Comparative analysis of the repertoire of insulin-reactive B cells in type 1 diabetes-prone and resistant mice.
Seropositivity for autoantibodies against multiple islet antigens is associated with development of autoimmune type 1 diabetes (T1D), suggesting a role for B cells in disease. The importance of B cells in T1D is indicated by the effectiveness of B cell-therapies in mouse models and patients. B cells contribute to T1D by presenting islet antigens, including insulin, to diabetogenic T cells that kill pancreatic beta cells. The role of B cell receptor (BCR) affinity in T1D development is unclear. Here, we employed single cell RNA sequencing to define the relationship between BCR affinity for insulin and B cell phenotype during disease development. We utilized immunoglobulin (Ig) heavy chain (VH125) mouse models in which high-affinity insulin-reactive B cells (IBCs) were previously shown to be anergic in diabetes-resistant VH125.C57BL/6-H2g7 and activated in VH125. NOD mice developing disease. Here, high-affinity IBCs were found in the spleen of prediabetic VH125. NOD mice and exhibited marginal zone or follicular phenotypes. Ig light chains expressed by these B cells are unmutated and biased toward Vκ4-74 and Vκ4-57 usage. Receptors expressed by anergic high-affinity IBCs of diabetes-resistant VH125.C57BL/6-H2g7 are also unmutated; however, in this genetic background light chains are polymorphic relative to those of NOD. Light chains derived from NOD and C57BL/6-H2g7 genetic backgrounds conferred divergent kinetics of binding to insulin when paired with the VH125 heavy chain. These findings suggest that relaxation of tolerance mechanisms in the NOD mouse leads to accumulation and partial activation of B cells expressing germline encoded high-affinity BCRs that support development of autoimmunity.


Prediction Model for Infectious Disease Health Literacy Based on Synthetic Minority Oversampling Technique Algorithm.
Improving health literacy in infectious diseases is a direct manifestation of the solid advance in disease control and prevention. Our study is aimed at exploring applying synthetic minority oversampling technique (SMOTE) in the prediction assessment of whether residents and business employees have infectious disease health literacy. The Chinese resident infectious disease health literacy evaluation scale was used to investigate the associated variables. The screened variables were input variables and the presence or absence of infectious diseases health literacy as outcome variables. Logistic regression, random forest, and support vector machine (SVM) models were built in the data sets before and after treatment by the SMOTE algorithm, respectively, and the performance of the models was evaluated by receiver operating characteristic curves (ROC). Logistic regression, random forest, and SVM achieved accuracies of 0.828, 0.612, and 0.654 before SMOTE algorithm processing, and the areas under the ROC curves (AUCs) of the three models were 0.754, 0.817, and 0.759, respectively. The accuracies were 0.938, 0.911, and 0.894 after SMOTE algorithm processing, and the AUCs of the three models were 0.913, 0.925, and 0.910, respectively. The random forest model based on the SMOTE has high application value in assessing whether residents versus enterprise employees have infectious disease health literacy.


Omega-3 polyunsaturated fatty acids preserve retinal function in type 2 diabetic mice.
Diabetic retinopathy (DR) is associated with hyperglycemia-driven microvascular pathology and neuronal compromise in the retina. However, DR is also linked to dyslipidemia. As omega-3 (ω-3) polyunsaturated fatty acids (PUFAs) are protective in proliferative retinopathy, we investigated the capacity of ω-3PUFAs to preserve retinal function in a mouse model of type 2 diabetes mellitus (T2DM). Male leptin-receptor-deficient (db/db) mice were maintained for 22 weeks (4 weeks-26 weeks of life) on calorically and compositionally matched diets, except for 2% enrichment in either ω-3 or ω-6PUFAs. Visual function was assessed at 9, 14 and 26 weeks by electroretinography. Retinal capillary and neuronal integrity, as well as glucose challenge responses, were assessed on each diet. The ω-3PUFA diet significantly preserved retinal function in the mouse model of T2DM to levels similar to those observed in nondiabetic control mice on normal chow. Conversely, retinal function gradually deteriorated in db/db mice on a ω-6PUFA-rich diet. There was also an enhanced ability of ω-3PUFA-fed mice to respond to glucose challenge. The protection of visual function appeared to be independent of cytoprotective or anti-inflammatory effects of ω-3PUFAs. This study identifies beneficial effects of dietary ω-3PUFAs on visual function in T2DM. The data are consistent with dyslipidemia negatively impacting retinal function. As ω-3PUFA lipid dietary interventions are readily available, safe and inexpensive, increasing ω-3PUFA intake in diabetic patients may slow the progression of vision loss in T2DM.


Profile of medical waste management in two healthcare facilities in Lagos, Nigeria: a case study.
Proper management and safe disposal of medical waste (MW) is vital in the reduction of infection or illness through contact with discarded material and in the prevention of environmental contamination in hospital facilities. The management practices for MW in selected healthcare facilities in Lagos, Nigeria were assessed. The cross-sectional study involved the use of questionnaires, in-depth interviews, focused group discussions and participant observation strategies. It also involved the collection, segregation, identification and weighing of waste types from wards and units in the representative facilities in Lagos, Nigeria, for qualitative and quantitative analysis of the MW streams. The findings indicated that the selected Nigerian healthcare facilities were lacking in the adoption of sound MW management (MWM) practices. The average MW ranged from 0.01 kg/bed/day to 3.98 kg/bed/day. Moreover, about 30% of the domestic waste from the healthcare facilities consisted of MW due to inappropriate co-disposal practices. Multiple linear regression was applied to predict the volume of waste generated giving a correlation coefficient (R(2)) value of 0.99 confirming a good fit of the data. This study revealed that the current MWM practices and strategies in Lagos are weak, and suggests an urgent need for review to achieve vital reversals in the current trends.


Medical and psychosexual outcome in women affected by complete gonadal dysgenesis.
Prenatal exposure to testicular hormones influences the development of brain structures and behavior in many non-human mammalian species. Less understood is the role of possessing a Y chromosome, independent of testicular hormones, on psychosexual differentiation. Phenotypic women affected by complete gonadal dysgenesis possess a 46,XY chromosome complement and streak gonads. This population is suitable to test the influence of an absence of androgens and Müllerian inhibiting substance on psychosexual development in genetic males. Three 46,XY women diagnosed with complete gonadal dysgenesis participated. Psychosexual development, medical outcome and knowledge of medical condition were assessed with a written questionnaire and a physical examination. All participants were healthy, compliant with their hormone therapy, and exhibited female-typical psychosexual development. However, participants were poorly informed about their condition and the fertility treatment options available to them. These data indicate no obvious role for genes on the Y chromosome, outside of its pseudoautosomal region and SRY, on psychosexual differentiation in genetic males who do not produce testicular hormones. Greater efforts need to be made to educate affected women about their pregnancy options.


[Surgery of rectal carcinoma: 1997 status assessment].
The rectum and mesorectum are enclosed in a fascial sheath, the fascia propria, and represent an anatomical entity of abdominal origin. This package is a well-known anatomical and oncological base for radical rectal cancer excision. It is at present under discussion again under new aspects: The surgical and oncological quality of rectal cancer excision is largely surgeon-dependent. Modern rectal surgery is refined, with sharp, very precise dissection respecting the relevant fascial planes, identifying and protecting the autonomous pelvic nerves and achieving radical locoregional tumor clearance, thus virtually eliminating the serious problem of pelvic recurrence. In this overview the concept of total mesorectal excision (TME) is explained and open questions are discussed. It remains to be determined whether a refined and anatomically precise operative technique or the oncologic concept of TME are of primary importance, and also whether patient selection influences the results to some degree.


Molecular organization of the human Raf-1 promoter region.
A genomic DNA fragment containing the Raf-1 promoter region was isolated by using a cDNA extension clone. Nucleotide sequencing of genomic DNA clones, primer extension, and S1 nuclease assays have been used to identify the 5' ends of Raf-1 RNAs. Consistent with its ubiquitous expression, the Raf-1 promoter region had features of a housekeeping gene in that it was GC-rich (HTF-like), lacked TATA and CAAT boxes, and contained heterogeneous RNA start sites and four potential binding sites for the transcription factor SP1. In addition, an octamer motif (ATTTCAT), a potential binding site for the octamer family of transcription factors, was located at -734 base pairs. The Raf-1 promoter region drove reporter gene expression 30-fold over the promoterless reporter in Cos 7 cells.


Prolonged VV ECMO (265 Days) for ARDS without technical complications.
The usual duration of extracorporeal membrane oxygenation (ECMO) in patients with severe acute respiratory distress syndrome is 7-10 days. Prolonged duration ECMO (defined as greater than 14 days) is increasingly being documented with native lung recovery or as a bridge to lung transplantation. We report a case of prolonged duration ECMO (6,364 hours, 265 days) requiring no complete circuit exchange. As critical care improves, prolonged ECMO will continue to pose unique technological and ethical challenges that test our expectations of this treatment modality. There is a critical need for diagnostic modalities to provide objective assessment of native lung recovery in patients requiring prolonged duration ECMO.


Effect of 2-year placebo-controlled immunotherapy on airway symptoms and medication in patients with birch pollen allergy.
Birch pollen is a common allergen in northern, central, and eastern Europe. Earlier studies of specific immunotherapy using birch pollen extract were not placebo-controlled or were only preseasonal. Long-term, placebo-controlled studies with subcutaneously administered standardized birch pollen extract are lacking. The aim of this study was to evaluate the effect of immunotherapy with birch pollen extract on airway symptoms and use of medication in adult birch pollen-allergic patients in a double-blind, placebo-controlled trial. Forty-nine patients with histories of birch pollen allergy from the upper and lower airways, positive skin prick test and conjunctival provocation test results, and in vitro specific IgE to birch pollen (Betula verrucosa ) extract were included. Immunotherapy with birch pollen extract was given during 2 consecutive years in a double-blind, randomized, placebo-controlled study. Clinical symptom scores from the upper and lower airways and use of rescue medication were registered throughout the pollen season. Forty-six patients reached the maintenance dose and were maintained on that dose during the 2-year study. The median symptom scores during the 1997 and 1998 seasons were 1.3 and 2.6, respectively, in the specific immunotherapy group and 2.1 and 4.3, respectively, in the placebo group. The differences between the groups were significant (P =.05 in 1997 and P =.005 in 1998). The placebo group used significantly more rescue medication during both seasons than the specific immunotherapy group (P =.004 for 1997 and P =.004 for 1998). Specific immunotherapy with birch pollen extract is an effective and safe treatment for reducing clinical allergy symptoms and medication use in birch pollen-allergic patients during the pollen season.


[Management of older adults with COPD].
In older adults, the clinical condition of COPD is complicated and treatment often becomes difficult, because of existence of multimorbidity, such as nutritional deficiencies, thinness, sarcopenia, osteoporosis, cardiovascular disease, depression and cognitive impairment. Consideration based on each of coexistence is needed in the management of older adults with COPD. In end period of COPD, sleep disorder, depressive state and decline of ADL are often shown, in addition to the respiratory symptoms, such as dyspnea, cough and sputum. Financial strain for the nursing cost and medical equipment cost tend to become big year by year, utilization of social resources (i.e. application of respiratory disabilities and an insurance of the elderly care) is need to be considered.


The role of the Government in public health: a national perspective.
The main challenges today are complex systems problems, with equally complex solutions; there are problems that have the potential to affect all individuals at different levels, affecting health, the sustainability of health services, and potentially the long-term economic prosperity of the country. The evidence shows that unless people themselves are engaged, releasing their potential for action, supporting a cultural shift towards a health promoting society, it is unlikely that the necessary sustainable impact on obesity, diabetes and other chronic diseases will be achieved. By reflecting on experience in England, this article will provide an insight into the potential for change that can be generated by rebalancing the relationship between the state, the individual and civil society.


Clustering of Th cell epitopes on exposed regions of HIV envelope despite defects in antibody activity.
A long-standing question in the field of immunology concerns the factors that contribute to Th cell epitope immunodominance. For a number of viral membrane proteins, Th cell epitopes are localized to exposed protein surfaces, often overlapping with Ab binding sites. It has therefore been proposed that Abs on B cell surfaces selectively bind and protect exposed protein fragments during Ag processing, and that this interaction helps to shape the Th cell repertoire. While attractive in concept, this hypothesis has not been thoroughly tested. To test this hypothesis, we have compared Th cell peptide immunodominance in normal C57BL/6 mice with that in C57BL/6( micro MT/ micro MT) mice (lacking normal B cell activity). Animals were first vaccinated with DNA constructs expressing one of three different HIV envelope proteins, after which the CD4(+) T cell response profiles were characterized toward overlapping peptides using an IFN-gamma ELISPOT assay. We found a striking similarity between the peptide response profiles in the two mouse strains. Profiles also matched those of previous experiments in which different envelope vaccination regimens were used. Our results clearly demonstrate that normal Ab activity is not required for the establishment or maintenance of Th peptide immunodominance in the HIV envelope response. To explain the clustering of Th cell epitopes, we propose that localization of peptide on exposed envelope surfaces facilitates proteolytic activity and preferential peptide shuttling through the Ag processing pathway.


Effects of ocean acidification on dopamine-mediated behavioral responses of a coral reef damselfish.
We investigated whether CO2-induced ocean acidification (OA) affects dopamine receptor-dependent behavior in bicolor damselfish (Stegastes partitus). Damselfish were kept in aquaria receiving flow through control (pH ~ 8.03; pCO2 ~ 384 μatm) or OA (pH ~ 7.64; CO2 ~ 1100 μatm) seawater at a rate of 1 L min-1. Despite this relatively fast flow rate, fish respiration further acidified the seawater in both control (pH ~7.88; pCO2 ~ 595 μatm) and OA (pH ~7.55; pCO2 ~ 1450 μatm) fish-holding aquaria. After five days of exposure, damselfish locomotion, boldness, anxiety, and aggression were assessed using a battery of behavioral tests using automated video analysis. Two days later, these tests were repeated following application of the dopamine D1 receptor agonist SKF 38393. OA-exposure induced ceiling anxiety levels that were significantly higher than in control damselfish, and SKF 38393 increased anxiety in control damselfish to a level not significantly different than that of OA-exposed damselfish. Additionally, SKF 38393 decreased locomotion and increased boldness in control damselfish but had no effect in OA-exposed damselfish, suggesting an alteration in activity of dopaminergic pathways that regulate behavior under OA conditions. These results indicate that changes in dopamine D1 receptor function affects fish behavior during exposure to OA. However, subsequent measurements of seawater sampled using syringes during the daytime (~3-4 pm local time) from crevasses in coral reef colonies, which are used as shelter by damselfish, revealed an average pH of 7.73 ± 0.03 and pCO2 of 925.8 ± 62.2 μatm; levels which are comparable to Representative Concentration Pathway (RCP) 8.5 predicted end-of-century mean OA levels in the open ocean. Further studies considering the immediate environmental conditions experienced by fish as well as individual variability and effect size are required to understand potential implications of the observed OA-induced behavioral effects on damselfish fitness in the wild.


Attention-deficit/hyperactivity disorder: presentation and management in the Haitian American child.
A case study of a young Haitian American is presented that is illustrative of cultural issues that influence care of those with attention-deficit/hyperactivity disorder (ADHD). Medications are the preferred treatment for ADHD and can be combined with psychological intervention. However, many Haitians and Haitian Americans see psychoactive medications as leading to substance abuse or mental illness. Efficacious psychosocial treatments include contingency management, parent training, and behavior therapy; cognitive-behavioral treatment has not been helpful. Complementary and alternative medicine might have appeal; primary care physicians can help families to assess such treatments and not to be enticed by expensive ones of little benefit. A determinant of the treatment a family pursues is their perception of the cause of the ADHD behaviors. While there is no term for ADHD in the Haitian-Creole language, in the Haitian culture the behaviors consistent with the diagnosis might be interpreted as indicating a poorly raised child whose behavior could be modified by parental discipline, an intentionally bad child, or a psychically victimized child suffering from an "unnatural" condition. "Natural" ailments are attributed to natural forces (e.g., wind, temperature), while "unnatural" ones are attributed to bad spirits or punishment by God. Families may "lift their feet" (Leve pye nou: to see a Hougan or voodoo priest) to determine the unnatural cause. Haitian Americans often combine therapeutic foods that are considered cold in nature, natural sedatives and purgatives from herbal medicine, religious treatments, and Western medicine. Immigrants often lack support of extended families in an environment not supportive of their interpretation of child behaviors and traditionally accepted parental disciplinary style. Stigma, language, cultural conceptions, concerns about governmental agencies, and physician bias can all be barriers to care for immigrant families. Primary care and behavioral integration are useful in managing families from other cultures.


Extra electron in (H2O)24- cluster isomers: a theoretical study.
The isomers of (H(2)O)(24) (-) tetrakaidecahedral cluster are studied by applying the Becke-3-parameter density functional theory and Lee-Yang-Parr correlation functional (B3LYP) and 6-311++G** basis set. Three isomers are selected on the basis of stabilization energy values. The vertical electron dissociation energies (VDE) of these isomers are 1.353, 0.404, and 0.258 eV, respectively. The experimental VDE value of 1.31 eV [J. Chem. Phys. 92, 3980 (1990)] for this cluster size is in excellent agreement with that calculated for isomer 1, suggesting the dominance of this isomer in the experiment. Four water molecules in this isomer share most of the -1 charge. These four water molecules have non-H-bonding H (NHB H) atoms turned toward the cavity, and the inward turned H atoms exhibit a significant lowering of O-H stretch frequency compared to that of a monomer. Isomers 2 and 3 have all 12 NHB H atoms projected outward and have the -1 charge distributed among 7-8 water molecules on the cluster surface.


Plectranthus amboinicus and rosemary (Rosmarinus officinalis L.) essential oils effects on performance, antioxidant activity, intestinal health, immune response, and plasma biochemistry in broiler chickens.
This work aimed to assess the effects of Plectranthus amboinicus essential oil (PAE) and rosemary (Rosmarinus officinalis L.) essential oil (ROE) as feed additives on performance, antioxidant activity, intestinal microbiota, intestinal morphology, immune response, and plasma biochemistry using 320 unsexed 1-day-old Ross 308 broiler chickens. The chickens were assigned randomly into four treatments containing eight replicates with 10 chickens each. Treatment diets included a basal diet as a control group, 100 mg/kg PAE, 200 mg/kg PAE, and 100 mg/kg ROE. ROE affected the growth performance in the starter phase by improving (p = .01) the feed conversion ratio (FCR) compared with the control diet. Glutathione peroxidase (GPx) and superoxide dismutase (SOD) activity in the plasma were elevated (p < .0001) by both feed additives. Supplementation of additives could increase (p < .006) total antioxidant capacity (TAC). Furthermore, malondialdehyde (MDA) values in the breast (p < .0001) and thigh (p < .001) for all supplemented diets were less than the control group. The essential oils (EOs) reduced (p < .005) coliform counts in the ileum and increased (p = .029) lactic acid bacteria counts. In addition, villus height (VH) and crypt depth (CD) increased, whereas the density of goblet cells decreased in the small intestine when feed additives were included. Also, the antibody titers against sheep red blood cells (SRBC) and Newcastle disease virus (NDV) were increased (p < .0001) by EOs. Plasma total protein (p = .04) and globulin (p = .02) were increased, and cholesterol was reduced (p = .002) by supplemented diets. Our study revealed that PAE could effectively improve the antioxidant activity, intestinal microbiota population, intestinal morphology, immune response, and plasma biochemistry parameters in broiler chickens.


Examining the effect of task constraints on the emergence of creative action in young elite football players by using a method combining expert judgement and frequency count.
In adult football, small-sided games are associated with increased action variability and suggested to promote more creative actions compared to regular 11v11 formats. This aligns with predictions from an ecological approach to perception and action that creative actions emerge in environments that grant variability in action, instead of being an expression of the individual player's ability to generate ideas. To further evidence for this prediction, the current study aimed to expand this observation to elite youth football players. To this end, the number of different and creative actions in 4v4 small-sided game and a 11v11 regular-sided game among 10- to 12-year-old elite football players were examined. We analyzed a total of 7922 actions, which were categorized for type and creativity. Based on a subset of these actions, a panel of elite football coaches judged action types occurring below 0.5% as significantly more creative than more frequent action types. Hence, we used an occurrence of 0.5% as threshold to distinguish creative actions from non-creative actions. The results showed that the total number of actions, the number of different action types, the number creative actions and the number of different creative action types was significantly higher for the small-sided game format than the regular-sided game. In conclusion, this study confirms that in elite youth football, small-sided games induce a more variable and creative action repertoire. This shows that practitioners can design learning environments that promote the emergence of creative actions.


Foegraecumoside O and P, a Pair of Triterpenoid Saponins with a 4/5/6 Fused Tricyclic Oleanane Carbon Skeleton from Lysimachia foenum-graecum Hance.
Lysimachia foenum-graecum Hance (Primulaceae) is a medicinal plant used for cold, pain, ascariasis, etc., in China. Triterpenoid saponins have been found to be the main components of this genus. In this work, a pair of oleanane-type triterpenoid saponins with an unprecedented 4/5/6 fused tricyclic skeleton, foegraecumoside O (1) and foegraecumoside P (2) were isolated from the butanol fraction of the aerial parts of L. foenum-graecum. Their structures were determined using chemical methods and extensive spectroscopic analyses, along with quantum chemical calculations. Compound 2 displayed moderate cytotoxicity against HepG2, MGC-803, T24, NCI-H460, A549, and A549/CDDP (drug-resistant lung-cancer cell line) with IC50 at 12.4-19.2 μM in an MTT assay, comparing with the positive control doxorubicin, which had IC50 at 0.53-4.92 μM, but was inactive for A549/CDDP. Furthermore, a possible biosynthetic pathway for forming compounds 1 and 2 was proposed.


Freemartinism in replacement ewe-lambs of the Ripollesa sheep breed.
The freemartinism syndrome affects almost all female calves born as co-twins to male calves, whereas little is known about this phenomenon in female sheep. Within this context, 1,185 ewe-lambs from the Ripollesa sheep breed were genotyped for the presence of oY1 polymorphism (a non-autosomal region of the Y chromosome). Neither ewe-lambs from single births (856) nor ewe-lambs from all-female multiple births (170) were revealed as freemartins, whereas five of 159 ewe-lambs from multiple births with male co-twins were freemartins (3.15 ± 1.38%). All freemartin ewe-lambs were confirmed by physical examination of external genitalia. The results confirm a low incidence of freemartinism from heterosexual twin pregnancies in Ripollesa sheep.


[Revascularization of the circumflex coronary artery--a new instrument and a technical method].
Exposure of the coronary arteries for the distal anastomosis of the saphenous vein or the internal mammary artery to the coronary arteries may be accomplished by a number of techniques. Commonly practiced techniques of having an assistant retract the heart over a gauze sponge or with a cotton glove may cause unwanted cardiac trauma or disturb topical cooling of the heart. This paper describes our experience in performing saphenous vein grafts to the circumflex coronary artery system with a new instrument. It is a "net-bandage" which is used usually in orthopedics, and we have named it "CX-net". The CX-net is placed behind the heart and drawn tight to the atrioventricular groove by right lateral retraction and securing the umbilical tapes to hemostasis on the right anterior chest wall. Retraction of the CX-net to the right and securing it to the right anterior chest wall tips up the cardiac apex to exposure the posterior surface of the left ventricle for access to the left circumflex coronary artery. By adopting this new instrument and technical method, revascularization of the circumflex coronary artery is performed safely and successfully.


Overcoming the bottleneck to widespread testing: a rapid review of nucleic acid testing approaches for COVID-19 detection.
The current COVID-19 pandemic presents a serious public health crisis, and a better understanding of the scope and spread of the virus would be aided by more widespread testing. Nucleic-acid-based tests currently offer the most sensitive and early detection of COVID-19. However, the "gold standard" test pioneered by the U.S. Centers for Disease Control and Prevention takes several hours to complete and requires extensive human labor, materials such as RNA extraction kits that could become in short supply, and relatively scarce qPCR machines. It is clear that a huge effort needs to be made to scale up current COVID-19 testing by orders of magnitude. There is thus a pressing need to evaluate alternative protocols, reagents, and approaches to allow nucleic-acid testing to continue in the face of these potential shortages. There has been a tremendous explosion in the number of papers written within the first weeks of the pandemic evaluating potential advances, comparable reagents, and alternatives to the "gold-standard" CDC RT-PCR test. Here we present a collection of these recent advances in COVID-19 nucleic acid testing, including both peer-reviewed and preprint articles. Due to the rapid developments during this crisis, we have included as many publications as possible, but many of the cited sources have not yet been peer-reviewed, so we urge researchers to further validate results in their own laboratories. We hope that this review can urgently consolidate and disseminate information to aid researchers in designing and implementing optimized COVID-19 testing protocols to increase the availability, accuracy, and speed of widespread COVID-19 testing.


Achilles Tendon Allograft with Semitendinosus Autograft Reinforcement Is a Successful Treatment for Chronic Patellar Tendon Rupture: Report of Two Cases.
Rupture of the patellar tendon must be diagnosed urgently because reconstruction of the extensor mechanism produces better results when it is performed in acute conditions. Reconstruction of chronic extensor mechanism rupture on the contrary is very challenging. Several surgical techniques have been described using a variety of graft choices and fixation methods, but the optimal approach is still under debate. We report our experience of two cases of chronic patellar tendon rupture reconstruction using an Achilles tendon allograft reinforced by a vascularized ipsilateral semitendinosus tendon frame. The rapid functional recovery of the range of motion, only three months postoperatively, showed us that this reconstruction technique was effective.


SIRT2 suppresses adipocyte differentiation by deacetylating FOXO1 and enhancing FOXO1's repressive interaction with PPARgamma.
Sirtuin family of proteins possesses NAD-dependent deacetylase and ADP ribosyltransferase activities. They are found to respond to nutrient deprivation and profoundly regulate metabolic functions. We have previously reported that caloric restriction increases the expression of one of the seven mammalian sirtuins, SIRT2, in tissues such as white adipose tissue. Because adipose tissue is a key metabolic organ playing a critical role in whole body energy homeostasis, we went on to explore the function of SIRT2 in adipose tissue. We found short-term food deprivation for 24 h, already induces SIRT2 expression in white and brown adipose tissues. Additionally, cold exposure elevates SIRT2 expression in brown adipose tissue but not in white adipose tissue. Intraperitoneal injection of a beta-adrenergic agonist (isoproterenol) enhances SIRT2 expression in white adipose tissue. Retroviral expression of SIRT2 in 3T3-L1 adipocytes promotes lipolysis. SIRT2 inhibits 3T3-L1 adipocyte differentiation in low-glucose (1 g/l) or low-insulin (100 nM) condition. Mechanistically, SIRT2 suppresses adipogenesis by deacetylating FOXO1 to promote FOXO1's binding to PPARgamma and subsequent repression on PPARgamma transcriptional activity. Overall, our results indicate that SIRT2 responds to nutrient deprivation and energy expenditure to maintain energy homeostasis by promoting lipolysis and inhibiting adipocyte differentiation.


The shelf operation for hip dysplasia in adolescence.
Failure of normal acetabular development is inevitable in congenital dislocation of the hip when it is unrecognised until late infancy or early childhood. Numerous stabilising procedures have been described, one of the first being the shelf operation or acetabuloplasty. This procedure fell into disrepute because the shelf was often located too high or was too small to prevent upward migration of the femoral head. The technique described emphasises the importance of resecting the thickened capsule and exposing the lateral margin of the acetabulum to allow a substantial portion of the outer cortex of the ilium to be turned down both laterally and anteriorly over the femoral head. Twenty cases of acetabuloplasty have been followed up for an average period of nine years. The results have been assessed from the point of view of function, relief of pain, and degree of support of the femoral head as demonstrated radiologically. The shelf operation is a simple and safe procedure, and provided it gives adequate support to the subluxated femoral head it will ensure a stable, mobile joint capable of standing up to reasonable use for many years. If deterioration should occur in later life, total hip replacement may be undertaken more easily than if the joint had been allowed to undergo progressive subluxation.


Identification of Wheat LACCASEs in Response to Fusarium graminearum as Potential Deoxynivalenol Trappers.
Fusarium graminearum (F. graminearum) can cause huge yield reductions and contamination of grain with deoxynivalenol (DON), and thus is one of the most problematic pathogen of wheat worldwide. Although great efforts have been paid and great achievements have been made to control the pathogens, there is still a wide gap for understanding the mechanism underlying F. graminearum resistance. Plant LACCASEs (LACs) catalyze the oxidative polymerization of monolignols by reinforcing cell-wall of various cell types to provide mechanical support, xylem sap transportation, and defense against pest and pathogens. To date, little has been known about LAC genes in bread wheat and their potential roles in wheat-F. graminearum interaction. Through systematic analysis of the genome-wide homologs and transcriptomes of wheat, a total of 95 Triticum aestivum laccases (TaLACs) were identified, and 14 of them were responsive to F. graminearum challenge. 3D structure modelings of the 14 TaLAC proteins showed that only TaLAC78 contains the entire activity center for oxidation and the others lack the type 1 copper ion ligand (T1Cu). Both amino acid sequence alignment and three-dimensional reconstruction after amino acid mutation showed that the loss of T1Cu is not only related to variation of the key amino acid coordinating T1Cu, but also closely related to the flanking amino acids. Significantly differential temporal expression patterns of TaLACs suggested that their subfunctionalization might occur. Promoter array analysis indicated that the induction of TaLACs may be closely associated with salicylic acid signaling, dehydration, and low-oxygen stress under F. graminearum infection. Molecular docking simulation demonstrated that TaLACs can not only catalyze lignin as a substrate, but also interact with DON, which may be docked into the binding position of the monolignols, where the LACs recognize substrates. The current study provides clues for exploring the novel functions of TaLACs in wheat resistance to F. graminearum, and TaLACs maybe candidates for conferring a high level of resistance against F. graminearum in wheat.


Cell culture platform with mechanical conditioning and nondamaging cellular detachment.
Cells implanted after injury may remodel undesirably with improper mechanical stimulation from surrounding tissue. Proper conditioning of tissue engineered constructs before implantation can lead to suitable tissue architectures, along with an extracellular matrix (ECM) environment that more closely mimics native tissue. Additionally, cell implantation without bulky polymeric scaffolding is often desirable. Previous researchers have created devices capable of applying mechanical forces to cells (e.g., stretch) but cellular removal from these devices, such as by trypsin, often results in irreversible damage. Conversely, devices are available that can detach intact cells, but these are inelastic, nonstretchable substrates. We have created a cell culture platform that allows for mechanical conditioning and then subsequent nondamaging detachment of those cells. We have modified silicone culture surfaces, to incorporate thermally responsive polymers of N-isopropylacrylamide (NIPAAm) to create an elastic substrate that can also change surface properties with temperature change. A copolymer of NIPAAm and 10percent w/w acrylic acid (AAc) was conjugated to an amine-bonded silicone surface through carbodiimide chemistry. Cells were able to attach to the resulting surfaces at 37 degreeC and showed detachment by rounded morphology at 25degreeC. Following mechanical stretching, cells were still able to spontaneously detach from these modified silicone surfaces with temperature change.


MDA5 attenuate autophagy in chicken embryo fibroblasts infected with IBDV.
1. The role of melanoma differentiation-associated protein 5 (MDA5) in infectious bursal disease virus (IBDV)-induced autophagy was studied in chicken embryos.2. Chicken embryo fibroblasts (CEF) were used as the research model and small interfering RNA (siRNA), western blot, indirect enzyme-linked immunosorbent assay (ELISA), real-time fluorescence quantitative polymerase chain reaction (PCR) and transmission electron microscopy were used to detect autophagy, IBDV replication, CEF damage, and activation of both MDA5 and its signalling pathway.3. The results showed that CEF infected with IBDV activated the intracellular MDA5 signalling pathway and caused autophagy via inactivation of the AKT/mTOR pathway. While autophagy promotes IBDV proliferation, MDA5 weakens IBDV-induced CEF autophagy thus inhibiting IBDV replication and protecting CEF cells.4. The results indicated that chMDA5 can be activated by IBDV and attenuate CEF autophagy caused by IBDV infection, thereby inhibiting IBDV replication. This study provided a foundation for further exploring the relationship between viruses, autophagy and the pathogenic mechanism of the MDA5 pathway involved in IBDV.


Ventilation with low tidal volumes during upper abdominal surgery does not improve postoperative lung function.
Prolonged postoperative decrease in lung function is common after major upper abdominal surgery. Evidence suggests that ventilation with low tidal volumes may limit the damage during mechanical ventilation. We compared postoperative lung function of patients undergoing upper abdominal surgery, mechanically ventilated with high or low tidal volumes. This was a double-blind, prospective, randomized controlled clinical trial. One hundred and one patients (age ≥ 50 yr, ASA ≥ II, duration of surgery ≥ 3 h) were ventilated with: (i) high [12 ml kg(-1) predicted body weight (PBW)] or (ii) low (6 ml kg(-1) PBW) tidal volumes intraoperatively. The positive end-expiratory pressure was 5 cm H(2)O in both groups and breathing frequency adjusted to normocapnia. Time-weighted averages (TWAs) of forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV(1)) until 120 h after operation were compared (P<0.025 considered statistically significant). Secondary outcomes were oxygenation, respiratory and non-respiratory complications, length of stay and mortality. The mean (sd) values of TWAs of FVC and FEV(1) were similar in both groups: FVC: 6 ml group 1.8 (0.7) litre vs 12 ml group 1.6 (0.5) litre (P=0.12); FEV(1): 6 ml group 1.4 (0.5) litre vs 12 ml group 1.2 (0.4) litre (P=0.15). FVC and FEV(1) at any single time point and secondary outcomes did not differ significantly between groups. Prolonged impaired lung function after major abdominal surgery is not ameliorated by low tidal volume ventilation.


Inhaled treatment of COPD: a Delphi consensus statement.
Global Initiative for Chronic Obstructive Lung Disease (GOLD) global strategy (2015) provides guidance for the treatment of chronic obstructive pulmonary disease (COPD) with different first-choice options per GOLD category without specification. To evaluate the level of medical experts' consensus on their preferred first-choice treatment within different COPD categories. A two-round Delphi Panel consisting of 15 questions was completed by Belgian pulmonologists (n=31) and European (n=10) COPD experts. Good consensus was reached by both expert groups for long-acting bronchodilators instead of short-acting bronchodilators as first-choice treatment in GOLD A. Single bronchodilation with long-acting muscarinic antagonist (LAMA) was preferred over long-acting β2-agonist (LABA) and LABA/LAMA as first-choice treatment in GOLD B and GOLD C. For GOLD D patients based on the forced expiratory volume in 1 second (FEV1)<50%, a very good consensus was reached for LAMA/LABA as first-choice treatment. For GOLD D patients based on frequent or severe exacerbations, there was a good consensus for LABA/LAMA/inhaled corticosteroids (ICS) as first choice in the Belgian group. According to the European experts, both LABA/LAMA and LABA/LAMA/ICS could be the first choice for these patients. Belgian and European experts recommend long-acting bronchodilators as first-choice treatment. Treatment containing ICS was found only appropriate in patients with FEV1<50% and ≥2 moderate exacerbations or 1 severe exacerbation/year.


Sociodemographic Status of Patients Seeking Routine Scaling and Polishing in a Resource Challenged Environment.
To assess the sociodemographic profile of patients seeking routine scaling and polishing in a resource challenged setting in Ibadan, Nigeria Study design: A retrospective review of dental records of patients presenting for scaling and polishing at the Periodontology Clinic of a tertiary hospital in Ibadan, Nigeria over a period of one year was done. Two groups were identified; those seeking routine scaling and polishing and those referred as a result of periodontal disease or from other clinics. The age, gender, religion, marital status and socioeconomic status were obtained from the records of each patient. Analysis was done using SPSS version 16. The level of statistical significance was set at 5%. A total of 295 patients with a mean age of 42.5 (±17.7) years had scaling and polishing done over the period; 100 (33.9%) came routinely and 195 (66.1%) were referred. There were 151 (51.2%) males and 144 (48.8%) females. The majority (83.2%) were Christians. Their socioeconomic class ranged from skilled workers (21.4%), through unskilled workers (22.7%) to dependants (55.9%). A higher proportion of Christians than Muslims presented routinely for the procedure, 35.8% vs. 20.4% (p = 0.037). The proportion of skilled workers, unskilled workers and dependants who came for routine scaling and polishing were 46.0%, 25.4% and 32.7% respectively (p = 0.038). Socioeconomic status was found, on multivariate analysis, to significantly predict seeking for routine scaling and polishing. Socioeconomic status is a determinant of seeking for routine scaling and polishing in a resource poor country.


Septic arthritis of the pubic symphysis: a case report.
Septic arthritis of the pubic symphysis, so called osteomyelitis pubis is the infection which involves pubic symphysis and its joint. It is a rare condition, representing less than one percent of all cases of osteomyelitis. It affects most frequently young athletes and women undergoing gynecologic or urologic surgery. It presents itself with fever and pubic pain which irradiates to the genitals and increases when hip is mobilized, and this fact produces gait claudication. Diagnosis is based on clinic supported by microbiologic culture results, image methods, and proteins augment during acute phase. The etiologic agents most commonly found are Staphylococcus aureus, followed by gram-negative bacilli, and polymicrobial infection in recent pelvis surgery. The antibiotic treatment is adjusted depending on the microbiological diagnosis, adding NSAIDs, and bed rest. We report a 16 year-old male presenting with pubic pain and fever. Magnetic resonance imagery showed arthritis of the pubic symphysis. The patient was treated with antibiotics with a good clinical response.


[Endometrectomy. Analytical study of 20 cases].
Endometrial removal represents a therapeutic alternative to hysterectomy. Through a retrospective study of 20 cases of endometrial removal colleted over a period of 4 years, the authors try to determine the indications of this therapeutic method, its efficiency, its advantages as well as its contra indications. Average age of the patients was 44 years. Average parity was 4. Functional menstrual disorders were found in 90% of cases. Gynaecological examination revealed a uterus of normal size in 85% of cases, and increased in size in 15% of cases. All the women had a preoperative diagnostic hysteroscopy. A simple endometrectomy was performed in 70% of the cases, an endometrectomy with a polypectomy in 25% of the cases and an endométrectomy with a myomectomy in 5% of the cases. The rate of success was 90%. We had a case of uterine perforation, because of uncontrollable bleeding a hysterectomyhad to be carried out in 2 cases. Endometrectomy is an alternative to hysterectomy in cases of menorrhagia due to mild functional disorders resistant to medical treatment.


Basal cell carcinoma developing in a nevus flammeus.
A 44-year-old man with Sturge-Weber syndrome developed a basal cell carcinoma at the site of a nevus flammeus on his right cheek, which had been treated with a course of grenz rays at six years of age without obvious improvement. He also exhibited erythematous papulovesicular lesions on the upper trunk, which histologically proved to be transient acantholytic dermatosis. The association of nevus flammeus and basal cell carcinoma is extremely rare; to the best of our knowledge, only four similar cases have been previously reported.


Conversion From Once-Daily Prolonged-Release Tacrolimus to Once-Daily Extended-Release Tacrolimus in Stable Liver Transplant Recipients.
After organ transplant, strategies to simplify the therapeutic regimen may improve adherence and prevent rejection and/or graft loss. The aim of the present study was to evaluate the safety of conversion from once-daily prolonged-release tacrolimus (Advagraf; Astellas Pharma Europe Limited, Middlesex, UK) to once-daily extended-release tacrolimus (Envarsus; Chiesi SAS, Nanterre, France) in stable adult liver transplant recipients. This observational study inclu-ded 44 liver transplant patients (median age of 59 y; 63.6% men; median delay after transplant of 72.5 mo). Conversion was based on a 1:0.70 proportion. Mean dose of tacrolimus was 2.65 ± 1.24 mg/day before conversion and 2.09 ± 1.68 mg/day after conversion (P < .05), with ratio of 1:0.79. Mean serum tacrolimus trough level increased after conversion (4.92 ± 1.65 vs 5.60 ± 2.89 ng/mL; P < .05), with ratio of 1:1.14. Six months after conversion, mean dose of tacrolimus was 1.65 ± 0.93 mg/day (ratio of 1:0.62) and mean serum tacrolimus trough level was 4.82 ± 1.85 ng/mL, similar to the initial level before conversion. At the end of follow-up, 2 patients had returned to once-daily prolonged-release tacrolimus because of adverse effects (allergy, digestive trouble), which resolved thereafter. The mean cost of tacrolimus therapy was 5.54 ± 2.29 Euros/patient/day before conversion and 4.11 ± 2.32 Euros/patient/day after conversion (P < .05). Conversion from prolonged-release to extended-release tacrolimus in stable liver transplant patients is safe and cost-effective; however, initially, dose adaptations and careful monitoring are required.


The influence of postharvest processing and storage of foodstuffs on the bioavailability of flavonoids and phenolic acids.
Postharvest processing and storage not only influence the content and composition of flavonoids and phenolic acids in foodstuffs, thereby altering the amount of potentially bioavailable bioactive compounds, but can also modify their chemical form. Moreover, due to the intensive metabolism during absorption, the metabolites circulating in blood differ from the parent compounds found in food. Thus, it is difficult to predict potential in vivo effects of phenolic compounds merely by their contents in foodstuffs. Their specific bioavailability needs to be determined. This review considers studies regarding the bioavailability of flavonoids and phenolic acids from foodstuffs that meet the following criteria: providing actual concentrations of flavonoids and phenolic acids in blood plasma, body tissues, or urine, comparing differently stored or processed foods (excluding studies that use supplements or pure substances), and considering the high interindividual variability by repeated measurements in the same individuals. Only a few studies meet all of these criteria. In conclusion, processing and storage of food can have either positive or negative effects on the bioavailability of flavonoids and phenolic acids because these treatments may not only change the content, but also the chemical form of these compounds.


Resurgence of Organomanganese(I) Chemistry. Bidentate Manganese(I) Phosphine-Phenol(ate) Complexes.
As part of the United Nations 2019 celebration of the periodic table of elements, we are privileged to present our studies with the element manganese in this Forum Article series. Catalysis with organomanganese(I) complexes has recently emerged as an important area with the discovery that pincer manganese(I) complexes that can activate substrates through metal-ligand cooperative mechanisms are active (de)hydrogenation catalysts. However, this rapidly growing field faces several challenges, and we identify these in this Forum Article. Some of our efforts in addressing these challenges include using alternative precursors to Mn(CO)5Br to prepare manganese(I) dicarbonyl complexes, the latter of which is usually a component of active catalysts. Specifically, the synthesis of a new bidentate phosphine-phenol ligand along with its corresponding coordination chemistry of five new manganese(I) complexes is described. The complexes having two phenol-phenolate moieties interact with the secondary coordination sphere to enable facile loss of the bromido ligand and even one of the CO ligands to afford manganese(I) dicarbonyl centers.


[Comparison of protein composition and activities of pilose antler processed by different methods].
To elucidate the influence of processing conditions on pilose antlerś therapic effects, the protein composition and activities were compared on three kinds of pilose antler processed by lyophilization, freezing and traditional short-time heating, respectively. The concentration of the water soluble protein in freeze-dried pilose antler was 126.54 mg/g (Folin-Phenol assay), which was 13.1 times higher than that of heating processed antler. These proteins distributed widely in SDS-PAGE electrophoresis and the protein band between 50.0 kDa approximately 60.0 kDa achieved the highest concentration. The water extract of freeze-dried antler promoted the proliferation and IGF-I secretion of rat osteogenic-like cell UMR-106 by 245.25% ( MTT assay) and 66.36 ng/ml, which was respectively 2.2 times and 1.2 times of those of heating processed antler. The same candidate inhibited the growth of human hepatic carcinoma cell BEL-7402 by the highest rate of 47.64% , which was 1.4 times of heating processed antler. The activities of frozen fresh pilose antler were lower than those of its freeze-dried counterpart, but were much higher than those of heating processed antler. The results indicated that lyophilization help to remain the activity of pilose antlerś proteins as much as possible and improve its efficacy.


[I, Robot: artificial intelligence, uniqueness and self-consciousness].
The cinematographic version of the science fiction classical book by Isaac Asimov (I, Robot) is used as a starting point, from the Artificial Intelligence perspective, in order to analyze what it is to have a self. Uniqueness or the exchange impossibility and the continuity of being one self are put forward to understand the movie's characters as well as the possibilities of feeling self conscious.


Prenatal sonographic diagnosis of hemivertebra.
To describe our experience in prenatal diagnosis of hemivertebra. This is a case series of patients referred to our tertiary medical center over a 3-year period. All fetuses were scanned by high-resolution real-time scanners. The apparent vertebral anomaly was assessed in a real-time manner by a joint team of obstetricians, sonographers, and pediatric orthopedic surgeons. A complete anomaly survey of other fetal organs was performed on each fetus. All patients were given proper counseling by the same joint team. All patients had detailed obstetric and neonatal follow-up. Prenatal sonograms, neonatal medical records, and clinical courses were evaluated retrospectively. During the 3 years, 6 cases of hemivertebra were identified in our department. Gestational age at diagnosis was 14 to 23 weeks. Two patients had conception by assisted reproductive technology. Associated anomalies included VATER syndrome (vertebral defects, imperforate anus, tracheoesophageal fistula, and radial and renal dysplasia), gastroschisis, and pyelectasis. Outcomes in fetuses without major associated anomalies were fair. Diagnosis of isolated hemivertebra might be associated with a favorable outcome. The 3 key factors in achieving an optimal spine at maturity, early diagnosis, anticipation, and prevention of deterioration, might be enhanced by our joint multidisciplinary approach to the diagnosis of skeletal anomalies.


[The use of the platysma myocutaneous flap for reconstruction in the head-neck area -- a retrospective study].
Following extended tumor resections in the head-neck area options immediate defect reconstruction is needed to reduce healing time and improve rehabilitation. Reconstruction of significant areas of mucosal defects is best accomplished by introduction of a pliable regional transplant. The platysma myocutaneous flap has been used for defect reconstruction in head and neck area since more than 20 years. Its popularity is limited. Since 2001 in our department the platysma mucocutaneous flap is used for such reconstructions. We present a retrospective study evaluating our experience with the platysma myocutaneous flap. From 2001-2003 25 patients have been subjected to surgical reconstruction applying the platysma mucocutaneous flap. The primary tumor was located in 16 patients (64 %) in the oropharynx, in 5 patients (20 %) in the hypopharynx and in 4 patients (16 %) in the oral cavity. Evaluation was based on medical records including the operative reports. All patients get a follow up in our outpatient clinic. The platysma flap is easy to harvest and has a low general risk level. Complications are minor and may be avoided by exact preoperative planning. Necrosis of the skin-muscle-flap was observed only after resection of the A. carotis externa (two cases). In these 2 cases an operative revision was necessary (stenting of the pharynx or secondary reconstruction by pectoralis major-flap). The resection of the A. facialis (three cases) did not lead to a serious complication. Considering the exact indication the platysma flap is suitable for reconstruction of surface defects in the pharynx and oral cavity. A special attention is given to the ipsilateral vascular supply and the length of the muscular pedicel. It proved to be a cost effective method due to the less time and personal expenditure.


HPLC determination of naproxen in plasma.
An assay method using isocratic HPLC with fluorometric detection for the determination of naproxen sodium in plasma is presented. A reverse phase Microbondapack column was used with a mobile phase consisting of 42% acetonitrile and 58% water adjusted to pH 3 using phosphoric acid. The fluorometric detector with an excitation wavelength of 270 nm and emission wavelength of 340 nm provided high sensitivity and no interferences from plasma constituents. Plasma samples were injected to HPLC without any extraction. The method was precise and reproducible as was demonstrated by replicate analysis of pooled plasma sample containing 0.5-80 microg/ml naproxen sodium.


Glycosphingolipids of normal bovine and enzootic bovine leukosis lymph node cells.
We analyzed glycosphingolipids from normal lymph node cells of seven cattle and lymph node cells of eight cattle with enzootic bovine leukosis. The neutral glycosphingolipids and gangliosides were analyzed by thin-layer chromatography. Both normal and tumorous lymph node cells had GlcCer, LacCer, and GbOse3Cer as major neutral glycosphingolipids. In the ganglioside fraction, GM3 was the predominant component in both normal and tumorous lymph node cells, and another component, ganglioside Gx fraction, was also prominent in tumorous lymph node cells. The structure of this ganglioside Gx fraction was elucidated by thin-layer chromatography, sugar analysis, neuraminidase digestion, and permethylation studies. This ganglioside Gx fraction was found to be a mixture of four ganglioside species. The structures of individual gangliosides Gx (1 to 4) were characterized as follows. 1: GD3, NeuAc alpha 2-8NeuAc alpha 2-3Gal1-4Glc-Cer. 2: GD3, NeuAc alpha 2-8NeuGc alpha 2-3Gal1-4Glc-Cer. 3: GD3, NeuGc alpha 2-8NeuAc alpha 2-3Gal1-Glc-Cer. 4: GD3, NeuGc alpha 2-8NeuGc alpha 2-3Gal1-4Glc-Cer. These GD3 species may be formed as a result of the induced synthesis inassociation with malignant transformation.


Role of Free Radicals and Biotransformation in Trichloronitrobenzene-Induced Nephrotoxicity In Vitro.
This study determined the comparative nephrotoxic potential of four trichloronitrobenzenes (TCNBs) (2,3,4-; 2,4,5-; 2,4,6-; and 3,4,5-TCNB) and explored the effects of antioxidants and biotransformation inhibitors on TCNB-induced cytotoxicity in isolated renal cortical cells (IRCC) from male Fischer 344 rats. IRCC were incubated with a TCNB up to 1.0 mM for 15-120 min. Pretreatment with an antioxidant or cytochrome P450 (CYP), flavin monooxygenase (FMO), or peroxidase inhibitor was used in some experiments. Among the four TCNBs, the order of decreasing nephrotoxic potential was approximately 3,4,5- > 2,4,6- > 2,3,4- > 2,4,5-TCNB. The four TCNBs exhibited a similar profile of attenuation of cytotoxicity in response to antioxidant pretreatments. 2,3,4- and 3,4,5-TCNB cytotoxicity was attenuated by most of the biotransformation inhibitors tested, 2,4,5-TCNB cytotoxicity was only inhibited by isoniazid (CYP 2E1 inhibitor), and 2,4,6-TCNB-induced cytotoxicity was inhibited by one CYP inhibitor, one FMO inhibitor, and one peroxidase inhibitor. All of the CYP specific inhibitors tested offered some attenuation of 3,4,5-TCNB cytotoxicity. These results indicate that 3,4,5-TCNB is the most potent nephrotoxicant, free radicals play a role in the TCNB cytotoxicity, and the role of biotransformation in TCNB nephrotoxicity in vitro is variable and dependent on the position of the chloro groups.


Fine specificity of autoantibodies to La/SSB: epitope mapping, and characterization.
The B cell epitope mapping of La/SSB was performed using 20mer synthetic peptides overlapping by eight amino acids covering the whole sequence of the protein. IgG, purified from sera of five patients with systemic lupus erythematosus (SLE) and four sera from patients with primary Sjögren's syndrome (pSS) were tested against the overlapping synthetic peptides. Peptides highly reactive with purified IgG were those spanning the regions 145-164, 289-308, 301-320 and 349-368 of the La protein. Determination of the minimum required length of the antigenic determinants disclosed the following epitopes: 147HKAFKGSI154, 291NGNLQLRNKEVT302, 301VTWEVLEGEVEKEALKKI318 and 349GSGKGKVQFQGKKTKF364. Predicted features and molecular similarities of the defined epitopes were investigated using protein databases. The La epitope 147HKAFKGSI154 presented 83.3% similarity with the 139HKGFKGVD146 region of human myelin basic protein (MBP) and 72% similarity with the fragment YKNFKGTI of human DNA topoisomerase II. Peptides corresponding to these sequences cross-reacted with anti-La/SSB antibodies. Sixty-three sera with anti-La/SSB antibodies from patients with pSS or SLE, 35 sera without anti-La/SSB antibodies from patients with SS or SLE and 41 sera from age/sex-matched healthy blood donors were tested against biotinylated synthetic epitope analogues in order to determine their sensitivity and specificity for the detection of anti-La/SSB antibodies. Anti-La/SSB were detected with various frequencies ranging from 20% to epitope 147HKAFKGSI154 to 100% to epitope 349GSGKGKVQGKKTKF364. The overall sensitivity and specificity using all assays with the synthetic peptides were found to be 93.6% and 85.6%, respectively. In conclusion, antibodies to La/SSB constitute a heterogeneous population, directed against different linear B cell epitopes of the molecule. The epitope 147HKAFKGSI154 presents molecular similarity with fragments of two other autoantigens, i.e. human MBP and DNA topoisomerase II. Finally, synthetic epitope analogues exhibit high sensitivity and specificity for the detection of anti-La/SSB antibodies.


[Anti-androgen withdrawal syndrome].
Since the mid-forties androgen deprivation is regarded the standard treatment of incurable prostate cancer. Antiandrogens can be given either as monotherapy or in combination with bilateral orchidectomy or gonadotropin-releasing-hormone analoga. Recently reports have been published that withdrawal of antiandrogens in patients with hormone-resistant prostate cancer caused reduction of PSA and clinical improvement. Thus, in patients who progress under maximal androgen blockade or antiandrogen-monotherapy the antiandrogen should first be withdrawn and-in case of monotherapy-be replaced by GnRH-analoga. In approximately 30-50% of the cases a reduction of serum-PSA can be expected lasting for approx. 6 months. In some patients an improvement of symptoms and objective remission is observed.


The effect of orthostasis on recurrence quantification analysis of heart rate and blood pressure dynamics.
The purpose of this paper is to investigate the effect of orthostatic challenge on recurrence plot based complexity measures of heart rate and blood pressure variability (HRV and BPV). HRV and BPV complexities were assessed in 28 healthy subjects over 15 min in the supine and standing positions. The complexity of HRV and BPV was assessed based on recurrence quantification analysis. HRV complexity was reduced along with the HRV magnitude after changing from the supine to the standing position. In contrast, the BPV magnitude increased and BPV complexity decreased upon standing. Recurrence quantification analysis (RQA) of HRV and BPV is sensitive to orthostatic challenge and might therefore be suited to assess changes in autonomic neural outflow to the cardiovascular system.


The use of MitraClip to prevent posttranscatheter aortic valve replacement left ventricular "suicide".
Patients with concomitant severe aortic stenosis (AS) and left ventricular outflow tract (LVOT) obstruction undergoing transcatheter aortic valve replacement (TAVR) are at risk for hemodynamic collapse due to a sudden decrease in afterload causing worsening LVOT obstruction. We present a case of an 88-year-old female with symptomatic, severe AS, and LVOT obstruction with systolic anterior motion (SAM) of the mitral leaflet in whom alcohol septal ablation was contraindicated secondary to a chronic total occlusion of the right coronary artery that filled retrograde via septal collaterals. MitraClip at the time of TAVR was successfully performed to treat SAM with subsequent stabilization of LVOT gradients despite treatment of the patient's AS. This novel approach may represent a feasible option to prevent hemodynamic complications after TAVR in patients with significant LVOT obstruction secondary to SAM and AS.


A retrospective evaluation of digital wound imaging to predict response to hyperbaric oxygen treatment.
As new wound care treatments become available, correct initial treatment selection and dynamic modification of regimens, based on wound response to treatment, must be applied to improve outcomes and reduce cost. One alternative is wound morphometry using digital wound images to evaluate wound response to treatment in realtime. To determine whether wound area measurements taken during the first 3 weeks of hyperbaric oxygen treatment predict eventual treatment response and how demographic and disease factors impact hyperbaric oxygen treatment response, a retrospective study using digital wound images, demographic data, and available clinical laboratory values was conducted. Participants included 29 wound care patients with nonhealing wounds of the lower extremities receiving treatment at a hyperbaric wound care facility. Conventional wound care (ie, debridement, dressing changes, and topical agents) plus hyperbaric oxygen treatment (100% oxygen breathing at 2.4 atmospheres absolute for 90 minutes) given once every weekday for up to 20 weeks was provided. Graphical analysis of normalized wound area over time revealed two groups: minimal responders (n=13) and robust responders (n=16). Minimal response was characterized by delayed onset of wound area reduction and virtual cessation of reduction by week 3. Robust response was continuous, sustained, and resulted in average wound area reduction of 80% by end of treatment, compared to 47% in minimally responsive patients. Age, blood glucose, and serum creatinine significantly affected the wound healing response to hyperbaric oxygen treatment (P<0.05). Digital images obtained during the first 3 weeks of treatment predicted if a patient is minimally responsive to hyperbaric oxygen treatment with 100% accuracy. Area measurements obtained in this manner can be used to identify patients minimally responsive to hyperbaric oxygen treatment, enabling rapid assessment of treatment response to make timely changes in therapy in order to optimize treatment outcomes.


Smoking status and lipid levels in adults of different ethnic origins: the Jerusalem Lipid Research Clinic Program.
Jerusalem Lipid Research Clinic Program. International Journal of Epidermiology 1984; 13: 177-183. The relationship between cigarette smoking and plasma lipids and lipoproteins was examined in a random sample of 1115 male and 563 female adult participants in the Jerusalem Lipid Research Clinics Program. Differences in plasma lipids and lipoproteins, cigarette smoking, alcohol consumption, and body mass index were demonstrated between the four country of origin groups in both sexes. Using multiple linear regression analysis, an inverse association was shown between smoking and HDL cholesterol, significant only in females (p less than 0.001). Potential confounding variables-Quetelet's index of body mass, alcohol consumption, age, and country of origin groups-revealed only a weak effect on the smoking-HDL-cholesterol association. Examination of an interaction between origin group and smoking showed the same smoking-lipid level association in each of the four country of origin groups, and in both sexes. A strong association was found between smoking and LDL-cholesterol only in females (p less than 0.01). Triglycerides and VLDL-cholesterol showed a weak association with smoking in this study.


Developing an emotional distress item bank for cancer patients.
Emotional distress is common among cancer patients during and after treatment. Many instruments have been used to measure emotional distress; however, none of them has emerged as a standard. Although the diversity of instruments has some merit, the lack of a common measure limits our ability to compare studies. This paper describes how we constructed a 46-item emotional distress bank. Using expert judgment, we selected a pool of items with emotional content from this six-instrument set. Rasch rating scale analysis helped us identify a set of general distress items with good model fit and a measurement gap causing floor effects. Additional items were written to augment the measure where found deficient. The resulting set of items reflects a spectrum of positive and negative affect. The measure demonstrated excellent reliability (person separation reliability = .96) and a wide range of emotional distress and was able to distinguish among levels of disease severity.


Mild dilatation of the fetal kidney: a follow-up study.
To assess morbidity in children with mild prenatally detected pelvicalyceal dilatation and to document the natural history of this ultrasound finding in post-natal life. A retrospective (on-going) study was carried out in 29 children (39 kidneys) with mild dilatation confined to the pelvis and/or calices confirmed on initial post-natal ultrasound scan. Re-evaluation was carried out at a mean age of 4.2 years (range 1.5-7.8). Clinically, each patient's history, height, weight and blood pressure were recorded. On ultrasound examination the renal length, collecting system appearances and dimensions were recorded. Vesico-ureteric reflux was demonstrated in 1 of 14 infants who underwent neonatal micturating cystourethrography. During cumulative follow-up totaling 122 years, there were only two documented episodes of urological morbidity, i.e. one episode of unexplained haematuria and one of urinary tract infection. By a mean age of 4.2 years the ultrasound appearances had reverted to normal in 69% of kidneys. In 31% dilatation persisted and was unchanged or diminished in severity. No case of increasing dilatation was seen. Renal growth was normal in 97% of kidneys. Mild dilatation of the fetal urinary tract is a common prenatal ultrasound finding. When confined to the renal pelvis and/or calices it is of doubtful clinical significance and is associated with a low level of morbidity in infancy and early childhood. Invasive investigation in post-natal life is not justified.


THE EVOLVING GENETIC HISTORY OF A POPULATION OF LATHYRUS SYLVESTRIS: EVIDENCE FROM TEMPORAL AND SPATIAL GENETIC STRUCTURE.
We analyze patterns of genetic microdifferentiation within a natural population of Lathyrus sylvestris, a perennial herb with both sexual reproduction and clonal growth. In a population from the northern foothills of the Pyrénées in southwestern France, a combined demographic and genetic investigation enabled the study not only of spatial genetic structure of the population, but also of the history of the population's spatial genetic structure over time. Excavation of all individuals allowed identification of clonemates. Age of each individual was determined by counting annual growth rings in the taproot, a method tested with individuals of known age planted in experimental gardens. Each individual was mapped, and genotypes of all individuals were determined using allozyme markers for a number of polymorphic loci. Distribution patterns and spatial genetic structure, both for all individuals and for different age classes, were analyzed using spatial autocorrelation statistics (Geary's Index, Moran's Index). Patterns of gene flow within the population were also studied using F-statistics and tests for random associations of alleles. Because age, allele frequencies, and location were known for each individual, it was possible to study how spatial genetic structure changed over time. Results from all these diverse approaches are consistent with one another, and clearly show the following: (1) founder effects, with the study transect being first colonized by individuals at either end of the transect that were homozygous for different alleles at one marker locus; (2) a difference in spatial distribution of individuals originated from sexual reproduction (seedlings) and from clonal growth (connected individuals); (3) restricted gene flow, due to inbreeding among related, clumped individuals; and (4) increase in heterozygote deficit within the youngest cohort of individuals. The results indicate that genetic differentiation in time was much less marked than differentiation in space. Nevertheless, the results revealed that the studied population is experiencing demographic and genetic variation in time, suggesting that it is not at equilibrium. On the one hand, spatial structuring is becoming less marked due to the recombination of founder genotypes; on the other hand, as establishment of new individuals increases, a new spatial structure emerges due to mating between relatives.


Thyroid Dysfunction in Patients with Metabolic Syndrome: A Cross-Sectional, Epidemiological, Pan-India Study.
This study was conducted to assess the prevalence and clinical and epidemiological factors of thyroid dysfunction (TD) in Indian patients diagnosed with metabolic syndrome (MetS). In this cross-sectional study, 432 adults with an established diagnosis of MetS were enrolled across ten centers in India. Anthropometric measurements and vital signs were noted. Blood samples were tested for hemogram, coagulogram, lipid profile, and thyroid function. Fasting plasma glucose (FPG) and fasting plasma insulin were used for the calculation of homeostasis model assessment-estimated insulin resistance (HOMA-IR). Overt hypothyroidism was defined as thyroid-stimulating hormone (TSH) > 4.50 μIU/mL with free thyroxine (FT4) < 0.8 ng/dL and free triiodothyronine (FT3) < 1.4 pg/mL; subclinical hypothyroidism as TSH > 4.50 μIU/mL with FT4 = 0.8-1.8 ng/dL and FT3 = 1.4-4.4 pg/mL; overt hyperthyroidism as TSH < 0.45 μIU/mL with FT4 > 1.8 ng/dL and FT3 > 4.4 pg/mL; and subclinical hyperthyroidism as TSH < 0.45 μIU/mL with FT4 = 0.8-1.8 ng/dL and FT3 = 1.4-4.4 pg/mL. About 121 out of 432 patients (28%) were diagnosed with TD (mean age ± SD: 47.9 ± 10.96 years), with women predominance (75% versus 25%). Most patients were in the >45 years of age group (men: 63%; women: 59%). TD was associated with high waist circumference (99.17%), reduced high-density lipoprotein-C (87.60%), raised HOMA-IR (86.78%), systolic blood pressure (77.69%), diastolic blood pressure (59.50%), fasting glucose (58.68%), and triglycerides (33.06%). Overt hypothyroidism was reported in 17.59% (N = 76) of patients. Subclinical hypothyroidism, overt hypothyroidism, and subclinical hyperthyroidism were reported in 8.10%, 1.60%, and 0.70% patients with newly occurred TD, respectively. No case of overt hyperthyroidism was present in these patients. Hypothyroidism was the most common TD in Indian patients with MetS. A large proportion of TD cases diagnosed during the study highlight the need for vigilant thyroid screening in patients with MetS in a real-life setting.


Identification of a second transforming gene, rasn, in a human multiple myeloma line with a rearranged c-myc allele.
Multiple myeloma is a disease characterized by a long, slowly progressive phase and a final, more aggressive one. Little is known about the mechanism of transformation of myeloma cells, although the clinical characteristics of the disease suggest a multi-step process. Recently, a myeloma cell line, NCI-H929, was isolated from a patient with aggressive preterminal disease and found to have a rearranged myc allele. This myeloma cell line has been further characterized in a focus formation assay to determine whether its unusual growth characteristics were associated with a second activated transforming gene. We now report that the NCI-H929 myeloma cell line has an activated rasn allele in addition to a rearranged myc allele. This is the first identification of an activated transforming gene in a multiple myeloma cell line; furthermore, the characterization of two independently activated oncogenes in this B cell malignancy has implications for both the pathogenesis and evolution of the disease.


Supramolecular architectures in two 1:1 cocrystals of 5-fluorouracil with 5-bromothiophene-2-carboxylic acid and thiophene-2-carboxylic acid.
In solid-state engineering, cocrystallization is a strategy actively pursued for pharmaceuticals. Two 1:1 cocrystals of 5-fluorouracil (5FU; systematic name: 5-fluoro-1,3-dihydropyrimidine-2,4-dione), namely 5-fluorouracil-5-bromothiophene-2-carboxylic acid (1/1), C5H3BrO2S·C4H3FN2O2, (I), and 5-fluorouracil-thiophene-2-carboxylic acid (1/1), C4H3FN2O2·C5H4O2S, (II), have been synthesized and characterized by single-crystal X-ray diffraction studies. In both cocrystals, carboxylic acid molecules are linked through an acid-acid R22(8) homosynthon (O-H...O) to form a carboxylic acid dimer and 5FU molecules are connected through two types of base pairs [homosynthon, R22(8) motif] via a pair of N-H...O hydrogen bonds. The crystal structures are further stabilized by C-H...O interactions in (II) and C-Br...O interactions in (I). In both crystal structures, π-π stacking and C-F...π interactions are also observed.


The effect of surface demineralization of cortical bone allograft on the properties of recombinant adeno-associated virus coatings.
Freeze-dried recombinant adeno-associated virus (rAAV) coated structural allografts have emerged as an approach to engender necrotic cortical bone with host factors that will persist for weeks following surgery to facilitate revascularization, osteointegration, and remodeling. However, one major limitation is the nonporous cortical surface that prohibits uniform distribution of the rAAV coating prior to freeze-drying. To overcome this we have developed a demineralization method to increase surface absorbance while retaining the structural integrity of the allograft. Demineralized bone wafers (DBW) made from human femoral allograft rings demonstrated a significant 21.1% (73.6+/-3.9% versus 52.5+/-2.6%; p<0.001) increase in percent surface area coating versus mineralized controls. Co-incubation of rAAV-luciferase (rAAV-Luc) coated DBW with a monolayer of C3H10T1/2 cells in culture led to peak luciferase levels that were not significantly different from soluble rAAV-Luc controls (p>0.05), although the peaks occurred at 60h and 12h, respectively. To assess the transduction efficiency of rAAV-Luc coated DBW in vivo, we first performed a dose response with allografts containing 10(7), 10(9) or 10(10) particles that were surgically implanted into the quadriceps of mice, and assayed by in vivo bioluminescence imaging (BLI) on days 1, 3, 5, 7, 10, 14, and 21. The results demonstrated a dose response in which the DBW coated with 10(10) rAAV-Luc particles achieved peak gene expression levels on day 3, which persisted until day 21, and was significantly greater than the 10(7) dose throughout this time period (p<0.01). A direct comparison of mineralized versus DBW coated with 10(10) rAAV-Luc particles failed to demonstrate any significant differences in transduction kinetics or efficiency in vivo. Thus, surface demineralization of human cortical bone allograft increases its absorbance for uniform rAAV coating, without affecting vector transduction efficiency.


Activation of the signal transducers and activators of the transcription 3 pathway in alveolar epithelial cells induces inflammation and adenocarcinomas in mouse lung.
The lung is an organ for host defense to clear up pathogens through innate and adaptive immunity. This process involves up-regulation of proinflammatory cytokines and chemokines that lead to activation of the signal transducers and activators of the transcription 3 (Stat3) signaling pathway. Overexpression of Stat3C in alveolar type II epithelial cells of CCSP-rtTA/(tetO)(7)-Stat3C bitransgenic mice leads to severe pulmonary inflammation, including immune cell infiltration and up-regulation of proinflammatory cytokines and chemokines in the lung. As a consequence, spontaneous lung bronchoalveolar adenocarcinoma was observed in bitransgenic mice. Aberrantly expressed genes in the bitransgenic model were identified and served as biomarkers for human bronchoalveolar adenocarcinoma. During tumorigenesis, genes that are critical to epithelial cell proliferation in lung development were reactivated. Therefore, Stat3 is a potent proinflammatory molecule that directly causes spontaneous lung cancer in vivo.


Synthesis and Evaluation of Biological Activity of Antimicrobial--Pro-Proliferative Peptide Conjugates.
Skin represents the largest organ of the human body and plays a crucial role in its protection from the negative impact of the outside environment, maintains its homeostasis, enables sensory interaction and thermoregulation. The traumatized skin tissue undergoes several phenotype switches due to progressive reoxygenation and release of cytokine and growth factors, that activate mechanisms of reparative processes. However, in case of wounds colonized with pathogenic microflora natural regenerative mechanisms become substantially impaired, that could lead to chronic inflammatory states with non-healing skin lesions. Herein, we present the initial results of our studies aimed at the design of bifunctional peptide-based compounds. The chemical approach, that was utilized in this work, was based on the conjugation of antimicrobial peptides with the peptides, that have potential pro-proliferative and/or cytoprotective activity towards human keratinocytes and fibroblasts, in order to obtain antimicrobials with reduced cytotoxicity or compounds that maintain both activities, i.e. inhibit bacterial or fungi growth and activate cell proliferation/migration in in vitro tests. As a result, we obtained a group of peptide conjugates that effectively inhibited the growth of selected bacterial and fungi strains and were able to stimulate proliferation and migration of keratinocytes and fibroblasts under their effective microbicidal concentrations.


Paeoniflorin suppresses neuronal ferroptosis to improve the cognitive behaviors in Alzheimer's disease mice.
Aim of this research was to examine the impact of paeoniflorin (Pae) in suppressing the occurrence of ferroptosis in individuals with Alzheimer's disease (AD). The study utilized APP/PS1 mice with AD as the experimental subjects. Following the administration of Pae, the cognitive behaviors of mice were evaluated and the key indexes of ferroptosis were measured, as well as levels of oxidative stress (OS). For in-vitro experiments, Erastin was adopted for inducing the ferroptosis of PC12 cells, and the level of cell ferroptosis was detected after Pae treatment. Pae improved the cognitive ability of AD mice, reduced the level of ferroptosis, decreased the iron ion and MAD levels in brain tissues, and increased SOD expression. In PC12 cells, Pae suppressed the Erastin-induced ferroptosis, mitigated oxidative damage, and reduced the level of ROS. Based on the findings from our research, it was observed that Pae exhibited a specific binding affinity to P53, leading to the suppression of ferroptosis. This mechanism ultimately resulted in the improvement of nerve injury in mice with AD.


Mitochondrial Division Inhibitor 1 (mdivi-1) Protects Neurons against Excitotoxicity through the Modulation of Mitochondrial Function and Intracellular Ca2+ Signaling.
Excessive dynamin related protein 1 (Drp1)-triggered mitochondrial fission contributes to apoptosis under pathological conditions and therefore it has emerged as a promising therapeutic target. Mitochondrial division inhibitor 1 (mdivi-1) inhibits Drp1-dependent mitochondrial fission and is neuroprotective in several models of brain ischemia and neurodegeneration. However, mdivi-1 also modulates mitochondrial function and oxidative stress independently of Drp1, and consequently the mechanisms through which it protects against neuronal injury are more complex than previously foreseen. In this study, we have analyzed the effects of mdivi-1 on mitochondrial dynamics, Ca2+ signaling, mitochondrial bioenergetics and cell viability during neuronal excitotoxicity in vitro. Time-lapse fluorescence microscopy revealed that mdivi-1 blocked NMDA-induced mitochondrial fission but not that triggered by sustained AMPA receptor activation, showing that mdivi-1 inhibits excitotoxic mitochondrial fragmentation in a source specific manner. Similarly, mdivi-1 strongly reduced NMDA-triggered necrotic-like neuronal death and, to a lesser extent, AMPA-induced toxicity. Interestingly, neuroprotection provided by mdivi-1 against NMDA, but not AMPA, correlated with a reduction in cytosolic Ca2+ ([Ca2+]cyt) overload and calpain activation indicating additional cytoprotective mechanisms. Indeed, mdivi-1 depolarized mitochondrial membrane and depleted ER Ca2+ content, leading to attenuation of mitochondrial [Ca2+] increase and enhancement of the integrated stress response (ISR) during NMDA receptor activation. Finally, lentiviral knockdown of Drp1 did not rescue NMDA-induced mitochondrial fission and toxicity, indicating that neuroprotective activity of mdivi-1 is Drp1-independent. Together, these results suggest that mdivi-1 induces a Drp1-independent protective phenotype that prevents predominantly NMDA receptor-mediated excitotoxicity through the modulation of mitochondrial function and intracellular Ca2+ signaling.


Treatment options and new therapeutic approaches in atopic dermatitis.
Many patients with atopic dermatitis feel that their treatment is ineffective and 25% may be noncompliant with treatments involving corticosteroids. Developing safe and effective pharmacologic alternatives to steroids has presented a challenge to physicians and drug researchers. A new class of nonsteroid immunomodulators, topical calcineurin inhibitors, overcome some of the difficulties and concerns associated with steroid use. The introduction of new drug therapies reinforces the importance of dermatology nursing in managing atopic dermatitis.


Genome-Wide Detection of CNVs and Association With Body Weight in Sheep Based on 600K SNP Arrays.
Copy number variations (CNVs) are important genomic structural variations and can give rise to significant phenotypic diversity. Herein, we used high-density 600K SNP arrays to detect CNVs in two synthetic lines of sheep (DS and SHH) and in Hu sheep (a local Chinese breed). A total of 919 CNV regions (CNVRs) were detected with a total length of 48.17 Mb, accounting for 1.96% of the sheep genome. These CNVRs consisted of 730 gains, 102 losses, and 87 complex CNVRs. These CNVRs were significantly enriched in the segmental duplication (SD) region. A CNVR-based cluster analysis of the three breeds revealed that the DS and SHH breeds share a close genetic relationship. Functional analysis revealed that some genes in these CNVRs were also significantly enriched in the olfactory transduction pathway (oas04740), including members of the OR gene family such as OR6C76, OR4Q2, and OR4K14. Using association analyses and previous gene annotations, we determined that a subset of identified genes was likely to be associated with body weight, including FOXF2, MAPK12, MAP3K11, STRBP, and C14orf132. Together, these results offer valuable information that will guide future efforts to explore the genetic basis for body weight in sheep.


Usage and cost of first-line drugs for patients referred to inpatient anthroposophic integrative care or inpatient conventional care for stress-related mental disorders--a register based study.
Stress-related mental disorders (SRMD) are common and costly. Rehabilitation strategies, including pharmacotherapy, may be complicated to evaluate. Previous research has indicated increased quality of life and self-rated health for SRMD patients that receive a combination of conventional and complementary therapies, i.e. integrative care. The aim of this retrospective registry study was to explore and contrast the prescription of first-line drugs for SRMD patients referred to hospital inpatient anthroposophic integrative care (AIC) or inpatient conventional care (CC). SRMD patients that had received AIC or CC were identified through high-quality inpatient registry data from Stockholm County Council and matched by available background characteristics including diagnosis (ICD-10: F43), age, gender and socio-economics. General disease load was estimated by analysis of ICD-10 chapter data. The Swedish Prescribed Drug Register was then used to investigate purchased defined daily doses (DDD) and cost of drugs from 90-days before/after, and 180-days before/after, the first visits (index) to AIC and CC respectively. First-line drug categories were Anatomical Therapeutic Chemical classification codes N05A (antipsychotics), N05B (anxiolytics), N05C (hypnotics and sedatives) and N06A (antidepressants). There were no statistically significant differences between the AIC (n = 161) and the CC (n = 1571) cohorts in terms of background characteristics and the overall disease loads were similar between the groups the preceding year. At baseline, the prescription of first-line anxiolytics and antidepressants were not statistically different between groups whereas the prescription of antipsychotics and hypnotics/sedatives were lower for the AIC cohort. The overall change in drug prescriptions and costs during the investigated periods, both for the 90-days before/after and for the 180-days before/after the index visit, showed a general decrease within the AIC cohort with significantly less prescribed anxiolytics and hypnotics/sedatives. During the same time periods there was a general increase in prescriptions and costs of first-line drugs within the CC cohort. The overall disease loads were generally stable within both cohorts over time, except that the CC cohort had increased visits registered with an ICD-10 F-chapter diagnosis the year after index. The results suggests that there may be different drug utilization patterns for SRMD patients referred to AIC or CC. Different management strategies between AIC and CC providers, different SRMD disease severities and different preferences of patients referred to AIC and CC are hypothetical differentiating factors that may influence drug outcomes over time. Additional studies including prospective and randomized clinical trials are warranted to determine if there is a causal link between inpatient AIC and reduced drug utilization.


Modeling the electrophoretic mobility of analytes in binary solvent electrolyte systems in capillary electrophoresis using an artificial neural network.
An artificial neural network (ANN) methodology was used to model the electrophoretic mobility of basic analytes in binary solvent electrolyte systems. The electrophoretic mobilities in pure solvent electrolytes, and the volume fractions of the solvents in mixtures were used as input. The electrophoretic mobilities in mixed solvent buffers were employed as the output of the network. The optimized topology of the network was 3-3-1. 32 experimental mobility data sets collected from the literature were employed to test the correlation ability and prediction capability of the proposed method. The mean percentage deviation (MPD) between the experimental and calculated values was used as an accuracy criterion. The MPDs obtained for different numerical analyses varied between 0.21% and 13.74%. The results were also compared with similar calculated mobilities which were derived from the best multiple linear model from the literature. From these results it was found that the ANN methodology is superior to the multiple linear model.


The myocardium and brain SPECT findings in organophosphate poisoning.
A case of organophosphate poisoning is presented by using Tc-99m HMPAO (hexamethyl propylenamine oxime) brain SPECT (single photon emission computer tomography) and Tc-99m Sestamibi myocardial SPECT findings in the acute recovery and delayed phases. On the 4th day, brain SPECT imaging showed the perfusion defects in the left parietal lobe of the brain. On the 5th day myocardium scintigraphy also revealed the anterolateral wall perfusion defect. The myocardial defect became more prominent but brain defect was smaller than before, on the 19th day of the therapy. Two months later, on the third examinations of the brain and myocardium, their imagings were both normal.


Effect of vitamin C supplementation on concentrations of vitamins C and E in fasting plasma.
Vitamin C may 'spare' vitamin E, but this has not to date been confirmed as occurring in vivo. The aim of this study was to test the effect of dietary supplementation with vitamin C on total and lipid standardised vitamin E concentrations in fasting plasma, the hypothesis being that increased vitamin C intake leads to improved vitamin E levels. In this single-blinded study, 12 apparently healthy adults (seven men, five women) took 1 g/day vitamin C for 28 days, with a 28-day placebo-controlled run-in cycle and a 28-day placebo-controlled washout cycle. Concentrations of ascorbic acid, total vitamin E (as total tocopherols) and lipid standardised vitamin E (Vit ELS, expressed as mol vitamin E/mmol total cholesterol plus triglycerides) were measured in fasting plasma after each cycle. Results showed that vitamin C supplementation led to significant increases in ascorbic acid, total vitamin E and Vit ELS. These findings indicate that, by a combination of a vitamin E 'sparing' effect perhaps via improved redox recycling of vitamin E in vivo and a lipid lowering effect, increased intake of vitamin C could increase plasma vitamin E levels, and possibly vitamin E status. Further study of possible in vivo interrelationships between vitamins C and E, and the role of vitamin C in lipid metabolism, is needed.


Cefazolin Prophylaxis for Total Joint Arthroplasty: Obese Patients Are Frequently Underdosed and at Increased Risk of Periprosthetic Joint Infection.
One of the most effective prophylactic strategies against periprosthetic joint infection (PJI) is administration of perioperative antibiotics. Many orthopedic surgeons are unaware of the weight-based dosing protocol for cefazolin. This study aimed at elucidating what proportion of patients receiving cefazolin prophylaxis are underdosed and whether this increases the risk of PJI. A retrospective study of 17,393 primary total joint arthroplasties receiving cefazolin as perioperative prophylaxis from 2005 to 2017 was performed. Patients were stratified into 2 groups (underdosed and adequately dosed) based on patient weight and antibiotic dosage. Patients who developed PJI within 1 year following index procedure were identified. A bivariate and multiple logistic regression analyses were performed to control for potential confounders and identify risk factors for PJI. The majority of patients weighing greater than 120 kg (95.9%, 944/984) were underdosed. Underdosed patients had a higher rate of PJI at 1 year compared with adequately dosed patients (1.51% vs 0.86%, P = .002). Patients weighing greater than 120 kg had higher 1-year PJI rate than patients weighing less than 120 kg (3.25% vs 0.83%, P < .001). Patients who were underdosed (odds ratio, 1.665; P = .006) with greater comorbidities (odds ratio, 1.259; P < .001) were more likely to develop PJI at 1 year. Cefazolin underdosing is common, especially for patients weighing more than 120 kg. Our study reports that underdosed patients were more likely to develop PJI. Orthopedic surgeons should pay attention to the weight-based dosing of antibiotics in the perioperative period to avoid increasing risk of PJI.


Roles of membrane structure and phase transition on the hyperosmotic stress survival of Geobacter sulfurreducens.
Geobacter sulfurreducens is a delta-proteobacterium bacteria that has biotechnological applications in bioremediation and as biofuel cells. Development of these applications requires stabilization and preservation of the bacteria in thin porous coatings on electrode surfaces and in flow-through bioreactors. During the manufacturing of these coatings the bacteria are exposed to hyperosmotic stresses due to dehydration and the presence of carbohydrates in the medium. In this study we focused on quantifying the response of G. sulfurreducens to hyperosmotic shock and slow dehydration to understand the hyperosmotic damage mechanisms and to develop the methodology to maximize the survival of the bacteria. We employed FTIR spectroscopy to determine the changes in the structure and the phase transition behavior of the cell membrane. Hyperosmotic shock resulted in greatly decreased membrane lipid order in the gel phase and a less cooperative membrane phase transition. On the other hand, slow dehydration resulted in increased membrane phase transition temperature, less cooperative membrane phase transition and a small decrease in the gel phase lipid order. Both hyperosmotic shock and slow dehydration were accompanied by a decrease in viability. However, we identified that in each case the membrane damage mechanism was different. We have also shown that the post-rehydration viability could be maximized if the lyotropic phase change of the cell membrane was eliminated during dehydration. On the other hand, lyotropic phase change during re-hydration did not affect the viability of G. sulfurreducens. This study conclusively shows that the cell membrane is the primary site of injury during hyperosmotic stress, and by detailed analysis of the membrane structure as well as its thermodynamic transitions it is indeed possible to develop methods in a rational fashion to maximize the survival of the bacteria during hyperosmotic stress.


Antigenic Variation in H5N1 clade 2.1 Viruses in Indonesia From 2005 to 2011.
Influenza A (H5N1) virus, has spread to several countries in the world and has a high mortality rate. Meanwhile, the virus has evolved into several clades. The human influenza A (H5N1) virus circulating in Indonesia is a member of clade 2.1, which is different in antigenicity from other clades of influenza A (H5N1). An analysis of the antigenic variation in the H5 hemagglutinin gene (HA) of the influenza A (H5N1) virus strains circulating in Indonesia has been undertaken. Several position of amino acid mutations, including mutations at positions 35, 53, 141, 145, 163, 174, 183, 184, 189, and 231, have been identified. The mutation Val-174-Iso appears to play an important role in immunogenicity and cross-reactivity with rabbit antisera. This study shows that the evolution of the H5HA antigenic variation of the influenza A (H5N1) virus circulating in Indonesia from 2005 to 2011 may affect the immunogenicity of the virus.