (MOR) and hydrogen evolution reaction (HER) within an integrated electrolytic system may offer the advantages of enhanced kinetics of the anode, reduced energy consumption, and the production of high-purity hydrogen. Herein, it is reported the construction of Ni─MoN nanorod arrays supported on a nickel foam substrate (Ni─MoN/NF) as a bifunctional electrocatalyst for electrocatalytic hydrogen production and selective methanol oxidation to formate. Remarkably, The optimal Ni─MoN/NF catalyst displays exceptional HER performance with an overpotential of only 49 mV to attain 10 mA cm-2 in acid, and exhibits a high activity for MOR to achieve 100 mA cm-2 at 1.48 V in alkali. A hybrid acid/base electrolytic cell with Ni─MoN/NF electrode as anode and cathode is further developed for an integrated HER-MOR cell, which only requires a voltage of 0.56 V at 10 mA cm-2 , significantly lower than that of the HER-OER system (0.70 V). The density functional theory studies reveal that the incorporation of Ni effectively modulates the electronic structure of MoN, thereby resulting in enhanced catalytic activity. The unique combination of high electrocatalytic activity and excellent stability make the Ni─MoN/NF catalyst a promising candidate for practical applications in electrocatalytic hydrogen production and methanol oxidation.


Wireless pulmonary artery pressure monitoring guides management to reduce decompensation in heart failure with preserved ejection fraction.
No treatment strategies have been demonstrated to be beneficial for the population for patients with heart failure (HF) and preserved ejection fraction (EF). The CardioMEMS Heart Sensor Allows Monitoring of Pressure to Improve Outcomes in NYHA Class III Heart Failure Patients (CHAMPION) trial was a prospective, single-blinded, randomized controlled clinical trial testing the hypothesis that hemodynamically guided HF management decreases decompensation leading to hospitalization. Of the 550 patients enrolled in the study, 119 had left ventricular EF ≥40% (average, 50.6%), 430 patients had low left ventricular EF (<40%; average, 23.3%), and 1 patient had no documented left ventricular EF. A microelectromechanical system pressure sensor was permanently implanted in all participants during right heart catheterization. After implant, subjects were randomly assigned in single-blind fashion to a treatment group in whom daily uploaded pressures were used in a treatment strategy for HF management or to a control group in whom standard HF management included weight-monitoring, and pressures were uploaded but not available for investigator use. The primary efficacy end point of HF hospitalization rate >6 months for preserved EF patients was 46% lower in the treatment group compared with control (incidence rate ratio, 0.54; 95% confidence interval, 0.38-0.70; P<0.0001). After an average of 17.6 months of blinded follow-up, the hospitalization rate was 50% lower (incidence rate ratio, 0.50; 95% confidence interval, 0.35-0.70; P<0.0001). In response to pulmonary artery pressure information, more changes in diuretic and vasodilator therapies were made in the treatment group. Hemodynamically guided management of patients with HF with preserved EF reduced decompensation leading to hospitalization compared with standard HF management strategies. http://www.clinicaltrials.gov. Unique identifier: NCT00531661.


Alloimmunization due to red cell antibodies in Rhesus positive Omani Pregnant Women: Maternal and Perinatal outcome.
This study is aimed to determine the prevalence of alloimmunization due to antibodies to red blood cell (RBC) antigens (other than rhesus [Rh] antigen) and report the maternal, perinatal, and neonatal outcomes. A retrospective review of medical records of all patients with minor RBCs antibodies alloimmunization who were followed and delivered at Sultan Qaboos University Hospital, Oman from June 2011 to June 2013. Maternal characteristics, antibody type, antibody titer in addition to perinatal and neonatal outcomes were reviewed. There were 1160 patients with Rh positive status in the study. The most common ABO blood group was O, followed by A, B, and AB. We found 33 out of 1160 Rh positive women alloimmunized with minor RBCs antibodies that gave a prevalence of minor RBCs alloimmunization of 2.7%. The most frequent antibody was anti-E 38%, followed by anti-c 17% and anti-kell 17%. 6 of these 33 patients were identified to have significant antibody titer, and two cases showed evidence of fetal anemia. Only one case required an intrauterine blood transfusion. The most common neonatal complication was jaundice in 53%, followed by respiratory distress syndrome in 28%. Two cases complicated by neonatal anemia required a postnatal blood transfusion. Alloimmunization with anti-E, anti-c, and anti-kell were the most common antibodies among the study group. Minor RBCs alloimmunization was an important cause of neonatal morbidity.


Adolescent perfectionism: Structural features of the Frost Multidimensional Perfectionism Scale and correlates with attachment and psychopathology.
Perfectionism is recognized as a significant risk factor for psychopathology. Emerging research links attachment to perfectionism in adult and college-age samples. The Frost Multidimensional Perfectionism Scale (FMPS) has been used in adults and adolescents with a variety of factor structures found. This study sought to establish the factor structure in a general adolescent sample prior to testing for associations between perfectionism, attachment, and psychopathology in the same sample. A cross-sectional survey design was used. Confirmatory factor analysis, and correlational and regression analyses were employed. A total of 290 adolescents, aged 12-18 years, were recruited from a state secondary school. All completed the FMPS along with brief measures of attachment and psychopathology. Exploratory and confirmatory factor analyses failed to replicate previously published models, and a new six-item, 1-factor model representing perfectionism was found instead. This new variable was then used to establish a role for perfectionism and attachment anxiety in predicting internalizing problems. Perfectionism also correlated with conduct problems and hyperactivity. This study established a novel factor structure for the FMPS, allowing proof of principle of the role of perfectionism in a relationship with attachment and psychopathology, which after replication, may inform new interventions for perfectionism. Caution is noted about the use of extant perfectionism measures that are not properly developmentally informed and which do not capture the dynamic nature of adolescence and adolescent perfectionism. Perfectionism is a feature of adolescent psychopathology, including internalizing and externalizing problems. Perfectionism is associated with attachment anxiety and together contributes to internalizing problems. Current conceptualizations of perfectionism may not capture the specific developmental and dynamic aspects of adolescence and should not be regarded as a stable personality trait.


Genomics and environmental hypoxia: what (and how) we can learn from the transcriptome.
Recent developments in molecular biology have shown that the classic "one gene, one RNA, one protein" model is inadequate to account for the transcriptional complexity apparent in higher organisms. Current understanding of the transcriptome (the -ome term for the entire complement of transcripts in a cell, tissue, or organism) suggests that genes can produce many different transcripts due to variable start and termination sites and alternate splicing, and that much of the extragenic (the region believed to lay outside genes) genome is also transcribed, producing a bewildering array of noncoding RNAs (ncRNA), including antisense transcripts and microRNAs that are thought to be involved in the posttranscriptional regulation of gene expression. As part of the attempt to understand this plethora of biological information, researchers have developed new technologies that permit the assessment of thousands of transcripts simultaneously. The resulting transcription profile provides a high-resolution and highly informative snapshot of gene activity in the tissue. The two most common of these methodological strategies are microarrays, which are based on hybridization technology, and serial (or cap) analysis of gene expression (SAGE or CAGE), which is based on DNA sequencing. This paper reviews the basic principles underlying these technologies and describes how they have been applied to understanding the molecular events that underlie the response to environmental hypoxia.


Expression of lysophosphatidic acid receptors in the human lower esophageal sphincter.
Lysophosphatidic acid (LPA) is a bioactive lipid that is involved in a variety of physiological and pathological processes occurring in the gastrointestinal tract. It acts via six distinct types of receptors, LPA1, LPA2, LPA3, LPA4, LPA5 and LPA6, which belong to the family of G protein-coupled receptors. The aim of the present study was to detect the expression of the LPA receptors in the human lower esophageal sphincter (LES). Quantitative polymerase chain reaction and western blotting were used to analyze the expression of LPA1-6 receptors in sling and clasp fibers from the human LES. The results showed that the protein and mRNA expression levels of various LPA receptors were significantly different. Specifically, the mRNA and protein expression levels of the LPA1 receptor were higher compared with those of the other receptors. The prevalence of the LPA1 receptor mRNA and protein indicates that the LPA1 receptor is likely to be involved in the regulation of human LES functions.


"Matching" consent to purpose: The example of the Matchmaker Exchange.
The Matchmaker Exchange (MME) connects rare disease clinicians and researchers to facilitate the sharing of data from undiagnosed patients for the purpose of novel gene discovery. Such sharing raises the odds that two or more similar patients with candidate genes in common may be found, thereby allowing their condition to be more readily studied and understood. Consent considerations for data sharing in MME included both the ethical and legal differences between clinical and research settings and the level of privacy risk involved in sharing varying amounts of rare disease patient data to enable patient matches. In this commentary, we discuss these consent considerations and the resulting MME Consent Policy as they may be relevant to other international data sharing initiatives.


Genetic variability in CYP2E1 and catalase gene among currently and formerly alcohol-dependent male subjects.
The present study explored whether specific single-nucleotide polymorphisms in alcohol metabolic pathway are associated with alcohol dependence or alcohol-related psychopathological symptoms. Three groups of male unrelated subjects were included: 101 currently alcohol-dependent patients, 100 formerly alcohol-dependent subjects and 97 healthy controls. The following questionnaires were implemented: AUDIT, Zung Depression and Anxiety scale, Brief Social Phobia Scale, Yale-Brown Obsessive Compulsive Scale, Obsessive Compulsive Drinking Scale and Buss-Durkee Hostility Inventory. All the subjects were genotyped for CYP2E1 c.-1053C>T and CAT c.-262C>T. Statistically significant differences in the distribution of genotypes and alleles for CAT c.-262C>T polymorphism were observed among the three investigated groups. We observed a higher frequency of CAT -262T allele in alcohol-dependent subjects (OR = 1.74, 95% CI = 1.164-2.610). Among currently dependent patients CAT -262T allele carriers had higher AUDIT scores (P = 0.023), while CYP2E1-1053T allele carriers had significantly higher YBOCS-obsession subscale scores (P = 0.005) and Zung Anxiety Scale scores (P = 0.011). Our findings suggest that the CAT c.-262C>T genetic polymorphism influences the susceptibility to alcohol dependence and severity of alcohol dependence, while CYP2E1 c.-1053C>T polymorphism influences the expression of obsessive-compulsive and anxiety symptoms.


Comparative evaluation of temporal fascia and dermal fat graft in the management of temporomandibular joint ankylosis.
Temporomandibular joint (TMJ) ankylosis is a debilitating condition usually afflicting children and young adults, causing long-term functional, aesthetic, and severe psychological impacts on the lives of these patients. To compare the postoperative outcomes after using one of the most commonly employed inter-positional graft, i.e., temporalis fascia, and a recently introduced 'more suitable' graft, i.e., dermal fat. A prospective study in which 20 patients of TMJ ankylosis were randomly assigned into two groups of 10 patients each. Temporalis fascia was used as an inter-positional graft in one group, while dermal fat graft was used in the other group. Post-surgical clinical parameters were evaluated, including interincisal mouth-opening and pain. Interincisal mouth opening at six months was greater in group A (32.1 ± 12.93) as compared to group B (33.8 ± 4.89), but statistically, it was not significant (P = 0.478). The mean pain score in group A was 4.60 ± 1.17, 1.50 ± 0.70, 0.20 ± 0.42 on day 1, 7, and 15, respectively. The mean pain score in group B was 4.10 ± 0.99, 1.30 ± 0.48, 0.20 ± 0.42 on day 1, 7, and 15, respectively. Both the graft materials work well in terms of maximum interincisal opening. For more clarification, a larger sample size with a longer duration of follow-up is needed to validate the study.


Bioinspired Supramolecular Lubricating Hydrogel Induced by Shear Force.
Bioinspired lubricating materials are great challenge toward artificial joints. In this contribution, we synthesize a bioinspired hydrogel by combining a thixotropic supramolecular network and polymer double network, exhibiting a unique shear-responsive lubricating property. The disassembly of the N-fluorenylmethoxycarbonyl-l-tryptophan supramolecular network triggered by shear force will endow lubricating function to the hydrogel; meanwhile PAAm and PVA double network acts as the supporting skeleton with high mechanical property. This work will bring new insight on the design of artificial lubricating joint.


Avascular necrosis and the blood supply of the femoral head.
Postmortem femoral artery perfusion revealed abnormalities in the femoral head pattern of vessels in steroid-treated renal transplant patients as compared with controls. Degenerative changes were found in some of the arteries and arterioles of the hip capsule and femoral head in the renal transplant patients. Two of these patients' femoral heads showed microfocal avascular necrosis. Although high-dose steroids were used in these patients, none had suffered clinically from hip disease while alive. These findings suggest the possibility that local arterial disease may be involved in the pathogenesis of avascular necrosis.


Stabilization process in Saccharomyces intra and interspecific hybrids in fermentative conditions.
We evaluated the genetic stabilization of artificial intra- (Saccharomyces cerevisiae) and interspecific (S. cerevisiae × S. kudriavzevii) hybrids under wine fermentative conditions. Large-scale transitions in genome size and genome reorganizations were observed during this process. Interspecific hybrids seem to need fewer generations to reach genetic stability than intraspecific hybrids. The largest number of molecular patterns recovered among the derived clones was observed for intraspecific hybrids, particularly for those obtained by rare-mating. Molecular marker analyses revealed that unstable clones could change during the industrial process to obtain active dry yeast. When no changes in molecular markers and ploidy were observed after this process, no changes in genetic composition were confirmed by comparative genome hybridization, considering the clone as a stable hybrid. According to our results, under these conditions, fermentation steps 3 and 5 (30-50 generations) would suffice to obtain genetically stable interspecific and intraspecific hybrids, respectively.


A Multicenter Epidemiological and Pathogenic Characteristics Study of Community-Acquired Bacterial Meningitis Children in China: Results from the Chinese Pediatric Bacterial Meningitis Surveillance (CPBMS) 2019-2020.
To explore the epidemiological and pathogenic characteristics of children with community-acquired bacterial meningitis. A multicenter, retrospective study was conducted among CABM patients under 15 years old from 33 hospitals in China from 2019 to 2020. The medical record, laboratory, and microbiological data were collected and analyzed. A total of 1610 children with CABM were identified and presented at a median onset age of 45 days of whom 955 (59.3%) were males. CABM occurred mostly in infants <1 year of age (84.0%, 1352/1610). In etiology-confirmed cases, the pathogens were isolated from CSF culture in 515 (32.0%), 400 (24.8%) in blood culture, and 186 (11.6%) both in CSF and blood culture. In total, 126 pathogens were identified through CSF mNGS in 330 CABM cases; 21 S. pneumoniae isolates were detected in 83 CABM cases by antigen detection method. Major pathogens were E. coli (195, 24.7%), GBS (170, 21.5%), and S. pneumoniae (157, 19.9%). GBS (29.3%, 22/75) was the first pathogen of CABM in neonates aged 0-6 days old, while E. coli (44.7%, 76/170) in 7 to 28 days of age; S. pneumoniae (96.2%, 151/157) was the most common pathogen in >3 months old cases. About 9.7% (19/195) strains of E. coli produced ultra‑broad‑spectrum β‑lactamases. The common intracranial imaging complications were subdural effusion and (or) empyema in 349 (21.7%), hydrocephalus in 233 (14.5%), and cerebral abscess in 178 (11.1%). A total of 389 (24.2%) cases were completely cured and 1088 (67.6%) cases improved. Among 166 patients (10.3%) with adverse outcomes, 32 cases (2.0%) died, and 37 cases (2.3%) relapsed. The onset age of CABM in children is usually within 1 year of age, especially <3 months. The primary pathogens in infants less than 3 months old are E. coli and GBS, and the dominant pathogen in children older than 3 months old is S. pneumoniae. Subdural effusion and (or) empyema and hydrocephalus are common complications. CABM should not be excluded even if CSF leukocyte counts are within normal range. Due to the low detection rate of pathogens in children with CABM, standardized CSF bacteriological examination should be paid more attention to increase the pathogen detection rate. Non‑culture CSF detection methods may facilitate pathogenic diagnosis.


Percutaneous full endoscopic posterior decompression of thoracic myelopathy caused by ossification of the ligamentum flavum.
Ossification of ligamentum flavum (OLF) is the leading cause of progressive thoracic myelopathy (TM) in East Asian countries. Surgical decompression is the general treatment for TM. This study investigated the application of percutaneous full endoscopic posterior decompression (PEPD) for the treatment of thoracic OLF. Eighteen patients with TM were treated by PEPD under local anaesthesia. Patients had an average age of 59.1 years and single-level lesions mostly at the lower thoracic vertebrae. Computed tomography and magnetic resonance imaging were used to classify the OLF. The pre- and postoperative neurological statuses were evaluated using the American Spinal Injury Association (ASIA) sensory and motor score, modified Japanese Orthopaedic Association (mJOA) score and Frankel grade. OLF for all patients was classed as lateral, extended, and enlarged types without comma and tram track signs. Decompression was completed, and a dome-shaped laminotomy was performed through limited laminectomy and flavectomy. Dural tears in 2 patients were the only observed complication. The average score of ASIA sensory and motor, mJOA, as well as the Frankel grade improved significantly after surgery at an average follow-up time of 17.4 months. The average recovery rate (RR) was 47.5% as calculated from the mJOA scores. According to RR, 10 cases were classified as good, 4 cases fair, and 4 cases unchanged. For patients with thoracic OLF at a single level and lateral, extended, and enlarged types without comma and tram track signs, it is safe and reliable to perform PEPD, which has satisfactory clinical results. These slides can be retrieved under Electronic Supplementary Material.


Effect of training load on sleep parameters and biochemical fatigue markers in elite swimmers.
The effect of strenuous exercise on sleep patterns in swimmers is equivocal. Therefore, the purpose of the study was to describe possible changes in sleep parameters among elite swimmers subjected to different training loads (TL). Methods: Eighteen elite swimmers (8 females) were monitored across two high-volume preparatory 1-wk periods (P1, P2) and a lower-volume tapering 1-wk period (P3) before a major competition. Internal (the session rating of perceived exertion [sRPE]) and external TL (training duration and volume) were measured, along with several sleep indices (e.g., bedtime, get-up time, sleep time, wake after sleep onset [WASO]). Serum measurements of urea, creatine kinase (CK), testosterone and cortisol were taken before and after training sessions at the beginning (Mondays) and end (Fridays) of each micro cycle. Athlete TL decreased significantly in a stepwise manner from P1 to P2 and from P2 to P3. Of all sleep parameters, only significant differences in bedtime and get-up time emerged (P3 > P1 and/or P2). Sleep duration (~6.3 h) or quality (WASO: 41-45 min) were also unaffected by TL. CK levels declined from P1 to P3 (d = -0.8), and from P2 to P3 (d = -0.6). Positive exercise-induced changes in CK were also seen in each training period. The other biomarkers did not show the same temporal or acute patterns. Irrespective of the TL, the monitored swimmers experienced insufficient and fragmented sleep across this study. Neither sleep quality nor quantity were affected by different magnitudes of TL. Among the biochemical markers of fatigue, baseline plasma CK activity best reflected the physiological response to TL.


Engineered collagen hydrogels for the sustained release of biomolecules and imaging agents: promoting the growth of human gingival cells.
We present here the in vitro release profiles of either fluorescently labeled biomolecules or computed tomography contrast nanoagents from engineered collagen hydrogels under physiological conditions. The collagen constructs were designed as potential biocompatible inserts into wounded human gingiva. The collagen hydrogels were fabricated under a variety of conditions in order to optimize the release profile of biomolecules and nanoparticles for the desired duration and amount. The collagen constructs containing biomolecules/nanoconstructs were incubated under physiological conditions (ie, 37°C and 5% CO2) for 24 hours, and the release profile was tuned from 20% to 70% of initially loaded materials by varying the gelation conditions of the collagen constructs. The amounts of released biomolecules and nanoparticles were quantified respectively by measuring the intensity of fluorescence and X-ray scattering. The collagen hydrogel we fabricated may serve as an efficient platform for the controlled release of biomolecules and imaging agents in human gingiva to facilitate the regeneration of oral tissues.


Primary Breast Atypical Lipomatous Tumor/ Well-Differentiated Liposarcoma and Dedifferentiated Liposarcoma.
Atypical lipomatous tumor/well-differentiated liposarcoma (ALT/WDL) and its higher-grade counterpart, dedifferentiated liposarcoma (DDL), are extraordinarily rare tumors in the breast. The main differential diagnostic consideration of primary breast ALT/WDL is malignant phyllodes tumor with liposarcomatous differentiation, and the main differential diagnostic consideration of DDL in the breast is metaplastic breast carcinoma, particularly the spindle cell type, with heterologous sarcomatous differentiation. These differential diagnoses may be particularly challenging when evaluating limited core needle biopsy sampling. MDM2 and/or CDK4 protein overexpression and gene amplification are beneficial ancillary studies that can help establish the diagnosis of primary breast ALT/WDL and DDL, and effectively rule out the diagnoses of malignant phyllodes tumor and metaplastic breast carcinoma.


Abnormal beta-adrenergic transmembrane signaling in rabbits with adriamycin-induced cardiomyopathy.
We investigated alterations in the beta-adrenergic receptor-adenylate cyclase system in rabbits with congestive heart failure induced by adriamycin cardiotoxicity. A dose of 24 mg/kg adriamycin was administered over 16 weeks in 16 rabbits. Five of them died and 4 of them could not tolerate the full dose of adriamycin. Complete data were obtained in the remaining 7 rabbits. Another 7 rabbits received physiological saline for the same period and served as controls. Plasma norepinephrine concentration increased in adriamycin-treated rabbits, but not in the control rabbits. Cardiac output was lower in the adriamycin-treated group than in the control group. Both the left and right ventricular end-diastolic pressure were higher in the adriamycin-treated group. The density of myocardial beta-adrenergic receptors and the norepinephrine content were reduced in both ventricles in the adriamycin-treated group. Basal and isoproterenol-, sodium fluoride- and forskolin-stimulated adenylate cyclase activities were lower in the adriamycin-treated group. Thus, alterations in beta-adrenergic signaling occurred in both ventricles in animals with chronic biventricular failure induced by adriamycin. These may be the result of post-receptor abnormalities, including abnormalities of guanine nucleotide-binding proteins or of the catalytic unit of adenylate cyclase.


Association Between Psychosocial Stress and Brain Aging: Results of the Population-Based Cohort Study of Health in Pomerania (SHIP).
Recent studies suggest that psychosocial factors can have an impact on brain health. Yet, it is unclear whether psychosocial stress affects aging of the brain. The aim of the study was to investigate the association between psychosocial stress and brain aging. Data from the German population-based cohort Study of Health in Pomerania (N=991; age range 20-78 years) were used to calculate a total psychosocial stress score by combining subscores from five domains: stress related to the living situation, the occupational situation, the social situation, danger experiences, and emotions. Associations with brain aging, indicated by an MRI-derived score quantifying age-related brain atrophy, were estimated by using regression models adjusted for age, gender, education, diabetes, problematic alcohol consumption, smoking, and hypertension. The relative risk ratio for advanced brain aging was 1.21 (95% CI=1.04-1.41) for stress related to emotions in fully adjusted models. The interactions between stress related to emotions and mental health symptoms were also significantly associated with advanced brain aging. The association between higher total psychosocial stress and brain aging was not statistically significant. These findings highlight that high stress related to emotions is associated with advanced brain aging. To protect brain health in older age, more research is needed to explore the role of emotional distress.


Effects of temperature on gene expression patterns in Leptospira interrogans serovar Lai as assessed by whole-genome microarrays.
Leptospirosis is an important zoonosis of worldwide distribution. Humans become infected via exposure to pathogenic Leptospira spp. from infected animals or contaminated water or soil. The availability of genome sequences for Leptospira interrogans, serovars Lai and Copenhageni, has opened up opportunities to examine global transcription profiles using microarray technology. Temperature is a key environmental factor known to affect leptospiral protein expression. Leptospira spp. can grow in artificial media at a range of temperatures reflecting conditions found in the environment and the mammalian host. Therefore, transcriptional changes were compared between cultures grown at 20 degrees C, 30 degrees C, 37 degrees C, and 39 degrees C to represent ambient temperatures in the environment, growth under laboratory conditions, and temperatures in healthy and febrile hosts. Data from direct pairwise comparisons of the four temperatures were consolidated to examine transcriptional changes at two generalized biological conditions representing mammalian physiological temperatures (37 degrees C and 39 degrees C) versus environmental temperatures (20 degrees C and 30 degrees C). Additionally, cultures grown at 30 degrees C then shifted overnight to 37 degrees C were compared with those grown long-term at 30 degrees C and 37 degrees C to identify genes potentially expressed in the early stages of infection. Comparison of data sets from physiological versus environmental experiments with upshift experiments provided novel insights into possible transcriptional changes at different stages of infection. Changes included differential expression of chemotaxis and motility genes, signal transduction systems, and genes encoding proteins involved in alteration of the outer membrane. These findings indicate that temperature is an important factor regulating expression of proteins that facilitate invasion and establishment of disease.


Alkaline Stability of Anion-Exchange Membranes.
Recently, the development of durable anion-exchange membrane fuel cells (AEMFCs) has increased in intensity due to their potential to use low-cost, sustainable components. However, the decomposition of the quaternary ammonium (QA) cationic groups in the anion-exchange membranes (AEMs) during cell operation is still a major challenge. Many different QA types and functionalized polymers have been proposed that achieve high AEM stabilities in strongly alkaline aqueous solutions. We previously developed an ex situ technique to measure AEM alkaline stabilities in an environment that simulates the low-hydration conditions in an operating AEMFC. However, this method required the AEMs to be soluble in DMSO solvent, so decomposition could be monitored using 1H nuclear magnetic resonance (NMR). We now report the extension of this ex situ protocol to spectroscopically measure the alkaline stability of insoluble AEMs. The stability ofradiation-grafted (RG) poly(ethylene-co-tetrafluoroethylene)-(ETFE)-based poly(vinylbenzyltrimethylammonium) (ETFE-TMA) and poly(vinylbenzyltriethylammonium) (ETFE-TEA) AEMs were studied using Raman spectroscopy alongside changes in their true OH- conductivities and ion-exchange capacities (IEC). A crosslinked polymer made from poly(styrene-co-vinylbenzyl chloride) random copolymer and N,N,N',N'-tetraethyl-1,3-propanediamine (TEPDA) was also studied. The results are consistent with our previous studies based on QA-type model small molecules and soluble poly(2,6-dimethylphenylene oxide) (PPO) polymers. Our work presents a reliable ex situ technique to measure the true alkaline stability of AEMs for fuel cells and water electrolyzers.


Angiogenesis in vasculitides.
Vasculitides, including Wegener's granulomatosis, Takayasu's arteritis, giant cell arteritis, Kawasaki disease, Behçet disease, thromboangiitis obliterans and erythema elevatum diutinum, are inflammatory diseases of blood vessel wall characterized by myointimal proliferation, fibrosis and thrombus formation leading to stenosis or occlusion of the vascular lumen, and finally to tissue ischemia. In these diseases the hypoxic environment subsequent to stenosis or occlusion of the vascular lumen is a potent signal for the generation of new blood vessels. Angiogenesis may be a compensatory response to ischemia and to the increased metabolic activity and may be also a further inflammatory stimulus because endothelial cells of newly-formed vessels express adhesion molecules and produce colony-stimulating factors and chemokines for leukocytes.


Arogenate (pretyrosine) is an obligatory intermediate of L-tyrosine biosynthesis: confirmation in a microbial mutant.
Wild-type Brevibacterium flavum has been shown to possess arogenate dehydrogenase activity and to lack prephenate dehydrogenase, thereby providing presumptive evidence that arogenate (previously named "pretyrosine") is an obligatory intermediate of L-tyrosine biosynthesis. A similar enzymological pattern has been discerned in extracts made from wild-type cultures of various species of cyanobacteria. Application of rigorous molecular genetic criteria in confirmation of the exclusive role of arogenate in L-tyrosine synthesis was made possible by the isolation of an auxotrophic mutant exhibiting a nutritional requirement for L-tyrosine. The mutant was found to lack activity for arogenate dehydrogenase and to accumulate substantial amounts of arogenate behind the mutant block during starvation for L-tyrosine.


Direct relation between the low-energy spin excitations and superconductivity of overdoped high-Tc superconductors.
The dynamic spin susceptibility, chi(")(omega), has been measured over the energy range of 2</=omega</=10 meV for overdoped La2-xSrxCuO4. Incommensurate (IC) spin excitations are observed at 8 K for all superconducting samples for 0.25</=x</=0.28 with chi(") peaking at approximately 6 meV. The IC peaks at 6 meV become smaller in intensity with increasing x and, finally, become unobservable for a sample with x=0.30 which has no bulk superconductivity. The maximum chi(") decreases linearly with T(c)(onset) in the overdoped region, implying a direct cooperative relation between the spin fluctuations and the superconductivity.


Attenuated p53 activation in tumour-associated stromal cells accompanies decreased sensitivity to etoposide and vincristine.
Alterations in the tumour suppressor p53 have been reported in tumour-associated stromal cells; however, the consequence of these alterations has not been elucidated. We investigated p53 status and responses to p53-activating drugs using tumour-associated stromal cells from A375 melanoma and PC3 prostate carcinoma xenografts, and a spontaneous prostate tumour model (TRAMP). p53 accumulation after treatment with different p53-activating drugs was diminished in tumour-associated stromal cells compared to normal stromal cells. Tumour-associated stromal cells were also less sensitive to p53-activating drugs - this effect could be reproduced in normal stromal cells by p53 knockdown. Unlike normal stromal cells, tumour stromal cells failed to arrest in G(2) after etoposide treatment, failed to upregulate p53-inducible genes, and failed to undergo apoptosis after treatment with vincristine. The lower levels of p53 in tumour stromal cells accompanied abnormal karyotypes and multiple centrosomes. Impaired p53 function in tumour stroma might be related to genomic instability and could enable stromal cell survival in the destabilising tumour microenvironment.


Congenital Nasolacrimal Duct Obstruction: Comparison of Two Different Treatment Algorithms.
To clarify the most appropriate treatment regimen for congenital nasolacrimal duct obstruction (CNLDO). A retrospective observational analysis was performed of patients undergoing probing with or without intubation to treat CNLDO in a single institution (Royal Victoria Hospital, Belfast) from 2006 to 2011. Based on exclusion criteria, 246 eyes of 177 patients (aged 0 to 9.8 years with a mean age of 2.1 years) were included in this study: 187 (76%) eyes had successful outcome at first intervention with primary probing, whereas 56 (23%) eyes underwent secondary intervention. There were no significant differences by gender, age, or obstruction complexity between the successful and unsuccessful patients with first intervention. For those patients requiring secondary intervention, 16 of 24 (67%) eyes had successful probing, whereas 22 of 24 (92%) had successful intubation. Patients with intubation as a secondary procedure were significantly more likely to have a successful outcome (P = .037). Statistical analysis was performed using the Fisher's exact test and Barnard's exact test. Primary probing for CNLDO has a high success rate that is not adversely affected by increasing age. This study also indicates that if initial probing is unsuccessful, nasolacrimal intubation rather than repeat probing yields a significantly higher success rate. [J Pediatr Ophthalmol Strabismus. 2016;53(5):285-291.].


The use of warfarin as thromboprophylaxis for lower limb arthroplasty.
Most orthopaedic surgeons in the UK use some form of prophylaxis against venous thromboembolic events. Warfarin has been recommended as one of the preferred methods to use. The period of in-hospital postoperative rehabilitation has reduced significantly since lower limb arthroplasty was introduced. We sought to identify and quantify any delay in discharge associated in using warfarin as chemical prophylaxis. During a 12-week period, all patients undergoing a lower limb arthroplasty procedure were identified and any delay in discharge related to their warfarin prophylaxis was recorded. Of the 25 arthroplasties performed in this time period, 17 (68%) were subject to a delay. The total delay in discharge was 39 days. When the standard warfarin dosing protocol was followed, 33% of patients were still delayed. When the protocol was not followed, only 23% were delayed. The majority of deviations from the protocol led to a shorter hospital stay. Patients using warfarin prophylaxis generate an additional cost of 417 pounds related to bed occupancy. There is considerable scope for significantly reducing this cost by moving the early postoperative anticoagulation monitoring into the community. Delayed discharge is an important consideration in the economic issues that surround the choice of thromboprophylaxis.


Suppressive effect of microRNA-29b on hepatic stellate cell activation and its crosstalk with TGF-β1/Smad3.
The microRNA (miR)-29 family is closely associated with fibrotic processes by virtue of its low expression in many tissues during organ fibrosis. The present study investigated whether miR-29b overexpression suppressed hepatic stellate cell (HSC) activation and its interactions with transforming growth factor (TGF)-β1/mothers against decapentaplegic homolog 3 (Smad3), a classical signal transduction pathway contributing to the activation of HSCs. The results showed that transfection of LX-2 (human HSC) cells with miR-29b mimic or pSUPER-Smad3 silencing (si)RNA resulted in significantly increased expression of miR-29b and decreased expression of Smad3. miR-29b overexpression inhibited proliferation of LX-2 cells 24 h after transfection. Both miR-29b overexpression and Smad3 silencing antagonized the effects of TGF-β1 on the expression of α-smooth muscle actin (α-SMA) and collagen type I (col-1). Furthermore, infection with miR-29b mimics suppressed Smad3 and TGF-β1 expression, suggesting that miR-29b inhibited LX-2 activation mediated by both Smad3 and TGF-β1. Nevertheless, primary miR-29a/b1, miR-29b2/c and mature miR-29b were downregulated by TGF-β1 and stimulated by Smad3 silencing, suggesting that TGF-β1/Smad3 signalling pathway regulate not just mature miR-29b but also its transcription. In summary, our results show overwhelming evidence corroborating the suppressive effect of miR-29b on TGF-β1-induced LX-2 cell activation. The results also revealed the existence of crosstalk between miR-29b and TGF-β1/Smad3 during LX-2 activation, suggesting a feedback loop between miR-29b and TGF-β1/Smad3 signalling that promotes liver fibrosis. Copyright © 2016 The Authors. Cell Biochemistry and Function published by John Wiley & Sons, Ltd.


The impact of Gam-COVID-Vac, an Adv5/Adv26 COVID-19 vaccine, on the biomarkers of endothelial function, coagulation and platelet activation.
COVID-19 vaccines have played a critical role in controlling the COVID-19 pandemic. Although overall considered safe, COVID-19 vaccination has been associated with rare but severe thrombotic events, occurring mainly in the context of adenoviral vectored vaccines. A better understanding of mechanisms underlying vaccine-induced hypercoagulability and prothrombotic state is needed to improve vaccine safety profile. We assessed changes to the biomarkers of endothelial function (endothelin, ET-1), coagulation (thrombomodulin, THBD and plasminogen activator inhibitor, PAI) and platelet activation (platelet activating factor, PAF, and platelet factor 4 IgG antibody, PF4 IgG) within a three-week period after the first (prime) and second (boost) doses of Gam-Covid-Vac, an AdV5/AdV26-vectored COVID-19 vaccine. Blood plasma collected from vaccinees (n = 58) was assayed using ELISA assays. Participants were stratified by prior COVID-19 exposure based on their baseline SARS-CoV-2-specific serology results. We observed a significant post-prime increase in circulating ET-1, with levels sustained after the boost dose compared to baseline. ET-1 elevation following dose 2 was most pronounced in vaccinees without prior COVID-19 exposure. Prior COVID-19 was also associated with a mild increase in post-dose 1 PAI. Vaccination was associated with elevated ET-1 up to day 21 after the second vaccine dose, while no marked alterations to other biomarkers, including PF4 IgG, were seen. A role of persistent endothelial activation following COVID-19 vaccination warrants further investigation.


Nitric oxide-releasing particles inhibit phagocytosis in human neutrophils.
We have constructed a yeast (Saccharomyces cerevisiae) particle capable of releasing NO, by loading heat-killed yeast particles with a hydrophobic NO-generating substance, GEA-5171. This particle decreased phagocytosis in solution, as measured with flow cytometry, to about 80% of control values. Phagocytosis on a surface, as counted under the microscope, was also decreased by about 20%. The nitric oxide furthermore counteracted the production of oxygen metabolites by neutrophils to about 20% of control values. The inhibitory effect was most pronounced for the intracellular production, as could be seen when neutrophils preincubated with NO-releasing particles were stimulated with chemotactic agent (FMLP) or phorbol ester (PMA). In conclusion, NO has inhibitory effects on both phagocytosis and the respiratory burst of neutrophils. Since nitric oxide is a hydrophobic gas and an air pollutant, there is a possibility that it accumulates in particles which then become more resistant to elimination.


Alternatives to antibiotics in semen extenders: a review.
Antibiotics are added to semen extenders to be used for artificial insemination (AI) in livestock breeding to control bacterial contamination in semen arising during collection and processing. The antibiotics to be added and their concentrations for semen for international trade are specified by government directives. Since the animal production industry uses large quantities of semen for artificial insemination, large amounts of antibiotics are currently used in semen extenders. Possible alternatives to antibiotics are discussed, including physical removal of the bacteria during semen processing, as well as the development of novel antimicrobials. Colloid centrifugation, particularly Single Layer Centrifugation, when carried out with a strict aseptic technique, offers a feasible method for reducing bacterial contamination in semen and is a practical method for semen processing laboratories to adopt. However, none of these alternatives to antibiotics should replace strict attention to hygiene during semen collection and handling.


[Subclinical hypothyroidism--a condition that must be treated?].
Subclinical hypothyroidism, defined as serum thyrotropin above the upper reference limit with normal estimates of free thyroxin in serum, has a prevalence in Denmark of 2%. Several investigations have shown that patients with subclinical hypothyroidism have subtle symptoms and signs of mild thyroid failure. Whether these patients require treatment or not is a controversial issue due to a lack of convincing evidence regarding the beneficial effects of hormone replacement, especially in patients with serum TSH <10 mU/L. However, when it comes to treatment of pregnant or fertile women planning pregnancy, no doubt prevails, as normal thyroid function is important for optimal pregnancy outcome.


Continuous care intervention with carbohydrate restriction improves physical function of the knees among patients with type 2 diabetes: a non-randomized study.
In a previous study, we assessed a novel, remotely monitored carbohydrate restricted diet regimen including nutritional ketosis in patients with type 2 diabetes and reported significant improvements in weight, glycemic control, abdominal fat and inflammation from baseline to 2 years. Knee outcome measures were collected as a secondary outcome in the trial. This study aims to assess the effect of this intervention on knee functional scores and to identify if changes in weight, central abdominal fat (CAF), glycemic status and high sensitivity C-reactive protein (hsCRP) were associated with its improvement. This prospective analysis included continuous care intervention (CCI, n = 173) and usual care (UC, n = 69) trial participants with type 2 diabetes that reported knee pain at baseline. Knee outcome measures included the Knee injury and Osteoarthritis Outcome Score (KOOS) pain, symptoms, activities of daily living (ADL), sports and recreation function, and knee-related quality of life subscales, and total KOOS score were assessed from baseline to 2 years. Missing data at each time point were replaced with multiple imputation under the assumption of missing at random. To assess if the primary analysis of the knee scores changed under plausible missing not at random assumptions, sensitivity analysis was also performed using pattern mixture models. In CCI, we also assessed factors associated with the improvement of knee scores. In the primary analysis, CCI participants demonstrated a statistically significant improvement in total KOOS and all KOOS individual subscale scores at 1 year and maintained through 2 years as opposed to UC patients who showed no significant changes from baseline to 2 years. The significant improvement in total KOOS and its individual subscale scores from baseline to 2 years remained relatively stable in CCI in the sensitivity analysis under different missing not at random scenarios confirming the robustness of the findings from the primary analysis. Approximately 46% of the CCI participants met the 10 points minimal clinically important change at 2 years. A reduction in CAF was associated with improvement in total KOOS and KOOS ADL, while a decrease in hsCRP was associated with improvement in KOOS symptoms scores. A very low carbohydrate intervention including nutritional ketosis resulted in significant improvements in knee pain and function among patients with T2D. The improvements in knee function were likely secondary to a reduction in central adiposity and inflammation. Future research on the applicability of this intervention in radiographically confirmed OA patients is important. Clinical trial registration: NCT02519309 (10/08/2015).


Salivary IgA and IgG in oral lichen planus and oral lichenoid reactions diseases.
The objective of this study was to assess the level of salivary IgA and IgG in oral lichen planus (OLP) and oral lichenoid reactions (OLR) patients as diagnostic factors to the differential diagnosis of OLP, OLR diseases. Saliva sample were obtained from 50 OLP, 50 OLR patients and 50 healthy subjects between April 2010 and October 2011. The clinical relevant data taken into account were: Demographical data, previous medication, and level of salivary IgA and IgG. Each sample was assessed to determine the level of salivary IgA by ELISA test and salivary IgG by radial immune diffusion. The mean of salivary IgA and IgG in patients were 119.01 ± 114.18 mic/ml and 3.25 ± 1.81 mic/ml, respectively. There were no significant differences for salivary IgA and IgG between OLP and OLR, but the mean of salivary IgA and IgG in OLP and OLR patients were significantly more than normal group (P-value < 0.05). The cut-off value was set at >72 mic/ml for salivary IgA in both OLP and OLR groups and set at >3.7 mic/ml for salivary IgG. On comparing the AUCs, there was no significant difference between AUCs for IgA (0.715 ± 0.05vs. 0.69 ± 0.5, for OLP and OLR patients, respectively,P-value = 0.7) and IgG (0.681 ± 0.05 vs. 0.548 ± 0.06, for OLP and OLR patients, respectively, P-value = 0.1). Our results showed that the level of salivary IgA and IgG in OLP and OLR patients is higher than healthy controls, but they cannot be used as diagnostic factors to the differential diagnosis of OLP and OLR.


Pharmacological Inhibition of Glutaminase 1 Attenuates Alkali-Induced Corneal Neovascularization by Modulating Macrophages.
Corneal neovascularization (CoNV) in response to chemical burns is a leading cause of vision impairment. Although glutamine metabolism plays a crucial role in macrophage polarization, its regulatory effect on macrophages involved in chemical burn-induced corneal injury is not known. Here, we elucidated the connection between the reprogramming of glutamine metabolism in macrophages and the development of alkali burn-induced CoNV. Glutaminase 1 (GLS1) expression was upregulated in the mouse corneas damaged with alkali burns and was primarily located in F4/80-positive macrophages. Treatment with a selective oral GLS1 inhibitor, CB-839 (telaglenastat), significantly decreased the distribution of polarized M2 macrophages in the alkali-injured corneas and suppressed the development of CoNV. In vitro studies further demonstrated that glutamine deprivation or CB-839 treatment inhibited the proliferation, adhesion, and M2 polarization of bone marrow-derived macrophages (BMDMs) from C57BL/6J mice. CB-839 treatment markedly attenuated the secretion of proangiogenic factors, including vascular endothelial growth factor-A (VEGF-A) and platelet-derived growth factor-BB (PDGF-BB) from interleukin-4- (IL-4-) regulated M2 macrophages. Our findings revealed that GLS1 inhibition or glutamine deprivation prevented alkali-induced CoNV by inhibiting the infiltration and M2 polarization of macrophages. This work suggests that pharmacological GLS1 inhibition is a feasible and effective treatment strategy for chemical burn-related CoNV in humans.


Radiotherapy followed by aurora kinase inhibition targets tumor-propagating cells in human glioblastoma.
Glioblastoma (GBM) is the most common malignant primary brain tumor. Radiotherapy fails to eliminate subpopulations of stem-like tumor-propagating cells (TPC), resulting in tumor regrowth. To identify kinases that promote TPC self-renewal rather than increasing proliferation in human GBM cultures, we screened a library of 54 nonselective tool compounds and determined their kinase inhibitor profiles in vitro. Most compounds inhibited aurora kinase (AURK) activity and blocked TPC self-renewal, while inducing GBM cell polynucleation and apoptosis. To prevent regrowth by TPCs, we used a priming dose of radiation followed by incubation with the pan-AURK inhibitor VX680 to block self-renewal and induce apoptosis in GBM cultures. In mice xenografted with human GBM cells, radiotherapy followed by VX680 treatment resulted in reduced tumor growth and increased survival relative to either monotherapy alone or VX680 treatment before radiation. Our results indicate that AURK inhibition, subsequent to radiation, may enhance the efficacy of radiotherapy by targeting radioresistant TPCs in human GBMs.


Caution in treating transsphenoidal encephalocele with concomitant moyamoya disease.
A basal encephalocele is a rare congenital malformation involving a cranial bone defect and cystic-like herniation through the defect. Moyamoya is a rare cerebrovascular disease of unclear etiology involving occlusion of the distal internal carotids and formation of collateral vascular networks. Both diseases have been correlated with optic disc anomalies, hypopituitarism, and midfacial defects. We present a case of a 2-year-old boy with a midline facial cleft who underwent surgical correction of a basal encephalocele. His moyamoya disease may have contributed to a vascular complication. There is growing evidence indicating an overlap in disease profiles for these two rare diseases. In addition, molecular evidence indicates elevated levels of fibroblast growth factor and transforming growth factor in both diseases, suggesting common molecular pathways.


C-terminal pro-endothelin-1 offers additional prognostic information in patients after acute myocardial infarction: Leicester Acute Myocardial Infarction Peptide (LAMP) Study.
Endothelin-1 is elevated in heart failure (HF) and after acute myocardial infarction (AMI) and gives prognostic information on mortality. Another part of its precursor, C-terminal pro-endothelin-1 (CT-proET-1), is more stable in circulation and ex vivo. We investigated the cardiovascular prognostic value post-AMI of CT-proET-1 and compared it to N-terminal pro-B-type natriuretic peptide (NTproBNP), a marker of death and HF. We measured plasma CT-proET-1 and NTproBNP in 983 consecutive post-AMI patients (721 men, mean age 65.0 +/- [SD] 12.2 years), 3 to 5 days after chest pain onset. There were 101 deaths and 49 readmissions with HF during follow-up (median 343, range 0-764 days). C-terminal pro-endothelin-1 was raised in patients with death or HF compared to survivors (median [range] [pmol/L], 119.0 [14.0-671.0] vs 73.0 [4.6-431.0], P < .0001). Using a Cox proportional hazards logistic model, log CT-proET-1 (HR 6.82) and log NTproBNP (HR 2.62) were significant independent predictors of death or HF (along with age, sex, history of AMI, and therapy with beta-blockers). The areas under the receiver operating curve for CT-proET-1, NTproBNP, and the logistic model with both markers were 0.76, 0.76, and 0.81 respectively. Findings were similar for death and HF as individual end points. The endothelin system is known to be activated post AMI. C-terminal pro-endothelin-1 is a powerful predictor of adverse outcome, along with NTproBNP. CT-proET-1 may represent a clinically useful marker of prognosis after AMI.


In vitro Antibacterial Activity of Doripenem against Gram-Negative Blood Isolates in a Korean Tertiary Care Center.
Doripenem is the most recently introduced antimicrobial agent of the carbapenem class. It is a valuable therapeutic option in the context of increasing antimicrobial resistance to imipenem and meropenem among gram-negative bacilli (GNB) clinical isolates. However, clinicians are usually reluctant to prescribe doripenem, because susceptibility to doripenem is not automatically reported by most clinical laboratories and the in vitro activity of doripenem against clinically significant GNB isolates remains uncertain. We investigated the in vitro antibacterial activity of doripenem in GNB blood isolates in a tertiary care center. Over a period of 10 months, 212 adult bacteremia cases were treated at the study hospital. Doripenem susceptibility testing was performed for the 212 blood isolates by the disk diffusion method, and clinical data were collected. Among the blood isolates, the rate of doripenem resistance (7.5%) was lower than that of imipenem (12.9%) or other anti-GNB antimicrobial agents, except amikacin (2.1%). Almost all imipenem-susceptible GNB blood isolates (181/182, 99.5%) were susceptible to doripenem. Whereas doripenem resistance was rarely observed in Enterobacteriaceae (2/181, 1.1%), it was frequently observed in patients with non-fermentatative GNB (12/27, 44.4%), hospital-acquired infections (7/27, 25.9%), and pneumonia (11/49, 22.4%). Doripenem exhibited more potent in vitro activity against GNB blood isolates than other anti-GNB antimicrobial agents in a tertiary care center where it was infrequently prescribed compared with other carbapenems. However, its clinical utility may be limited due to the increasing number of carbapenem-resistant non-fermentative GNB infections.


High expression of miR-493-5p positively correlates with clinical prognosis of non small cell lung cancer by targeting oncogene ITGB1.
Increasing evidence supports that microRNA (miRNA)-mediated gene regulation plays a significant functional role in cancer progression. To investigate the expression and clinical significance of ITGB1 in non small cell lung cancer (NSCLC), the expression levels of ITGB1 in NSCLC tissues and human normal lung tissues were analyzed in silico using genes microarray, KEGG pathway and hierarchical clustering analysis followed by validation with quantitative RT-PCR. Our results showed that ITGB1 was upregulated in NSCLC tissues when compared with normal lung tissues. Survival analysis based on the qRT-PCR data established that ITGB1 expression was attentively related to the prognosis of NSCLC, and patients with higher ITGB1 expression had shorter overall survival (OS). Moreover, ITGB1 was confirmed to be a direct target of miR-493-5p. Furthermore, concomitant high expression of ITGB1 and low expression of miR-493-5p correlated with a shorter median OS and PFS in NSCLC patients. In conclusion, our results provide the first evidence that ITGB1 is a direct target of miR-493-5p suggesting that ITGB1 and miR-493-5p may have potential prognostic value and may be useful as tumor biomarkers for the diagnosis of NSCLC patients.


[Poor weight gain, recurrent metabolic alkalosis and hypokalemia in a neonate].
The study reports a female neonate with a gestational age of 29+2 weeks and a birth weight of 1 210 g. Ten minutes after birth, the neonate was admitted to the hospital due to shortness of breath. Several days after birth, the neonate presented with hyperglycemia, polyuria, and poor weight gain, accompanied by azotemia, hypochloremic metabolic alkalosis, hypokalemia, and hyponatremia. Laboratory examinations showed elevated levels of aldosterone, renin, and angiotensin II. Gene detection revealed SLC12A1 gene mutation. Neonatal Bartter syndrome was thus confirmed. The neonate was treated with sodium and potassium supplements, and was followed up for 8 months. During the follow-up, the mental and neural development of the neonate was almost normal at the corrected age, and regular reexaminations showed slight metabolic alkalosis and almost normal electrolyte levels. For the neonates who have the symptoms of unexplainable polyurine and electrolyte disorders, it is important to examine the levels of aldosterone, renin and angiotensin. A definite diagnosis of neonatal Bartter syndrome can be made based on the presence of SLC12A1 gene mutation.


Production of dextransucrase and dextran by Leuconostoc mesenteroides immobilized in calcium-alginate beads: II. Semicontinuous fed-batch fermentations.
Cells of Leuconostoc mesenteroides immobilized in calcium alginate beads were used to produce dextransucrase (DS) in three sequential cycles of semicontinuous fed-batch fermentations. Each cycle consisted of a fed-batch DS production period of 24 h followed by a batch dextran production period for another 24 h. Free, suspended cells were used in only one cycle of fed-batch DS production followed by a dextran production period. It was impractically tedious to separate and reuse free cells. Increasing sucrose feed rate from 5 to 10 g/L h led to increases of the total enzymatic activity by about 88% with immobilized cells and by about 100% with free cells. In DS fed-batch semicontinuous fermentation, total enzymatic activity produced by immobilized cells was 1.35 and 1.56 times greater than that produced by free cells with respective sucrose feeding rates of 10 and 5 g/L h. These increases in enzyme productivity with immobilized cells, however, required total overall operating times three times longer (three cycles) than with free cells (one cycle). Growing the microorganism at optimum conditions for DS production also increased the dextran yield and shortened the time of conversion of sucrose to dextran, regardless of whether the cells were free or immobilized. Moreover, during three cycles of semicontinuous operation (144 h) immobilized cells produced more than three times as much dextran as free cells during one cycle (24 h).


Characterization of H2 -Splitting Products of Frustrated Lewis Pairs: Benefit of Fast Magic-Angle Spinning.
Proton spectroscopy in solid-state NMR on catalytic materials offers new opportunities in structural characterization, in particular of reaction products of catalytic reactions such as hydrogenation reactions. Unfortunately, the 1 H NMR line widths in magic-angle spinning solid-state spectra are often broadened by an incomplete averaging of 1 H-1 H dipolar couplings. We herein discuss two model compounds, namely the H2 -splitting products of two phosphane-borane Frustrated Lewis Pairs (FLPs), to study potentials and limitations of proton solid-state NMR experiments employing magic-angle spinning frequencies larger than 100 kHz at a static magnetic field strength of 20.0 T. The 1 H lines are homogeneously broadened as illustrated by spin-echo decay experiments. We study two structurally similar materials which however show significant differences in 1 H line widths which we explain by differences in their 1 H-1 H dipolar networks. We discuss the benefit of fast MAS experiments up to 110 kHz to detect the resonances of the H+ /H- pair in the hydrogenation products of FLPs.


[Supraventricular tachycardia caused by dual conduction paths in the atrioventricular junction].
An intracardiac electrophysiological study of 23 patients with a history of frequent attacks of supraventricular tachycardia showed that one of the underlying mechanisms of tachycardia development was reciprocation in the atrioventricular conjunction caused by binary conduction occurring in this structure (longitudinal dissociation). Two electrophysiological variants of reciprocal atrioventricular tachycardia were identified, namely ortho- and antidromal. The electrophysiological criteria for the diagnosis of both variants of reciprocal atrioventricular tachycardias are presented.


Effects of alcohol on plasma lipoproteins and cholesterol and triglyceride metabolism in man.
To define the effects of moderate alcohol intake on cholesterol and triglyceride metabolism in man, twelve patients were hospitalized on a metabolic ward and were fed defined diets for 10 weeks. Each patient underwent testing of plasma lipid and lipoprotein levels, of cholesterol metabolism (absorption, fecal excretion, bile saturation), and of triglyceride metabolism [turnover of triglycerides in chylomicrons and very low density lipoproteins (VLDL)]. This testing was done twice, first during a 4-week control period and then during a 4-week period in which 630 calories of alcohol were either added to or substituted for baseline calories. This increased the average baseline caloric intake by only 24% (range 20% to 30% depending on the initial caloric intake). Addition of alcohol to the baseline diet did not cause weight gain in lean individuals. Obese individuals' responses were more variable, and 3/6 definitely gained weight when the diet was supplemented with alcohol. In addition, obese subjects appeared to be more susceptible to the hyperlipidemic effects of alcohol; whereas 4/6 obese patients developed increased total triglyceride and VLDL-triglyceride concentrations when alcohol was administered, concentrations increased with alcohol administration in only 1/6 lean individuals. High density lipoprotein (HDL) cholesterol increased in all volunteers. Low density lipoprotein (LDL) levels did not change. Metabolic studies showed increased transport of VLDL-triglycerides in overweight patients but not in normal weight individuals; increased transport of VLDL-triglycerides in the former was associated with delayed clearance of chylomicron triglycerides. Alcohol consumption did not affect lipoprotein lipase or hepatic triglyceride lipase in six patients in whom these enzyme activities were measured. In the amounts of alcohol taken in this study, no changes were observed in absorption, synthesis, or excretion of bile acids, or percent saturation of gallbladder bile with cholesterol.


A unique device, the disc space-fitted distraction device, for anterior cervical discectomy and fusion: early clinical and radiological evaluation.
To perform interbody distraction and to obtain spinal curvature correction during anterior cervical discectomy and fusion (ACDF), the authors recently adopted a new stand-alone device, a disc space-fitted distraction device (DFDD). In this preliminary report the authors introduce this unique device and discuss some advantages in terms of short-term clinical and radiological evaluations. The most unique aspect of the DFDD is the function of gentle distraction at anterior disc space with maximum lordotic correction of up to 8 degrees while rotating a screw at the front of the device. Additional advantages are related to its configuration such as disc space-matched shape in all dimensions, tapering contour for easy insertion into the disc space, multiple spikes to avoid dislodgment, wider contact area to the vertebral endplate for diminishing sinking process, and sufficient space for accommodation of bone-conductive materials. Twenty-four patients who have been observed more than 12 months after ACDF were involved in this evaluation. The objective clinical outcome, measured by the Neurological Cervical Spine Scale, was significantly improved. In radiological evaluation, statistically significant improvement compared with preoperative values was noted on the curvature index, C2-7 curvature, and disc angle (p < 0.01) throughout the entire postoperative period, up to 12 months. A high fusion rate and remodeling process around the implants were also observed. The DFDD may have some advantages over other devices-its distraction action, diminished sinking, and early solid bone union resulted in maintaining sufficient correction of the spinal curvature. This corrected spinal curvature may play an important role in preventing progressive adjacent-disc degeneration subsequent to ACDF in the long term.


Membrane potential and cancer progression.
Membrane potential (Vm ), the voltage across the plasma membrane, arises because of the presence of different ion channels/transporters with specific ion selectivity and permeability. Vm is a key biophysical signal in non-excitable cells, modulating important cellular activities, such as proliferation and differentiation. Therefore, the multiplicities of various ion channels/transporters expressed on different cells are finely tuned in order to regulate the Vm . It is well-established that cancer cells possess distinct bioelectrical properties. Notably, electrophysiological analyses in many cancer cell types have revealed a depolarized Vm that favors cell proliferation. Ion channels/transporters control cell volume and migration, and emerging data also suggest that the level of Vm has functional roles in cancer cell migration. In addition, hyperpolarization is necessary for stem cell differentiation. For example, both osteogenesis and adipogenesis are hindered in human mesenchymal stem cells (hMSCs) under depolarizing conditions. Therefore, in the context of cancer, membrane depolarization might be important for the emergence and maintenance of cancer stem cells (CSCs), giving rise to sustained tumor growth. This review aims to provide a broad understanding of the Vm as a bioelectrical signal in cancer cells by examining several key types of ion channels that contribute to its regulation. The mechanisms by which Vm regulates cancer cell proliferation, migration, and differentiation will be discussed. In the long term, Vm might be a valuable clinical marker for tumor detection with prognostic value, and could even be artificially modified in order to inhibit tumor growth and metastasis.


[The influence of laser irradiation with different power densities on incisional wound healing in healthy and diabetic rats].
The optimal parameters of low level laser therapy (LLLT) are still under debate. It has been documented that a dose or 5 J/cm2 would be capable to accelerate the wound healing process in patients. However, the optimal delivering form, i.e. power intensity, is unknown. Therefore, the aim of our study was to compare different power densities of LLLT. Sixteen male Sprague-Dawley rats were included in this experiment and randomized into two groups, normal healthy group and streptozotocine induced diabetic group. In general anesthesia four full thickness skin incisions were performed under standard aseptic conditions on the back of each rat and immediately closed using intradermal running suture. Three wounds were stimulated with diode laser (wavelength: 635 nm; daily dose 5 J/cm2; power densities: 1 mW/cm2, 5 mW/cm2 and 15 mW/cm2) each with different power density while the fourth wound served as control. Six days after surgery animals were sacrificed and samples removed for histological evaluation. Our study demonstrated that LLLT positively influences wound healing. The most significant changes were observed in wounds stimulated at the highest power density 15 mW/cm2. Since using the highest power density the shortest time is needed to achieve the optimal daily dose of 5 J/cm2, it can be suggested that 15 mW/cm2 might be optimal parameter for such a therapy in patients.


International standards: the World Organisation for Animal Health Terrestrial Animal Health Code.
This paper provides a description of the international standards contained in the TerrestrialAnimal Health Code of the World Organisation for Animal Health (OIE) that relate to the prevention and control of vector-borne diseases. It identifies the rights and obligations of OIE Member Countries regarding the notification of animal disease occurrences, as well as the recommendations to be followed for a safe and efficient international trade of animals and their products.


Abnormal cervical smear in hereditary mucoepithelial dysplasia: a case report.
Hereditary mucoepithelial dysplasia is a disorder that involves the mucosa, skin, hair, eyes, and lungs. It is an autosomal dominant condition, although sporadic cases have been reported. The syndrome is caused by an abnormality in desmosomes and gap junctions. We report a case of abnormal cervical smear in an affected individual. Vaginal, oral, and urinary cytological smears show a lack of epithelial cell maturation, large paranuclear cytoplasmic vacuoles, and cytoplasmic strand-shaped inclusions. Abnormal Pap cervical tests have been reported in affected individuals. It has been found that a misinterpretation of abnormal from a cervical smear may lead to an unnecessary hysterectomy. We believe this disorder should be brought to the attention of colposcopists because misinterpreted abnormal cervical Pap tests can lead to unnecessary treatment in such affected individuals.


Attainment of maximal exercise criteria in boys and men.
This study tested the hypothesis that the occurrence of a VO(2) plateau at maximal exercise would be greater in men versus boys. Secondary indicators of maximal effort also were examined. Sixteen boys (10.7+/-0.6 yrs) and 21 men (22.5+/-2.0 yrs) performed a graded exercise test on a treadmill at a constant speed of 8.04 km x hr(-1) with 2.5% increments in elevation. The men also performed a second test at 11.26 km x hr(-1) with similar increases in slope. At 8.04 km x hr(-1) , VO(2) max was 52.3+/-6.0 and 52.5+/-5.1 ml x kg(-1) x min(-1) in boys and men, respectively (p>0.05). In the men, VO(2) max (53.3+/-5.4 ml x kg(-1) x min(-1) ) was higher (p<0.05) in the faster protocol. The percentage of men achieving the criterion was nearly double the percentage of boys (23.8 vs 12.5%), although the difference was not significant. Age-specific criteria heart rate (HR) and respiratory exchange ratio (RER) were achieved in a similar manner; however, more men (100%) than boys (86.7%) achieved an age-specific blood lactate (BLa) criterion (p<0.05). Plateau achievement increased to 33.0% in the 11.26 km x hr(-1) protocol, but was not significantly different from 8.04 km x hr(-1). HR, RER and BLa criteria achievement were comparable. Maturation may influence the achievement of a plateau and BLa criteria, but not age-specific criteria for RER or HR.


ISCORS Catalog of References to Parameter Values and Distributions Used in Environmental Pathway Modeling for Cleanup of Sites Contaminated with Radioactivity.
Federal and state regulatory agencies that are concerned with issues of environmental management have adopted approaches toward policy-making that are dose- and risk-informed. To that end they (and others) have developed environmental models and computer codes to mimic the transport of contaminants along air, water, food-chain, and related pathways for estimating potential exposures, doses, and risks to individuals, populations, and ecosystems. Their calculations commonly find application in the planning of remediation, and thereafter in the demonstration of compliance with federal and state cleanup standards. As the models and codes have become more sophisticated, so also have requirements on the accuracy and level of detail of the numerical point values and probability distributions of environmental transfer factors and other parameters that serve as input parameters to them. In response to this growing need, the federal Interagency Steering Committee On Radiation Standards (ISCORS) and the Argonne National Laboratory have developed an on-line, national repository of information on parameter values and distributions of known provenance and demonstrated utility. The ISCORS Catalog of References to Parameter Values and Distributions Used in Environmental Pathway Modeling for Cleanup of Sites Contaminated with Radioactivity is a web-based, indexed compilation of references, compendia, databases, and other sources of peer-reviewed information on parameters. It does not itself contain numerical point values or distributions for any particular parameter, but rather it provides links or directions to sites or other published materials where such information can be obtained. Designed to be user-friendly, easily searchable, and readily up-dateable, the Catalog is being filled, after some initial priming, mainly through on-line submissions of proposed references by the Catalog users themselves. The relevant information on a proposed reference is submitted to ISCORS in a simple, standardized format; it is vetted (with acceptance criteria such as publication in a peer-reviewed technical journal, or appearance in a formally-issued federal agency report) and then added semi-automatically to the Catalog. Built around a relational database, the system offers subject- and text-search capabilities, provides information on parameter definitions and methods of measurement, on transport/exposure pathways, and on standard models and codes. The Catalog is intended for use by (and being populated by) the professionals, managers, and others involved or interested in the application of pathway modeling to estimate doses and risks associated with sites contaminated with radioactive or other hazardous materials.


Emergent multisystemic Enterococcus infection threatens endangered Christmas Island reptile populations.
Multisystemic infections with a morphologically unusual bacterium were first observed in captive critically endangered Lister's geckos (Lepidodactylus listeri) on Christmas Island in October 2014. Since then the infection was identified in another captive critically endangered lizard species, the blue-tailed skink (Cryptoblepharus egeriae) and two species of invasive geckos; the four clawed gecko (Gehyra mutilata) and Asian house gecko (Hemidactylus frenatus), in a wide geographic range across the east side of the island. The Gram and periodic acid-Schiff positive cocci to diplococci have a propensity to form chains surrounded by a matrix, which ultrastructurally appears to be formed by fibrillar capsular projections. The bacterium was associated with severe and extensive replacement of tissues, but minimal host inflammatory response. Attempts to grow the organism in culture and in embryonated eggs were unsuccessful. Molecular characterisation of the organism placed it as a novel member of the genus Enterococcus. Disease Risk Analyses including this organism should now be factored into conservation management actions and island biosecurity.


Pregnancy outcome in spontaneous twins versus twins who were conceived through in vitro fertilization.
The purpose of this study was to compare maternal and neonatal complications in spontaneous versus in vitro fertilization twins. Twin gestations that were delivered from 1995 to 2000 were reviewed. Cases consisted of 56 in vitro fertilization twins, each of which was matched to two control mothers by age and parity. They were compared regarding various maternal and neonatal complications. In vitro fertilization twins were more likely to have preterm labor compared with control twins, with no difference in the incidences of pregnancy-induced hypertension, gestational diabetes mellitus, placenta previa, or preterm premature rupture of membranes between the two groups. The cesarean delivery rate was significantly higher in cases of twins who were conceived by in vitro fertilization (76.8% vs 58.0%, P=.026), despite a similar rate of elective cesarean delivery and the incidence of nonvertex twin A in both groups. The preterm delivery rate was significantly higher (67.9% vs 41.1%, P=.002) and the gestational age was significantly lower (35+/-3 weeks vs 36+/-3 weeks, P=.043) in cases compared with control subjects. Both twins were, on the average, 230 g lighter in the in vitro fertilization group compared with the control group. However, intrauterine growth restriction was more frequent in the control group (36.6% vs 25%, P=.044). There was a significantly higher incidence of admission to the neonatal intensive care unit, respiratory distress syndrome, a need for mechanical ventilation, and pneumothorax in cases compared with control subjects. When compared with spontaneous twins, in vitro fertilization twins are more likely to be delivered by cesarean delivery and to have a higher incidence of preterm birth and prematurity-related respiratory complications with a longer nursery stay.


Modifiable patient factors are associated with the late decline in renal function following liver transplantation.
Strategies to delay or avoid the long-term decline in renal function and progression to chronic kidney disease (CKD) in liver transplant recipients remain unclear. Our aim was to examine the change in estimated GFR (eGFR) from six months after liver transplantation, and to identify modifiable factors associated with a faster rate of decline. This was a single-center retrospective study of 97 patients who underwent elective liver transplantation and survived ≥ 5 yr. eGFR was estimated using the MDRD6-variable equation, and the annualized change in eGFR was determined using simple linear regression. The baseline eGFR was 75 mL/min/1.73 m(2) . Thereafter, eGFR declined at a mean rate of 1.08 mL/min/1.73 m(2) per year. 49% had a decline in renal function greater than the rate expected with aging. Decline in eGFR was an independent predictor of CKD by five yr post-transplant (p = 0.001). Multivariate modeling found a higher baseline eGFR (p < 0.001), female gender (p = 0.006), hypertension (p = 0.019), and dyslipidemia (p = 0.034) to be associated with a faster rate of decline in renal function. In conclusion, liver transplant recipients have a clinically relevant decline in eGFR from six months post-transplant. Prospective studies are required to examine the effects of aggressive blood pressure and lipid control on the development of CKD in this setting.


[Pain and palliative care. Comments by a witness].
Physical pain is well analysed by medical science, but still often neglected by the practicians. It is entangled with moral suffering at the end of life. The distinction between these two fundamental experiences is difficult but necessary for the care of patients. The concept of palliative care is far from being integrated by health professionals as well as by everybody, because it questions our finitude, the signification of life and human solidarity.


Critical care outreach 2: uncovering the underpinning philosophy and knowledge through collaborative reflection.
Critical care outreach (Outreach) was introduced as part of a government strategy to address increasing demands on limited intensive care (level 3) and high-dependency (level 2) resources. The discipline of Outreach developed rapidly and, as a result, the fundamental philosophical theories and sources of knowledge that underpin its practice remain, at least to some extent, unexplored, and their contribution to practice overlooked. It is important that we understand these philosophical theories and sources of knowledge so that we are able to provide sound rationale and guidance for practice and address the increasing pressure to demonstrate effectiveness. The authors argue that the complex situations encountered and managed by Outreach are not entirely amenable to traditional forms of measurement, and that its impact on patient care is, therefore, not readily acknowledged. In applying a model of collaborative reflection, this study analyses the management of a clinical case by a nurse consultant in Outreach. In doing so, it explores the realities of practice by deconstructing the complexity of a particular situation and highlights the variety of knowledge that contributes to effective Outreach practice.


Absent MicroRNAs in Different Tissues of Patients with Acquired Cardiomyopathy.
MicroRNAs (miRNAs) can be found in a wide range of tissues and body fluids, and their specific signatures can be used to determine diseases or predict clinical courses. The miRNA profiles in biological samples (tissue, serum, peripheral blood mononuclear cells or other body fluids) differ significantly even in the same patient and therefore have their own specificity for the presented condition. Complex profiles of deregulated miRNAs are of high interest, whereas the importance of non-expressed miRNAs was ignored. Since miRNAs regulate gene expression rather negatively, absent miRNAs could indicate genes with unaltered expression that therefore are normally expressed in specific compartments or under specific disease situations. For the first time, non-detectable miRNAs in different tissues and body fluids from patients with different diseases (cardiomyopathies, Alzheimer's disease, bladder cancer, and ocular cancer) were analyzed and compared in this study. miRNA expression data were generated by microarray or TaqMan PCR-based platforms. Lists of absent miRNAs of primarily cardiac patients (myocardium, blood cells, and serum) were clustered and analyzed for potentially involved pathways using two prediction platforms, i.e., miRNA enrichment analysis and annotation tool (miEAA) and DIANA miRPath. Extensive search in biomedical publication databases for the relevance of non-expressed miRNAs in predicted pathways revealed no evidence for their involvement in heart-related pathways as indicated by software tools, confirming proposed approach.


Photodistributed sarcoidosis: a case report and approach to management.
Sarcoidosis is an idiopathic disease, characterized by non-caseating granulomas in multiple organs/tissues. Cutaneous involvement occurs in approximately one-quarter of patients with a wide variety of presenting morphologies. This case report describes a case of photodistributed sarcoidosis, a rare cutaneous variant, with systemic involvement. A 42-year-old man presented with a history of a pruritic, rash with photoexacerbated annular plaques along with arthralgias and bone pain. Compared to previous reports of photodistributed sarcoidosis, our case presented with annular plaques rather than papules, and there was no prior exposure to ionizing radiation. He was treated successfully with prednisone and hydroxychloroquine. It is important to include sarcoidosis in the differential of photodistributed dermatoses.


Spontaneous Resolution of Optic Neuropathy in Sphenoid Wing Meningioma.
The authors describe herein a case of optic neuropathy in progesterone receptor positive sphenoid wing meningioma of the greater wing which demonstrated spontaneous recovery with conservative management.