Proximal lower extremity chronic venous outflow obstruction: recognition and treatment.
As postthrombotic disease becomes better understood, the importance of venous outflow obstruction is recognized increasingly. It appears that obstruction of the iliac vein is particularly important and results in more severe symptoms than more distal segmental blockages. Unfortunately, no accurate invasive or noninvasive test for the evaluation of obstruction is available. In fact, it is not known what degree of venous stenosis should be considered hemodynamically "critical." Thus, currently it is impossible to detect borderline obstructions of potential hemodynamic significance. A high index of suspicion must be maintained. The diagnosis relies on clinical signs and symptoms, and treatment must be based on results of morphologic investigations such as transfemoral phlebography or, preferably, intravascular ultrasonography. Percutaneous iliac venous balloon dilation and insertion of a stent offers a safe and efficient method to correct pelvic venous obstruction. It is less invasive and relatively safer than open surgery and can, therefore, be offered to a larger group of patients. Furthermore, initial percutaneous management does not preclude subsequent bypass or reflux surgery. Although the technique is recent and follow-up relatively short, there is cautious optimism that this treatment will be useful and replace bypass surgery for iliac venous obstruction.


Design, synthesis, and pharmacological evaluation of N-bicyclo-5-chloro-1H-indole-2-carboxamide derivatives as potent glycogen phosphorylase inhibitors.
As a result of the various N-bicyclo-5-chloro-1H-indole-2-carboxamide derivatives with a hydroxy moiety synthesized in an effort to discover novel glycogen phosphorylase (GP) inhibitors, 5-chloro-N-(5-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl)-1H-indole-2-carboxamide (5b) was found to have potent inhibitory activity. The introduction of fluorine atoms both at a position adjacent to the hydroxy group and in the central benzene moiety lead to the optically active derivative 5-chloro-N-[(5R)-1,3,6,6-tetrafluoro-5-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl]-1H-indole-2-carboxamide (25e(alpha), which was the most potent compound in this series (IC(50)=0.020microM). This compound inhibited glucagon-induced glucose output in cultured primary hepatocytes with an IC(50) value of 0.69microM, and showed oral hypoglycemic activity in diabetic db/db mice at 10mg/kg. Compound 25e(alpha) also had an excellent pharmacokinetic profile, with high oral bioavailability and a long plasma half-life, in male SD rats. The binding mode of 25e(alpha) to this molecule and the role of fluorine atoms in that binding were speculated in an enzyme docking study.


Hemoglobin concentration of pastoral nomads permanently resident at 4,850-5,450 meters in Tibet.
This paper presents data on the hemoglobin concentration of a sample of 103 pastoral nomads who are lifelong residents of Phala, at 4,850-5,450 m, on the northern plateau of the Tibet Autonomous Region of the Peoples' Republic of China. This native population resides at the highest altitude of which we are aware and is thus exposed to the most extreme chronic hypoxic stress. However, they do not exhibit the most pronounced physiological adaptations, i.e., hemoglobin concentrations exceeding those found in all other high-altitude populations. Adult male and female mean hemoglobin concentrations of 18.2 and 16.7 gm/dl, respectively, were found. These data, in conjunction with earlier studies of ethnic Tibetans living at 3,400 m, demonstrate a pattern of increasing hemoglobin concentration (erythrocytosis) at increasing altitude of residence in the Himalayas and Tibet. At the same time, however, the hemoglobin concentration is lower than that found among Andean highlanders. These new data raise the possibility of quantitative population differences in hematological adaptation to high altitude hypoxia.


Vascularized urethroplasty flaps. The use of vascularized flaps of preputial and penopreputial skin for urethral reconstruction in hypospadias.
The long-term growth potential offered by vascularized urethroplasty flaps has allowed the author to operate on patients with hypospadias between 8 months and 2 years of age with excellent morphofunctional and psychological results and a short hospitalization. The author argues that the one-stage procedure is the best approach, supported by an analysis of more than 5000 cases treated in the Plastic Surgery Department of the Bambino Gesù Hospital in Rome since 1972.


Early postoperative prediction of cerebral damage after pediatric cardiac surgery.
Cerebral damage is a serious complication of pediatric cardiac surgery. Early prediction of actual risk can be useful in counseling of parents, and in early diagnosis and rehabilitation therapy. Also, if all children at risk could be identified therapeutic strategies to limit perioperative cerebral damage might be developed. The aim of this study is to create a mathematical model to predict risk of neurologic sequelae within 24 hours after surgery using simple and readily available clinical measurements. The hospital records of 534 children after cardiac surgery were reviewed. Variables examined were age at operation, diagnosis, use of cardiopulmonary bypass, arterial and central venous oxygen saturation, serum glucose, lactate and creatine kinase, mean arterial pressure, and body temperature. The endpoint for each study patient was the occurrence or lack of occurrence of seizures, movement or developmental disorders, cerebral hemorrhage, infarction, hydrocephalus, or marked cerebral atrophy. Univariate and multivariate regression analyses were used to evaluate the predictive power of the investigated factors as well as to create a predictive model. In 6.26% of children symptoms of cerebral damage were found. Significant risk factors were age at surgery, more complex malformations, metabolic acidosis, and increased lactate (odds ratio: age, 0.882/yr [0.772-1.008]; complex malformations, 10.32 [1.32-80.28]; arterial pH more than 7.35 to 0.4 [0.18-0.89]; lactate -1.018 per mg/dL [1.006-1.03]). It is possible to quantify the risk of appearance of symptoms of cerebral damage after cardiac surgery within 24 hours using simple and readily available clinical measurements.


Do responsive sleep interventions impact mental health in mother/infant dyads compared to extinction interventions? A pilot study.
Methods to improve sleep in infants commonly involve some ignoring (extinction) but are often unpopular with mothers worried about infant distress when left to cry. Alternative more responsive methods are needed. This pilot study evaluated stress, maternal depressive symptomology and sleep in mother/infant dyads, between Responsive, Controlled Crying and Control groups. From 199 mother/infant dyads from any cultural background, 41 infants 4-12 months were randomly allocated to Responsive (RG, n = 15), Controlled Crying (CCG, n = 18) or Controls (Treatment as Usual, TAUG, n = 8), with 10 withdrawing after randomisation. Infant sleep (7-day sleep diaries) and stress (oral cortisol on two nights), maternal self-reported stress (Subjective Units of Distress, SUDS), maternal perceived infant distress (MPI-S) and symptoms of maternal depression (Edinburgh Post-natal Depression Scale, EPDS) were measured four times across 8 weeks. Sleep duration was not different between groups but Responsive woke less (p = .008). There were no differences in cortisol between groups across time points. Maternal SUDS was positively correlated with infant cortisol and MPI-S (p < 0.05) and mothers in the Responsive group were significantly less stressed (p = 0.02) and reported less symptoms of depression (p < 0.05). Findings in this small sample show Responsive methods are comparable to the extinction (Controlled Crying) in sleep outcomes but from a relational and maternal mental health perspective, are less stressful, offering families potential choices of sleep interventions.


Bone substitute biomedical material of multi-(amino acid) copolymer: in vitro degradation and biocompatibility.
Degradable polymers with good mechanical strength as bone repair biomaterials have been paid more attention in biomedical application. In this study, a multi-(amino acid) copolymer consisting of 6-aminocaproic acid and five natural amino acids was prepared by a reaction of acid-catalyzed condensation. The results revealed that the copolymer could be slowly degradable in Tris-HCl solution, and lost its initial weight of 31.9 wt% after immersion for 12 weeks, and the changes of pH value of Tris-HCl solution were in range from 6.9 to 7.4 during soaking. The compressive strength of the copolymer decreased from 107 to 68 MPa after immersion for 12 weeks. The proliferation and differentiation of MG-63 cells on the copolymer significantly increased with time, and the cells with normal phenotype extended and spread well on the copolymer surfaces. When the copolymer was implanted in muscle and bone defects of femoral cortex of dogs for 12 weeks, the histological evaluation confirmed that the copolymer exhibited excellent biocompatibility and more effective osteogenesis in vivo. When implanted into cortical bone defects of dogs, the copolymer could be combined directly with the natural bone without fibrous capsule tissue between implants and host bone. The results indicated that the multi-(amino acid) copolymer with sufficient strength, good biocompatibility and osteoconductivity had clinical potential for load-bearing bone repair or substitution.


Syntheses of 3-ethylidenequinuclidine derivatives as squalene synthase inhibitors. Part 2: enzyme inhibition and effects on plasma lipid levels.
Squalene synthase (E.C. 220.127.116.11) is a microsomal enzyme which catalyzes the reductive dimerization of two molecules of farnesyl diphosphate to form squalene, and is involved in the first committed step in cholesterol biosynthesis. It is an attractive target for hypocholesterolemic and hypotriglyceridemic strategies. We synthesized a series of 3-ethylidenequinuclidine derivatives, and evaluated their ability to inhibit squalene synthase in vitro and to lower non-HDL cholesterol levels in hamsters. 3-Ethylidenequinuclidine derivatives incorporating an unsubstituted 9H-carbazole moiety reduced plasma non-HDL cholesterol levels and did not affect plasma transaminase levels, indicating a lack of hepatotoxicity. Among the novel compounds, (Z)-2-[2-(quinuclidin-3-ylidene)ethoxy]-9H-carbazole hydrochloride 8 (YM-53579) and (E)-2-[2-fluoro-2-(quinuclidin-3-ylidene)ethoxy]-9H-carbazole hydrochloride 28 (YM-53601) were potent inhibitors of squalene synthase derived from human hepatoma cells, with IC(50) values of 160 and 79 nM, respectively. They also reduced plasma non-HDL cholesterol levels in hamsters by approximately 50 and 70%, respectively, at an oral dose of 50 mg/kg/day for 5 days.


Relationship Between Cesarean Delivery Rate and Maternal and Neonatal Mortality.
Based on older analyses, the World Health Organization (WHO) recommends that cesarean delivery rates should not exceed 10 to 15 per 100 live births to optimize maternal and neonatal outcomes. To estimate the contemporary relationship between national levels of cesarean delivery and maternal and neonatal mortality. Cross-sectional, ecological study estimating annual cesarean delivery rates from data collected during 2005 to 2012 for all 194 WHO member states. The year of analysis was 2012. Cesarean delivery rates were available for 54 countries for 2012. For the 118 countries for which 2012 data were not available, the 2012 cesarean delivery rate was imputed from other years. For the 22 countries for which no cesarean rate data were available, the rate was imputed from total health expenditure per capita, fertility rate, life expectancy, percent of urban population, and geographic region. Cesarean delivery rate. The relationship between population-level cesarean delivery rate and maternal mortality ratios (maternal death from pregnancy related causes during pregnancy or up to 42 days postpartum per 100,000 live births) or neonatal mortality rates (neonatal mortality before age 28 days per 1000 live births). The estimated number of cesarean deliveries in 2012 was 22.9 million (95% CI, 22.5 million to 23.2 million). At a country-level, cesarean delivery rate estimates up to 19.1 per 100 live births (95% CI, 16.3 to 21.9) and 19.4 per 100 live births (95% CI, 18.6 to 20.3) were inversely correlated with maternal mortality ratio (adjusted slope coefficient, -10.1; 95% CI, -16.8 to -3.4; P = .003) and neonatal mortality rate (adjusted slope coefficient, -0.8; 95% CI, -1.1 to -0.5; P < .001), respectively (adjusted for total health expenditure per capita, population, percent of urban population, fertility rate, and region). Higher cesarean delivery rates were not correlated with maternal or neonatal mortality at a country level. A sensitivity analysis including only 76 countries with the highest-quality cesarean delivery rate information had a similar result: cesarean delivery rates greater than 6.9 to 20.1 per 100 live births were inversely correlated with the maternal mortality ratio (slope coefficient, -21.3; 95% CI, -32.2 to -10.5, P < .001). Cesarean delivery rates of 12.6 to 24.0 per 100 live births were inversely correlated with neonatal mortality (slope coefficient, -1.4; 95% CI, -2.3 to -0.4; P = .004). National cesarean delivery rates of up to approximately 19 per 100 live births were associated with lower maternal or neonatal mortality among WHO member states. Previously recommended national target rates for cesarean deliveries may be too low.


Formulation and characterization of lipid-based drug delivery system of raloxifene-microemulsion and self-microemulsifying drug delivery system.
Raloxifene, a second-generation selective estrogen receptor modulator (SERM) used to prevent osteoporosis in postmenopausal women is administered orally in the form of a tablet. The absolute bioavailability of the drug is only 2% because of extensive hepatic first-pass metabolism. Lipid-based formulations are reported to reduce the first-pass metabolism by promoting its lymphatic uptake. In the present investigation, microemulsion and Self-Microemulsifying Drug Delivery System (SMEDDS) formulations of Raloxifene were prepared. The prepared formulations were characterized for drug loading, size, transparency, zeta potential, Transmission Electron Microscopy (TEM) and in vitro intestinal permeability. The results indicated that high drug loading, optimum size and desired zeta potential and transparency could be achieved with both SMEDDS and microemulsion. The TEM studies indicated the absence of aggregation with both the systems. The in vitro intestinal permeability results showed that the permeation of the drug from the microemulsion and SMEDDs was significantly higher than that obtained from the drug dispersion and marketed formulation. Lipid based formulations such as microemulsion and Self Microemulsifying drug delivery systems are expected to increase the oral bioavailability as evidenced by the increased intestinal permeation.


Expression of intermediate filaments in different human epithelial and mesenchymal tumors.
Fifty primary gastrointestinal and breast carcinomas, four embryonal rhabdomyosarcomas, six nonmuscular mesenchymal malignant tumors and one mesothelioma have been studied to determine what type of intermediate filaments they express, using affinity purified antibodies to prekeratin, vimentin and desmin and FITC or peroxidase labeled second antibodies. The tissues were alcohol fixed and paraffin embedded before use. In all carcinoma cases the tumor cells are stained by antibodies to prekeratin, while the vimentin antibody only decorates the stroma. Prekeratin positive tumor cells are not only seen in well differentiated tumors, but also in signet ring cell carcinomas. In the case of rhabdomyosarcoma the tumor cells clearly were decorated by antibodies to desmin, while the vimentin antibody only stained very few tumor cells. In cases of nonmuscular mesenchymal tumors, the tumor cells could only be labeled by antibodies to vimentin and not by antibodies to prekeratin or desmin. In biphasic tumors like mesothelioma, different parts of the tumor were separated by antibodies to prekeratin and vimentin.


HDAC1 inhibits beige adipocyte-mediated thermogenesis through histone crotonylation of Pgc1a/Ucp1.
Obesity, one of the most serious public health issues, is caused by the imbalance of energy intake and energy expenditure. Increasing energy expenditure via induction of adipose tissue browning has become an appealing strategy to treat obesity and associated metabolic complications. Although histone modifications have been confirmed to regulate cellular energy metabolism, the involved biochemical mechanism of thermogenesis in adipose tissue is not completely understood. Herein, we report that class I histone deacetylases (HDAC) inhibitor MS275 increased PGC1α/UCP1 protein levels in inguinal white adipose tissue (iWAT) concomitant with elevated energy expenditure, reduced obesity and ameliorated glucose tolerance compared to control littermates. H3K18cr and H3K18ac levels were elevated after MS275 treatment. MS275 also promoted the transcription of Pgc1α and Ucp1 by enhancing the enrichment of H3K18cr and H3K18ac in the Pgc1α/Ucp1 enhancer and promoter, with a notable increase in H3K18cr. Mechanistically, the deletion of Hdac1 in beige adipocyte increases H3K18cr levels in enhancers and promoters of Pgc1α and Ucp1 genes, regulated the chromosomal state, thereby affecting the transcription of Pgc1α/Ucp1. Taken together, HDAC1 inhibits beige adipocyte-mediated thermogenesis through histone crotonylation of Pgc1a/Ucp1. This finding may provide a therapeutic strategy through increasing energy expenditure in obesity and related metabolic disorders.


Cardiovascular risk factors and disease among non-European immigrants living in Catalonia.
To describe the prevalence and incidence of cardiovascular risk factors, established cardiovascular disease (CVD) and cardiovascular medication use, among immigrant individuals of diverse national origins living in Catalonia (Spain), a region receiving large groups of immigrants from all around the world, and with universal access to healthcare. We conducted a population-based analysis including >6 million adult individuals living in Catalonia, using the local administrative healthcare databases. Immigrants were classified in 6 World Bank geographic areas: Latin America/Caribbean, North Africa/Middle East, sub-Saharan Africa, East Asia and South Asia. Prevalence calculations were set as of 31 December 2017. Immigrant groups were younger than the local population; despite this, the prevalence of CVD risk factors and of established CVD was very high in some immigrant subgroups compared with local individuals. South Asians had the highest prevalence of diabetes, and of hyperlipidemia among adults aged <55 years; hypertension was highly prevalent among sub-Saharan Africans, and obesity was most common among women of African and South Asian ancestry. In this context, South Asians had the highest prevalence of coronary heart disease across all groups, and of heart failure among women. Heart failure was also highly prevalent in African women. The high prevalence of risk factors and established CVD among South Asians and sub-Saharan Africans stresses the need for tailored, aggressive health promotion interventions. These are likely to be beneficial in Catalonia, and in countries receiving similar migratory fluxes, as well as in their countries of origin.


A new procedure to reinforce fixed provisional restorations.
The typical unreinforced fixed partial denture provisional restoration commonly fails because of fractures and loss of cement retention. A procedure to reinforce the provisional restoration with a substructure of orthodontic band material has dramatically increased the longevity of this restoration. The procedure requires commonly available materials without a significant increase in cost or construction time.


The relationship between automatic thoughts and depression in a cognitive-behavioral treatment for people living with HIV/AIDS: Exploring temporality and causality.
Depression in people living with HIV/AIDS (PLWHA) is highly prevalent and related to worse adherence to antiretroviral therapy, but is amenable to change via CBT. Cognitive-behavioral therapy for adherence and depression (CBT-AD) specifically addresses negative automatic thoughts (ATs) as one component of the treatment. There is little research on the temporal nature of the relation between ATs and depression. HIV-positive adults with depression (N=240) were randomized to CBT-AD, information/supportive psychotherapy for adherence and depression (ISP-AD), or one session of adherence counseling alone (ETAU). ATs were self-reported (Automatic Thoughts Questionnaire; ATQ) and depression was assessed by blinded interview (Montgomery-Asberg Depression Rating Scale; MADRS) at baseline, and 4-, 8-, and 12-months. We performed autoregressive cross-lagged panel models. Broadly, decreases in ATs were followed by decreases in depression, but decreases in depression were not followed by decreases in ATs. In CBT-AD, decreases in ATs were followed by decreases in depression, and vice versa. However, in the ISP group, while depression and ATs both significantly influenced each other, not all relations were in the direction expected. This study adds to the evidence base for cognitive interventions to decrease depression in individuals with a chronic medical condition, HIV/AIDS.


Tracking Changes of Social Distancing in the United States of America after Outbreak of Coronavirus Disease (COVID-19) at the Early Stage.
This research examines social distancing changes over time, and by region of the United States after the COVID-19 pandemic began. We utilized information on social distancing from the Google Community Mobility Reports. We performed one-way repeated-measure analysis of variance (RM-ANOVA) to examine the overall changes in the 6 types of social distancing from baseline to the 12-week follow-up (March 1 to May 24, 2020). We applied a 2-way RM-ANOVA to evaluate the effects of time and 4 regions on social distancing. According to one-way RM-ANOVA results, social distancing tended to increase until Time 3 (March 30 to April 12) and 4 (April 13 to April 26), before decreasing again, regardless of the area. The 2-way RM-ANOVA results revealed that the social distancing variations in the 6 area types over time were statistically significant in each region, along with the interaction of regions and time. Compared to other regions, social distancing was the highest in the Northeast area, except in park areas. We found that social distancing can be influenced not only by contagion changes, but also by regional differences. Understanding the features of social distancing can play a significant role in helping society build a promising COVID-19 prevention model.


Platelet activity measured by a rapid turnaround assay identifies coronary artery bypass grafting patients at increased risk for bleeding and transfusion complications after clopidogrel administration.
We sought to establish a metric for easily estimating bleeding and transfusion risks for cardiac surgery patients after antiplatelet agent use. Deidentified records of patients who underwent coronary artery bypass grafting (CABG) at our institution (January 2010-June 2011) were searched for patients without identified risk factors for excessive bleeding who underwent documented P2Y12 testing after clopidogrel administration (n = 276). Clinical outcomes were analyzed according to whether preoperative platelet function was higher (platelet reactivity units [PRUs], ≥237) or lower (PRU, <237) and according to preoperative PRU cutoffs: high (>290, or no clopidogrel), intermediate (200-290), or low (<200). Eighty-five patients (57%) received allogeneic blood products at 24 hours or less postoperatively: 33 (22%) received fresh frozen plasma, and 57 (38%) received platelets. The median 12-hour chest tube output (CTO) was 350 mL (interquartile range, 260-490 mL); CTO was "high" (>437 mL) in 62 (42%) of the clopidogrel-treated patients. Lower-PRU patients were more likely to receive coagulation factors (odds ratio [OR], 2.82; P = .0004) and to have high CTO or coagulation factor transfusion (OR, 2.35; P = .02) than higher-PRU patients. Likewise, intermediate- and low-PRU patients had incrementally greater incidences of high CTO (OR, 1.72; P = .002) and coagulation factor transfusion (OR, 2.08; P < .0001) than high-PRU/no clopidogrel patients. High CTO or coagulation factor transfusion was more frequent in intermediate-PRU (OR, 2.67; P = .02) and low-PRU (OR, 5.08; P = .0002) patients than in high-PRU/no clopidogrel patients. Among clopidogrel-treated CABG patients, preoperative platelet function testing can identify those at increased risk for postoperative bleeding and transfusion.


Mechanochemically synthesized silicotungsten acidified ZVI composite for persulfate activation: Enhancement of the electron transfer and Fe slowly release mechanism.
Zero-valent iron (ZVI) is a promising technology for groundwater treatment, and its efficiency primarily depends on the electron transfer. However, there are still some problems such as low electron efficiency of ZVI particles and high yield of iron sludge that limits the performance, which warrant further investigation. In our study, a silicotungsten acidified ZVI composite (m-WZVI) was synthesized by ball milling to activate PS to degrade phenol. m-WZVI has a better performance on phenol degradation (with a removal rate of 91.82%) than ball mill ZVI(m-ZVI) with persulfate (PS) (with a removal rate of 59.37%). Compared with m-ZVI, the first-order kinetic constant (kobs) of m-WZVI/PS is 2-3 times higher than that of the others. Iron ion was gradually leached in m-WZVI/PS system, being only 2.11 mg/L after 30 min, having to avoid excessive consumption of active substances. The underlying mechanisms of m-WZVI for PS activation mainly include: 1) were elucidated through different characterizations analyses that accounted for silictungstic acid (STA) can be combined with ZVI, and a new electron donor (SiW124-) was obtained, which improved the transfer rate performance of electrons for activating PS; 2) singlet oxygen (1O2) is the main active substance for phenol degradation, but other radicals also played an important role. Therefore, m-WZVI has good prospects for improving the electron utilization of ZVI.


Civil commitment practices in 1977: troubled semantics and/or troubled psychiatry.
This paper examines the practice of involuntary mental hospitalization through examination of criteria used for committment in a sample of 200 civil commitment certificates. Special reference is made, following previous research, to criteria used to describe the person deemed dangerous to himself or to others. The relevance of the findings of present practices in mental health is discussed. New procedures which facilitate presentation of factual evidence, and which eliminate gratuitous information, are required without delay.


Serum folate associated with nonalcoholic fatty liver disease and advanced hepatic fibrosis.
The role played by serum folate in the progression of nonalcoholic fatty liver disease (NAFLD) remains controversial. The purpose of this study was to investigate the association of serum folate with NAFLD and advanced liver fibrosis (AHF). We conducted a cross-sectional study with 5417 participants using 2011-2018 NHANES data. Multiple logistic regression analysis and propensity score matching analysis were used to investigate the association of serum folate with NAFLD and AHF. In the completely adjusted model, participants in the high serum folate group had a 27% (OR 0.73, 95% CI 0.62, 0.87, p = 0.0003) and 53% (OR 0.47, 95% CI 0.35, 0.63, p < 0.0001) lower odds of suffering from NAFLD and AHF, respectively, compared to the low serum folate group. The similar results in propensity score matching further validated the above association. Stratified analysis showed that the negative correlation of serum folate with NAFLD and AHF demonstrated a broad consistency across populations. The results of this study indicate that higher serum folate level was associated with lower odds of NAFLD and AHF among US adults. Further prospective studies are necessary due to the limitations of cross-sectional studies.


SR57746A: a survival factor for motor neurons in vivo.
SR57746A(1-[2-(naphth-2-yl)ethy]]-4-(3-trifluoromethyl phenyl)-1,2,5,6-tetrahydropyridine, hydrochloride) is a non-peptide compound which has been shown to exhibit a wide range of neurotrophic effects both in vitro and in vivo. Here we examine the ability of SR57746A on axotomized spinal motor neuron death in the developing rat spinal cord. After postnatal unilateral section of rat sciatic nerve, there was approximately a 50% survival of motor neurons in the fourth lumbar segment (L4). Intraperitoneal injection of SR57746A for consecutive 14 days rescued motor neuron death but did not preserve the motor neuron diameter both on axotomy and non-axotomy side. These results suggest that SR57746A is a survival factor for motor neurons in vivo and may serve as therapeutic agent for damaged motor neurons.


Biomagnetic measurements of spontaneous brain activity in epileptic patients.
In the last few years there has been an increasing interest in the magnetic activity due to bioelectrical currents flowing in the brain. In this paper preliminary results are reported concerning spontaneous magnetic brain activity in 36 patients affected by different kinds of brain disease; in most of these cases the symptoms were induced by localized pathology (atrophies, scars, tumors). Measurements were carried out with the simultaneous recording of the EEG. At present one of the most interesting features of magnetic detection seems to be its high localizing ability in cases of cortical foci, and sometimes its ability to show activities not evident in the EEG. These features seem to be very encouraging for the search for technical improvements, with the aim of making the magnetic technique a candidate for current diagnostic purposes.


Evaluation of Adjuvant Treatments for T1 N0 M0 Triple-Negative Breast Cancer.
Adjuvant chemotherapy remains the only recommended treatment for patients with triple-negative breast cancer (TNBC). However, the existing evidence is not enough to recommend adjuvant therapies to patients with T1 N0 M0 TNBC. To evaluate the association of different adjuvant therapies with survival outcome in patients with T1 N0 M0 TNBC stratified by cancer stage and age. Postoperative patients diagnosed as having T1 N0 M0 TNBC between 2010 and 2015 who were enrolled in the Surveillance, Epidemiology, and End Results cancer registry program were included in this population-based cohort study. Data analysis was performed from March 27, 2019, to August 10, 2020. Chemotherapy and radiotherapy. Kaplan-Meier curve and univariate and multivariable Cox proportional hazards regression analyses were performed to compare overall survival (OS) and breast cancer-specific survival (BCSS) between the different treatments. A cohort of 7739 eligible patients (mean [SD] age, 59.5 [12.4] years; all female) were included in the present study. The 5-year OS of the total patients was 91.7% (95% CI, 90.9%-92.5%), and median follow-up was 45 months (95% CI, 44-46 months). Patients aged 70 years and older or with T1a TNBC were more likely to receive adjuvant radiotherapy than chemotherapy. Although any adjuvant therapy could improve OS in T1 N0 M0 TNBC, only chemotherapy was associated with significantly better breast cancer-specific survival (BCSS adjusted hazard ratio: 0.657; 95% CI, 0.460-0.939; P = .02). Adjuvant radiotherapy after breast-conserving surgery was associated with better OS and BCSS in patients aged 70 years and older but not in those younger than 70 years. For patients with T1c BC, chemotherapy after breast-conserving surgery or other surgery was associated with improved OS, whereas only chemotherapy after other surgery was associated with better BCSS. The findings of this cohort study suggest that adjuvant therapies could improve OS in patients with T1 N0 M0 TNBC, whereas only chemotherapy was associated with better BCSS. Older patients with early-stage TNBC may benefit from adjuvant radiotherapy. Administration of adjuvant therapies to patients with different ages and cancer stages should be discussed carefully, which necessitates guidance from updated guidelines.


Limb-sparing surgery versus amputation for dogs with bone tumors.
Recently, limb-sparing surgeries have been used in the treatment of dogs with malignant bone tumors. These new techniques are fraught with potential complications. As amputation is a time-honored technique in veterinary medicine for the control of primary bone tumors, the use of newer, more complicated surgeries such as limb sparing may be considered controversial. In this article, amputation and limb sparing are discussed with reference to case selection, outcome, and possible complications.


The Host-Pathogen Interplay: A Tale of Two Stories within the Cornea and Posterior Segment.
Ocular infectious diseases are an important cause of potentially preventable vision loss and blindness. In the following manuscript, we will review ocular immunology and the pathogenesis of herpesviruses and Pseudomonas aeruginosa infections of the cornea and posterior segment. We will highlight areas of future research and what is currently known to promote bench-to-bedside discoveries to improve clinical outcomes of these debilitating ocular diseases.


Predictors of chronic pain and level of physical function in total knee arthroplasty: a protocol for a systematic review and meta-analysis.
One in five patients undergoing total knee arthroplasty (TKA) experience unchanged or worse pain and physical function 1 year after surgery. Identifying risk factors for unfavourable outcomes is necessary to develop tailored interventions to minimise risk. There is a need to review more current literature with updated methodology that addresses the limitations of earlier systematic reviews and meta-analyses. We present a Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols compliant protocol for a systematic review and meta-analysis of predictors of chronic pain and impaired function after TKA. This review will include prospective longitudinal observational studies, or randomised trials (including cluster and crossover designs) that report arm-wise predictors of chronic postsurgical pain or impaired physical function at 3 months, 6 months or 12 months. A comprehensive literature search of studies published between 2000 and 2019 will be performed in Medline, Embase, CINAHL, Cochrane Library and PEDro. Blinded assessment with consensus agreement will be applied for inclusion of studies, data extraction and assessment of bias risk (Quality in Prognosis Studies tool). The co-primary outcomes, pain and impaired function, at 12 months after TKA will be analysed separately. Estimates of association between each outcome and any preoperative or intraoperative factor that may predict chronic pain or impaired physical function will be extracted from the included studies, where possible. For randomised studies, results will only be extracted from TKA arms (or the first period of crossover trials). Estimates of association from the primary evidence will be synthesised narratively, and quantitatively using multivariate meta-analysis to provide 'pooled' estimates of association. Subgroup and sensitivity analyses will be performed. Certainty of evidence for each predictor will be derived from the Grading of Recommendations Assessment, Development and Evaluation framework. No ethical issues are associated with this project. The results from this review will be published in peer-reviewed journals and presented at international conferences. CRD42018079069.


Over-expression of TSPO in the hippocampal CA1 area alleviates cognitive dysfunction caused by lipopolysaccharide in mice.
The translocator protein 18kDa (TSPO) is closely related to regulation of immune/inflammatory response. However, the putative role and signaling mechanisms of TSPO in regulation of neuroinflammation remain unclear. GV287 lentiviral vectors mediating TSPO over-expression were injected into bilateral hippocampal CA1 areas to test whether TSPO over-expression was neuroprotective in lipopolysaccharide (LPS)-induced mice model. Finasteride, a blocker of allopregnanolone production, was used to test whether the protective effects were related to steroideogenesis. The results demonstrated that TSPO over-expression increased progesterone and allopregnanolone synthesis. TSPO over-expression in CA1 area improved LPS-induced cognitive deficiency in mice and this cognitive improvement was reversed by finasteride administration. These data suggest that up-regulation of TSPO level during neuroinflammation may be an adaptive response mechanism, a way to provide more neurosteroids. We confer that TSPO could be an attractive drug target for controlling neuroinflammation in the future.


Nurse-led stroke aftercare addressing long-term psychosocial outcome: a comparison to care-as-usual.
To examine whether nurse-led stroke aftercare is beneficial for long-term psychosocial outcome of community-dwelling persons with stroke. Comparative effectiveness research design in which a prospective stroke aftercare cohort (n = 87) was compared to care-as-usual (n = 363) at six- and 12-months post stroke. Changes over time in cognitive and emotional problems experienced in daily life, fatigue and stroke impact on daily life were examined for stroke aftercare only. Multilevel modelling was used to compare stroke aftercare to care-as-usual concerning anxiety and depression symptoms, social participation and quality of life, over time. Sample characteristics did not differ between cohorts except for stroke type and on average, more severe stroke in the stroke aftercare cohort (p < 0.05). Following stroke aftercare, anxiety and emotional problems decreased significantly (p < 0.05), whereas care-as-usual remained stable over time in terms of anxiety. No significant changes over time were observed on the other outcome domains. Nurse-led stroke aftercare showed to be beneficial for emotional well-being in comparison to care-as-usual. Providing psychoeducation and emotional support seem effective elements but adding other therapeutic elements such as self-management strategies might increase the effectiveness of nurse-led stroke aftercare.Implications for rehabilitationRoutine stroke follow-up care should pay attention to psychosocial and emotional outcome in a systematic manner, in addition to secondary prevention.Healthcare professionals such as (specialized) nurses are needed to appropriately address the hidden cognitive and emotional consequences of stroke.Providing psychoeducation and emotional support in stroke aftercare diminish insecurities and worries in community-dwelling persons with stroke, leading to better outcomes.


Independent temporal lobe epilepsy in patients with tuberous sclerosis complex.
Tuberous sclerosis complex (TSC) is a rare disease that involves multiple organs, including the brain; approximately 80%-90% of TSC patients exhibit TSC-associated epilepsy. Independent temporal lobe epilepsy (TLE), TSC-unrelated epilepsy, is particularly rare in patients with TSC. Here, we describe three patients with TSC with independent TLEs that were confirmed by stereo-electroencephalography (EEG), postoperative pathological findings, and seizure outcome at follow-up. The patients were retrospectively enrolled at two centers; their ictal epileptiform discharge onsets were determined using electrode contacts in the hippocampus during stereo-EEG. The three patients underwent anterior temporal lobectomies and remained seizure-free at 1-5 years after surgery. Postoperative pathological examinations confirmed hippocampal sclerosis in all three patients. Furthermore, postoperative intelligence quotient improvement was evident in one patient, while the quality of life was improved in two patients at 12 months after surgery.


Ultrahigh anisotropic carrier mobility in ZnSb monolayers functionalized with halogen atoms.
The experimental fabrication of novel two-dimensional ZnSb inspires us to explore the tunability of its fundamental physical properties. In this work, we present the density functional theory simulations on the mechanical, electronic and transport properties of the two-dimensional ZnSb monolayers functionalized with halogen atoms. It is found that the halogen atoms prefer to form ionic bonds with Sb atoms and these ZnSbX (X = Cl, Br and I) monolayers are very flexible with Young's moduli ranging from 24.02 N m-1 to 30.16 N m-1 along the armchair and zigzag directions. The pristine ZnSb monolayer sheet exhibits metallic phase while the functionalization can lead to a metal-to-semiconductor transition with band gaps as large as 0.55 eV. The transport study reveals a large tunability with the hole mobility reaching 43.44 × 103 cm2 V-1 s-1 along the armchair direction and the electron mobility as high as 36.99 × 103 cm2 V-1 s-1 along the zigzag direction. In contrast, the electron mobility along the armchair direction and the hole mobility along the zigzag direction are of relatively small magnitude. The ultrahigh carrier mobility together with the directional anisotropy can boost the separation of photo-excited electron-hole pairs. The finite band gaps and exceptional transport property of ZnSbX monolayers render them new materials with promising applications in flexible optoelectronic and nanoelectronic devices.


N2O-free low-flow anesthesia technique for children.
The use of N2O during low-flow anesthesia (LFA) causes difficulty in predicting inspired gas mixtures and oxygen concentration due to accumulation. An alternative technique, which uses a mixture of oxygen and air and a morphine infusion to replace N2O, has been evaluated in children during LFA, and the clinical effects and composition of gases in the system are presented here. Thirty-five children aged 2-13 years undergoing major urogenital surgery were recruited into the study. Following a standardized induction, anesthesia was maintained with 2% sevoflurane in combination with a morphine infusion. After induction with 4 l min(-1), flow rates were reduced to 2 l min(-1) and finally to 1 l min(-1) at 10 min (0.5 l oxygen + 0.5 l air). The delivered oxygen concentration, oxygen saturation and the inspired and expired O2 sevoflurane and CO2 concentrations were recorded from the start of induction to the end of anesthesia. The duration of LFA was 132+/-89 min. The concentration of oxygen delivered by the flow meters during this period was 55-60%. Although the changes in inspired and expired oxygen and sevoflurane and inspired CO2 related to the duration of LFA were statistically significant (P < 0.0001), they were not clinically relevant. All vital parameters were stable. Four patients required supplemental morphine and nine presented emergence agitation. We concluded that an N2O-free LFA technique with 0.5 l min(-1) of air and 0.5 l min(-1) of O2 supplemented by sevoflurane and a morphine infusion is safe and effective in children. The resulting high-inspired oxygen concentration prevents occurrence of hypoxic gas mixtures, and the use of supplemental morphine compensates for the absence of N2O and overcomes the possibility of light anesthesia arising from a decrease in the inspired sevoflurane concentration.


Schizotypy and subjective well-being in university students.
One hundred and thirty-nine university students completed measures of schizotypy and subjective well-being (SWB). Inverse associations were found between schizotypy and SWB scores. These results provide evidence that diminished SWB is characteristic along the schizophrenia continuum. Further research is required to determine the mechanisms by which schizotypal individuals experience reduced life satisfaction.


[Rupture of the distal biceps tendon and its treatment].
Rupture of the distal tendon of the biceps muscle is an uncommon injury. It mostly happens to strong men whose biceps muscle are contracted and overstretched unexpectedly. Contrary to the good results after conservative treatment of the numerous ruptures of the proximal tendons the distal tendon must always be surgically reconstructed. Three cases of rupture of the distal biceps tendon are reported and their good results are shown following an modified operation originally described by PLATT.


Vitamin B-sensitized photo-oxidation of dopamine.
Kinetics and mechanism of the photo-oxidation of the natural catecholamine-type neurotransmitter dopamine (DA) has been studied in aqueous solution, under aerobic conditions, in the presence of riboflavin (Rf, vitamin B(2)) as a photosensitizer. Results indicate the formation of a weak dark complex Rf-DA, with a mean apparent association constant K(ass) = 30 m(-1), only detectable at DA concentrations much higher than those employed in photochemical experiments. An intricate mechanism of competitive reactions operates upon photoirradiation. DA quenches excited singlet and triplet states of Rf, with rate constants of 4.2 x 10(9) and 2.2 x 10(9) m(-1) s(-1), respectively. With the catecholamine in a concentration similar to that of dissolved molecular oxygen in air-saturated water, DA and oxygen competitively quench the triplet excited state of Rf, generating superoxide radical anion (O(2)) and singlet molecular oxygen (O(2)((1)Delta(g))) by processes initiated by electron and energy-transfer mechanisms, respectively. Rate constants values of 1.9 x 10(8) and 6.6 x 10(6) m(-1) s(-1) have been obtained for the overall and reactive (chemical) interaction of DA with O(2)((1)Delta(g)). The presence of superoxide dismutase increases both the observed rates of aerobic DA photo-oxidation and oxygen uptake, due to its known catalytic scavenging of O(2), a species that could revert the overall photo-oxidation effect, according to the proposed reaction mechanism. As in most of the catecholamine oxidative processes described in the literature, aminochrome is the DA oxidation product upon visible light irradiation in the presence of Rf. It is generated with a quantum yield of 0.05.


Insight into the role of the Bateman domain at the molecular and physiological levels through engineered IMP dehydrogenases.
Inosine 5'-monophosphate (IMP) dehydrogenase (IMPDH) is an ubiquitous enzyme that catalyzes the NAD+ -dependent oxidation of inosine 5'-monophosphate into xanthosine 5'-monophosphate. This enzyme is formed of two distinct domains, a core domain where the catalytic reaction occurs, and a less-conserved Bateman domain. Our previous studies gave rise to the classification of bacterial IMPDHs into two classes, according to their oligomeric and kinetic properties. MgATP is a common effector but cause to different effects when it binds within the Bateman domain: it is either an allosteric activator for Class I IMPDHs or a modulator of the oligomeric state for Class II IMPDHs. To get insight into the role of the Bateman domain in the dissimilar properties of the two classes, deleted variants of the Bateman domain and chimeras issued from the interchange of the Bateman domain between the three selected IMPDHs have been generated and characterized using an integrative structural biology approach. Biochemical, biophysical, structural, and physiological studies of these variants unveil the Bateman domain as being the carrier of the molecular behaviors of both classes.


Loss of PM2.5 nitrate from filter samples in central California.
Evaporative loss of particulate matter (with aerodynamic diameter < 2.5 microm, [PM2.5]) ammonium nitrate from quartz-fiber filters during aerosol sampling was evaluated from December 3, 1999, through February 3, 2001, at two urban (Fresno and Bakersfield) and three nonurban (Bethel Island, Sierra Nevada Foothills, and Angiola) sites in central California. Compared with total particulate nitrate, evaporative nitrate losses ranged from < 10% during cold months to > 80% during warm months. In agreement with theory, evaporative loss from quartz-fiber filters in nitric acid denuded samplers is controlled by the ambient nitric acid-to-particulate nitrate ratio, which is determined mainly by ambient temperature. Accurate estimation of nitrate volatilization requires a detailed thermodynamic model and comprehensive chemical measurements. For the 14-month average of PM2.5 acquired on Teflon-membrane filters, measured PM2.5 mass was 8-16% lower than actual PM2.5 mass owing to nitrate volatilization. For 24-hr samples, measured PM2.5 was as much as 32-44% lower than actual PM2.5 at three California Central Valley locations.


OsHSD2 interaction with and phosphorylation by OsCPK21 is essential for lipid metabolism during rice caryopsis development.
Rice calcium-dependent protein kinase 21 (OsCPK21) is specifically and highly expressed throughout reproductive development and plays a critical role in rice pollen development by indirectly regulating the MIKC*-type MADS box transcription factor. However, little is known about the function of OsCPK21 in rice caryopsis development. In this study, we performed an in vitro pull-down experiment followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis and identified hydroxysteroid dehydrogenase 2 (HSD2) as a candidate OsCPK21-interacting protein in 25 DAF (days after flowering) rice caryopses. Then, we verified the interaction between OsCPK21 and OsHSD2 using yeast two-hybrid and bimolecular fluorescence assays and revealed the in vitro phosphorylation of OsHSD2 by OsCPK21. Furthermore, oscpk21 and oshsd2 mutants were generated by the CRISPR/Cas9 technique, and we found that the lipid profiles were drastically changed in both oscpk21 and oshsd2, implying that OsHSD2 phosphorylated by OsCPK21 regulates lipid abundance in caryopsis development, thereby providing a potential target for the genetic improvement of rice grain quality in future lipid-related breeding and biotechnology applications.


Efficient extraction of RNA from mammalian tissue.
RNA extraction from mammalian tissue has been compared using the different deproteinizing agents: a) guanidine-HCl, b) guanidinium-thiocyanate, c) buffer-saturated phenol, or d) buffer-saturated phenol followed by a proteinase K digestion of the aqueous phase. Both solid tissues (first, second, and third trimester fetal bovine pancreas), and human white blood cell populations were studied. Degradation, as seen in citric acid-urea agarose gels, and the ability to serve as templates for cell-free protein synthesis were used as criteria to assess the efficiency of the different methods. We conclude that employing buffer-saturated phenol with proteinase K digestion is a superior method for consistent extraction of relatively undegraded RNA in quantitative amounts from mammalian tissue.


Ca2+ release from the sarcoplasmic reticulum of barnacle myofibrillar bundles initiated by photolysis of caged Ca2+.
1. Ca2(+)-induced Ca2+ release (CICR) from the sarcoplasmic reticulum was measured by isometric tension recording from barnacle myofibrillar bundles. Laser-induced photolysis of the caged calcium molecule, nitr-5, was used to generate a rapid jump in free Ca2+ (within 1 ms) at the site of the sarcoplasmic reticulum, thus overcoming delays due to Ca2+ diffusion from the bathing solution. 2. The method consisted of equilibrating a myofibrillar bundle (100 micrograms diameter) in a solution containing 0.1 mM-nitr-5 (initial pCa 6.8-6.6) and then exposing it to a UV laser pulse. The resulting phasic contraction had an amplitude of up to 100% maximum tension (P0) in some preparations and a mean half-time for the rise of tension of 2.3 s at 12 degrees C. Longer half-times were obtained at low pulse energies. 3. Pre-treatment of the myofibrillar bundles with ryanodine (10(-4) M) or the detergent Triton X-100 abolished a large part of the phasic contraction, confirming its dependence on SR Ca2+ release. The small tonic response which remained had a shorter rise half-time than the Ca2(+)-induced Ca2+ release response and was attributed to direct activation of the myofibrils by Ca2+ released from the nitr-5. 4. The size of the photolytic Ca2+ jump was estimated from the amplitude of the fast tension component. By increasing the laser pulse energy or the initial Ca2+ loading of the nitr-5, the post-photolysis pCa was varied from 6.7 to 6.0; the CICR response increased in size over this pCa range. 5. Direct activation of Triton-treated myofibrils by photolysis of 2.0 mM-nitr-5 (initial pCa 6.4) gave contractions of up to 100% P0 and a mean rise half-time of 164 ms at 12 degrees C (n = 9 for contractions greater than 40% P0). Both the amplitude and the rate of these contractions were dependent on the laser pulse energy. 6. The Ca2(+)-induced Ca2+ release responses obtained with nitr-5 photolysis were significantly slower than the fastest rate of tetanus development which has been recorded from intact fibres of barnacle muscle (mean half-time = 177 ms at 12 degrees C). This could mean that either Ca2(+)-induced Ca2+ release is less efficient in isolated myofibrillar bundles than in intact fibres or that Ca2(+)-induced Ca2+ release is not the primary Ca2+ releasing mechanism in excitation-contraction coupling in barnacle muscle.


Identity of dihydrodiol dehydrogenase and 3 alpha-hydroxysteroid dehydrogenase in rat but not in rabbit liver cytosol.
Dihydrodiol dehydrogenase and 3 alpha-hydroxysteroid dehydrogenase activity in rat and rabbit liver cytosol have been analyzed by isoelectric focussing and subsequent activity staining. Identity of the two enzymes in rat liver cytosol is demonstrated. At least 4 main enzyme forms possessing dihydrodiol dehydrogenase activity can be detected in rabbit liver cytosol. However, in this species, only one of these forms has measurable activity towards 3 alpha-hydroxysteroids.


Knowledge Levels and Predictors of Venous Thromboembolism among Pregnant Women in Nigeria: A Cross-Sectional Survey for the 'Move for Flow' Programme.
Pregnancy is a significant risk factor for Venous Thromboembolism (VTE) which results in high maternal and perinatal morbidity and mortality rates. Awareness creation is one of the preventable strategies of VTE. To this effect, we designed the 'Move for Flow' program aimed at maternal health education on VTE, its symptoms and preventive strategies. For the best implementation of this program, the current knowledge level of the relevant population is of great interest in guiding the program design and implementation. To assess the knowledge levels of VTE among Nigerian pregnant women. In this cross-sectional survey, 1000 pregnant women residing in Enugu, Nigeria, completed a structured questionnaire which assessed their knowledge of VTE, its risk factors and prevention strategies. Quantitatively, their knowledge levels were categorized as no, poor, average and good knowledge. The majority of the respondents did not know about pregnancy-related deep vein thrombosis (DVT) (80.8%) and pulmonary embolism (PE) (88.9). Predictors of DVT knowledge levels include husbands' level of education (at most secondary education) (AOR = 4.2; 95%CI = 2.554-6.816; p = <0.001) and maternal age (AOR = 0.9; 95% CI = 0.930-0.999; p = 0.044) while predictors of PE knowledge level include husbands' level of education (at most secondary education) (AOR = 2.1; 95%CI = 1.005-4.436; p = 0.048) and maternal occupation (professionals) (AOR = 0.4; 95% CI = 0.219- 0.794; p = 0.008). Pregnant women are unaware of pregnancy-related VTE in Enugu, Nigeria. Immediate designing and implementation of the 'Move for Flow' program are recommended to improve maternal knowledge levels of VTE.


Complete genome of Mycetocola spongiae MSC19T isolated from deep-sea sponge Cacospongia mycofijiensis indicates the adaptation to deep-sea environment and sponge-microbe symbioses.
Genome of Mycetocola spongiae MSC19T, a novel marine sponge-associated Actinobacteria isolated from the Mariana Trench sponge Cacospongia mycofijiensis, was sequenced. The genome has one circular chromosome of 3,196,754 bp, with an average GC content of 66.43 mol%, and 2887 coding sequences. Gene annotation shows that M. spongiae MSC19T possesses series of genes related to adaptation to deep-sea environmental stresses including cold shock, heat shock, osmotic stress and oxidative stress. Genes encoding for heavy metal resistance, multidrug resistance and multiple natural product biosynthesis which are crucial for survival in the extreme environment are also detected in the genome. The potentials to synthesize kinds of vitamins and eukaryotic-like proteins indicates the possible nutrient exchange and mutual recognization between M. spongiae MSC19T and its sponge host. The genome provides insights into the stress resistance and ecological fitness of bacterial symbionts in the deep-sea sponge holobionts.


Chronic TCR-MHC (self)-interactions limit the functional potential of TCR affinity-increased CD8 T lymphocytes.
Affinity-optimized T cell receptor (TCR)-engineered lymphocytes targeting tumor antigens can mediate potent antitumor responses in cancer patients, but also bear substantial risks for off-target toxicities. Most preclinical studies have focused on T cell responses to antigen-specific stimulation. In contrast, little is known on the regulation of T cell responsiveness through continuous TCR triggering and consequent tonic signaling. Here, we addressed the question whether increasing the TCR affinity can lead to chronic interactions occurring directly between TCRs and MHC-(self) molecules, which may modulate the overall functional potency of tumor-redirected CD8 T cells. For this purpose, we developed two complementary human CD8 T cell models (i.e. HLA-A2 knock-in and knock-out) engineered with incremental-affinity TCRs to the HLA-A2/NY-ESO-1 tumor antigen. The impact of HLA-A2 recognition, depending on TCR affinity, was assessed at the levels of the TCR/CD3 complex, regulatory receptors, and signaling, under steady-state conditions and in kinetic studies. The quality of CD8 T cell responses was further evaluated by gene expression and multiplex cytokine profiling, as well as real-time quantitative cell killing, combined with co-culture assays. We found that HLA-A2 per se (in absence of cognate peptide) can trigger chronic activation followed by a tolerance-like state of tumor-redirected CD8 T cells with increased-affinity TCRs. HLA-A2pos but not HLA-A2neg T cells displayed an activation phenotype, associated with enhanced upregulation of c-CBL and multiple inhibitory receptors. T cell activation preceded TCR/CD3 downmodulation, impaired TCR signaling and functional hyporesponsiveness. This stepwise activation-to-hyporesponsive state was dependent on TCR affinity and already detectable at the upper end of the physiological affinity range (KD ≤ 1 μM). Similar findings were made when affinity-increased HLA-A2neg CD8 T cells were chronically exposed to HLA-A2pos-expressing target cells. Our observations indicate that sustained interactions between affinity-increased TCR and self-MHC can directly adjust the functional potential of T cells, even in the absence of antigen-specific stimulation. The observed tolerance-like state depends on TCR affinity and has therefore potential implications for the design of affinity-improved TCRs for adoptive T cell therapy, as several engineered TCRs currently used in clinical trials share similar affinity properties.


Morphological changes in CNS of rats treated with perhexiline maleate (pexid).
The basic cellular lesion in CNS of suckling rats treated with Pexid was studied by light and electron miroscopy. The most pronounced abnormality, the formation of various intracytoplasmic inclusions, was found in neurons, astrocytes, oligodendrocytes, ependymal cells, endothelial cells and fibroblasts. These abnormal inclusions were generally membrane-bound, although clearly non-membrane-bound inclusions were occasionally found. The several internal patterns of the inclusions were (1) lamellar, both concentric and parallel, (2) reticular and (3) crystalloid. These alterations were completely reversed following withdrawal of the drug. The structural characteristics of the abnormal inclusions in Pexid-treated animals were similar to those found with certain hypocholesterolemic, neuroleptic, anorectic, and antimalarial drugs. This suggests that the inclusions occurring within the cells of animals treated with any of these drugs may develop in a similar manner, and that the formation of such inclusions is likely to be a form of cellular reaction common to certain metabolic disturbances.


Hairpin coding end opening is mediated by RAG1 and RAG2 proteins.
Despite the importance of hairpin opening in antigen receptor gene assembly, the molecular machinery that mediates this reaction has not been defined. Here, we show that RAG1 plus RAG2 can open DNA hairpins. Hairpin opening by RAGs is not sequence specific, but in Mg2+, hairpin opening occurs only in the context of a regulated cleavage complex. The chemical mechanism of hairpin opening by RAGs resembles RSS cleavage and 3' end processing by HIV integrase and Mu transposase in that these reactions can proceed through alcoholysis. Mutations in either RAG1 or RAG2 that interfere with RSS cleavage also interfere with hairpin opening, suggesting that RAGs have a single active site that catalyzes several distinct DNA cleavage reactions.


Impact of atrial fibrillation on the rate of mild cognitive impairment in the elderly.
Mild cognitive impairment (MCI) in patients with cardiovascular risks is a transitional state to vascular dementia but which still has a possibility of being managed. The objectives of this study were to assess the impact of atrial fibrillation (AF) on cognitive performances in the elderly in comparison with similar cardiovascular risks. One hundred unselected patients were included in AF+ and AF- groups. Patients with prodromal Alzheimer disease as shown by semantic cueing test, and those suffering from major cognitive decline according to DSM 5 criteria were evaluated separately from those patients analysed for vascular cognitive impairment. MCI was distinguished with the help of the Montreal cognitive assessment and the mood status was studied with the geriatric depression scale. AF+ patients predominantly had paroxysmal type of AF with a mean duration of 6.3 years, with 77% of the patients being on anticoagulation. AF- patients had arterial hypertension. Prevalence of MCI was significantly higher among AF- patients, possibly due to lower rates of BP control. These study results show less impact of AF itself on cognitive performances in comparison with uncontrolled hypertension.


MiR-590-5p Inhibits Oxidized- LDL Induced Angiogenesis by Targeting LOX-1.
Oxidized low-density lipoprotein (ox-LDL) is, at least in part, responsible for angiogenesis in atherosclerotic regions. This effect of ox-LDL has been shown to be mediated through a specific receptor LOX-1. Here we describe the effect of miR-590-5p on ox-LDL-mediated angiogenesis in in vitro and in vivo settings. Human umbilical vein endothelial cells (HUVECs) were transfected with miR-590-5p mimic or inhibitor followed by treatment with ox-LDL. In other experiments, Marigel plugs were inserted in the mice subcutaneous space. Both in vitro and in vivo studies showed that miR-590-5p mimic (100 nM) inhibited the ox-LDL-mediated angiogenesis (capillary tube formation, cell proliferation and migration as well as pro-angiogenic signals- ROS, MAPKs, pro-inflammatory cytokines and adhesion-related proteins). Of note, miR-590-5p inhibitor (200 nM) had the opposite effects. The inhibitory effect of miR-590-5p on angiogenesis was mediated by inhibition of LOX-1 at translational level. The inhibition of LOX-1 by miR-590-5p was confirmed by luciferase assay. In conclusion, we show that MiR-590-5p inhibits angiogenesis by targeting LOX-1 and suppressing redox-sensitive signals.


Combination of annular pancreas and partial situs inversus: a multiple organ malrotation syndrome associated with duodenal obstruction.
A combination of annular pancreas and partial situs inversus has been encountered in three babies who presented as duodenal obstruction. All the abnormalities can be explained on the basis of multiple organ malrotation involving the duodenum, pancreas, liver, stomach, and indirectly, the spleen; hence, the term multiple organ malrotation syndrome (MOMS). The heart maintains its normal left side location in this condition. Similarly the remaining small bowel, large bowel, and appendix are normally located. It is proposed that the triad of intestinal obstruction as suggested by vomiting and visible peristalsis, left-sided liver in the presence of laevocardia, and radiographic appearance of reversed double bubble, be considered as indicating MOMS.


Antibacterial mechanism of action and in silico molecular docking studies of Cupressus funebris essential oil against drug resistant bacterial strains.
The primary objective of this research work was to study the antibacterial effects of Cupressus funebris essential oil (EO) against various drug resistant bacterial pathogens along with studying the molecular docking interactions of the major components of the EO with the key bacterial proteins/enzymes. Gas chromatography-mass spectrometry was used to analyse the chemical composition of the Cupressus funebris EO. The initial antibacterial screening was performed by using disc diffusion and microdilution methods. Scanning electron microscopy was also performed in order to study effects of the EO on bacterial cell morphology. Further, molecular docking studies were performed using Autodock Vina and results were visualised by BIOVIA Discovery Studio. The chemical composition of the EO showed the presence of 15 components with citronellal, terpinene-4-ol, α-phellandrene and 1,8-cineole as the major components of the EO. Results indicated that the EO of Cupressus funebris exhibited dose-dependent as well as time dependent antibacterial effects. The scanning electron microscopy indicated that the Cupressus funebris EO led to membrane rupture and permeabilization of the bacterial cells. Molecular docking studies indicated that the major compounds of the EO (citronellal and terpinene-4ol) showed strong interactions with the active site of the bacterial DNA gyrase enzyme explaining the antibacterial mode of action of the EO. Ciprofloxacin was also used for docking which showed stronger interactions with the target protein than citronellal or terpinene-4-ol. In conclusion, the major findings of the current study were that the EO of Cupressus funebris causes bacterial membrane rupture and permeabilization, shows time-dependent and dose-dependent antibacterial action, along with interacting with crucial bacterial enzyme viz., DNA gyrase as indicated by molecular docking studies.


[Nuclear medicine diagnosis of lung embolism through the combined perfusion-ventilation scintigraphy].
Perfusion lung scanning has improved the diagnosis of pulmonary embolism. Additional ventilation scanning has decreased the number of false positive results, considerably. The incidence of pulmonary embolism, demonstrated by combined perfusion ventilation scanning, in our patients with phlebothrombosis, comprised 54%.


Antiphospholipid Syndrome - A Case Report of Pulmonary Thromboembolism, Followed with Acute Myocardial Infarction in Patient with Systemic Sclerosis.
We are presenting an uncommon case of pulmonary embolism, followed with an acute myocardial infarction, in a patient with progressive systemic sclerosis. A female 40 years of age was admitted with signs of pulmonary embolism, confirmed with CT scan, which also reviled a thrombus in the right ventricle. The patient had medical history of systemic sclerosis since the age of 16 years. She suffered an ischemic stroke 6 years ago, but she was not taking any anticoagulant or antithrombotic medications ever since. She received a treatment with thrombolytic therapy, and subsequent UFH, but, on the second day after receiving fibrinolysis, she felt chest pain accompanied with ECG changes consistent for ST-segment elevation myocardial infarction (STEMI). Urgent coronary angiography was undertaken, which reviled cloths causing total occlusion in 4 blood vessels, followed with thromboaspiration, but without successful reperfusion. Several hours later the patient developed rapid deterioration with letal ending. During the very short hospital course, blood sampling reviled presence of antiphospholipid antibodies. The acquired antiphospholipid syndrome is common condition in patients with systemic autoimmune diseases, but relatively rare in patients with systemic sclerosis. Never the less, we have to be aware of it when treating the patients with systemic sclerosis.


[Effect of pre-existing lipids on calcinosis of swine heart valve bioprostheses. A study of a dynamic in vitro model].
Calcification is one of the main causes of failure of porcine bioprosthetic heart valves, a problem which has not been satisfactorily solved to date. Previous studies have shown that calcification is decreased in porcine heart valves that have undergone treatment for lipid extraction. The relation between lipid distribution and calcification of seven new commercially available porcine bioprosthetic heart valves (St. Jude Medical, Bioimplant) is assessed by Sudan red III staining to show preexisting lipids. All porcine bioprosthetic valves contained lipids to different degrees. Five valves were subjected to the pulsatile accelerated calcification process for 4 weeks. Distribution and level of calcification were evaluated by radiography and compared to the Sudan red-stained fatty areas. Comparison of the calcifications detected by radiography and the macroscopically detected lipids showed a coincidence of 57-66%. Two porcine bioprosthetic valves were histologically prepared and stained with Hematoxylin and von Kossa's stain, respectively. By light microscopy, the von Kossa staining revealed microcalcifications and polarizing microscopic investigation showed birefractive substances in areas with lipid deposits. These preexisting substances in porcine valve tissue may play a determinative role in the calcification of the tissue. Substantial studies are necessary to further determine the role of preexisting lipids in calcification.


Early EPS/ICD strategy in survivors of acute myocardial infarction with severe left ventricular dysfunction on optimal beta-blocker treatment. The BEta-blocker STrategy plus ICD trial.
This multicentre prospective randomised trial was undertaken to evaluate the usefulness of an electrophysiological study (EPS)-guided/implantable cardioverter defibrillator (ICD) strategy in patients at high risk of sudden death (SD) early after myocardial infarction (MI). Previous studies have shown the benefits of such a strategy only in high-risk patients late after MI. We enrolled 143 survivors of acute MI (<1 month) with left ventricular ejection fraction < or = 35% and either frequent (> or =10/h) premature ventricular complexes (PVCs), or depressed heart rate variability (SDNN < 70 ms) or abnormal signal-averaged ECG, who were able to tolerate optimised beta-blocker therapy (68 +/- 40 mg/day of metoprolol). Of these, 138 were randomised, in a 2:3 ratio, to two therapeutic strategies: conventional (CONV) strategy (n = 59) or EPS-guided/ICD strategy (n = 79). The latter resulted in ICD implantation in 24 inducible patients and in CONV therapy in the remaining 55. During a mean follow-up of 540 +/- 378 days, 26 patients (19%) died: nine (6.5%) SD, nine (6.5%) non-SD, and four (3%) non-cardiac death; in four patients (3%) the cause of death was unknown. The actuarial overall mortality for the CONV and EPS-guided/ICD arms was 18% vs 14% after 1 year and 29.5% vs 20% after 2 years, respectively (P = 0.3 and 0.2). Despite optimal therapy, mortality remains significant in high-risk patients following MI. Although there is a trend in favour of EPS-guided/ICD, our data are insufficient to demonstrate a survival benefit of this strategy early after MI.


Proteomic and physiological responses of contrasting two different heat-resistant orchardgrass genotypes to heat stress.
As an important forage crop worldwide, the growth and productivity of orchardgrass are greatly impacted by high temperatures. However, little information is known about how orchardgrass proteomic changes under heat conditions. Therefore, the present study investigated the proteomics and physiological changes in 667 [AKZ-NRGR667 (heat-tolerant)] and 7602 [PI237602 (heat-sensitive)] under heat stress (40/35 °C). In addition, the responses of translational regulating of heat stress in orchardgrass were analyzed through proteomic changes using the tandem mass tags (TMT) technique. Together, 410 differentially expressed proteins (DEPs) were identified from two orchardgrass genotypes under heat at 24 h. Proteomics analyses indicated that proteins related to substance metabolism, photosynthesis, and heat shock proteins (HSPs) were differentially expressed under heat stress and control conditions. Moreover, a large proportion of HSPs were expressed in the heat-tolerant genotype as compared to the heat-sensitive genotype. In conclusion, genotype 667 has higher adaptability and repairing capability due to stronger heat tolerance capacity that can make it more suited to sustaining its survival and growth than genotype 7602. These findings can provide the basis for genetic improvements in orchardgrass and other crops facing high-temperature stress or heat environment that may lead to heat resistance or tolerance.


[Current possibilities of radiodiagnosis in liver tumors].
The report deals with potential of present-day techniques for radiological imaging, differential diagnosis and working out of modalities of treatment for primary and metastatic hepatic tumors. Results of complex examination (ultrasound, CT, MRI, PET using fluorine -18 FDG) of patients with benign and malignant tumors are discussed. Sensitivity and specificity of each procedure have been identified to be used in diagnosis of large-size tumors.


c-MYC activation in primary and metastatic ductal adenocarcinoma of the pancreas: incidence, mechanisms, and clinical significance.
Amplification and overexpression of c-MYC is a common event in various neoplasias. Recently, comparative genomic hybridization (CGH) of primary pancreatic adenocarcinomas revealed a distinct high-level amplification of 8q23-qter, suggesting that c-MYC located on 8q24 may be a candidate oncogene. To evaluate the biological significance and prognostic value of c-MYC activation in pancreatic carcinoma, we performed interphase fluorescence in situ hybridization (FISH) and immunohistochemistry on a series of 69 primary pancreatic adenocarcinomas, 19 corresponding lymph node metastases, and 5 pancreatic intraductal lesions. Dual color FISH using a probe for c-MYC (8q24) and a centromeric probe for chromosome 8 revealed amplification of c-MYC in 32.3% and 29.4% of primary and metastatic tumors, respectively. Immunostaining identified c-MYC protein overexpression in 43.5% of primaries and 31.6% of metastases. Low concordance between positive FISH and immunostaining (13.4%) suggests multiple independent regulatory pathways of c-MYC activation. Statistical evaluation revealed significant correlation (alpha = 0.033) between c-MYC protein overexpression and histopathological tumor grade but absence of correlation with tumor stage or lymph node status. Analysis of pancreatic intraductal lesions showed c-MYC amplification and protein overexpression in two of five cases in which invasive carcinoma exhibited identical aberrations. We conclude that deregulation of c-MYC protein is common in pancreatic cancer and that it may be involved in early neoplastic development and progression rather than in locoregional spread of invasive cancer.


Three versus 12-month dual antiplatelet therapy duration in patients with acute coronary syndrome undergoing percutaneous coronary intervention: A meta-analysis of randomized controlled trials.
The American Heart Association/American College of Cardiology guidelines on dual antiplatelet therapy (DAPT) recommend at least 12 months of a P2Y12 inhibitor and low dose aspirin in patients with an acute coronary syndrome (ACS) treated with a stent. Since that recommendation, several randomized controlled trials (RCTs) have studied an abbreviated duration of DAPT in ACS. Therefore, we sought to perform a meta-analysis of RCTs comparing 3- versus 12-month DAPT in patients presenting with ACS undergoing percutaneous coronary intervention (PCI). PubMed, Embase, and Cochrane Central databases were searched until July 31, 2022, for RCTs comparing 3- versus 12-month DAPT in patients with ACS undergoing PCI. Outcomes assessed were major adverse cardiovascular events (MACE), cardiovascular mortality, all-cause mortality, myocardial infarction (MI), stent thrombosis (ST) and bleeding. A random-effects model was used to calculate pooled relative risk (RR) and 95% confidence intervals (CI). We included 5 trials comprising 16,781 patients with an ACS that underwent PCI. There was no significant difference in MACE (RR: 0.92; 95% CI: 0.76-1.11), cardiovascular mortality (RR: 1.26; 95% CI: 0.38-4.17), or all-cause mortality (RR: 0.92; 95% CI: 0.48-1.77) between the 2 groups. In addition, there was no difference in rates of MI (RR: 0.98; 95% CI: 0.74-1.30), or ST (RR: 1.30; 95% CI: 0.55-3.05) between 3- and 12-month DAPT. However, compared with 12-month DAPT, 3-month DAPT significantly reduced risk of major bleeding (RR: 0.53; 95% CI: 0.43-0.64). In patients with ACS undergoing PCI, 3-month DAPT reduced risk of bleeding without evidence of harm.


Role of Platelet Transfusion in the Reversal of Anti-Platelet Therapy.
Antiplatelet therapy is extensively used in the primary and secondary prophylaxis of arterial thrombotic disorders. Aspirin, the most commonly used antiplatelet agent, is a cyclooxygenase-1 inhibitor and considered a mild to moderate inhibitor of platelet function. Therefore, often a second antiplatelet agent is necessary in certain clinical conditions requiring greater inhibition of platelet function. An adenosine diphosphate (ADP) receptor, P2Y12, is an important target for this purpose; several agents inhibit this receptor providing potent antiplatelet effect. One of the side effects of these agents is bleeding, which in some patients may require reversal of antiplatelet effect. Similarly, patients undergoing emergent surgeries may benefit from reversal of antiplatelet effect to avoid excessive surgical bleeding. This article reviews current literature on this topic.


Comparative Study of Traditional Chinese Medicine and Western Medicine in the Treatment of Coronavirus.
Taking the process of treating coronavirus disease 2019 (COVID-19) with Western medicine and traditional Chinese medicine (TCM) as the research object, this article compares the characteristics of Western medicine and TCM from the perspectives of aetiology, pathogenesis, diagnosis, and treatment. Western medicine and TCM each has its own theoretical system. Each has its own exposition in explaining the etiology and pathogenesis of the disease, and each has its own characteristics and advantages in diagnosis and treatment. Integrating TCM and Western medicine can improve the effect of treatment by forming a coordinated traditional Chinese and Western medicine treatment method.


Common bile duct perfusion combined with operative cholangiography.
A series of 223 patients undergoing cholecystectomy has been studied. In 204 patients the common bile duct was perfused with saline at a pressure of 30 cm. The rate of flow has been analysed as a means of determining the presence of common bile duct stones, this being confirmed on the evidence of operative cholangiography or exploration of the duct. The results suggest that flow studies can be more consistently obtained than cholangiograms, which were not available for technical reasons in 8.0 per cent of patients in this series. The results of flow studies are comparable with those of cholangiography in confirming the normality of the common bile duct but are less reliable in detecting stones. The reliability is such that if radiological facilities are not available, flow studies are an acceptable alternative. In none of these patients was stenosis of the sphincter of Oddi detected. If this clinical entity does exist, it is rare and of little significance.


In-vitro activity of imipenem against 100 strains of serotype b and nontypable Haemophilus influenzae, including strains resistant to ampicillin, chloramphenicol or both.
Imipenem, along with ampicillin, chloramphenicol, ceftazidime, aztreonam and ceftriaxone were tested against 100 clinical isolates of Haemophilus influenzae. Eighty-eight of the isolates were serotype b, 35 isolates were beta-lactamase producers, and five isolates were chloramphenicol resistant. Inoculum densities of 1 X 10(3), 1 X 10(5) and 1 X 10(8) cfu/ml were tested for all isolates. MIC90s and MBC90s at the two lower inoculum densities for imipenem, ceftazidime, aztreonam and ceftriaxone were in the susceptible range for all categories of isolates tested. Imipenem, ceftazidime and aztreonam displayed elevated MBC90s at the high inoculum density. The effect of the high inoculum density upon the ceftriaxone MBC90 was below the level of detection afforded by the study design.


The burden of tuberculosis among adolescents and young adults in five Asian countries from 1990 to 2019.
Previous studies have shown that the risk of tuberculosis (TB) increases dramatically during adolescence. The objective of this article was to analyze the burdens and trends of TB incidence and mortality rates in Asian adolescents and young adults. Time series ecological study of TB incidence and mortality rates of adolescents and young adults aged 10-24 years from 1990 to 2019, using data extracted from the Global Burden of Disease website for 5 Asian countries. The annual percentage change was calculated by joinpoint regression analysis to estimate the trends in the age-standardized incidence rate (ASIR) and age-standardized death rate (ASDR). The highest ASIR per 100,000 person-years in 2019 was in Mongolia [74 (95% uncertainty interval (UI), 51 to 105)], while the lowest was in Japan [4 (95% UI, 2 to 6)]. The highest ASDR per 100,000 person-years was in Mongolia [2 (95% UI, 1 to 3)], while the lowest was in Japan [0.009 (95% UI, 0.008 to 0.010)]. As the absolute number of cases and deaths decreased from 1990 to 2019, the ASIRs and ASDRs in all five countries also decreased. Our finding revealed that although all five countries in Asia experienced descending TB incidence and mortality trend in past three decades, the trends were especially significant in developed countries and varied across geographic regions. This study may be crucial in helping policymakers make decisions and allocate appropriate resources to adolescent TB control strategies.


Expression and localization of tight junction-associated proteins in human hair follicles.
Tight junctions (TJ) are barrier-forming intercellular junctions selectively sealing cells and controlling the paracellular pathway. They have been well-characterized in simple epithelia and endothelia but have only recently been described in stratified epithelia such as epidermis, oesophagus and oral mucosa. Various epithelial layers which are partly in morphogenic continuity with the epidermis and develop therefrom during early fetal life, build the human hair follicle. The barrier function of these epithelial layers seems to be important for the universal continuity of the barrier represented by the skin. We show the presence of the TJ proteins ZO-1, occludin, and various claudins in the hair follicle and demonstrate their impressive heterogeneous distribution pattern within a given stratum as well as within its different epithelial layers. Coexpression of the various TJ proteins, arguing for typical TJ structures, can be observed especially in cell layers facing the hair shaft and the stratum corneum, and in addition at the border between the outer and inner root sheaths. Usually they are found in close proximity to desmosomal and adherens junction proteins. The morphological and biological importance of these findings and the possible roles of TJ in hair follicles, e.g. in follicular penetration, are discussed.


Executive summary of the diagnosis and treatment of bacteremia and endocarditis due to Staphylococcus aureus. A clinical guideline from the Spanish Society of Clinical Microbiology and Infectious Diseases (SEIMC).
Bacteremia and infective endocarditis caused by Staphylococcus aureus are common and severe diseases. Optimization of treatment is fundamental in the prognosis of these infections. The high rates of treatment failure and the increasing interest in the influence of vancomycin susceptibility in the outcome of infections caused by both methicillin-susceptible and -resistant isolates have led to research on novel therapeutic schemes. The interest in the new antimicrobials with activity against methicillin-resistant staphylococci has been extended to susceptible strains, which still carry the most important burden of infection. New combinations of antimicrobials have been investigated in experimental and clinical studies, but their role is still being debated. Also, the appropriateness of the initial empirical therapy has acquired relevance in recent years. The aim of this guideline is to update the 2009 guidelines and to provide an ensemble of recommendations in order to improve the treatment of staphylococcal bacteremia and infective endocarditis, in accordance with the latest published evidence.


Fatigue in the radiation therapy patient: current management and investigations.
Fatigue is one of the most common and distressing symptoms experienced by cancer patients. Research conducted over the past few years has documented that initiation of radiation therapy typically results in significant increases in fatigue severity. Preliminary evidence suggests that, among disease-free patients, this heightened fatigue remits to levels approaching those reported before initiation of treatment in the weeks or months after treatment completion. Potential sources of fatigue are varied and may include anemia, cytokine activation, psychological distress, concomitant symptoms and side effects, and concurrent medications. Efforts to manage fatigue in cancer patients should focus on correcting potential etiologies and relieving symptoms. For patients experiencing fatigue related to anemia, treatment with an erythropoietic agent should be considered. Preliminary evidence suggests that moderate exercise during radiation therapy may also be helpful in relieving fatigue. Additional research is needed to evaluate the effectiveness of these therapies as well as other intervention strategies, such as the use of antidepressant and psychostimulant medications.


Intraoral nerve sheath myxoma: case report and systematic review of the literature.
Oral nerve sheath myxoma (NSM) is an uncommon benign neoplasm with Schwann-cell origin, which is frequently mistaken for neurothekeoma. We report a case of NSM on the buccal mucosa in a 42-year-old woman. This case is compared with previously reported cases and a systematic review is performed. We conducted a case report and systematic review of oral cases considered true NSMs. A literature search was performed using PubMed, Lilacs, Scielo, Cochrane, SciVerse Scopus, Web of Science, and Embase electronic database. Twenty-five cases of oral NSM were included in the systematic review. Oral NSM is rare and may represent a diagnostic challenge for pathologists. To confirm the diagnosis of NSM, the evaluation of S-100 protein expression or other neural marker is essential. The use of the terms NSM and neurothekeoma as synonymous or as variants of the same tumor should be avoided, because they are clearly distinct lesions.


From single to multiple microcoil flow probe NMR and related capillary techniques: a review.
Nuclear magnetic resonance (NMR) spectroscopy is one of the most important and powerful instrumental analytical techniques for structural elucidation of unknown small and large (complex) isolated and synthesized compounds in organic and inorganic chemistry. X-ray crystallography, neutron scattering (neutron diffraction), and NMR spectroscopy are the only suitable methods for three-dimensional structure determination at atomic resolution. Moreover, these methods are complementary. However, by means of NMR spectroscopy, reaction dynamics and interaction processes can also be investigated. Unfortunately, this technique is very insensitive in comparison with other spectrometric (e.g., mass spectrometry) and spectroscopic (e.g., infrared spectroscopy) methods. Mainly through the development of stronger magnets and more sensitive solenoidal microcoil flow probes, this drawback has been successfully counteracted. Capillary NMR spectroscopy increases the mass-based sensitivity of the NMR spectroscopic analysis up to 100-fold compared with conventional 5-mm NMR probes, and thus can be coupled online and off-line with other microseparation and detection techniques. It offers not only higher sensitivity, but in many cases provides better quality spectra than traditional methods. Owing to the immense number of compounds (e.g., of natural product extracts and compound libraries) to be examined, single microcoil flow probe NMR spectroscopy will soon be far from being sufficiently effective as a screening method. For this reason, an inevitable trend towards coupled microseparation-multiple microcoil flow probe NMR techniques, which allow simultaneous online and off-line detection of several compounds, will occur. In this review we describe the current status and possible future developments of single and multiple microcoil capillary flow probe NMR spectroscopy and its application as a high-throughput tool for the analysis of a large number of mass-limited samples. The advantages and drawbacks of different coupled microseparation-capillary NMR spectroscopy techniques, such as capillary high-performance liquid chromatography-NMR spectroscopy, capillary electrophoresis-NMR spectroscopy, and capillary gas chromatography-NMR spectroscopy, are discussed and demonstrated by specific applications. Another subject of discussion is the progress in parallel NMR detection techniques. Furthermore, the applicability and mixing capability of tiny reactor systems, termed "microreactors" or "micromixers," implemented in NMR probes is demonstrated by carbamate- and imine-forming reactions.


Analysis of the twenty-six largest outbreaks of tuberculosis in Aragon using whole-genome sequencing for surveillance purposes.
The incidence of tuberculosis in Aragon, Spain, is around ten cases per 100,000 inhabitants. Since 2004, a molecular surveillance protocol has been carried out; therefore, all M. tuberculosis strains are genotyped. Recently, whole-genome sequencing has been implemented for relevant isolates. The aim of this work is to characterise at the molecular level the causative strains of the 26 largest outbreaks of the community (including ten or more cases), genotyped by IS6110-RFLP and causing 26% of tuberculosis cases. To achieve this objective, two or three isolates of each IS6110-cluster belonging to different years were selected for sequencing. We found that strains of lineages L4.8, L4.3 and L4.1.2 were the most frequent. The threshold of 12 SNPs as the maximum distance for confirming the belonging to an outbreak was met for 18 of the 26 IS6110-clusters. Four pairs of isolates with more than 90 SNPs were identified as not belonging to the same strain, and four other pairs were kept in doubt as the number of SNPs was close to 12, between 14 and 35. The study of Regions of Difference revealed that they are lineage conserved. Moreover, we could analyse the IS6110 locations for all genome-sequenced isolates, finding some frequent locations in isolates belonging to the same lineage and certain IS6110 movements between the paired isolates. In the vast majority, these movements were not captured by the IS6110-RFLP pattern. After classifying the genes containing SNP by their functional category, we could confirm that the number of SNPs detected in genes considered as virulence factors and the number of cases the strain produced were not related, suggesting that a particular SNP is more relevant than the number. The characteristics found in the most successful strains in our community could be useful for other researchers in epidemiology, virulence and pathogenesis.


Regulatory T Cells in Autoimmune Diabetes: Mechanisms of Action and Translational Potential.
Since the discovery of specialized T cells with regulatory function, harnessing the power of these cells to ameliorate autoimmunity has been a major goal. Here we collate the evidence that regulatory T cells (Treg) can inhibit Type 1 diabetes in animal models and humans. We discuss the anatomical sites and molecular mechanisms of Treg suppressive function in the Type 1 diabetes setting, citing evidence that Treg can function in both the pancreatic lymph nodes and within the pancreatic lesion. Involvement of the CTLA-4 pathway, as well as TGF-β and IL-2 deprivation will be considered. Finally, we summarize current efforts to manipulate Treg therapeutically in individuals with Type 1 diabetes. The translation of this research area from bench to bedside is still in its infancy, but the remarkable therapeutic potential of successfully manipulating Treg populations is clear to see.


CT-urography: a nationwide survey by the Italian Board of Urogenital Radiology.
Computed tomography-urography is currently the imaging modality of choice for the assessment of the whole urinary tract, giving the possibility to detect and characterize benign and malignant conditions. In particular, computed tomography-urography takes advantage from an improved visualization of the urinary collecting system due to acquisition of delayed scan obtained after excretion of intravenous contrast medium from the kidneys. Nevertheless, the remaining scans are of great help for identification, characterization, and staging of urological tumors. Considering the high number of diseases, urinary segment potentially involved and patients' features, scanning protocols of computed tomography-urography largely vary from one clinical case to another as well as selection and previous preparation of the patient. According to the supramentioned considerations, radiation exposure is also of particular concern. Italian radiologists were asked to express their opinions about computed tomography-urography performance and about its role in their daily practice through an online survey. This paper collects and summarizes the results.


Characteristics and outcomes of patients admitted for acute heart failure in a single-centre study.
Acute heart failure represents a medical condition with very high mortality. Accurate risk stratification can help physicians to improve the health care about these patients. The aim of our study was to characterize real-life patients admitted for acute heart failure in a specific region with one tertiary medical centre and to describe risk factors of short-term and long-term mortality. We performed a retrospective analysis of patients admitted from January 2017 to December 2017 to Department of cardiology of the tertiary medical centre University Hospital in Hradec Kralove. We identified 385 patients admitted for acute heart failure to the standard care and intensive care unit. The median of age was 74 years (IQR 67.5-80) and 34% of patients were female. Hospital admission was due to de novo heart failure in 222 (57.7%) patients. The most common comorbidities were arterial hypertension (77.7%), dyslipidaemia (67.3%) and coronary artery disease (63.1%). Coronary artery disease (52.7% of cases) and valve disease (28.1% of cases) were the most common aetiologies of heart failure. The all-cause in-hospital mortality was 12.7%, 30-day mortality was 14.6% and 1 year mortality was 34%. Among risk factors of in-hospital mortality, the most significant factors were haemodialysis during the hospitalization [odds ratio (OR) 15.82, 95% confidence interval (CI) 2.96-84.57, P = 0.0008], chronic heart failure (OR 4.27, 95% CI 1.66-11.03, P = 0.001) and STEMI as a precipitating factor of heart failure (OR 4.19, 95% CI 1.23-14.25, P = 0.023). Haemodialysis during the hospitalization (OR 4.28, 95% CI 1.17-15.61, P = 0.025) and the comorbidity depression and anxiety (OR 3.49, 95% CI 1.45-8.39, P = 0.005) were the most significant risk factors of long-term mortality. Our study confirms very high mortality rates among patients with acute heart failure underlying poor prognosis of these patients. Comorbidities (peripheral artery disease, atrial fibrillation, chronic heart failure and depression and anxiety), precipitating factors of heart failure (myocardial infarction with ST segment elevation), complications occurring during the hospitalization (acute kidney injury, pulmonary ventilation for respiratory failure and haemodialysis) and the age of patients should be included in the risk stratification of in-hospital, 30 day and 1 year mortality.


The First Discovery of Pogonophora (Annelida, Siboglinidae) in the East Siberian Sea Coincides with the Areas of Methane Seeps.
Pogonophora or siboglinid tubeworms (Annelida, Siboglinidae) have been found in the East Siberian Sea for the first time. On the basis of the results of molecular phylogenetic analysis, the found specimens are presumably assigned to the genus Oligobrachia. The stations where the siboglinid tubeworms have been found are located in the area of methane seeps. This confirms the previously stated hypothesis about relationship of siboglinid tubeworm distribution with the areas of underwater methane seeps.


Polymorphisms in the DBH and DRD2 gene regions and smoking behavior.
The DRD2 TaqI A and DBH-1021 C/T polymorphisms were genotyped in smoking alcoholics (N = 100), non-alcoholic smokers (N = 120) and nonsmoking controls (N = 112). Alcoholic and non-alcoholic smokers presented a higher frequency of the DRD2 TaqI A1 allele (P = 0.04) than non-smoking controls. Individuals who had at least one DBH-1021 T allele smoked fewer cigarettes per day than CC homozygotes (P = 0.03). These results are coherent with the expected effects of these polymorphisms on dopaminergic function.