CD44 is a marker for the outer pillar cells in the early postnatal mouse inner ear.
Cluster of differentiation antigens (CD proteins) are classically used as immune cell markers. However, their expression within the inner ear is still largely undefined. In this study, we explored the possibility that specific CD proteins might be useful for defining inner ear cell populations. mRNA expression profiling of microdissected auditory and vestibular sensory epithelia revealed 107 CD genes as expressed in the early postnatal mouse inner ear. The expression of 68 CD genes was validated with real-time RT-PCR using RNA extracted from microdissected sensory epithelia of cochleae, utricles, saccules, and cristae of newborn mice. Specifically, CD44 was identified as preferentially expressed in the auditory sensory epithelium. Immunohistochemistry revealed that within the early postnatal organ of Corti, the expression of CD44 is restricted to outer pillar cells. In order to confirm and expand this finding, we characterized the expression of CD44 in two different strains of mice with loss- and gain-of-function mutations in Fgfr3 which encodes a receptor for FGF8 that is essential for pillar cell development. We found that the expression of CD44 is abolished from the immature pillar cells in homozygous Fgfr3 knockout mice. In contrast, both the outer pillar cells and the aberrant Deiters' cells in the Fgfr3 ( P244R/ ) (+) mice express CD44. The deafness phenotype segregating in DFNB51 families maps to a linkage interval that includes CD44. To study the potential role of CD44 in hearing, we characterized the auditory system of CD44 knockout mice and sequenced the entire open reading frame of CD44 of affected members of DFNB51 families. Our results suggest that CD44 does not underlie the deafness phenotype of the DFNB51 families. Finally, our study reveals multiple potential new cell type-specific markers in the mouse inner ear and identifies a new marker for outer pillar cells.


Thyroid-stimulating hormone receptor and thyroid hormone receptors are involved in human endometrial physiology.
To study the expression, distribution, and function of thyroid-stimulating hormone receptor (TSHR) and thyroid hormone receptors (TR) α1, α2, and β1 in human endometrium. Experimental clinical study. University hospital. 31 fertile women. Endometrial biopsy samples obtained throughout the menstrual cycle. Real-time reverse transcriptase polymerase chain reaction, immunohistochemistry and Western blot to study the expression of TSHR, TRα1, TRα2, and TRβ1 messenger RNA (mRNA) and proteins in human endometrium. We found TSHR, TRα1, TRα2 and TRβ1 mRNA and proteins expressed in human endometrium. Immunostaining for TSHR in the luminal epithelium and TRα1 and β1 in the glandular and luminal epithelium increased statistically significantly on luteinizing hormone (LH) days 6 to 9, coinciding with appearance of pinopodes. Endometrial stromal and Ishikawa cells expressed mRNA for TSHR, TR, and iodothyronine deiodinases 1-3. After 48 hours, TSH significantly increased leukemia inhibitory factor (LIF) and LIF receptor (LIFR) messenger RNA (mRNA) in endometrial stromal cells, but decreased their expression in Ishikawa cells. Glucose transporter 1 mRNA was up-regulated by TSH in Ishikawa cells. We found that TSH statistically significantly increased secretion of free triiodothyronine (T3) and total thyroxin (T4) by Ishikawa cells compared with nonstimulated cells. Thyroid hormones are directly involved in endometrial physiology.


A multicentre prevalence study in Europe on Giardia duodenalis in calves, with molecular identification and risk factor analysis.
The present study aimed to obtain data on the occurrence of Giardia duodenalis in calves in four major cattle rearing countries in Europe (Germany, UK, France and Italy), along with genotyping data and risk factors associated with these infections. A total of 2072 calves were sampled on 207 farms. The majority of the animals were Holstein dairy or mixed Holstein calves (n=1565 or 75.5%), and were female (n=1640 or 79.1%). The average age was 7.8 weeks (SD=4.1; median=7; range=2-16 weeks). All fecal samples were tested using a commercially available monoclonal antibody-based ELISA. The overall apparent prevalence of G. duodenalis for the four countries was 45.4% (n=942/2072) and the overall farm prevalence was 89.9% (186/207), with differences in both animal and farm prevalence between the four countries. The prevalence was significantly higher in animals up to 8 weeks (OR=1.88; P<0.001) compared to older calves, and several management factors including contact with the Dam, Frequency of cleaning of the Maternity Pens, and Disinfection of the Calf Housing were found to be associated with infection. Positive samples were withheld for genotyping using the β-giardin and triose phosphate isomerase gene: G. duodenalis assemblage E was most prevalent, although 43% of the isolates were typed as assemblage A, with differences in between countries. Furthermore, 32% of the examined samples was found to be a mixed assemblage A and E infection, which is consistent with previous reports. The results of the present study confirm previous findings in other European countries that G. duodenalis infections are common in calves. The infection especially occurs in animals younger than 2 months, and the proportion of positive animals gradually decreased with increasing age.


[Direct antibiotic sensitivity testing in the treatment of urinary tract infections in a nursing home].
Urinary tract infections occur frequently in nursing homes. Treatment is usually empiric without microbiological investigation. Because there is widespread resistance to the most frequently used antibiotics, we tested a relatively simple method (direct sensitivity testing for 7 antibiotics) to get information about the antibiotic resistance. The results, with 49 urine samples in the evaluation, showed a concordance of our direct sensitivity test with conventional culture (the golden standard) of 89.8% (35/342 evaluations were not in concordance). The concordance for the result 'sensitive' was 98.8% (3/240 results showed 'false-sensitive'), and the the result 'resistant' 68.6% (32/342 results showed 'false-resistant'). Urinary tract infections in the nursing home can be treated more quickly and more adequately with antibiotics with the information obtained by direct sensitivity testing. This method can be recommended as an alternative to empiric treatment.


Farm and management variables linked to fecal shedding of Campylobacter and Salmonella in commercial squab production.
A cross-sectional study was performed to determine the relationship of farm variables and management practices to fecal shedding of Campylobacter or Salmonella on commercial squab (young pigeon) farms. A detailed survey provided information on biosecurity, cleaning and disinfection, bird health, vector control, and loft and pen. Twenty pigeons on each of 12 farms were cultured before and after the producers completed a voluntary quality assurance training program (QAP), based on principles of hazard analysis critical control point (HACCP). The prevalence of positive samples for Salmonella and C. jejuni was 1/480 (0.21%) and 19/480 (3.96%), respectively. Campylobacter was present on one farm during both visits; three farms during the first visit, and three farms during the second visit. Analysis by fixed-effects logistic regression showed the probability of having a positive C. jejuni culture was increased by not using dry manure in the nesting material, not cleaning shipping crates, cleaning landing boards, and by increased frequency of chemical disinfection of water. Having a positive parent and higher numbers of squab per pen (density) were also associated with higher odds of being positive for C. jejuni. Factors not associated with a positive C. jejuni culture included, other avian species on the farm, type of shipping crate, covered drinkers, fly problems, bird age, level of nest box within the loft, and QAP training. Prevalence of food safety pathogens was extremely low on the squab facilities tested as compared with reports from commercial broiler or turkey flocks. This observation suggests that one or more farm variables or management practices were effectively reducing infection, or possibly a species-related difference existed in carriage rates and shedding of pathogens. These results emphasize critical control points for food safety pathogens may vary widely, and the formulation of effective QAP programs are dependent on science-based knowledge of diverse animal production systems.


Novel ATP-competitive MEK inhibitor E6201 is effective against vemurafenib-resistant melanoma harboring the MEK1-C121S mutation in a preclinical model.
Many clinical cases of acquired resistance to the BRAF inhibitor vemurafenib have recently been reported. One of the causes of this acquired resistance is the BRAF downstream kinase point mutation MEK1-C121S. This mutation confers resistance to not only vemurafenib, but also to the allosteric MEK inhibitor selumetinib (AZD6244). Here, we investigated the pharmacologic activities and effectiveness of the novel MEK inhibitor E6201 against BRAF (v-raf murine sarcoma viral oncogene homolog B1)-V600E mutant melanoma harboring the MEK1-C121S mutation. A cell-free assay confirmed that E6201 is an ATP-competitive MEK inhibitor, meaning it has a different binding mode with MEK compared with allosteric MEK inhibitors. E6201 is more effective against BRAF-V600E mutant melanoma compared with BRAF wild-type melanoma based on MEK inhibition. We found that the acquired MEK1-C121S mutation in BRAF-V600E mutant melanoma conferred resistance to both vemurafenib and selumetinib but not E6201. The effectiveness of E6201 in this preclinical study is a result of its binding with MEK1 far from the C121S point mutation so the mutation is unable to influence the MAPK pathway inhibitory activity. These results support further clinical investigation of E6201.


Comparing implementations of penalized weighted least-squares sinogram restoration.
A CT scanner measures the energy that is deposited in each channel of a detector array by x rays that have been partially absorbed on their way through the object. The measurement process is complex and quantitative measurements are always and inevitably associated with errors, so CT data must be preprocessed prior to reconstruction. In recent years, the authors have formulated CT sinogram preprocessing as a statistical restoration problem in which the goal is to obtain the best estimate of the line integrals needed for reconstruction from the set of noisy, degraded measurements. The authors have explored both penalized Poisson likelihood (PL) and penalized weighted least-squares (PWLS) objective functions. At low doses, the authors found that the PL approach outperforms PWLS in terms of resolution-noise tradeoffs, but at standard doses they perform similarly. The PWLS objective function, being quadratic, is more amenable to computational acceleration than the PL objective. In this work, the authors develop and compare two different methods for implementing PWLS sinogram restoration with the hope of improving computational performance relative to PL in the standard-dose regime. Sinogram restoration is still significant in the standard-dose regime since it can still outperform standard approaches and it allows for correction of effects that are not usually modeled in standard CT preprocessing. The authors have explored and compared two implementation strategies for PWLS sinogram restoration: (1) A direct matrix-inversion strategy based on the closed-form solution to the PWLS optimization problem and (2) an iterative approach based on the conjugate-gradient algorithm. Obtaining optimal performance from each strategy required modifying the naive off-the-shelf implementations of the algorithms to exploit the particular symmetry and sparseness of the sinogram-restoration problem. For the closed-form approach, the authors subdivided the large matrix inversion into smaller coupled problems and exploited sparseness to minimize matrix operations. For the conjugate-gradient approach, the authors exploited sparseness and preconditioned the problem to speed up convergence. All methods produced qualitatively and quantitatively similar images as measured by resolution-variance tradeoffs and difference images. Despite the acceleration strategies, the direct matrix-inversion approach was found to be uncompetitive with iterative approaches, with a computational burden higher by an order of magnitude or more. The iterative conjugate-gradient approach, however, does appear promising, with computation times half that of the authors' previous penalized-likelihood implementation. Iterative conjugate-gradient based PWLS sinogram restoration with careful matrix optimizations has computational advantages over direct matrix PWLS inversion and over penalized-likelihood sinogram restoration and can be considered a good alternative in standard-dose regimes.


Effects of high-intensity interval training on functional performance and maximal oxygen uptake in comparison with moderate intensity continuous training in cancer patients: a systematic review and meta-analysis.
High-intensity interval training (HIIT) is an appropriate training modality to improve endurance and therefore contributes to physical performance. This review investigates the effect of HIIT on functional performance in cancer patients. We reviewed the relative peak oxygen uptake (relV̇O2PEAK) and meta-analytical compared HIIT with moderate intensity continuous training (MICT). Furthermore, we took various training parameters under consideration. A systematic literature search was conducted in Scopus, PubMed, and Cochrane Library databases. For the review, we included randomized controlled trials containing HIIT with cancer patients. From this, we filtered interventions with additional MICT for the meta-analysis. Outcomes of interest were various functional performance assessments and V̇O2MAX. The research yielded 584 records which fit the inclusion criteria, of which 31 studies with n=1555 patients (57.4±8.6 years) could be included in the overall review and 8 studies in the meta-analysis (n=268, 59.11±5.11 years) regarding relV̇O2PEAK. Different functional outcomes were found, of which walking distance (+8.63±6.91% meters in 6-min walk test) and mobility (+2.7cm in sit and reach test) improved significantly due to HIIT. In terms of relV̇O2PEAK, the performance of cancer patients was improved by HIIT (10.68±6.48%) and MICT (7.4±4.29%). HIIT can be favored to increase relV̇O2PEAK (SMD 0.37; 95% CI 0.09-0.65; I2=0%; p=0.009). Effect sizes for relV̇O2PEAK improvements correlate moderately with total training volume (Spearman's ρ=0.49; p=0.03), whereas percentage increases do not (Spearman's ρ=0.24; p=0.14). Functional and physical outcomes were positively altered by different HIIT protocols and forms of implementation, whereas a tendency toward more effectiveness of HIIT vs. MICT was found for relV̇O2PEAK. Future studies should include functional parameters more often, to finally allow a comparison between both training protocols in this regard.


The Challenges in Chemotherapy and Stem Cell Transplantation for Light-Chain Amyloidosis.
Light-chain (AL) amyloidosis is a systemic syndrome characterized by progressive organ dysfunction leading to organ failure and death. The heart is the most commonly involved organ and the leading determinant of short- and long-term survival. Pathogenic free light chains, fragments of intact immunoglobulins, are the amyloidogenic proteins and are secreted by clonal bone marrow plasma cells. The goal of therapy is to cut off the supply of these light chains to allow organ recovery. Therapies for AL amyloidosis are based on therapies used to treat multiple myeloma, which is a more common plasma cell disorder. However, because patients with AL amyloidosis have organ dysfunction, including multiorgan involvement, they generally have poor treatment tolerance and increased treatment toxicity. Unfortunately, the consequences of toxicity and difficulty in tolerating treatment may result in a fatal outcome. Therefore, treatment should balance the goal of achieving a rapid and meaningful reduction in the circulating light chains while maximizing patient safety. This approach is best achieved by a multidisciplinary approach involving related medical disciplines. This review describes the challenges of managing patients with AL amyloidosis and provides a guide for physicians with a specific focus on cardiac management. We address the role of autologous stem cell transplantation vs standard-intensity therapies in a risk-adapted approach and discuss the management of commonly encountered toxicities. Guidance on response assessment, including organ response, is provided. With expansion in treatment options, we anticipate continuous improvement in outcome for this disease. Nonetheless, early diagnosis remains the best approach to improve disease burden and outcome.


Knowledge, attitudes and practices towards viral haemorrhagic fevers amongst healthcare workers in urban and rural public healthcare facilities in the N'zérékoré prefecture, Guinea: a cross-sectional study.
The 2013-2016 Ebola epidemic in West Africa began in Guinea's Forest region, a region now considered to be at high risk for future epidemics of viral haemorrhagic fevers (VHF). Good knowledge, attitudes and practices towards VHF amongst healthcare workers in such regions are a central pillar of infection prevention and control (IPC). To inform future training in IPC, this study assesses the knowledge, attitudes and practices (KAP) towards VHF amongst healthcare workers in public healthcare facilities in the most populated prefecture in Forest Guinea, and compares results from urban and rural areas. In June and July 2019, we interviewed 102 healthcare workers in the main urban and rural public healthcare facilities in the N'zérékoré prefecture in Forest Guinea. We used an interviewer-administered questionnaire adapted from validated KAP surveys. The great majority of respondents demonstrated good knowledge and favourable attitudes towards VHF. However, respondents reported some gaps in preventive practices such as VHF suspect case detection. They also reported a shortage of protective medical equipment used in everyday clinical work in both urban and rural healthcare facilities and a lack of training in IPC, especially in rural healthcare facilities. However, whether or not healthcare workers had been trained in IPC did not seem to influence their level of KAP towards VHF. Three years after the end of the Ebola epidemic, our findings suggest that public healthcare facilities in the N'zérékoré prefecture in Forest Guinea still lack essential protective equipment and some practical training in VHF suspect case detection. To minimize the risk of future VHF epidemics and improve management of outbreaks of infectious diseases in the region, current efforts to strengthen the public healthcare system in Guinea should encompass questions of supply and IPC training.


N-(5'-phosphoribosyl)anthranilate isomerase-indol-3-ylglycerol phosphate synthetase of tryptophan biosynthesis. Relationship between the two activities of the enzyme from Escherichia coli.
Further evidence is presented to confirm the previous conclusion that the enzyme from Escherichia coli catalysing the two sequential reactions in tryptophan biosynthesis, N-(5'-phosphoribosyl)anthranilic acid (PRA) --> 1-(o-carboxyphenyl-amino)-1-deoxyribulose 5-phosphate (CdRP) --> indol-3-ylglycerol phosphate (InGP)+CO(2)+H(2)O, consists of a single polypeptide chain. The kinetic properties of the enzyme demonstrate that intermediate CdRP formed from PRA must dissociate from the enzyme before it can be converted into InGP. It is concluded that there are two distinct and non-overlapping catalytic sites on the enzyme for the two reactions. The expected complementation between a mutationally altered form of the enzyme lacking the first reaction and a mutationally altered form lacking the second reaction has been demonstrated in vitro by InGP formation from PRA. This system thus exhibits intracistronic complementation with a non-oligomeric protein gene product.


An illustrated checklist of the genus Elymnias Hübner, 1818 (Nymphalidae, Satyrinae).
We review the genus Elymnias Hübner, 1818, a morphologically diverse satyrine butterfly clade involved in multifarious Batesian mimicry relationships throughout Asia and Africa. A variety of different model species are mimicked, and many Elymnias species are sexually dimorphic mimics, with males and females resembling different model species. We revise species and subspecies delimitations in light of an integrative taxonomic investigation using external morphology, male and female genital morphology, and a multi-locus molecular phylogeny. There is little interspecific genitalic variation among species in this group, and previous taxonomists therefore relied almost entirely on wing patterns. Our molecular phylogenetic analysis reveals several examples of polymorphism or wing pattern divergence within a single species currently classified as two or more different species. We also found examples of wing pattern convergence among disparate lineages that mimic the same widespread model species. Frequently, two or more phenotypically similar species were classified as a single species. This comprehensive checklist reviews all names associated with Elymnias to align its taxonomy with the evolutionary history of the group. All available information on nomenclature, type localities, repositories of type specimens, and geographical distributions is summarized, and images of adult specimens and genitalia are provided along with distribution maps of all species and selected subspecies. We identify 2 species incertae sedis, establish 15 monophyletic species groups (including 1 species unplaced in any species group), and make 49 taxonomic changes, including 35 new synonyms, 7 new combinations (2 of which have new status), 1 resurrected combination, 1 resurrected subspecies, and 7 status changes.


Distant infusion of saline may enlarge coagulation volume during radiofrequency ablation of liver tissue using cool-tip electrodes without impairing predictability.
Our aim was to evaluate the capability of a Cool-tip electrode to create larger coagulation volumes combined with a low-flow (0.1 mL/min) perfusion of hypertonic saline at a distance of 2 mm (hybrid applicator) without reducing either predictability or sphericity of the coagulation zone. A total of 48 radiofrequency ablations were performed on a total of 12 adult pigs: 24 with the Cool-tip (group 1) and 24 with the hybrid applicator (group 2). Volumes and diameters were assessed both macroscopically and with imaging techniques (ultrasound and MRI). Digital reconstruction techniques were also used. Reproducibility of the coagulations was assessed by means of the coefficient of variation. The macroscopic assessment showed a significantly larger coagulation zone in group 2 than in group 1, both with (19.40 ± 11.38 cm(3) vs 9.16 ± 5.62 cm(3); p < 0.001) and without (19.54 ± 11.39 cm(3) vs 9.21 ± 5.74 cm(3); p < 0.001) digital reconstruction. Differences were also significant in the MRI assessment. The minimum transverse diameter was also significantly (p < 0.01) larger in group 2 than group 1: 2.46 ± 0.61 versus 1.86 ± 0.55 cm for macroscopic assessment, 2.33 ± 0.96 versus 1.69 ± 0.53 cm for ultrasound, and 2.41 ± 0.58 versus 1.8 ± 0.52 cm for MRI. The coefficient of variation was similar in both groups. The results suggest that low-flow perfusion of hypertonic saline at 2 mm from a Cool-tip electrode could increase coagulation zone volume without reducing predictability.


Downregulation of circRNA_0000285 Suppresses Cervical Cancer Development by Regulating miR197-3p-ELK1 Axis.
Circular RNAs (circRNAs) are involved in the development of human cancers, including cervical cancer (CC). However, the role and mechanism of the circRNA hsa_circ_0000285 (circ_0000285) in CC development remain largely unknown. Thirty paired CC and adjacent normal tissue samples were harvested. CC cell lines SiHa and HeLa were cultured in this study. The expression of circ_0000285, miR197-3p and ELK1 was detected via qRT-PCR or Western blot. CC development was assessed via cell viability, colony formation, apoptosis, cell cycle, and autophagy using MTT, colony-formation assays, flow cytometry and Western blot. The target association was analyzed via dual luciferase-reporter assay, RNA immunoprecipitation, and RNA pull-down. The role of circ_0000285 in CC in vivo was analyzed using a xenograft model. circ_0000285 abundance was enhanced in CC tissue and cells and mainly located in cytoplasm. Silence of circ_0000285 suppressed cell viability and colony formation, arrested the cell cycle at the G0/G1 phase, and induced apoptosis and autophagy in CC cells. miR197-3p was targeted by circ_0000285, and miR197-3p knockdown reversed the effect of circ_0000285 silence on CC development. miR197-3p directly targeted ELK1 to inhibit CC development. circ_0000285 regulated ELK1 by modulating miR197-3p. Knockdown of circ_0000285 reduced xenograft tumor growth in vivo. Knockdown of circ_0000285 repressed CC development by increasing miR197-3p and decreasing ELK1.


Impact of winter roads on boreal peatland carbon exchange.
Across Canada's boreal forest, linear disturbances, including cutlines such as seismic lines and roads, crisscross the landscape to facilitate resource exploration and extraction; many of these linear disturbances cross peatland ecosystems. Changes in tree canopy cover and the compression of the peat by heavy equipment alter local thermal, hydrological, and ecological conditions, likely changing carbon exchange on the disturbance, and possibly in the adjacent peatland. We measured bulk density, water table, soil temperature, plant cover, and CO2 and CH4 flux along triplicate transects crossing a winter road through a wooded fen near Peace River, Alberta, Canada. Sample plots were located 1, 5, and 10 m from the road on both sides with an additional three plots on the road. Productivity of the overstory trees, when present, was also determined. The winter road had higher bulk density, shallower water table, higher graminoid cover, and thawed earlier than the adjacent peatland. Tree productivity and CO2 flux varied between the plots, and there was no clear pattern in relation to distance from the road. The plots on the winter road acted as a greater CO2 sink and greater CH4 source compared to the adjacent peatland with plots on the winter road emitting on average (standard error) 479 (138) compared to 41 (10) mg CH4 m-2 day-1 in the adjacent peatland. Considering both gases, global warming potential increased from 70 to 250 g CO2 e m-2 year-1 in the undisturbed area to 2100 g CO2 e m-2 year-1 on the winter road. Although carbon fluxes on any given cutline through peatland will vary depending on level of compaction, line width and vegetation community shifts, the large number of linear disturbances in Canada's boreal forest and slow recovery on peatland ecosites suggest they could represent an important anthropogenic greenhouse gas source.


Accuracy and Precision of the COSMED K5 Portable Analyser.
The main aims of this study were to determine the accuracy of the portable metabolic cart K5 by comparison with a stationary metabolic cart (Vyntus CPX), to check on the validity of Vyntus CPX using a butane combustion test, and to assess the reliability of K5 during prolonged walks in the field. For validation, measurements were consecutively performed tests with both devices at rest and during submaximal exercise (bicycling) at low (60 W) and moderate intensities (130-160 W) in 16 volunteers. For the reliability study, 14 subjects were measured two times during prolonged walks (13 km, at 5 km/h), with the K5 set in mixing chamber (Mix) mode. Vyntus measured the stoichiometric RQ of butane combustion with high accuracy (error <1.6%) and precision (CV <0.5%), at VO2 values between 0.788 and 6.395 L/min. At rest and 60 W, there was good agreement between Vyntus and K5 (breath-by-breath, B×B) in VO2, VCO2, RER, and energy expenditure, while in Mix mode the K5 overestimated VO2 by 13.4 and 5.8%, respectively. Compared to Vyntus, at moderate intensity the K5 in B×B mode underestimated VO2, VCO2, and energy expenditure by 6.6, 6.9, and 6.6%, respectively. However, at this intensity there was an excellent agreement between methods in RER and fat oxidation. In Mix mode, K5 overestimated VO2 by 5.8 and 4.8%, at 60 W and the higher intensity, respectively. The K5 had excellent reliability during the field tests. Total energy expenditure per Km was determined with a CV for repeated measurements of 4.5% (CI: 3.2-6.9%) and a concordance correlation coefficient of 0.91, similar to the variability in VO2. This high reproducibility was explained by the low variation of FEO2 measurements, which had a CV of 0.9% (CI: 0.7-1.5%) combined with a slightly greater variability of FECO2, VE, VCO2, and RER. In conclusion, the K5 is an excellent portable metabolic cart which is almost as accurate as a state-of-art stationary metabolic cart, capable of measuring precisely energy expenditure in the field, showing a reliable performance during more than 2 h of continuous work. At high intensities, the mixing-chamber mode is more accurate than the B×B mode.


Diagnosing PTSD in early childhood: an empirical assessment of four approaches.
Prior studies have argued that the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria were insensitive for diagnosing posttraumatic stress disorder (PTSD) in young children. Four diagnostic criteria sets were examined in 284 3- to 6-year-old trauma-exposed children. The DSM-IV criteria resulted in significantly fewer cases (13%) compared to an alternative algorithm for young children (PTSD-AA, 45%), the proposed DSM-5 posttraumatic stress in preschool children (44%), and the DSM-5 criteria with 2 symptoms that are under consideration by the committee (DSM-5-UC, 49%). Using DSM-IV as the standard, the misclassification rate was 32% for PTSD-AA, 32% for DSM-5, and 37% for DSM-5-UC. The proposed criteria sets showed high agreement on the presence (100%), but low agreement on the absence (58-64%) of diagnoses. The misclassified cases were highly symptomatic, M = 7 or more symptoms, and functionally impaired, median = 2 domains impaired. The additional symptoms had little impact. Evidence for convergent validation for the proposed diagnoses was shown with elevations on comorbid disorders and Child Behavior Checklist Total scores compared to a control group (n = 46). When stratified by age (3-4 years and 5-6 years), diagnoses were still significantly elevated compared to controls. These findings lend support to a developmental subtype for PTSD.


Detection of human papillomavirus high-risk genotypes in rural women of Lucknow, North India.
Human papilloma virus (HPV) has been widely implicated in cervical carcinogenesis and 90% of carcinoma cervix cases are due to high-risk HPV infection. This study was done to find the high-risk HPV genotypes in the rural women of Lucknow, North India. HPV-DNA testing has been carried out in 130 cases of squamous intraepithelial lesions (SILs) of the cervix to find HPV status and type of high-risk HPV genotype infecting the rural women. These cases were collected from the rural cervical cancer screening program carried out in the villages of West Lucknow, North India. HPV status in 130 SIL cases revealed HPV positivity in only 17 cases (13.1%), whereas the remaining 113 cases were HPV negative (86.9%). HPV genotypes detected in the study were HPV-18, HPV-31, HPV-33, and HPV-35. HPV positivity was found highly associated with the young and sexually active group of women complaining of vaginal discharge. High HPV infection rate was also seen with multiparity and illiteracy as majority of women attending the camps were multiparous and illiterate. The present study revealed highly oncogenic HPV-18 alone or in combination with multiple infections of high-risk genotypes - 31, 33, and 35 - in the rural women of Lucknow, North India. Since HPV vaccine currently available in India is for HPV-16 and HPV-18 combined, efforts should be made to make region-specific vaccine according to their prevalence in that particular state of the country to provide effective HPV vaccination.


Cytological instability in tumors of Picea glauca.
Smear preparations of cells taken from primary explants of normal and adjacent tumor wood of Picea glauca showed completely regular mitotic behavior in the normal cells, with the great majority of cells diploid (22 chromosomes), a few tetraploid, but almost none aneuploid. Tumor tissue was extremely unstable, with numbers ranging from 3 to more than 70, with a high proportion of aneuploids but otherwise normal-appearing mitoses. The relation of this mitotic instability to other data on these tumors is pointed out.


Prevalence of autoantibodies related to some autoimmune disorders in patients with chronic idiopathic thrombocytopenic purpura.
We investigated the prevalence of antinuclear antibody (ANA), thyroid antimicrosomal (AMA) and antithyroglobulin (ATA), antigliadin (AGA) immunoglobulin G (IgG)-A, anti-endomisium (EMA) IgG-A, and tissue transglutaminase (tTG) IgG-A in 87 patients with chronic idiopathic thrombocytopenic purpura (cITP) and in 95 healthy controls. Antinuclear antibody positivity was found in 13 of 87 patients and 3 of 95 controls (P = .007). Antithyroglobulin positivity was found in 27 of patients and in 7 of the controls (P < .001). AMA positivity was found in 20 of patients and 8 of the controls (P = 0.008). Antigliadin IgG was positive in 17 patients and 1 controls (P < .001) whereas Antigliadin IgA was positive in 9 of patients and in 1 of the controls (P = .007). Anti-endomisium (IgG and IgA were not different between both groups. Tissue transglutaminase IgG was detected in 7 of patients and in 1 of the controls (P = .029). Tissue transglutaminase IgA was detected in 5 of patients and in none of the controls (P = .023). We believe that larger studies are needed to determine the long-term impact and clinical importance of these autoantibodies.


The Correlation Between 1p/19q Codeletion, IDH1 Mutation, p53 Overexpression and Their Prognostic Roles in 41 Turkish Anaplastic Oligodendroglioma Patients.
To observe the correlation between 1p/19q codeletion, isocytrate dehydrogenase-1 (IDH1) mutation and p53 protein overexpression and their prognostic value in Turkish anaplastic oligodendroglioma patients who were treated with adjuvant radiotherapy and temozolomide chemotherapy. We retrospectively evaluated 41 patients who were diagnosed as anaplastic oligodendroglioma. Thirty-five patients received standard radiotherapy. Twenty-six patients received standard temozolomide chemoterapy concurrent to radiotherapy. Chromosome 1p/19q codeletion was observed in 19 of 41 patients (46%) via Fluorescent In Situ Hybridisation (FISH) technique. Twenty-six patients (63%) showed positive immunoreaction with anti-IDH1 antibody. Six patients (15%) showed positive immunoreaction with anti-p53 antibody. A statistically significant correlation was determined between chromosome 1p/19q codeletion and IDH1 mutation (p < 0.0001). The patients who had tumors with chromosome 1p/19q codeletion and p53 overexpression were mutually exclusive. The mean estimated Progression Free Survival (PFS) of the patients who had tumors with chromosome 1p/19q codeletion and/or IDH1 mutation was determined to be significantly longer than that of the patients without these genetic changes, regardless of the treatment modality (p=0.006, p=0.004). PFS of the patients who received adjuvant chemotherapy and whose tumors had chromosome 1p/19q codeletion or IDH1 mutation was significantly longer than that of the patients without these genetic changes (p=0.001, p < 0.0001). Chromosome 1p/19q codeletion and/or IDH1 mutation are favorable prognostic factors in anaplastic oligodendroglioma patients, in terms of PFS.


A glucose-6-phosphate dehydrogenase stain for frozen human skeletal muscle biopsy specimens. A sensitive indicator of fiber degeneration.
The glucose-6-phosphate dehydrogenase (G6PD) stain was adapted to skeletal muscle by using homogenate assays and quantitative cytochemical stains to determine the "correct" localization. For both feline and human skeletal muscles, the appropriate level of phenazine methosulfate eliminated fiber typing, which was falsely localizing the rate-limiting, bound reduced form of NADPH rather than the soluble G6PD. Use of a viscous solution of polyvinyl alcohol was necessary to prevent enzyme diffusion. Under these conditions, G6PD produced a mild myoplasmic stain with even sarcoplasmic reticulum granularity in human biopsy specimens. Fibers that were degenerating or regenerating by hematoxylin-eosin or alkaline phosphatase stains yielded an intense myoplasmic G6PD stain. Additional degenerating fibers were also often detectable with G6PD staining. No increased staining was found in denervated or atrophic fibers. Absence of staining (after 2 hours) was not a reliable indicator of G6PD deficiency, although it could be used for preliminary screening of muscle biopsy specimens.


Extruded soybean meal increased feed intake and milk production in dairy cows.
The objective of this study was to assess the effects of 2 extruded soybean meals (ESBM) processed at 2 extruder temperatures, 149°C (LTM) and 171°C (HTM), on performance, nutrient digestibility, milk fatty acid and plasma amino acid profiles, and rumen fermentation in lactating dairy cows. Nine multiparous Holstein cows were included in a replicated 3×3 Latin square design experiment with three 28-d periods. The control diet contained 13% solvent-extracted soybean meal (SSBM; 53.5% crude protein with 74.1% ruminal degradability and 1.8% fat), which was replaced with equivalent amount (dry matter basis) of LTM (46.8%, 59.8%, and 10.0%) or HTM (46.9%, 41.1%, and 10.9%, respectively) ESBM in the 2 experimental diets (LTM and HTM, respectively). The diets met or exceeded the nutrient requirements of the cows for net energy of lactation and metabolizable protein. The 2 ESBM diets increased dry matter intake and milk yield compared with SSBM. Feed efficiency and milk composition were not affected by treatment. Milk protein yield tended to be increased by ESBM compared with SSBM. Milk urea N and urinary urea N excretions were increased by the ESBM diets compared with SSBM. Concentration of fatty acids with chain length of up to C17 and total saturated fatty acids in milk fat were generally decreased and that of C18 and total mono- and polyunsaturated fatty acids was increased by the ESBM diets compared with SSBM. Blood plasma concentrations of His, Leu, and Val were increased by HTM compared with LTM and SSBM. Plasma concentration of Met was decreased, whereas that of carnosine was increased by the ESBM diets. Treatments had no effect on rumen fermentation, but the proportion of Fibrobacter spp. in whole ruminal contents was increased by HTM compared with SSBM and LTM. Overall, data from this crossover experiment suggest that substituting SSBM with ESBM in the diet has a positive effect on feed intake and milk yield in dairy cows.


General Surgery Trainee Cases Over Time: Postgraduate Year Matters.
Trainees and attending surgeons alike have concerns about resident and fellow operative volume/breadth, competency, and overall readiness for practice. This is an important topic within surgical graduate medical education. Our goal was to analyze the change in general surgery trainee operative experience over time by postgraduate year. Institutional operative records from two corresponding three-month time periods in 2009 and 2018 at the residency program's main hospital site were reviewed. Cases assisted on by general, vascular, or thoracic surgery trainees were included. The number of cases per level, combination of trainees in each case, and categories of cases were compared over time. There were 1940 cases in 2009 and 1967 cases in 2018 over the respective time periods. The distribution of trainees was different (P < .001), with a similar number of PGY-1 and fellow cases, a decrease in PGY-2 and PGY-5 cases, and an increase in PGY-3 and PGY-4 cases. The number of cases with two trainees, double scrubbed cases, increased from 19.6% to 26.8% (P < .001). In addition, there were differences in the resident years that double scrubbed cases together, an increase in robotic and endovascular surgery, and a decrease in open cases. This analysis of cases shows that resident operative volume over approximately a decade has been largely preserved, with some change in the distribution of cases based on trainee level, an increase in cases with more than one trainee, and a rise of minimally invasive surgery with a corresponding decrease in open cases.


Polymerase chain reaction assay for diagnosis of potentially toxinogenic Corynebacterium diphtheriae strains: correlation with ADP-ribosylation activity assay.
We have developed a polymerase chain reaction assay for the clinical diagnosis of potentially toxinogenic strains of Corynebacterium diphtheriae, the causative agent of diphtheria. A 910-bp amplification product, overlapping a DNA portion encoding both fragments of the diphtheria toxin, has been found in 28 among the 36 strains tested. In addition, effective toxin production, as evidenced by the ability of bacterial culture supernatants to ADP ribosylate eukaryotic elongation factor 2, was determined. In every case, the presence of an amplification product correlated with an ADP-ribosylation activity, thus confirming the diagnosis. The polymerase chain reaction assay herein described is very rapid (2 h) compared with the Elek immunodiffusion test or the guinea pig lethality test. It can provide a convenient and reliable method for laboratories involved in the identification of toxinogenic corynebacteria.


The effect of therapeutic hypothermia on heart rate variability.
Heart rate variability (HRV) reflects integrity of the autonomic nervous system. However, no study has investigated the impact of therapeutic hypothermia (TH) on HRV measures in infants with hypoxic-ischemic encephalopathy (HIE). In this study, we evaluate the influence of temperature on measures of HRV for a group of infants with favorable outcomes, as compared with a control group of infants with unfavorable outcomes. Term-born infants with moderate-severe HIE underwent standard TH treatment and prospective electroencephalography (EEG) and electrocardiogram (ECG) recording. Infants with favorable outcome (no seizures, normal/mild EEG scores at 96 h, no magnetic resonance imaging brain injury and normal neurodevelopmental scores at 18 to 24 months) were matched on gestational age, sex and worst encephalopathy score to a group of infants with unfavorable outcomes. Time- and frequency-domain HRV measures were calculated from 60 min of ECG data obtained at three time points: 24 h (hypothermia), 48 h (hypothermia) and 96 h (normothermia). The effect of time and temperature were evaluated using repeated-measures analysis of variance. Sixteen infants were included (8 favorable, 8 unfavorable). For both groups of infants, an increase in the HR, RR and HF power was associated with an increase in temperature, but was not associated with any other HRV measure. In contrast, measures of HRV increased over time, as encephalopathy decreased, for infants with favorable outcomes (reflecting increased cortical-autonomic integration), but not for those with unfavorable outcomes. In general, the effect of hypothermia on measures of HRV is limited to changes in heart rate (bradycardia) and respiratory rate, as opposed to changes in true variability. This supports the hypothesis that persistent changes in HRV are driven by the underlying brain injury and not by the process of TH.


Factors determining hydrogel permeability.
Developing hydrogel membranes and coatings of appropriate permeability characteristics is key to the success of a number bioartificial organ technologies. Key principles relevant to the design and application of hydrogels for such applications were reviewed. The first key point is that permeability is a function of both transport and thermodynamic properties, the diffusion coefficient and partition coefficient, respectively, and that these parameters can be evaluated separately. Although the aspect of partitioning often emphasized is size exclusion, this review points out that many other relevant interactions come into play, especially hydrophobic and electrostatic interactions, and that these phenomena can dominate size exclusion. Similarly, while the diffusion coefficient also is strongly dependent upon size, other interactions can also cause diffusivity to deviate from theories which consider only solute size and gel swelling. For example, the heterogeneity of hydrogel networks can result in permeabilities that fail to decline as much as might be anticipated if networks were uniform.


The role of nuclear factor-kappaB in inflammatory lung disease.
Nuclear factor-kappaB (NF-kappaB) is one of the most important transcription factors; it has a key role in inflammatory and immune responses, cell adhesion, developmental signals, and anti-apoptosis process. Inflammatory lung diseases such as asthma and chronic obstructive pulmonary disease (COPD) are major causes of morbidity and mortality worldwide. In this review, we highlight the role of NF-kappaB in inflammatory lung disease, the strategies which block the activation of NF-kappaB, and the therapeutic approaches to treating inflammatory lung disease.


T cell-independent response to Brucella-insulin identifies a preimmune repertoire for insulin.
An early or preimmune repertoire for anti-insulin B cells was examined using the T cell-independent (TI) response to insulin conjugated to Brucella abortus (BA-ins). mAbs from the BA-ins response reflect a repertoire present 7 to 10 days before the first Ab-forming cells (AFC) are detected in primary T cell-dependent (TD) responses to insulin. Although 4 of 6 BA-ins mAb express IgG2 isotype, evidence for somatic mutation is limited. A total of 9 of 12 V regions are identical with known V(H) or Vkappa genes, and consensus sequences suggest two other V genes may be in germ-line configuration. The relative avidities (50% inhibition of binding) of TI anti-insulins cover a broad range and are consistent with a germ-line anti-insulin repertoire that is functionally diverse. The V(H)s of 5 mAb are from two subsets of J558 genes (205.1 and 186.3) that dominate the B cell pool of adult mice and are different from the V(H)s used by anti-insulin mAb in primary TD responses. One IgM anti-insulin (mAb 301) uses V(H)-J606 and Vkappa1, and this mAb binds beta cells. Other TI mAb use either Vkappa5 or Vkappa19.3 genes and are similar to Vkappa genes used by anti-insulin mAb from TD responses. The data show that mutations in germ-line genes are not required for measurable insulin binding by monospecific mAb from adult mice. The recurrent use of Vkappa genes in both early (TI response) and late (TD responses) suggest that these structures are important in insulin binding.


Early biotic stress detection in tomato (Solanum lycopersicum) by BVOC emissions.
We investigated impacts of early and mild biotic stress on Biogenic Volatile Organic Compounds (BVOC) emissions from tomato in order to test their potential for early (biotic) stress detection. Tomato plants were exposed to two common fungal pathogens, Botrytis cinerea and Oidium neolycopesici and the sap-sucking aphid Myzus persicae. Furthermore, plants were exposed to methyl jasmonate (MeJA) in order to identify BVOC emissions related to activation of jasmonic acid (JA) signalling pathway. These emissions where then used as a reference for identifying active JA signalling pathway in plants at early stages of biotic stress. After infection by the necrotrophic fungus B. cinerea, changes in BVOC emissions indicated that tomato plants had predominantly activated the jasmonic acid (JA) signalling pathway. The plants were able to modify their defence pathways in order to overcome fungal infection. When tomato plants were infected with the biotrophic fungus O. neolycopersici, only minor changes in BVOC emissions were observed with additional emissions of the sesquiterpene α-copaene. α-copaene emissions allowed the identification of general biotic stress in the plants, without pinpointing the actual triggered defence pathway. BVOC emissions during M. persicae attack had changed before the occurrence of visual symptoms. Despite low infestation rates, plants emitted methyl salicylate indicating activation of the SA-mediated defence pathway.


Prevalence and antimicrobial susceptibility of methicillin-resistant Staphylococcus aureus among pigs in Belgium.
The prevalence, distribution, and antimicrobial susceptibility of methicillin-resistant Staphylococcus aureus (MRSA) in Belgian pig farms has been investigated. To that end, nasal samples were collected from 1,500 pigs on 50 farms randomly selected over Belgium. Both closed (breeding or farrow-to-finish) and open (fattening) farms were included. Within closed farms different age groups were investigated. A total number of 663 (44%) pigs belonging to 34 (68%) farms carried MRSA. According to their management practice, MRSA was detected on 94% of the open farms and 56% of the closed farms. Focusing on the in-herd prevalence among fattening pigs for both management systems, a significantly higher rate was found in open farms (72%) compared to closed farms (26%). Within the closed farms, piglets (41%) showed a higher MRSA prevalence than sows (26%) and fattening pigs (26%). All strains tested were ST398 and showed mainly spa-type t011, as commonly found on pig herds in Europe. Less dominating spa-types were t034, t567, and t2970. The MRSA strains carried two SCCmec-types, type IVa or V. All 643 MRSA strains were resistant to tetracycline and additional resistances to trimethoprim (97%), lincosamides (73%), macrolides (56%), aminoglycosides (48%), and fluoroquinolones (32%) were found. Multiresistance (defined as resistance to four or more non-β-lactam antimicrobial classes) was found in 63% of the tested strains. In conclusion, a high prevalence of MRSA was found in Belgian pig farms, with the highest prevalence in open farms. In accordance with other European countries, age-related and management-related differences in MRSA prevalence were observed that should be considered when control strategies are outlined.


Comparison of insulin lispro mixture 25/75 with insulin glargine during a 24-h standardized test-meal period in patients with Type 2 diabetes.
To compare insulin lispro mixture (25% insulin lispro and 75% NPL; Mix 25/75) twice-daily plus oral glucose-lowering medications (metformin and/or sulphonylurea) with once-daily insulin glargine plus oral agents with respect to postprandial glycaemic control and other glucose and lipid parameters in patients with Type 2 diabetes inadequately controlled with insulin and/or oral glucose-lowering agents. This was a randomized, open-label, crossover study. Prestudy oral agents were continued and patients not already on oral agents were treated with metformin. Mix 25/75 and insulin glargine were adjusted over 3 months to attain premeal plasma glucose (PG) < 6.0 mmol/l and were then given during a 24-h in-patient test meal period with frequent PG, serum triglyceride (TG) and free fatty acid (FFA) measurements. Twenty patients (10 F/10 M; mean +/-sd age 54.0 +/- 10.7 years, body mass index 37.0 +/- 8.6 kg/m2, HbA1c 8.4 +/- 1.01%) participated. Mean doses were 23 U before the morning and 37 U before the evening meal for Mix 25/75 and 44 U for insulin glargine. The combined 2-h morning and evening meal postprandial plasma glucose (PPG) was not different between groups (9.2 +/- 2.04 vs. 9.9 +/- 1.66 mmol/l, P = 0.161). Mix 25/75 was associated with a lower mean 2-h PPG for all meals combined (9.0 +/- 1.88 vs. 9.9 +/- 1.80 mmol/l, P < 0.05) and lower mean 24-h PG (6.7 +/- 1.00 vs. 7.5 +/- 1.32 mmol/l, P < 0.01). Eight patients experienced mild hypoglycaemia (PG < 3.5 mmol/l) with Mix 25/75 and 3 with insulin glargine. The endpoint HbA1c was lower with Mix 25/75 (6.9 +/- 0.52% vs. 7.3 +/- 0.81%, P < 0.05). In a 24-h test-meal setting in 20 patients, Mix 25/75 insulin plus oral glucose-lowering agents was associated with lower mean PPG and 24-h PG, more mild hypoglycaemia and similar TG, FFA and fasting PG concentrations. HbA1c was lower with Mix 75/25 plus oral agents, although it may not have reached steady state due to ongoing dose adjustment.


Monoclonal antibodies to a MUC 4 peptide react with lung cancer.
The cDNA of mucin 4 (MUC 4) has been cloned from human tracheo-bronchial cDNA library and MUG 4 was demonstrated to be expressed in normal tracheobronchial and colonic mucosa. However, as there are no antibodies available, there is little information on the distribution of MUC 4 on normal and malignant tissues. A 22 amino-acid peptide (M4.22), derived from the MUC 4 cDNA sequence was synthesized and used to immunise mice and 2 monoclonal antibodies were produced and characterized by ELISA, immunoperoxidase staining and flow cytometry. By ELISA the two anti-MUG 4 mAbs reacted with the immunizing peptide (M4.22), but not with peptides derived from other mucins. By immunoperoxidase staining the mAbs reacted with native mucin expressed in normal colon and to a lesser extent with stomach, but not with normal lung. By contrast, the mAbs reacted most strongly (similar to 70%) with lung cancers. Using six-mer overlapping peptides the minimum number of amino acids in the epitopes detected by the mAbs were TPL (M4.171) and PLPV (M4.275). MUC 4 detected by the mAbs was of a molecular mass (180 kDa) by Western blotting. Using anti-MUC 4 mAbs non-large cell lung cancers were found to be MUC 4 positive compared with normal lung tissues which were negative. By contrast, normal colon was strongly positive but the expression was decreased in colon cancer. These findings could have diagnostic and therapeutic implication for lung cancer.


Malaysian children with spina bifida: relationship between functional outcome and level of lesion.
To determine the relationship between spinal lesion level and functional outcome in children with spina bifida. Prospective observational study of 66 children who attended the Spina Bifida Clinic from 1994-1997. Data were obtained from serial physical examination and parent interview to determine mobility status, neurosensory deficits, continence and school placement. Eighteen (27.3%) had high-level (thoracic and thoracolumbar), 27 (40.9%) intermediate (low lumbar) and 21 (31.8%) low-level (sacral) lesions. Children with high-level lesions experienced more mobility problems (independent ambulation, balance and use of appliances), than those with intermediate or low-level lesions (p<0.001). 58.8% of children with low-level lesions used diapers, compared with those with high (90%) or intermediate (100%) level lesions (p = 0.005), but there were no significant differences in the incidence of soiling or urinary incontinence among all three groups. There were no significant differences among the three groups in terms of school placement, skin breakdown, epilepsy or visual defect. Although there is good correlation between the level of the lesion and mobility in children with spina bifida, other measures of functional outcome like continence and school placement are more difficult to predict. These data are important for realistic counselling of families with newborns with spina and planning long term rehabilitation resources.


Mitochondrial polymorphism A10398G and Haplogroup I are associated with Fuchs' endothelial corneal dystrophy.
We investigated whether mitochondrial DNA (mtDNA) variants affect the susceptibility of Fuchs endothelial corneal dystrophy (FECD). Ten mtDNA variants defining European haplogroups were genotyped in a discovery dataset consisting of 530 cases and 498 controls of European descent from the Duke FECD cohort. Association tests for mtDNA markers and haplogroups were performed using logistic regression models with adjustment of age and sex. Subset analyses included controlling for additional effects of either the TCF4 SNP rs613872 or cigarette smoking. Our replication dataset was derived from the genome-wide association study (GWAS) of the FECD Genetics Consortium, where genotypes for three of 10 mtDNA markers were available. Replication analyses were performed to compare non-Duke cases to all GWAS controls (GWAS1, N = 3200), and to non-Duke controls (GWAS2, N = 3043). The variant A10398G was significantly associated with FECD (odds ratio [OR] = 0.72; 95% confidence interval [CI] = [0.53, 0.98]; P = 0.034), and remains significant after adjusting for smoking status (min P = 0.012). This variant was replicated in GWAS1 (P = 0.019) and GWAS2 (P = 0.036). Haplogroup I was significantly associated with FECD (OR = 0.46; 95% CI = [0.22, 0.97]; P = 0.041) and remains significant after adjusting for the effect of smoking (min P = 0.008) or rs613872 (P = 0.034). The 10398G allele and Haplogroup I appear to confer significant protective effects for FECD. The effect of A10398G and Haplogroup I to FECD is likely independent of the known TCF4 variant. More data are needed to decipher the interaction between smoking and mtDNA haplogroups.


Breaking the limits of structural and mechanical imaging of the heterogeneous structure of coal macerals.
The correlation between local mechanical (elasto-plastic) and structural (composition) properties of coal presents significant fundamental and practical interest for coal processing and for the development of rheological models of coal to coke transformations. Here, we explore the relationship between the local structural, chemical composition, and mechanical properties of coal using a combination of confocal micro-Raman imaging and band excitation atomic force acoustic microscopy for a bituminous coal. This allows high resolution imaging (10s of nm) of mechanical properties of the heterogeneous (banded) architecture of coal and correlating them to the optical gap, average crystallite size, the bond-bending disorder of sp(2) aromatic double bonds, and the defect density. This methodology allows the structural and mechanical properties of coal components (lithotypes, microlithotypes, and macerals) to be understood, and related to local chemical structure, potentially allowing for knowledge-based modeling and optimization of coal utilization processes.


Potential use of potassium efflux-deficient yeast for studying trafficking signals and potassium channel functions.
The activity of potassium (K(+)) channels critically depends on their density on the cell surface membrane, which is regulated by dynamic protein-protein interactions that often involve distinct trafficking signals on the cargo proteins. In this paper we explored the possibility of utilizing the Saccharomyces cerevisiae strain B31 for identification of the signal motifs that regulate surface expression of membrane proteins and for studying structure-function relationships of K(+) channels. B31 cells lack the K(+) efflux system and were reported to show overloaded K(+)-mediated growth inhibition in high K(+) media upon heterologous expression of a mammalian inwardly rectifying K(+) channel (Kir2.1). We show that while the expression of wild-type Kir2.1 channel inhibits the growth of B31 cells in high K(+) media, the human disease-causing mutations of Kir2.1 that abolish K(+) conduction (V302M) or surface trafficking (Δ314/315) fully restores the growth. The expression of two-pore-domain K(+) channel KCNK3 or KCNK9 also inhibited the growth of B31 in high K(+) media while C-terminal mutations that reduce their 14-3-3 protein-dependent cell surface trafficking restored the growth of B31. Finally, the expression of Kir2.1 channels that were C-terminally fused with known sequence motifs including ER retention/retrieval signals and an endocytosis signal allowed the growth of B31 in high K(+) media. These results demonstrate the potential of B31 yeast strain as a unique biological tool to screen the random peptide libraries for novel sequence signals that down-regulate surface expression of membrane proteins, as well as to systematically identify the structural determinants for cell surface trafficking and/or ion conductance of K(+) channels.


Ebola virus: immune mechanisms of protection and vaccine development.
Vaccination is one of our most powerful antiviral strategies. Despite the emergence of deadly viruses such as Ebola virus, vaccination efforts have focused mainly on childhood communicable diseases. Although Ebola virus was once believed to be limited to isolated outbreaks in distant lands, forces of globalization potentiate outbreaks anywhere in the world through incidental transmission. Moreover, since this virus has already been transformed into weapon-grade material, the potential exists for it to be used as a biological weapon with catastrophic consequences for any population vulnerable to attack. Ebola hemorrhagic fever (EHF) is a syndrome that can rapidly lead to death within days of symptom onset. The disease directly affects the immune system and vascular bed, with correspondingly high mortality rates. Patients with severe disease produce dangerously high levels of inflammatory cytokines, which destroy normal tissue and microcirculation, leading to profound capillary leakage, renal failure, and disseminated intravascular coagulation. Vaccine development has been fraught with obstacles, primarily of a biosafety nature. Case reports of acutely ill patients with EHF showing improvement with the transfusion of convalescent plasma are at odds with animal studies demonstrating further viral replication with the same treatment. Using mRNA extracted from bone marrow of Ebola survivors, human monoclonal antibodies against Ebola virus surface protein have been experimentally produced and now raise the hope for the development of a safe vaccine.


Eikenella corrodens prosthetic valve endocarditis in a patient with ulcerative colitis.
A 33-y-old male with ulcerative colitis developed prosthetic valve endocarditis (PVE) caused by Eikenella corrodens. The outcome of conservative treatment was successful. Only 2 cases of E. corrodens PVE were found in a survey of the English-language medical literature. In contrast to previous data indicating that eikenella infections usually derive from the oral cavity, our patient most likely acquired the infection by colonoscopy and mucosal biopsies, which were performed a few days before onset of the disease.


Differential gene expression in renal-cell cancer.
Renal-cell carcinoma (RCC) is an important cause of morbidity and mortality, and its incidence has been increasing. Malignant transformation is thought to be associated with changes in the expression of several genes, and this alteration in gene expression is believed to be critical to the development of the malignant phenotype. In this study, the expression of about 60,000 genes/expressed sequence tags in clear-cell RCC, normal kidney, and a set of diseased nonmalignant kidneys was determined with the use of the Affymetrix microarray technique, and differences in gene expression were analyzed. Many genes were found to be differentially expressed in these two sample sets. The genes that were expressed greater than four times more in RCC, those expressed only in RCC, and those expressed greater than two times more in RCC and also expressed in a limited number of other tissues were analyzed for their expression in a variety of other normal and diseased tissues. Some of the genes identified were overexpressed only in RCC among the tissues examined, and some were overexpressed in several other malignant tissues in addition to RCC. Other genes were overexpressed in RCC compared with normal kidney but were also overexpressed in diseased nonmalignant kidney or a variety of other normal tissues. All of the RCC samples could be clustered together, separate from the normal and diseased kidney samples, with the use of the Eisen clustering technique and a set of 50 genes. The observed changes in gene expression in RCC should help further the understanding of the biology of RCC and may be useful in diagnosis, treatment, and imaging.


Rhodohalobacter halophilus gen. nov., sp. nov., a moderately halophilic member of the family Balneolaceae.
A novel Gram-stain-negative, rod-shaped, facultatively anaerobic, oxidase-negative and catalase-positive bacterium, designated JZ3C29T, was isolated from a saltern located in Feicheng, PR China. JZ3C29T was tolerant of moderately saline conditions. Optimal growth occurred at 40 °C (range 20-50 °C) and pH 7.5-8.5 (range pH 7.0-9.0) with 8-10 % (w/v) NaCl (range 2-16 %). Phylogenetic analysis based on 16S rRNA gene sequences revealed that JZ3C29T shared highest similarity with Gracilimonas tropica CL-CB462T (90.5 %), Gracilimonas mengyeensis YIM J14T (90.5 %) and Gracilimonas rosea CL-KR2T (90.4 %) and less than 90.0 % similarity with other species of the phylum Bacteroidetes. The isolate formed a novel genus-level clade in the recently described family Balneolaceae. The polar lipid profile of the novel isolate consisted of diphosphatidylglycerol, phosphatidylethanolamine, three unidentified glycolipids, four unidentified phospholipids and two unidentified lipids. The dominant cellular fatty acids (>10 %) were summed feature 3 (C16 : 1ω7c and/or iso-C15 : 0 2-OH) and iso-C15 : 0 and the sole respiratory quinone was menaquinone 7 (MK-7). The DNA G+C content of JZ3C29T was 44.4 mol%. On the basis of these phenotypic and phylogenetic data, JZ3C29T should be classified as representing a novel genus and species within the family Balneolaceae, for which the name Rhodohalobacter halophilus gen. nov., sp. nov. is proposed. The type strain is JZ3C29T (=MCCC 1H00131T=KCTC 52046T=JCM 31413T).


Solving the military's health care dilemma for Medicare eligibles.
The U.S. military health system has undergone a number of changes; however, indications are that more are needed. A major issue is whether the system can provide the health care needed to the increasing number of military retirees and their family members who are eligible for Medicare. In this paper, the authors recommend, based on the reviewed evidence, a possible long-term solution to the issues affecting Medicare-eligible military retirees and their family members.


Multiple-Organ Complement Deposition on Vascular Endothelium in COVID-19 Patients.
Increased levels of circulating complement activation products have been reported in COVID-19 patients, but only limited information is available on complement involvement at the tissue level. The mechanisms and pathways of local complement activation remain unclear. The aim of this study was to investigate the deposition of complement components in the lungs, kidneys, and liver in patients with COVID-19 patients and to determine the pathway/s of complement activation. We performed immunofluorescence analyses of autopsy specimens of lungs, kidney, and liver from 12 COVID-19 patients who died of acute respiratory failure. Snap-frozen samples embedded in OCT were stained with antibodies against complement components and activation products, IgG, and spike protein of SARS-CoV-2. Lung deposits of C1q, C4, C3, and C5b-9 were localized in the capillaries of the interalveolar septa and on alveolar cells. IgG displayed a similar even distribution, suggesting classical pathway activation. The spike protein is a potential target of IgG, but its uneven distribution suggests that other viral and tissue molecules may be targeted by IgG. FB deposits were also seen in COVID-19 lungs and are consistent with activation of the alternative pathway, whereas MBL and MASP-2 were hardly detectable. Analysis of kidney and liver specimens mirrored findings observed in the lung. Complement deposits were seen on tubules and vessels of the kidney with only mild C5b-9 staining in glomeruli, and on the hepatic artery and portal vein of the liver. Complement deposits in different organs of deceased COVID-19 patients caused by activation of the classical and alternative pathways support the multi-organ nature of the disease and the contribution of the complement system to inflammation and tissue damage.


Systemic contact dermatitis induced by Rhus allergens in Korea: exercising caution in the consumption of this nutritious food.
Systemic contact dermatitis (SCD) develops when a person who was previously sensitized to an allergen is exposed to the same allergen via the systemic route. In East Asia, the use of lacquer for polishing furniture is common and a part of the traditional culture. Contact exposure to tableware polished with Rhus lacquer may lead to sensitization. In Korea, SCD is commonly observed after systemic exposure to Rhus, a nutritious food item consumed because of the common belief of it improving the immune system. In this study, we reviewed the medical records of 21 Korean patients with SCD caused by Rhus ingestion. We found that the most significant epidemiological factor for SCD was the season of the year. Furthermore, 66.67% of the patients presented with leucocytosis and 23.81% showed increased liver enzyme levels. It is important to educate people on the risks associated with the systemic ingestion of Rhus.


[Carpal tunnel syndrome: diagnostics and conservative treatment].
The Carpal tunnel syndrome is the most frequent entrapment neuropaphy of human. The Article is dedicated to diagnostics and conservative treatment this pathology. The early diagnostics and in time fixed treatment prevents the progress of the disease, raises the quality of life and allows to avoid surgical procedure. Big attention is given acupuncture reflexotherepy and infrared latherotherepy, which use raises the quality of the therapeutic influences.


Randomized trial of community health worker-led decision coaching to promote shared decision-making for prostate cancer screening among Black male patients and their providers.
Black men are disproportionately affected by prostate cancer, the most common non-cutaneous malignancy among men in the USA. The United States Preventive Services Task Force (USPSTF) encourages prostate-specific antigen (PSA) testing decisions to be based on shared decision-making (SDM) clinician professional judgment, and patient preferences. However, evidence suggests that SDM is underutilized in clinical practice, especially among the most vulnerable patients. The purpose of this study is to evaluate the efficacy of a community health worker (CHW)-led decision-coaching program to facilitate SDM for prostate cancer screening among Black men in the primary care setting, with the ultimate aim of improving/optimizing decision quality. We proposed a CHW-led decision-coaching program to facilitate SDM for prostate cancer screening discussions in Black men at a primary care FQHC. This study enrolled Black men who were patients at the participating clinical site and up to 15 providers who cared for them. We estimated to recruit 228 participants, ages 40-69 to be randomized to either (1) a decision aid along with decision coaching on PSA screening from a CHW or (2) receiving a decision aid along with CHW-led interaction on modifying dietary and lifestyle to serve as an attention control. The independent randomization process was implemented within each provider and we controlled for age by dividing patients into two strata: 40-54 years and 55-69 years. This sample size sufficiently powered the detection differences in the primary study outcomes: knowledge, indicative of decision quality, and differences in PSA screening rates. Primary outcome measures for patients will be decision quality and decision regarding whether to undergo PSA screening. Primary outcome measures for providers will be acceptability and feasibility of the intervention. We will examine how decision coaching about prostate cancer screening impact patient-provider communication. These outcomes will be analyzed quantitatively through objective, validated scales and qualitatively through semi-structured, in-depth interviews, and thematic analysis of clinical encounters. Through a conceptual model combining elements of the Preventative Health Care Model (PHM) and Informed Decision-Making Model, we hypothesize that the prostate cancer screening decision coaching intervention will result in a preference-congruent decision and decisional satisfaction. We also hypothesize that this intervention will improve physician satisfaction with counseling patients about prostate cancer screening. Decision coaching is an evidence-based approach to improve decision quality in many clinical contexts, but its efficacy is incompletely explored for PSA screening among Black men in primary care. Our proposal to evaluate a CHW-led decision-coaching program for PSA screening has high potential for scalability and public health impact. Our results will determine the efficacy, cost-effectiveness, and sustainability of a CHW intervention in a community clinic setting in order to inform subsequent widespread dissemination, a critical research area highlighted by USPSTF. The trial was registered prospectively with the National Institute of Health registry ( www.clinicaltrials.gov ), registration number NCT03726320 , on October 31, 2018.


Voice of the Victims: Accounts of Secondary Victimization With the Court System Among Homicide Co-victims.
The treatment homicide co-victims receive from the criminal justice system often leaves them aggrieved and feeling alienated. A neglected but important area of investigation is the courtroom workgroup's handling of murder cases. This exploratory study examines the nature and extent to which varying secondary victimization experiences are common among co-victims as the murder cases are processed through the court system. The sample consists of 27 co-victims connected to 24 separate cases where the murders occurred in a major metropolitan area in the southeastern United States. Drawing upon focus group data, Nvivo 10 was employed to identify themes that illustrate common secondary victimization experiences among co-victims along with positive and mixed reactions to court processes and personnel. The findings indicate that court requirements to provide notifications are infrequently met and attorney's practice to supply information about case progress and counseling to family members regarding plea-bargaining and sentencing decisions are greatly restrictive. When information is offered, it is often perceived as highly technical and when assistance is provided, it is frequently limited or intermittent. Despite the prevalence of negative experiences, there also were reports of positive interactions with the district attorney and victim advocates. The study concludes by identifying ways in which the courtroom workgroup can uphold the rights afforded to co-victims while at the same time meeting the duties and responsibilities of the workgroup.


The Effect of Combined Ezetimibe/Atorvastatin Therapy vs. Atorvastatin Monotherapy on the Erythrocyte Membrane Structure in Patients with Coronary Artery Disease: A Pilot Study.
Erythrocytes play an important role in atherogenesis. An excessive accumulation of cholesterol in erythrocyte membranes leads to disruption of the erythrocytes. The aim of the study was to compare the effect of two different hypolipidemic therapies on the structure of erythrocyte membranes. The study included 18 patients with angiographic confirmed coronary artery disease who, despite at least 6 months of hypolipidemic treatment, had not achieved LDL-C < 70 mg/dL and 18 healthy individuals as the control group. The following parameters were studied: total cholesterol level and erythrocyte membrane fluidity, lipid peroxidation, SH groups in membrane protein and plasma lipids. We observed a decrease in TC (20%), LDL-C (35%), level of lipid peroxidation (25%) and total cholesterol in erythrocytes (23%), and an increase in HDL-C (8%) and erythrocyte membrane fluidity of subsurface layers (14%) after 6 months of 10 mg atorvastatin + 10 mg ezetimibe therapy, in comparison with healthy controls. In the group treated with 40 mg atorvastatin for 6 months, decreased LDL-C (23%), lipid peroxidation (37%) and membrane cholesterol concentration (18%) was noted, as well as an increase in erythrocyte membrane fluidity in the subsurface layers (12%). Both the combination therapy and the monotherapy lead to an improvement of erythrocyte membrane structure, whose parameters reached values close to those in the control healthy group.


Body fat percentile curves for Korean children and adolescents: a data from the Korea National Health and Nutrition Examination Survey 2009-2010.
A valid assessment of obesity in children and adolescents is important due to significant change in body composition during growth. This study aimed to develop percentile curves of body fat and fat free mass using the Lambda, Mu, and Sigma method, and to examine the relationship among body mass index (BMI), fat mass and fat free mass in Korean children and adolescents, using the Korea National Health and Nutrition Examination Survey (KNHANES) 2009-2010. The study subjects were 834 for boys and 745 for girls aged between 10 and 18 yr. Fat mass and fat free mass were measured by dual-energy x-ray absorptiometry. The patterns of development in body fat percentage, fat mass and fat free mass differed for boys and girls, showing a decreased fat mass with an increased fat free mass in boys but gradual increases with age in girls. The considerable proportion of boys and girls with relatively normal fat mass appeared to be misclassified to be at risk of overweight based on the BMI criteria. Therefore, the information on the percentiles of body fat and fat free mass with their patterns would be helpful to complement assessment of overweight and obesity based on BMI for Korean children and adolescents.


Computational mechanical analysis of AO 44 A1, B1 and C1 fracture with Finite Element: Evaluation of screw, plate and k-wire fixation.
The aim of this study was to create AO 44 A1, B1 and C1 fractures using finite element analysis (FEA), to determine the stability of k-wire, intramedullary screw (IS) and plate-screw (PS) fixation methods in fracture Methods: Using FEA the post-reduction behaviour of AO 44 A1, B1 and C1 fractures with k-wire, IS and PS fixation methods was analysed and compared in terms of displacement and stress. The lowest amount of displacement was provided with the IS method in AO 44 A1 and B1. It was observed in the detection of 4 mm k-wire in AO 44 C1. The total displacement of the IS system used for fixation in AO 44 A1, B1 and C1 fractures was lower Conclusions: According to FEA results, the lowest amount of displacement was obtained with IS in AO 44 A1 and B1, while 4 mm K-wire fixation was achieved in AO 44 C1 fractures.


A simple method for simultaneous quantification of total arabinoxylans and fructans in wheat flour.
Current methods for measuring fructan and arabinoxylan concentrations in wheat flour are time-consuming, and each type of the polymers requires a separate method. Here, we report the development of a new method that allows simultaneous determination of arabinoxylan and fructan contents in wheat flour. The new method is based on a single hydrolysis procedure for both arabinoxylans and fructans and an optimized separation technique for all monomers released. Owing to the use of milder hydrolysis conditions that afforded higher recovery of pentoses, the level of arabinoxylans in wheat flour determined by this new method is slightly higher than that measured with the widely used hydrolysis protocol. On the basis of the finding that, for a given flour sample, the total fructose concentration after hydrolysis is highly correlated with its total fructan concentration, the fructan content of a wheat flour sample can thus be estimated directly by the total fructose content. By simplifying and combining the two separate methods used for arabonoxylan and fructan analysis, this new method enables the quantification of arabinoxylans and fructans in wheat flour using a single acid hydrolysis step and a single high-performance liquid chromatography run.


Dopamine causes ultrastructural changes in prolactin cells of tilapia (Oreochromis niloticus).
This study was undertaken to examine ultrastructural changes induced by dopamine in fish prolactin cells. Tilapia adenohypophyses were incubated with dopamine and evaluated by electron microscopy. The quantities of rough endoplasmic reticulum (RER) in prolactin cells increased and the number of secretory granules were decreased by dopamine (10(-6) mol/l) treatment. Another set of adenohypophysial tissues was placed back into control medium for 10 min following a 3 h incubation period with dopamine (10(-6) mol/l) (RE10 min group). This group had significantly less RER than the 3 h dopamine-treated tissue, and the shape of many granules in the RE10 min group changed from spherical to rod-like. In addition, some of the granule content appeared to diffuse out of granules since some were not fully surrounded by membrane. It was therefore hypothesized that the rod-shaped granules might be the result of prolactin secretion by diffusion.


Global response of Acidithiobacillus ferrooxidans ATCC 53993 to high concentrations of copper: A quantitative proteomics approach.
Acidithiobacillus ferrooxidans is used in industrial bioleaching of minerals to extract valuable metals. A. ferrooxidans strain ATCC 53993 is much more resistant to copper than other strains of this microorganism and it has been proposed that genes present in an exclusive genomic island (GI) of this strain would contribute to its extreme copper tolerance. ICPL (isotope-coded protein labeling) quantitative proteomics was used to study in detail the response of this bacterium to copper. A high overexpression of RND efflux systems and CusF copper chaperones, both present in the genome and the GI of strain ATCC 53993 was found. Also, changes in the levels of the respiratory system proteins such as AcoP and Rus copper binding proteins and several proteins with other predicted functions suggest that numerous metabolic changes are apparently involved in controlling the effects of the toxic metal on this acidophile. Using quantitative proteomics we overview the adaptation mechanisms that biomining acidophiles use to stand their harsh environment. The overexpression of several genes present in an exclusive genomic island strongly suggests the importance of the proteins coded in this DNA region in the high tolerance of A. ferrooxidans ATCC 53993 to metals.


Terphenyl-Based Bak BH3 alpha-helical proteomimetics as low-molecular-weight antagonists of Bcl-xL.
We describe a general method for the mimicry of one face of an alpha-helix based on a terphenyl scaffold that spatially projects functionality in a manner similar to that of two turns of an alpha-helix. The synthetic scaffold reduces the flexibility and molecular weight of the mimicked protein secondary structure. We have applied this design to the development of antagonists of the alpha-helix binding protein Bcl-x(L). Using a sequential synthetic strategy, we have prepared a library of terphenyl derivatives to mimic the helical region of the Bak BH3 domain that binds Bcl-x(L). Fluorescence polarization assays were carried out to evaluate the ability of terphenyl derivatives to displace the Bcl-x(L)-bound Bak peptide. Terphenyl 14 exhibited good in vitro affinity with a K(i) value of 0.114 muM. These terphenyl derivatives were more selective at disrupting the Bcl-x(L)/Bak over the HDM2/p53 interaction, which involves binding of the N-terminal alpha-helix of p53 to HDM2. Structural studies using NMR spectroscopy and computer-aided docking simulations suggested that the helix binding area on the surface of Bcl-x(L) is the target for the synthetic ligands. Treatment of human embryonic kidney 293 (HEK293) cells with terphenyl derivatives resulted in the disruption of the binding of Bcl-x(L) to Bax in intact cells.


Effect of H. pylori Infection on Cytokine Profiles and Oxidative Balance in Subjects with Chronic Alcohol Ingestion.
Different amounts of ingested alcohol can have distinct effects on the human body. However, there is limited research on chronic alcohol consumption with Helicobacter pylori infection. We sought to investigate the relationship between the cytokine profile, oxidative balance and H. pylori infection in subjects with chronic alcohol consumption. A total of 142 subjects were divided into three groups: 59 subjects with chronic alcohol ingestion and H. pylori infection (group A); 53 subjects with chronic alcohol ingestion without H. pylori infection (group B); and 30 control subjects (group C). The serum levels of CagA, interleukin (IL)-10, E-selectin, TNF-α, malondialdehyde (MDA) and superoxide dismutase (SOD) activity were measured by enzyme-linked immunosorbent assay (ELISA). We found that the ages and serum H. pylori CagA levels among the three groups, as well as both the mean drinking age and the mean daily alcohol consumption between groups A and B, were matched and comparable. Comparing the BMIs among the three groups, the BMI differences were found to be statistically significant (F=3.921, P<0.05). Compared with group C, the BMIs in groups A and B were significantly higher (P<0.001 and P<0.01, respectively); however, the BMI differences between group A and group B were not statistically significant (P>0.05). Additionally, no differences in the serum CagA levels were found in comparisons among the groups (all P>0.05). The serum IL-10 and E-selectin levels in group A were significantly lower than those in group B (serum IL-10: P<0.05; E-selectin: P<0.05). The serum IL-10 in group A was significantly higher than that in group C (P<0.01); the serum E-selectin levels in group A did not significantly differ compared with those in group C (P>0.05). Furthermore, the serum IL-10 and E-selectin levels in group B were significantly higher than those in group C (serum IL-10: P<0.001; E-selectin: P<0.05); however, the serum TNF-α levels did not differ among groups (all P>0.05). Although the serum levels of MDA and SOD in groups A and B were slightly lower than those in group C, there were no significant differences among groups (all P>0.05). In conclusion, we believe that H. pylori infection might cause a significant inhibition of certain cytokine profiles in subjects with chronic alcohol ingestion. Moreover, chronically ingested alcohol may exert an adjusted inflammatory effect, but there was no association between H. pylori infection, chronic alcohol consumption and oxidative balance.


An increase in multi-site practices: The shifting paradigm for gynecologic cancer care delivery.
To assess whether the number of practice sites per gynecologic oncologist (GO) and geographic access to GOs has changed over time. This is a retrospective repeated cross-sectional study using the 2015-2019 Physician Compare National File. All GOs in the 50 United States and Washington, DC, who had completed at least one year of practice were included in the study. All practice sites with complete addresses were included. Linear regression analyses estimated trends in GOs' number of practice sites and geographic dispersion of practice sites. Secondary analyses assessed temporal trends in the number of geographic areas served by at least one GO. Although there was no significant change in the number of GOs from 2015 to 2019 (n = 1328), there was a significant increase in the number of practice sites (881 to 1416, p = 0.03), zip codes (642 to 984, p = 0.03), HSAs (404 to 536, p = 0.04), and HRRs (218 to 230, p = 0.03) containing a GO practice. The mean number of practice sites (1.64 versus 2.13, p < 0.001) and dispersion of practice sites (0.03 versus 0.43 miles, p = 0.049) per GO increased significantly. Between 2015 and 2019, an increasing number of GOs have multi-site practices, and more geographic regions contain a GO practice. Improvements in geographic access to GOs may represent improved access to care for many women in the US, but its effect on patients, physicians, and geographic disparities is unknown.


Restraint stress alters nociceptin/orphanin FQ and CRF systems in the rat central amygdala: significance for anxiety-like behaviors.
Corticotropin releasing factor (CRF) is the primary mediator of stress responses, and nociceptin/orphanin FQ (N/OFQ) plays an important role in the modulation of these stress responses. Thus, in this multidisciplinary study, we explored the relationship between the N/OFQ and the CRF systems in response to stress. Using in situ hybridization (ISH), we assessed the effect of body restraint stress on the gene expression of CRF and N/OFQ-related genes in various subdivisions of the amygdala, a critical brain structure involved in the modulation of stress response and anxiety-like behaviors. We found a selective upregulation of the NOP and downregulation of the CRF1 receptor transcripts in the CeA and in the BLA after body restraint. Thus, we performed intracellular electrophysiological recordings of GABAA-mediated IPSPs in the central nucleus of the amygdala (CeA) to explore functional interactions between CRF and N/OFQ systems in this brain region. Acute application of CRF significantly increased IPSPs in the CeA, and this enhancement was blocked by N/OFQ. Importantly, in stress-restraint rats, baseline CeA GABAergic responses were elevated and N/OFQ exerted a larger inhibition of IPSPs compared with unrestraint rats. The NOP antagonist [Nphe1]-nociceptin(1-13)NH2 increased the IPSP amplitudes in restraint rats but not in unrestraint rats, suggesting a functional recruitment of the N/OFQ system after acute stress. Finally, we evaluated the anxiety-like response in rats subjected to restraint stress and nonrestraint rats after N/OFQ microinjection into the CeA. Intra-CeA injections of N/OFQ significantly and selectively reduced anxiety-like behavior in restraint rats in the elevated plus maze. These combined results demonstrate that acute stress increases N/OFQ systems in the CeA and that N/OFQ has antistress properties.


Mixed-species bird flocks re-assemble interspecific associations across an elevational gradient.
Understanding how non-trophic social systems respond to environmental gradients is still a challenge in animal ecology, particularly in comparing changes in species composition to changes in interspecific interactions. Here, we combined long-term monitoring of mixed-species bird flocks, data on participating species' evolutionary history and traits, to test how elevation affected community assemblages and interspecific interactions in flock social networks. Elevation primarily affected flocks through reassembling interspecific associations rather than modifying community assemblages. Specifically, flock networks at higher elevations (compared to low elevations) had stronger interspecific associations (larger average weighted degree), network connectivity (enhanced network density) and fewer subnetworks. A phylogenetic and functional perspective revealed that associations between similar species weakened, whereas connections between dissimilar and/or random species were unchanged or strengthened with elevation. Likewise, network assortativity for the traits of vertical stratum and breeding period declined with elevation. The overall pattern is a change from modular networks in the lowlands, where species join flocks with other species that have matching traits, to a more open, random system at high elevations. Collectively, this rewiring of interspecific networks across elevational gradients imparts network stability and resiliency and makes mixed-species flocks less sensitive to local extinctions caused by harsh environments.


Vitamin D Receptor Gene Polymorphism In Chronic Telogen Effluvium; A Case-Control Study.
Telogen effluvium (TE) is a form of alopecia characterized by diffuse hair shedding. Vitamin D receptor (VDR) plays a role in hair cycle regulation as it is expressed in follicular keratinocytes and dermal papilla cells. To investigate the association between Cdx1 and Taq1 VDR gene polymorphisms and chronic TE. Thirty female patients with chronic TE were selected and 30 healthy, age- and sex-matched volunteers were included as a control group. Detection of VDR gene polymorphisms Taq1 and Cdx1 was done by real-time polymerase chain reaction. Regarding Taq 1, CC genotype was present in 30% of cases versus 3.3% of controls. TC genotype was present in 33.3% of cases and 36.7% of controls. CC genotype was significantly associated with cases (P=0.01). It increases the risk of chronic TE by 14.7 folds. C allele was significantly associated with patient group (P=0.004). It increases the risk of disease occurrence by 3.1 folds. Regarding Cdx1, AA genotype was present in 6.7% of cases versus 3.3% of controls. GA genotype was present in approximately 30% of cases and 6.7% of controls. GA genotype was significantly associated with cases (P=0.03). It increases the risk of chronic TE by 6.3 folds. A allele was significantly associated with patient group (P=0.007). It increases the risk of disease occurrence by 3.8 folds. The main limitation is the small number of cases due to the time and financial constraints. Only chronic TE was analyzed, therefore, other types should be investigated in the following studies. After exposure to primary physical or mental stressor, hair follicles are stimulated to enter prematurely into telogen and shed out. In individuals with Taq1 and Cdx1 polymorphisms, the disease persists as a result of prevention of new anagen growth and inhibition of hair follicle stem cell proliferation.


Comparison of methods for detection of serum antibody to murine rotavirus.
Mice are frequently used as animal models for the study of rotaviral infections. Since natural infection is common in laboratory mice, it is important that rotaviral studies, as well as other studies utilizing suckling mice, employ animals of known immune status to murine rotavirus. A variety of homologous and heterologous enzyme immunoassay systems and an immunofluorescence technique were thus compared to determine the immunoassay that is most effective at detecting adult mice seropositive for rotaviral antibody. It was determined that a homologous enzyme immunoassay inhibition technique utilizing murine rotavirus-derived reagents was the most efficient serologic assay evaluated. A serologic response was consistently detected by this assay by 5 days after experimental rotaviral inoculation of adult mice. A homologous antibody-binding enzyme immunoassay, a heterologous inhibition enzyme immunoassay utilizing antigenically related simian rotavirus (SA-11) reagents, and an immunofluorescence technique utilizing Nebraska calf diarrhea virus antigens were found to be less sensitive for detecting serum antibody to murine rotavirus.


[Posttraumatic epilepsy. Clinical aspects and electrophysiological foundations].
The review of the syndrome is centered on time course, prognosis and prophylaxis. Prophylactic anticonvulsive treatment depends on the prognosis. The latter is dependent on the risk to develop epilepsy after a certain type of head injury. Treatment should begin in the high risk group of patients before seizures become overt. In order to avoid preventive treatment in unselected posttraumatic cases, predicting the risk in each case is most important. Therefore the literature was reviewed selecting injuries and complications of high risk. Knowledge on pathophysiologic mechanisms in the epileptogenic focus to a large extent stems from animal experiments using a model of chronic recurrent seizures. Basic electrophysiologic mechanisms responsible for focal electroencephalographic changes were studied by recording from single cells. Profound abnormalities in patterns of neuronal discharge were found as well as morphological and functional changes of glia in the epileptogenic scar. It appears that glia is important in generating focal electroencephalographic spiking. By controlling intercellular potassium transport glia modulates neuronal activity.


[Feasibility and possibility of Inoue stent graft for thoracic aortic aneurysms].
Open surgical repair is a traditional treatment for patients with thoracic aortic aneurysms. Despite recent advances in surgical techniques and anesthetic management, the surgical repair of thoracic aortic aneurysms is still associated with significant mortality and morbidity. Endovascular aneurysm repair of thoracic aortic aneurysms is emerging as an alternative method for repair in selected patients. Although endovascular stent grafting is less invasive than open surgical repair, involvement of branch vessels and precipitous curvature of the aortic arch limits the application of stent grafting. Inoue stent graft system consists of soft nitinol ring-type stent which enables very flexible stent graft, and it can well comply with the precipitous curvature of the aortic arch. The system also provides a stent graft with a side branch to manage the left subclavian artery. This system does not require the surgical revascularization of the left subclavian artery. In this report, we show the feasibility and possibility of Inoue stent graft system to manage the aortic arch aneurysm.


[Microbiocenosis and the status of the intestinal mucosa in alkylosing spondyloarthritis].
Intestinal microbiocenosis was examined in 53 patients with ankylosing spondyloarthritis (AS). Of these, 23 had the central and 30 presented with the peripheral form. 34 patients underwent endoscopic examinations (rectoromanoscopy, ileocolonoscopy). As a result, in 74% of cases with the central form of AS and in 80% of cases with the peripheral form of AS, alterations in the intestinal microflora were revealed, which can be regarded as intestinal dysbacteriosis (ID), with dysbacteriosis being more pronounced in patients with the peripheral form. In such patients it manifested by a considerable decrease of the amount of bifido- and lactoflora, which promoted the increment of the amount of opportunistic microorganisms, particularly Klebsiella. Macroscopic signs of nonspecific inflammation of the small and large intestines were identified in 63% of patients with the central and in 67% of those with the peripheral form of AS. Mean-while histomorphological study of biopsy specimens of the intestinal mucosa showed that all the examinees had chronic inflammation of varying degree.