BTLA blockade enhances Cancer therapy by inhibiting IL-6/IL-10-induced CD19high B lymphocytes.
The standard treatment for epithelial ovarian carcinoma (EOC) is surgery followed by platinum/paclitaxel-based chemotherapy, but the overall survival rate is poor. The purpose of this study was to investigate the therapeutic potential of chemotherapy combined with inhibition of B and T lymphocyte attenuator (BTLA) for clinical use to treat EOC. Initially, we evaluated the potential application of chemotherapy combined with anti-BTLA antibody in an animal model. We then analyzed the distribution and regulation of BTLA expression on immunocytes in vitro. Finally, we examined the correlation between BTLA expression levels in cancerous tissues and prognosis in 254 EOC cases. The combination of chemotherapy and anti-BTLA antibody for inhibiting BTLA significantly reduced peritoneal tumor volume and extended survival in tumor-bearing mice. In addition, BTLA could be identified mostly on B lymphocytes, especially on CD19hi B cells, rather than on T lymphocytes and natural killer cells. Under regulation of interleukins 6 and 10, more BTLA+CD19hi B lymphocytes could be induced through AKT and STAT3 signaling pathways. Detectable BTLA expression in ovarian cancerous tissues was associated with worse disease-free and overall survivals of EOC patients. BTLA detected in cancerous tissues can predict poor outcome of EOC patients. Inhibition of BTLA combined with chemotherapy can elevate immune activation and generate potent anti-tumor effects. Thus, the combination of chemotherapy and anti-BTLA antibody may hold potential clinical application for the treatment of EOC patients. The Trial Registration Number was NCT00854399.


Light and water treatment during the early grain filling stage regulates yield and aroma formation in aromatic rice.
The effect of light and water on aromatic rice remain largely unclear. A pot experiment was conducted to investigate the influences of light-water treatments (CK: natural light and well-watered conditions, WS: natural light and water-stressed conditions, LL: low light and well-watered conditions, LL-WS: low light and water-stressed treatment) on yield and 2-acetyl-1-pyrroline (2AP) formation in aromatic rice. Compared with CK, the light-water treatments decreased grain yield (10.32-39.19%) due to reductions in the filled grain percentage and total dry weight, in the regulation of biomass distribution, and in the attributes of gas exchange and antioxidant response parameters. The 2AP content in grains increased in the LL treatment (5.08-16.32%) but decreased in the WS treatment compared with that in CK. The changes in 2AP were associated with changes in 2AP formation-related traits and element content. Low light and water stress led to yield declines in aromatic rice, but low light alleviated the decrease in 2AP content caused by water stress.


Essential oils from tropical medicinal herbs and food plants inhibit biofilm formation in vitro and are non-cytotoxic to human cells.
The biofilm inhibition and eradication potential of essential oils (EOs) extracted from six tropical medicinal herbs and food plants [Psiadia arguta (PA), Psiadia terebinthina (PT), Citrus grandis (CGp), Citrus hystrix (CH), Citrus reticulata (CR), and Cinnamomum zeylanicum (CZ)] were assessed. The mechanism of inhibition was studied via quenching of efflux pump. Cytotoxicity was evaluated using Artemia salina assay and cell lines [human cervix carcinoma (HeLa), human lung fibroblast (MRC-5), and murine melanoma (B16F10)]. EOs of CH, CR, PA, and PT were found to be prospective antibiofilm agents (IC50 of 0.29, 0.59, 0.22, and 0.11 mg/mL against Staphylococcus epidermidis; 0.39, 0.54, 0.09, and 0.13 mg/mL against Escherichia coli; and 0.54, 0.90, 0.44 and 0.51 mg/mL against Candida albicans for CH, CR, PA, and PT, respectively). The simultaneous actions of the EOs and efflux pump inhibitor impacted on the resistance of the biofilms. LC50 of the EOs ranged from 223 to 583 µg/mL against A. salina. The non-cytotoxic concentration of the EOs varied from 200 to 300 µg/mL (HeLa and MRC-5), and 150-200 µg/mL (B16F10). EOs from these tropical medicinal herbs and food plants are useful sources of new antimicrobials with low cytotoxicity which could open new horizons in the drug development process.


Molecular characterization of NDRG4/Bdm1 protein isoforms that are differentially regulated during rat brain development.
We previously reported the identification of a novel gene, Bdm1/NDRG4, that was expressed predominantly in the postnatal rat brain and might possibly play a role in this process. We describe here the characterization of a NDRG4 protein in a developing and maturing rat brain. Antibody raised against glutathione S-transferase (GST)-NDRG4 fusion protein recognized four protein species of 38, 39, 41, and 45 kDa on Western blotting of proteins from differently staged rat brains. The 38-kDa form was revealed after birth, and the amount of this species peaked on postnatal day 15. The 39-kDa form became detectable after postnatal week 6. The 41-kDa form appeared late in embryogenesis, increased by postnatal day 15, and disappeared at postnatal week 6. The 45-kDa form was abundant during the late embryonic period and slightly decreased after birth. Subcellular fractionation of cerebra indicated that the NDRG4 protein was distributed mainly in the mitochondria and endoplasmic reticulum (ER). Detergent solubility assays and protease susceptibility demonstrated that in the ER NDRG4 protein is membrane-associated and luminally oriented. The 45-kDa isoform was induced during NGF-mediated neuronal differentiation of PC12 cells, but not by tunicamycin which causes ER stress. Differential expressions of NDRG4 protein isoforms may be a mechanism for modifying the NDRG4 function and for the formation of a functioning nervous system.


Problems in the acquisition of imagery mnemonics: three brain-damaged cases.
The literature provides little direction on how to overcome difficulties which some brain-damaged patients have in acquiring imagery mnemonics as a memory aid during the period of anterograde amnesia. For those interested in the therepeutic usefulness of imagery mediation, we provide a detailed account of the acquisition of some mnemonic skill in three brain-damaged patients who initially failed in using visual imagery mediators to recall words lists.


Bone and fat as a function of body weight in adult mammals.
Three independent data sets, for both bone and fat weight, in adult mammals, expressed as a function of body weight, were submitted to linear regression analysis of the log-log transformed data. For land mammals generally, weighing up to 6.6 metric tons, the slope of the best-fit regression line for skeletal weight is 1.073 +/- 0.021. This regression line underestimates skeletal weight in the elephant by about 40%. For cetaceans, varying in body weight from about 0.1 to over 100 metric tons, the slope of the best-fit regression line for skeletal weight is 1.133 +/- 0.044. Since the slopes for these two groups of mammals are not statistically different, and since cetaceans are normally shielded from gravity, due to buoyancy, it is suggested that the slope (1.073) in land mammals may not be an adaption to gravity. After pooling the data from the three data sets for fat, the resultant regression has a slope of 1.146 +/- 0.026. It is argued, on theoretical grounds, that slopes greater than 1.2-1.3 will not be found for the log-log regression of any major tissue on body weight, taken over the whole mammalian weight range.


History of immunoglobulin replacement.
The provision of antibodies to prevent and treat infection began with the application of "curative serum" in the first years of the last century. After the process of large-scale plasma fractionation was developed in the 1940s, the general use of immunoglobulin expanded. Intravenous immunoglobulin products became available in the 1970s, and their only use for the provision of antibodies governed the opinion of experts over the next decade. Modulation of inflammation and immunosuppression were introduced in treatment of inflammatory and autoimmune diseases and became accepted indications. The history of adverse events of treatment and their management are outlined in this article. Consensus indications and evidence-based off-label uses are discussed.


Editorial Commentary: The Everted Acetabular Labrum. It Is Not Just a Small Labrum.
Everted, hypoplastic acetabular labra represent a variant of acetabular rim development. It is important to be able to recognize this pathology on magnetic resonance imaging and at the time of hip arthroscopy. Proper intraoperative identification of this variant that does not make contact with the femoral head is critical to being able to successfully restore this contact, often through labral advancement, acetabuloplasty of the abnormal rim development, and occasionally labral augmentation. A broad awareness among hip arthroscopy surgeons of this topic will lead to improved clinical outcomes after hip arthroscopy for a challenging cohort.


IgE in the diagnosis and treatment of allergic disease.
Traditionally, the concept of allergy implied an abnormal response to an otherwise benign agent (eg, pollen or food), with an easily identifiable relationship between exposure and disease. However, there are syndromes in which the relationship between exposure to the relevant allergen and the "allergic" disease is not clear. In these cases the presence of specific IgE antibodies can play an important role in identifying the relevant allergen and provide a guide to therapy. Good examples include chronic asthma and exposure to perennial indoor allergens and asthma related to fungal infection. Finally, we are increasingly aware of forms of food allergy in which the relationship between exposure and the disease is delayed by 3 to 6 hours or longer. Three forms of food allergy with distinct clinical features are now well recognized. These are (1) anaphylactic sensitivity to peanut, (2) eosinophilic esophagitis related to cow's milk, and (3) delayed anaphylaxis to red meat. In these syndromes the immunology of the response is dramatically different. Peanut and galactose α-1,3-galactose (alpha-gal) are characterized by high- or very high-titer IgE antibodies for Ara h 2 and alpha-gal, respectively. By contrast, eosinophilic esophagitis is characterized by low levels of IgE specific for milk proteins with high- or very high-titer IgG4 to the same proteins. The recent finding is that patients with alpha-gal syndrome do not have detectable IgG4 to the oligosaccharide. Thus the serum results not only identify relevant antigens but also provide a guide to the nature of the immune response.


Unintended effects of the herbicides 2,4-D and dicamba on lady beetles.
Weed resistance to glyphosate and development of new GM crops tolerant to 2,4-dichlorophenoxyacetic acid (2,4-D) and dicamba is expected to lead to increased use of these herbicides in cropland. The lady beetle, Coleomegilla maculata is an important beneficial insect in cropland that is commonly used as an indicator species in safety evaluations of pesticides. Here, we examined the lethal and non-lethal effects of 2,4-D and dicamba active ingredients and commercial formulations to this lady beetle species, and tested for synergistic effects of the herbicides. Second instars of lady beetles were exposed to an experimental treatment, and their mortality, development, weight, sex ratio, fecundity, and mobility was evaluated. Using similar methods, a dose-response study was conducted on 2,4-D with and without dicamba. The commercial formulation of 2,4-D was highly lethal to lady beetle larvae; the LC90 of this herbicide was 13 % of the label rate. In this case, the "inactive" ingredients were a key driver of the toxicity. Dicamba active ingredient significantly increased lady beetle mortality and reduced their body weight. The commercial formulations of both herbicides reduced the proportion of males in the lady beetle population. The herbicides when used together did not act synergistically in their toxicity toward lady beetles versus when the chemistries were used independently. Our work shows that herbicide formulations can cause both lethal and sublethal effects on non-target, beneficial insects, and these effects are sometimes driven by the "inactive" ingredients. The field-level implications of shifts in weed management practices on insect management programs should receive further attention.


[Inflammation and host resistance against tumours. II. -- Antagonism between bradykinin and a fraction isolated from the supernatant of cultured malignant cells on the spreading of macrophages (author's transl)].
When murine peritoneal macrophages are incubated in presence of 10(-6) to 10(-8) M of bradykinin, their spreading is increased. When macrophages are incubated in presence of a low molecular weight fraction of the supernatant from cultured Lewis carcinoma's cells (AP) their spreading is decreased. When macrophages are incuated first with bradykinin and later on with AP, no inhibition of spreading is observed. When macrophages are incubated first with AP and later on with bradykinin, the increase of spreading is not observed.


Characteristics of nursing homes with high percentages of falls and falls with injuries among residents with obesity.
Obesity among United States nursing home (NH) residents is increasing. These residents have special care needs, which increases their risk for falls and falls with injuries. NH are responsible for ensuring the health of their residents, including minimizing falls. However, given the special care needs of residents with obesity, different factors may be important for developing programs to minimize falls among this group. We aimed to identify NH characteristics associated with falls and falls with injuries among residents with obesity. We used resident assessment data and logistic regression analysis. We found that rates of falls and falls with injuries among residents with obesity varied significantly based on for-profit status, size, acuity index, obesity rate among residents, and registered nurse hours per patient day. Recommendations are made as to how NH may be able to lower risk for falls and falls with injuries among their residents with obesity.


Interesterified palm oil impairs glucose homeostasis and induces deleterious effects in liver of Swiss mice.
Interesterified fats have largely replaced the partially hydrogenated oils which are the main dietary source of trans fat in industrialized food. This process promotes a random rearrangement of the native fatty acids and the results are different triacylglycerol (TAG) molecules without generating trans isomers. The role of interesterified fats in metabolism remains unclear. We evaluated metabolic parameters, glucose homeostasis and inflammatory markers in mice fed with normocaloric and normolipidic diets or hypercaloric and high-fat diet enriched with interesterified palm oil. Male Swiss mice were randomly divided into four experimental groups and submitted to either normolipidic palm oil diet (PO), normolipidic interesterified palm oil diet (IPO), palm oil high-fat diet (POHF) or interesterified palm oil high-fat diet (IPOHF) during an 8 weeks period. When compared to the PO group, IPO group presented higher body mass, hyperglycemia, impaired glucose tolerance, evidence of insulin resistance and greater production of glucose in basal state during pyruvate in situ assay. We also observed higher protein content of hepatic PEPCK and increased cytokine mRNA expression in the IPO group when compared to PO. Interestingly, IPO group showed similar parameters to POHF and IPOHF groups. The results indicate that substitution of palm oil for interesterified palm oil even on normocaloric and normolipidic diet could negatively modulate metabolic parameters and glucose homeostasis as well as cytokine gene expression in the liver and white adipose tissue. This data support concerns about the effects of interesterified fats on health and could promote further discussions about the safety of the utilization of this unnatural fat by food industry.


Perceived and Observed Treatment Gains Following PEERS: A Preliminary Study with Latinx Adolescents with ASD.
The Program for the Education and Enrichment of Relational Skills (PEERS) social skills intervention has demonstrated effectiveness for adolescents with autism spectrum disorder (ASD). However, studies have been limited by a lack of objective outcome measures and an underrepresentation of Latinx families. This pilot study extends the PEERS literature by utilizing an observational measure of conversational skills (Contextual Assessment of Social Skills; CASS) with a diverse sample of 13 adolescents with ASD (with parent groups conducted in English and Spanish simultaneously) and a control group of 11 neurotypical adolescents. Consistent with previous research, adolescents with ASD and their parents perceived improvements in social functioning following intervention, which were maintained four months later and corroborated by improvements in conversational skills.


[Preoperative accelerated radiotherapy for breast cancer--is it a historical delusion or a legitimate method of treatment?].
An effective procedure for preoperative chemoradiotherapy is suggested to intensify treatment of patients with extensive, local and/or regional, metastases of breast cancer. It uses medication followed by accelerated radiotherapy which offers the combined advantages of "concentrated" and "conventional" irradiation. High local and systemic effect is produced right at the outset thus making use of high-cost "first-line" cytostatics unnecessary and avoiding delay of surgical intervention.


Sensory involvement in distal myopathy (Welander).
Eleven patients with Welander distal myopathy were subjected to detailed sensory testing including measurements of perception thresholds for vibration and temperature in both hands and feet. The threshold values were compared with normal, age-corrected values and also with data from an age-matched control group consisting of patients with antecedent poliomyelitis with the same degree of paresis. The screening examination indicated impaired thermal sensibility in all 11 patients and impairment for at least one other sensory modality in 9 patients. In comparison with age-corrected normal values, the measured warm-cold difference limen was abnormal in the feet of 9 patients and the vibratory threshold at least at one test point in 6 patients. When compared with the data from the paretic controls, the thermal abnormality was significant with regard to warm and cold thresholds, the warm-cold difference limen and the heat pain threshold. The vibration threshold abnormality was significant in the feet. It is concluded that sensibility impairment is present in Welander's myopathy indicating a peripheral sensory neuropathy involving both unmyelinated (C-fibers) and myelinated fibers.


Changes of selected hematologic parameters during long-term immunoadsorption therapy.
Changes of selected hematologic parameters were studied in six patients treated with immunoadsorption for myasthenia gravis. The mean duration of therapy was 18.6months; 245 procedures were performed in total. Before and after each procedure the full blood count was examined. A decrease was noted in the hemoglobin concentration (median -7.27%) and in platelet count (median -5.63%) after each procedure. On the other hand, an increase in leukocyte count was noticed after each procedure (median 6.63%). However, in three patients, it was observed that with increasing numbers of procedures, the leukocyte count rises were lower during long-term treatment. We suppose that the decrease in hemoglobin concentration was induced both by the large volume of blood samples collected for laboratory testing and by the residual volume of blood which remains in the tubing. From the continuous decrease in leukocyte count after long-term treatment with immunoadsorption in our three patients, it may be concluded, that some type of immunomodulatory effect (immunosuppression) is involved.


Comparison of self-reported alcohol use with the alcohol biomarker phosphatidylethanol among young people in northern Tanzania.
The one-month Time Line Follow Back calendar (TLFB) and the Alcohol Use Disorders Identification Test (AUDIT) are used to collect self-reported alcohol intake data. We compared these instruments with the alcohol biomarker phosphatidylethanol (PEth) among young-people in northern Tanzania. AUDIT and TLFB were applied in a cross-sectional study of 202 young people (18-24 years), who reported using alcohol during the past year (103 male casual labourers; 99 college students). We assayed whole blood for PEth 16:0/18:1, using liquid chromatography-tandem mass spectrometry. For both self-report methods, alcohol consumption was high, particularly among men (e.g. a median of 54 drinks per month in labourers), and about half of male students (48%) reported hazardous or harmful levels of drinking (AUDIT ≥8). Almost half (49%) of participants were PEth-positive (median concentration 0.03μmol/L). There were significant positive correlations between reported total alcohol intake and PEth concentration in males (Spearman's correlation rs=0.65 in college students and rs=0.57 in casual labourers; p<0.001). Self-reported use in the past month was a sensitive marker of having a positive PEth result (≥0.01μmol/L) with 89% of those with a PEth positive result reporting alcohol use, and this was similar in all groups. The proportion of those with AUDIT scores ≥8 and AUDIT-C scores ≥6 among those with a high cut-off positive PEth result (≥0.30μmol/L) ranged between 94 and 100%. TLFB and AUDIT are sensitive measures to detect heavy alcohol use among young-people in northern Tanzania. They can be used to identify young people who may benefit from alcohol-focused interventions.


Chromatin proteins surrounding the d(G-T)n repeats and polyamine influence as revealed by photoaffinity labeling with reactive pd(A-C)6 derivatives.
The complementary-addressed modification of DNA and proteins in chromatin using photoreactive derivatives of pd(AC)6 has been studied. These oligonucleotides form complementary complexes with specific DNA sequences and modify both DNA and proteins in the vicinity of these regions, and can be used for investigation of the protein environment in DNA. We have demonstrated that photoreactive derivatives of oligonucleotides can quickly and efficiently modify chromatin proteins and seem to be promising for investigation of perturbations in chromatin structure during the cell cycle. A comparison between modified chromatin from synchronized cells has demonstrated differences in the sets of proteins modified in the S and G1/S phases of the cell cycle. An increase in spermine and spermidine concentrations leads to an increase in modification of definite chromatin proteins. It can be supposed that the B-Z transition that can be stabilized by the presence of natural polyamines is one of the reasons for the presence of single-stranded DNA regions, containing sets of (dG-dT)n and accessible for interaction with complementary oligonucleotides.


Patient-Provider Sexually Transmitted Infection Prevention Communication among Young Adult Sexual Minority Cisgender Women and Nonbinary Assigned Female at Birth Individuals.
Health care providers are an important source of sexually transmitted infection (STI) prevention information for young adult sexual minority women (SMW). However, very few studies have described patient-provider STI communication in this understudied and underserved population. We explore sexual minority women's experiences communicating with health care providers about sexual health, with particular attention to STI prevention, to inform programs and practices that address their unique needs and concerns. We conducted 29 in-depth interviews with sexual minority cisgender women and nonbinary assigned female at birth (AFAB) individuals aged 18-36 years. The sample included White (55%), Asian (31%), Black (17.2%), and Latina (3.4%) participants. We used thematic analysis with deductive and inductive coding to identify themes related to patient-provider STI prevention communication. Heteronormative health care provider assumptions inhibited participants' willingness to disclose their sexual orientation and discuss sexual health issues with providers. Most sexual health conversations focused on pregnancy and contraception, which many felt was irrelevant to them, and limited STI prevention recommendations to condom use. Participants reported that some providers lacked medical knowledge on AFAB-to-AFAB STI transmission and were not able to provide relevant STI prevention information. Providers' bias related to gender identity and race/ethnicity furthered some participants' mistrust generated from providers' heteronormative assumptions. Our study describes several barriers that AFAB sexual minorities felt inhibited their patient-provider sexual health communication. Interventions are needed to improve patient-provider STI prevention conversations with AFAB sexual minorities so they can access the sexual health information they need to effectively protect themselves from STIs.


Dynamic cerebral autoregulation in healthy adolescents.
: There is little information on the limits of cerebral autoregulation and the autoregulatory capacity in children. The aim of this study was to compare dynamic cerebral autoregulation between healthy adolescents and adults. : Seventeen healthy volunteers 12-17 years (n = 8) and 25-45 years (n = 9) were enrolled in this study. Bilateral mean middle cerebral artery flow velocities (Vmca; (cm/s)) were measured using transcranial Doppler ultrasonography (TCD). Mean arterial blood pressure (MAP) and end-tidal carbon dioxide were measured continuously during dynamic cerebral autoregulation studies. Blood pressure cuffs were placed around both thighs and inflated to 30 mmHg above the systolic blood pressure for 3 min and then rapidly deflated, resulting in transient systemic hypotension. The change of Vmca to change in MAP constitutes the autoregulatory response, and the speed of this response was quantified using computer model parameter estimation. The dynamic autoregulatory index (ARI) was averaged between the two sides. : Adolescents had significantly lower ARI (3.9 +/- 2.1 vs. 5.3 +/- 0.8; P=0.05), and higher Vmca (75.2 +/- 15.2 vs. 57.6 +/- 15.0; P<0.001) than adults. : The autoregulatory index is physiologically lower in normal adolescents 12-17 years of age than in adults.


Ventricular Tachycardia Ablation in Adult Congenital Heart Disease.
Patients with congenital heart disease (CHD) are at risk for late ventricular tachycardia (VT) and sudden cardiac death. Slow conducting anatomical isthmuses, bordered by unexcitable tissue created by valve annuli, ventricular incisions, and prosthetic material are the dominant substrate for macroreentrant monomorphic VTs in repaired CHD. These well-defined substrates allow for catheter or surgical transection with clear endpoints. This review elaborates on VT substrates in various CHD, and evolving mapping and ablation approaches. Because most research is conducted in patients with repaired tetralogy of Fallot, this malformation will serve as a paradigm.


Application of inorganic phosphate limitation to efficient isoprene production in Pantoea ananatis.
Establishment of an efficient isoprene fermentation process by adopting inorganic phosphate limitation as the trigger to direct metabolic flux to the isoprene synthetic pathway. We constructed isoprene-producing strains of Pantoea ananatis (a member of the Enterobacteriaceae family) by integrating a heterologous mevalonate pathway and a metabolic switch that senses external inorganic phosphate (Pi) levels. This metabolic switch enabled dual-phase isoprene production, where the initial cell growth phase under Pi-saturating conditions was uncoupled from the subsequent isoprene production phase under Pi-limiting conditions. In fed-batch fermentation using our best strain (SWITCH-PphoC/pIspSM) in a 1-l bioreactor, isoprene concentration in the off-gas was maintained between 300 and 460 ppm during the production phase and at 20 ppm during the cell growth phase, respectively. The strain SWITCH-PphoC/pIspSM produced totally 2·5 g l-1 of isoprene from glucose with a 1·8% volumetric yield in 48 h. This proof-of-concept study demonstrated that our Pi-dependent dual-phase production system using a P. ananatis strain as a producer has potential for industrial-scale isoprene fermentation. This Pi-dependent dual-phase fermentation process could be an attractive and economically viable option for the production of various commercially valuable isoprenoids.


Shape programmable magnetic pixel soft robot.
Magnetic soft robots (MSRs) can achieve controllable shape-morphing by magnetic programming to the magnetic elastomer. However, the magnetization profile is usually implemented on a continuous region and is unchangeable. The deformation and function design of MSR hence is limited. This study presents a programmable magnetic pixel soft robot (MPSR). By encapsulating liquid-metal/NdFeB composites into a Silicone shell, the thermal-magnetic response functional film with lattice-structure is fabricated, with the highest pixel resolution of 1 × 1 mm2. A piece of laser-assisted magnetic programming equipment is developed to implement magnetic encoding on discrete regions of the film. Therefore, a mathematical model is proposed to help calculate the magnetic codes according to the preset end shape. At last, several pixel-structure MPSRs are prepared and tested. Experimental results show that using the magnetic encoding technique, we can reconfigure the deformations and functions of the robot. This study provides a basis for the programmed shape regulation and motion design of the soft robot.


The Nutritious Eating with Soul (NEW Soul) Study: Study design and methods of a two-year randomized trial comparing culturally adapted soul food vegan vs. omnivorous diets among African American adults at risk for heart disease.
Previous research has found that African American (AA) vegetarians/vegans have a significantly lower body mass index and risk of hypertension compared to omnivores. The Nutritious Eating with Soul (NEW Soul) study partnered with local soul food restaurants/chefs to deliver two behavioral nutrition interventions to AA adults. NEW Soul examines the impact of two different culturally tailored diets (vegan and omnivorous low-fat) on changes in risk factors for cardiovascular disease (CVD). AA adults with overweight or obesity are recruited from the community in the Midlands of South Carolina. Eligible participants are randomized to follow one of two different culturally-adapted, soul food diets: a vegan diet emphasizing minimally-processed whole foods from plants or a low-fat omnivorous diet. Participants attend weekly group classes for the first six months, bi-weekly for the next six months, and monthly meetings for the last year. In addition to face-to-face content, participants also have access to private Facebook groups for their diet, podcasts, and online newsletters starting at six months. Primary outcomes include changes in body weight and CVD risk factors (lipids, blood pressure, glucose, and insulin) at 12 months. Secondary outcomes include changes in dietary intake. Participants complete assessments at baseline and at months 6, 12, and 24. The NEW Soul study is an innovative intervention aimed at improving dietary intake while maintaining traditional AA cultural food choices. Primary outcomes are expected by 2021.


ESR2 polymorphisms on prostate cancer risk: A systematic review and meta-analysis.
This meta-analysis was performed to address the association of 2 ESR2 gene polymorphisms (rs1256049 and rs4986938) with susceptibility to cancer. An extensive literature search for eligible candidate gene studies published before May 10, 2022, was conducted in PubMed, Medline, and Web of Science. The search strategy was as follows: (ESR2 OR ERβ OR ER beta OR estrogen receptor beta) AND (polymorphism OR mutation OR variation OR SNP OR genotype) AND (PCa OR PC OR prostate cancer). Potential sources of heterogeneity were sought out via trial sequential analysis, subgroup, and sensitivity analysis. Overall, a total of 10 articles involving 18,064 cases and 19,556 controls for 2 polymorphisms of the ESR2 gene were enrolled. In the stratified analysis of rs1256049, we found that Caucasians might be correlated with an increased risk of prostate cancer (PCa), while less susceptibility was found in Asians. We observed that rs4986938 was not associated with PCa risk. ESR2 rs1256049 polymorphism is associated with a higher risk of PCa in the Caucasian population and a lower risk of PCa in the Asian population.


Letter to the Editor - responses to Weisntein D, Simon M, Yehezkel E, Laron Z, Werner H. Insulin analogues display IGF-I-like mitogenic and antiactivity in cultured cancer cells.
We thank the team of Eli Lilly and Company for their critical appraisal of our study and for giving us the opportunity to clarify a number of points [1]. We agree with Kazda et al. that randomized clinical trials will best address any direct relationship between insulin analogues and cancer in man. We do not question the fact that tight control of blood glucose has dramatically advanced the lives of patients with diabetes. This article is protected by copyright. All rights reserved.


Parity and risk of developing breast cancer according to tumor subtype: A systematic review and meta-analysis.
Clinical breast cancer subtypes are categorized basing on the expression of hormone receptors and overexpression of the human epidermal growth factor receptor 2 (HER2). It is still unclear whether parity impact the risk of different breast cancer subtypes. We searched eight mainstream databases for published epidemiologic studies that assessed the relationship between parity and risk of breast cancer subtypes up to January 12, 2021. Parity number were unified into nulliparity and ever parity. The random-effects or fixed-effect models were used to calculate the pooled odds ratios (ORs) and 95% confidence intervals (CIs) among different subtypes. Restricted cubic spline analysis with four knots was applied to determine the relationship of parity number and risk of breast cancer subtypes. We pooled sixteen case-control and four cohort studies, and performed an analysis including 7795 luminal A, 3576 luminal B, 1794 HER2-overexpressing, and 5192 triple-negative breast cancer cases among 1135131 participants. The combined ORs for ever parity versus nulliparity indicated a 34% reduction in luminal A risk (OR=0.66, 95% CI: 0.56-0.78), and a 29% reduction in luminal B risk (OR=0.71, 95% CI: 0.63-0.81), there was no significant association in HER2-overexpressing or TNBC risk. In the dose-response analysis, we observed a potentially non-linear and gradually increasing protective relationship between the number of parity and luminal breast cancer risk. The effect of parity on breast cancer seems to vary among breast tumor subtypes, and it plays a protective role in luminal breast cancer.


Topology optimization design of three-dimensional multi-material and multi-body structure based on irregular cellular hybrid cellular automata method.
In recent years, Hybrid Cellular Automata Method (HCAM) has been successfully applied to solve structural topology optimization problems. However, there was no report on HCAM research of three-dimensional composite structure composed of multiple materials and multiple bodies. Therefore, in this paper, three-dimensional non-cube cells of irregular size (such as tetrahedral cells with adaptive changes inside length) and Finite Element Method (FEM) are introduced to extend HCAM, which is better and more flexibly to fit complex geometric shapes. Furthermore, a better structure configuration of multi-material and multi-body structure is obtained. The typical example study showed that the proposed topology optimization method could effectively remove the redundant materials of multi-material and multi-body structure, and the optimized structure configuration could still meet the requirements of the original condition after geometric reconstructed. Thus it provided a reference for the intelligent design of other products.


Protective role of quercetin and kaempferol against oxidative damage and photosynthesis inhibition in wheat chloroplasts under arsenic stress.
Arsenic (As) toxicity negatively impacts plant development, limits agricultural production, and, by entering the food chain, endangers human health. Studies on the use of natural and bioactive molecules in increasing plants' resistance to abiotic stressors, such as As, have gained increasing attention in the last few years. Flavonols are plant secondary metabolites with high potential in stress tolerance due to their roles in signal transmission. Therefore, the focus of this study was to examine the effects of two flavonols, quercetin (Q, 25 μM) and kaempferol (K, 25 μM), on growth parameters, photosynthesis, and chloroplastic antioxidant activity in wheat leaves under As stress (100 μM). As stress reduced the relative growth rate by 50% and relative water content by 25% in leaves. However, applying Q and/or K alleviated the As-induced suppression of growth and water relations. Exogenous phenolic treatments reversed the effects of As toxicity in photochemistry and maintained the photochemical quantum efficiency of the Photosystem II (Fv /Fm ). As exposure increased, the H2 O2 content in wheat chloroplasts by 42% and high levels of H2 O2 accumulation were also observed in guard cells in confocal microscopy images. Analysis of the chloroplastic antioxidant system has shown that Q and K applications increase the activity of antioxidant enzymes, including superoxide dismutase, peroxidase, and ascorbate peroxidase. Phenolic applications have induced the ascorbate-glutathione (AsA-GSH) cycle in charge of the protection of the cellular redox balance in different ways. It has been determined that Q triggers the AsA renewal, and K maintains the GSH pool. As a result, Q and K applications provide tolerance to wheat plants under As stress by increasing the chloroplastic antioxidant system activity and protecting photosynthetic reactions from oxidative damage. This study reveals the potential use of plant phenolic compounds in agricultural systems as a biosafe strategy to enhance plant stress tolerance, hence increasing yield.


Ultrastructural observations on the erythrocytes and thrombocytes of the tuatara, Sphenodon punctatus (Gray).
The erythrocytes of Sphenodon punctatus (Gray) are nucleated, ellipsoidal and flattened, and contain 55--65 microtubules in their marginal band. The thrombocytes are also flattened, ellipsoidal, nucleated cells and in electron-microscopic preparations occurred in aggregrates. The thrombocytes appeared to be 'activated' and possessed many pseudopodia which were devoid of organelles. The latter were concentrated in the perinuclear region and were encircled by a ring of microtubules. The organelles included ribosomes, mitochondria, membrane--bound dense material and numerous actin-like microfilaments. Cytoplasmic vacuoles contained a moderately dense, filamentous material and/or spheroidal electron-dense inclusions, beta-glycogen particles were scattered in the general cytoplasm and were most concentrated in the pseudopodia. The erythrocytes and thrombocytes of S. punctatus are compared with those in other vertebrates.


Site-Selective Installation of Nϵ -Modified Sidechains into Peptide and Protein Scaffolds via Visible-Light-Mediated Desulfurative C-C Bond Formation.
Post-translational modifications (PTMs) enhance the repertoire of protein function and mediate or influence the activity of many cellular processes. The preparation of site-specifically and homogeneously modified proteins, to apply as tools to understand the biological role of PTMs, is a challenging task. Herein, we describe a visible-light-mediated desulfurative C(sp3 )-C(sp3 ) bond forming reaction that enables the site-selective installation of Nϵ -modified sidechains into peptides and proteins of interest. Rapid, operationally simple, and tolerant to ambient atmosphere, we demonstrate the installation of a range of lysine (Lys) PTMs into model peptide systems and showcase the potential of this technology by site-selectively installing an Nϵ Ac sidechain into recombinantly expressed ubiquitin (Ub).


Antibodies against C1q in patients with systemic lupus erythematosus.
The first component of the classical pathway of complement (C1q) is considered to be involved in the pathogenesis of systemic lupus erythematosus (SLE). This view is based on the observation that a substantial number of patients with SLE develop hypocomplementemia with depletion of the classical pathway components, and C1q has been shown to play an important role in the clearance of immune complexes and apoptotic bodies. In addition, homozygous C1q deficiency is the strongest disease susceptibility gene for the development of SLE that has been characterised in humans. However, most SLE patients have no primary complement deficiency. Hypocomplementemia in SLE patients is a secondary event and often associated with antibodies against C1q (anti-C1q). Although anti-C1q have been found in a number of distinct autoimmune disorders, they are best described in patients with SLE where they strongly correlate with renal flares. Current data suggest that the occurrence of anti-C1q in SLE patients is necessary but not sufficient for the development of proliferative lupus nephritis, suggesting an interference with the normal function of the complement system.


Jacob Bronowski's principle of tolerance.
In The principle of tolerance, Jacob Bronowski discusses a vital but neglected characteristic of science: that ''all information is imperfect'', and ''our ability to work and act in the real world depends on our accepting a tolerance in our recognition and in our language''. The nineteenth century ideal that "science should speak the perfect factual truth has turned out to be inaccessible". But this should not be a cause for regret, because "if things had to be identical before you could recognize them, you would never recognize anything at all". The principle of tolerance is the judgment that two instances are sufficiently similar that we can treat them as the same for present purposes. "Tolerance - is the essential safeguard, the essential degree of coarseness which makes it possible to work with abstract entities in the real world". Too much tolerance and you are misled by random variation; too little tolerance and you lose valuable information. The most beneficial degree of tolerance must be a matter of judgment because it cannot be determined in advance. So, the best level of tolerance is known only retrospectively, by comparing the rate of progress of science when a greater or lesser degree of tolerance is assumed. The judgment of tolerance which led to the fastest scientific progress is justified as having been the best. Science therefore needs to tolerate different judgments of tolerance among scientists, allowing a multiplicity of levels of tolerance to coexist and compete. Bronowski's principle of tolerance locates the roots of science in the domain of human creativity, in the necessity for personal judgment in science, and in the provisional and progressive nature of scientific truth: "You have to tell the truth the way you see it. And yet you have to be tolerant of the fact that neither you nor the man you are arguing with is going to get it right".


Hepatitis B immune complex glomerulonephritis: simultaneous glomerular deposition of hepatitis B surface and e antigens.
A case of a 29-year-old homosexual male with chronic hepatitis B infection, cryoglobulinemia, and glomerulonephritis is described. The glomerular lesions were not readily classified, but exhibited features consistent with immune complex deposits, in both peripheral loop (predominantly epimembranous) and mesangial sites. Immunofluorescence studies, which included the use of a monoclonal antibody, showed that HBsAg was present in mesangial deposits but not in peripheral loop deposits. Immunoperoxidase studies employing HRP-conjugated anti-HBc and anti-HBe provided evidence that the epimembranous deposits contained HBe. Studies of the patient's serum revealed high titers of HBsAg, low titers of HBeAg, as well as anti-HBe and anti-HBc. The cryoglobulins contained small amounts of HBsAg, HBeAg, and anti-HBc, but anti-HBe and anti-HBs antibodies were not found. The possible mechanisms accounting for accumulation of HBsAg and HBeAg in glomeruli are discussed. In addition, the literature concerning the nature of hepatitis B antigens found in glomerular deposits is reviewed.


Emergence of superconductivity at 45 K by lanthanum and phosphorus co-doping of CaFe₂As₂.
Co-doping of lanthanum and phosphorus in CaFe₂As₂ induces superconductivity at 45 K. This superconducting transition temperature is higher than the 38 K transition in Ba₁-xKxFe₂As₂, which is the maximum found thus far among the 122 phases. Superconductivity with a substantial shielding volume fraction was observed at 0.12 ≤ x ≤ 0.18 and y = 0.06 in Ca₁-xLaxFe₂(As₁-yPy)₂. The superconducting phase of the present system seems to be not adjacent to an antiferromagnetic phase.


Prognostic features, human papillomavirus status, and epidermal growth factor receptor expression in oral squamous cell carcinoma in young adults.
There is still debate in literature about the survival outcomes of patients who have cancer of the oral cavity when young. Hence the aims were (1) to estimate disease-free survival, overall survival, and cause-specific survival in patients who developed oral cavity squamous cell carcinoma between 18 and 40 years of age and (2) to assess the clinicopathologic factors including detection of human papillomavirus and epidermal growth factor receptor (EGFR) overexpression in primary lesions affecting recurrence. This is a retrospective case-note review and reevaluation of histopathologic slides of patients treated more than 25 years. Descriptive statistics, Cox proportional hazard models, and Kaplan-Meier survival curves were used for statistical analysis. A total of 62 patients were treated, with mean follow-up of 11.4 years. Forty-five were oral tongue tumors and 43 had stage I or II disease. The 5-year disease-free survival was 73.5%. The 10-year overall survival and cause-specific survival rates were 81.8% and 83.4%, respectively. Smoking and alcohol intake were not seen as risk factors in this population. Multivariate modeling identified only nodal involvement as significantly associated with overall survival and only extracapsular spread as significantly associated with locoregional recurrence. At 5 years after treatment, the cause-specific survival was 100% for patients with low EGFR expression and 81.1% for patients with high EGFR expression (hazard ratio for high vs low, 3.1; 95% confidence interval, 0.4-406.9; P = .46). Human papillomavirus was not detected in all but 2 tumor specimens. Survival outcomes are quite good in young patients with oral cancer.


Nutrient shortage triggers the hexosamine biosynthetic pathway via the GCN2-ATF4 signalling pathway.
The hexosamine biosynthetic pathway (HBP) is a nutrient-sensing metabolic pathway that produces the activated amino sugar UDP-N-acetylglucosamine, a critical substrate for protein glycosylation. Despite its biological significance, little is known about the regulation of HBP flux during nutrient limitation. Here, we report that amino acid or glucose shortage increase GFAT1 production, the first and rate-limiting enzyme of the HBP. GFAT1 is a transcriptional target of the activating transcription factor 4 (ATF4) induced by the GCN2-eIF2α signalling pathway. The increased production of GFAT1 stimulates HBP flux and results in an increase in O-linked β-N-acetylglucosamine protein modifications. Taken together, these findings demonstrate that ATF4 provides a link between nutritional stress and the HBP for the regulation of the O-GlcNAcylation-dependent cellular signalling.


Evidence that trans-bilayer interdigitation of glycosphingolipid long chain fatty acids may be a general phenomenon.
'Interdigitation' is a term coined to describe the phenomenon whereby pure phosphatidylcholines with intramolecular fatty acid chain length heterogeneity when hydrated to form bilayers may insert the methyl ends of long fatty acids from one side across more than half of the membrane thickness to protrude amongst the acyl chains of the opposite side of the bilayer (Keough, K.M.W. and Davis, P.J. (1979) Biochemistry 18, 1453-1459; Huang, C. and Mason, J.T. (1986) Biochim. Biophys. Acta 864, 423-470). In this article we address the fate of long fatty acid chains of glycosphingolipids present as minor components in membranes of non-interdigitating phosphatidylcholines. In this pursuit, derivatives of galactosyl ceramide, lactosyl ceramide, globoside and GM1 were synthesized having either 18-carbon or 24-carbon fatty acid with a spin label covalently attached at C-16. Labelled glycolipids were incorporated at 1-2 mol% into bilayers of synthetic phosphatidylcholines, their mixtures with cholesterol, or natural egg phosphatidylcholine. In each case the C-16 carbon of the glycolipid long chain fatty acid showed considerably greater 'order' and immobility than did C-16 of the fatty acid which was similar in length to the host matrix phospholipids. We interpret this as strong evidence that the long chain fatty acid interdigitates across the mid point of the bilayer in the systems studied. Clearly this phenomenon did not require that the phospholipid host matrix have mixed chain lengths. Furthermore it was totally independent of glycolipid family: for a given host matrix and (glycolipid) fatty acid chain length the order parameter values found were the same amongst all four glycolipid families tested.


Robotic-assisted total knee arthroplasty in clinical practice: protocol for a randomised controlled trial.
Between 2 and 20% of patients who undergo total knee arthroplasty (TKA) report restricted motion and anterior knee pain. Non-optimal alignment of the implant components is a common cause of such complaints. Robotic-assisted TKA has been advocated to improve the accuracy of component positioning to match patients' anatomy and biomechanics. However, the advantages of robotic surgery over conventional freehand TKA are still unclear. The present study is a protocol for a single-blind clinical trial in which patients will be randomly allocated to undergo either robotic-assisted TKA or conventional freehand TKA. A restricted kinematic alignment with medial para-stellar approach shall be made in all patients. The present study follows the SPIRIT guidelines. The primary outcome of interest is to compare robotic TKA versus traditional freehand TKA in terms of patient-reported outcome measures (PROMs), length of hospitalisation, blood values, blood transfusion units, and range of motion. The second outcome of interest is to evaluate the accuracy of component positioning of robotic-assisted TKA compared to the conventional freehand TKA.Level of evidence Level I, randomised controlled trial.Registration German Registry of Clinical Trials (ID: DRKS00030614).


Corticosteroids in patients with antiovarian antibodies undergoing in vitro fertilization: a prospective pilot study.
Antiovarian autoantibodies (AOA) have been associated with reproductive failure, especially in in vitro fertilization (IVF) patients. Thus, the success rate of IVF might be improved by the use of corticosteroids. However, therapeutic trials with these drugs have yielded conflicting results, particularly because of heterogeneous inclusion criteria. Among women with previous IVF failure, we selected those who presented with a positive serum AOA assay, and analysed the efficacy of corticosteroids in improving the IVF outcome in these patients. One hundred patients with serum AOA detected by ELISA and at least two previously failed IVF attempts were selected. These patients underwent a further IVF cycle with 0.5 mg/kg prednisolone, started on the first day of the treatment cycle. In patients who became pregnant, corticosteroids were administered until the end of the first trimester of pregnancy and then progressively discontinued. AOA were assessed before and after oocyte retrieval. Clinical data of the corticosteroid-treated cycle were compared with data from the preceding IVF cycle for each patient. No adverse effects resulting from corticosteroids were observed. Post oocyte retrieval antiovarian IgG were significantly lower in corticosteroid-treated attempts when compared with the preceding cycles. Twenty-six pregnancies resulted in the birth of 30 healthy children. The pregnancy rate, implantation rate, and live birth rate were 38.8%, 17.8%, and 26.5% respectively in prednisolone-treated cycles. This study confirms the usefulness of corticosteroids in improving the success rate in a subset of patients with previous IVF failure and significant serum AOA levels.


A seroepidemiologic study of a measles outbreak, Yamagata Prefecture, Japan, 2017: The estimation of spreaders using serological assays in a measles elimination setting.
In regions where the endemic measles virus has been eliminated, early detection of contagious patients is important for preventing the spread of measles and sustaining elimination. To investigate whether serological assays can be used for the estimation of highly infectious patients with measles, we performed a seroepidemiologic study of a measles outbreak in Yamagata Prefecture, Japan, in 2017. We tested plaque reduction neutralization (PRN), IgG avidity, and gelatin particle agglutination (PA) assays in 31 patients with measles, subdivided into two super-spreaders, three spreaders, and 26 non-spreaders. Simultaneously, these results were compared with the cycle threshold (Ct) of a semi-quantitative real-time reverse transcription PCR for the measles virus from throat swab specimens. In the PRN assay, one super-spreader and two spreaders lacked protective antibodies. The IgG avidity assay showed that two super-spreaders and one spreader had low avidity. The PA assay indicated that two super-spreaders and two spreaders lacked protective antibodies. Comparison of the results of the three serological assays and Ct revealed that patients whose antibody titers were judged as low in the IgG avidity and PA assays showed low Ct (i.e., high viral load), whereas non-spreaders tended to show low viral load. Our preliminary seroepidemiologic analysis of a population of 31 patients with measles suggests that PA and IgG avidity assays may be used for the identification of super-spreader/spreader candidates. However, further investigations are necessary to validate the robustness of these serological assays in detecting contagious measles cases.


c-Jun-N Terminal Kinase-Mediated Degradation of γ-Glutamylcysteine Ligase Catalytic Subunit Inhibits GSH Recovery After Acetaminophen Treatment: Role in Sustaining JNK Activation and Liver Injury.
Aims: Acetaminophen (APAP) overdose is the most common cause of acute liver failure in the United States. Liver glutathione (GSH) depletion and sustained P-JNK (c-Jun-N-terminal kinase) activation are key modulators in the mechanism leading to hepatic necrosis. GSH depletion is directly related to the consumption of GSH by APAP metabolites N-acetyl-p-benzoquinone imine (NAPQI). We previously noticed that the glutamate-cysteine ligase catalytic subunit (GCLC), the rate-limiting enzyme in GSH synthesis, rapidly decreased at the same time P-JNK increased. Our aims were to determine if JNK was directly responsible for decreased GCLC causing impaired recovery of GSH and if this was an important factor in determining APAP hepatotoxicity. Results: Immunoprecipitation of JNK after APAP identified binding to GCLC. Expression of a site-directed mutated canonical JNK docking site in GCLC was resistant to degradation and led to rapid restoration of GSH and inhibited sustained JNK activation. The JNK-resistant GCLC markedly protected against necrosis and alanine aminotransferase (ALT) elevation. The proteolytic loss of GCLC was abrogated by inhibition of the proteasome, ubiquitination, or calpain. Innovation: Using mutated-GCLC resistant to JNK-induced degradation, the results allowed us to identify impaired GSH recovery as an important contributor to early progression of APAP toxicity after the metabolism of APAP and initial GSH depletion had occurred. Conclusion: Activated JNK interacts directly with GCLC and leads to proteolytic degradation of GCLC. Degradation of GCLC impairs GSH recovery after APAP allowing the continued activation of JNK. Conversely, rapid recovery of GSH inhibits the sustained activation of the mitogen-activated protein (MAP) kinase cascade and dampens APAP toxicity by suppressing the continued activation of JNK. Antioxid. Redox Signal. 38, 1071-1081.


Evidence for the involvement of hydroxyl radicals in nickel mediated enhancement of lipid peroxidation: implications for nickel carcinogenesis.
The administration of nickel to rats resulted in enhanced hepatic lipid peroxidation, levels of glutathione and iron with a concomitant decrease in glutathione peroxidase activity. These effects were dose dependent. Enhanced lipid peroxidation was found to be inhibited by the exogenous addition of ethylenediamine tetraacetic acid (EDTA), benzoate and ethanol while catalase and superoxide dismutase were ineffective in this regard. Our data strongly suggest the involvement of hydroxyl radicals in the nickel mediated enhancement of lipid peroxidation which may have their implications in the carcinogenicity of nickel compounds.


Onychodystrophy and tumor-stage mycosis fungoides confined to a single digit: report of a case and review of nail findings in cutaneous T-cell lymphoma.
Mycosis fungoides is often considered one of the great disease imitators presenting with a wide variety of clinical manifestations. We present a case of tumor-stage mycosis fungoides involving a single digit clinically presenting with diffuse swelling of the digit and onychodystrophy. Histologic findings included a reticular dermal lymphocytic infiltrate with increased ratio of CD4:CD8 cells. The patient was treated with radiation resulting in complete resolution. Nail involvement with mycosis fungoides has been scarcely reported, but when present ranges from 20-nail dystrophy to yellow discoloration. The disease often involves most of the nails when present.


Does heart failure increase the risk of incident cancer? A meta-analysis and systematic review.
Recently, several studies have demonstrated that heart failure (HF) may increase the risk of incident cancer. However, this association has not been statistically and systematically verified by any comprehensive pooled analyses. We performed a meta-analysis on cancer morbidity and co-mortality of adults with HF in a large sample size to explore the relationship between HF and the risk of developing cancer. From inception to April 2019, we searched PubMed and EMBASE for published relevant articles on patients with HF diagnosed with cancer afterwards, with reported outcomes of morbidity and mortality. Two investigators independently reviewed these included studies. Study data were independently extracted using predefined data extraction forms. Random and fixed-effects models were fit for the study duration. This analysis consisted of 4 cohort studies comprising 5,004,251 participants. The relative risk (RR) for incident cancer was 1.22 (95% confidence interval (CI), 1.13-1.33) indicating that patients with HF may have a higher risk of developing cancer. The pooled RR of co-mortality was 2.03 (95% CI, 1.13-3.65), indicating that HF associated with cancer increases the risk of mortality. In this meta-analysis and systematic review, our results demonstrated that heart failure may increase the risk of incident cancer and that HF associated with cancer increases the risk of mortality.


Community Barriers, Enablers, and Normative Embedding of Second Year of Life Vaccination in Ghana: A Qualitative Study.
Coverage rates for second year of life (2YL) vaccination still lag behind infant vaccination in most settings. We conducted a qualitative baseline study of community barriers and enablers to acceptance of 2YL vaccines in Ghana 4 years after introducing the second dose of the measles-containing vaccine. We conducted 26 focus group discussions in 2016 with men and women caregivers from mixed urban, peri-urban, and rural areas, as well as pastoralists, using semistructured topic guides based on the Health Belief Model theory. We conducted a thematic analysis of the discussion using NVivo software. We use Normalization Process Theory to contextualize results as a snapshot of a dynamic process of community adaptation to change to a well-established routine immunization schedule following 2YL introduction. Routine immunization for infants enjoys resilient demand, grounded in strong community norms despite surprisingly low levels of vaccine literacy. Despite best practices like integration with the established 18-month "weighing visit," demand for 2YL vaccination is still conditional on individual awareness and competition for limited maternal time, household resources, and other health concerns. An embedded norm that children should be fully vaccinated by 12 months originally sustained Expanded Programme for Immunization goals but now discouraged some caregivers from seeking vaccines for children perceived to be "too old" to vaccinate. Caregivers cited greater costs and inconvenience of taking older, heavier children in for vaccination and anticipated criticism from both community members and health care providers for coming "too late." Closing the 2YL vaccination coverage gap will ultimately require modifying embedded norms among caregivers and health care providers alike. Time is necessary but not sufficient to reach this goal. Progress can be accelerated by increasing the level of community and institutional engagement and adapting services where possible to minimize added costs to caregivers of vaccinating older children.


Health Related Quality of Life in Autistic Youth and Their Families.
The construct Quality of Life (QoL) involves a range of factors related to one's well-being. Individuals on the autism spectrum have been previously reported to have lower QoL. The purpose of the present study is to examine QoL in autistic individuals and their families and to evaluate associations between QoL and measures of functioning using the PedsQL 4.0. Thirty-six autistic youth (ages 9-21 years) and their caregivers completed the PedsQL. Caregivers completed additional measures of their children's adaptive, social, behavioral, and emotional functioning. Parents and youth generally agreed on the PedsQL, with the exception of the Social Functioning domain, which youth rated higher. The parent rated PedsQL did not correlate with most areas of caregiver-rated functioning; however, there were significant negative correlations between irritability and family functioning. Limitations of this study included small sample size; broad range of intellectual functioning; lack of sample diversity; and likely recruiting bias for a drug treatment study. Despite limitations, HRQoL is an important feature that should be measured in addition to features of autism or symptoms of co-occurring symptoms.


Propylsulfonic and arenesulfonic functionalized SBA-15 silica as an efficient and reusable catalyst for the acidolysis of soybean oil with medium-chain fatty acids.
The objective of this work was to develop a feasible ecofriendly process to produce medium-chain fatty acid (MCFA)-enriched structured lipids (SLs) in heterogeneous manners. For this purpose, the propyl-SO3H or arene-SO3H-modified SBA-15 materials were prepared through a surface functionalization of SBA-15 silica with propyl-SO3H and arene-SO3H groups. The organosulfonic acid-functionalized SBA-15 materials were characterized by Brönsted acidity determination, elemental analysis, XRD, C(13) MAS NMR, FT-IR, SEM, TG, TEM, and N2 adsorption-desorption techniques. Results showed that the propyl-SO3H and arene-SO3H groups were successfully tethered on the SBA-15 support, and the ordered mesoporous structure of SBA-15 silica was well retained after the organofunctionalization. This organic-inorganic hybrid material displayed high surface acidities and high activities in the acidolysis of soybean oil with caprylic or capric acid to produce SLs containing MCFAs. The influences of processing parameters on the reaction were investigated. The two studied catalysts showed an excellent recyclability for the reaction.


Immunologically distinct binding molecules for progesterone and RU38486 in the chick oviduct cytosol.
[3H]Progesterone and [3H]RU38486 binding in the chick oviduct cytosol is associated with macromolecules which sediment as 8 S and 4 S moieties, respectively, in molybdate-containing 5-20% sucrose gradients. The [3H]progesterone binding could be displaced by excess progesterone, but not by RU38486. Conversely, the [3H]RU38486 binding was able to compete with RU38486 but not by excess progesterone. A preparation containing antibodies against chick oviduct progesterone receptor recognized only the [3H]progesterone-receptor complex but not the 4 S, [3H]RU38486 binding component of the chick cytosol. In the calf uterus cytosol, [3H]R5020 (a synthetic progestin) and [3H]RU38486 were associated with 8 S molecules and the peaks of radioactivity were displaceable upon preincubation with radionert steroids. In addition, the complexes were recognized by antibodies to chick oviduct progesterone receptor. Our data suggest that in the chick oviduct cytosol, RU38486 does not bind to progesterone receptor, but interacts with an immunologically distinct macromolecule.


Handgrip strength asymmetry is associated with slow gait speed and poorer standing balance in older Americans.
Handgrip strength (HGS) asymmetry may help identify the functional asymmetries that contribute to mobility limitations. We sought to determine the associations of HGS asymmetry on gait speed and standing balance in older Americans. The analytic sample included 8,396 adults aged ≥65-years for the last wave in which they participated in the 2006-2016 Health and Retirement Study. Participants were categorized into asymmetry groups based on the degree of HGS asymmetry. Persons with gait speed <0.8 meters/second were slow. Balance scores ranged from 0-4 with lower scores representing poorer standing balance. Older Americans with 20.1%-30.0% asymmetry had 1.22 (95% confidence interval (CI): 1.05-1.42) greater odds for slow gait speed, while those with >30.0% asymmetry had 1.23 (CI: 1.05-1.44) greater odds. Persons with 10.1%-20.0%, 20.1%-30.0%, and >30% asymmetry had 1.09 (CI: 1.07-1.22), 1.23 (CI: 1.07-1.42) and 1.40 (CI: 1.22-1.61) greater odds for poorer static balance, respectively. Those in each individual asymmetry group had greater odds for slow gait speed: 1.14 (CI: 1.03-1.26) for >10.0%, 1.19 (CI: 1.07-1.33) for >20.0%, and 1.16 (CI: 1.01-1.35) for >30.0%. Similar results were observed for poorer balance: 1.20 (CI: 1.09-1.32) for >10.0%, 1.27 (CI: 1.15-1.41) for >20.0%, and 1.31 (CI: 1.16-1.49) for >30.0%. Every 10% asymmetry increase was associated with 1.62 (CI: 1.32-1.99) greater odds for poorer balance. The bimanual aspects of HGS asymmetry may reflect the bilateral movements required for mobility, and the relationship between upper and lower extremity strength and function may elucidate our findings.


Epigallocatechin-3-gallate protects immunity and liver drug-metabolism function in mice loaded with restraint stress.
(-)-Epigallocatechin-3-gallate (EGCG) is the most abundant polyphenolic compound present in green tea and has been shown to possess bio-activities. In this study, we investigated the protective effects of EGCG against restraint stress (RS)-induced liver injury and immunosuppression. EGCG (10, 20 and 40 mg/kg) was orally administered to mice daily for 7 days before modeling the restraint stress. lood, liver and broncho-alveolar lavage fluid (BALF) samples were collected and tested. We found that EGCG significantly reduced the release of stress hormones to weak restraint stress response. EGCG effectively improved hepatic damage by decreas the serum levels of alanine aminotransaminase (ALT) and aspartate transaminase (AST) in restraint-challenged mice. Furthermore, EGCG also significantly prevented the release of H2O2, NOS and 8-isoprostane, and reduced the levels of interleukin (IL)-1β, IL-2,and IL-6 restrained mice. EGCG can normal the level of cytochrome P450 (CYP450) 1A2, 2D22, 2E1 and 3A11 that induced by restraint stress., the inhibition status of T cells subsets in serum and gA in BALF were significantly relieved EGCG pretreatment. Taken together, our data suggest that EGCG possesse hepatic- and immune-protective properties against restraint stress through its anti-oxidant, anti-inflammatory and immunomodulatory activities.


Haptic model fabrication for undergraduate and postgraduate teaching.
Three series of cone-beam computed tomography (CBCT) patient data sets were obtained. These data were exported into DICOM and MIMICS (Materialise's Interactive Medical Image Control System; Materialise, Leuven, Belgium) and were imported for differentiation of various tissues (bone, teeth, and nerve). After transferring the data to an additive manufacturing machine, three-dimensional (3D) haptic models were fabricated using clear and opaque materials. These models were integrated into phantom heads normally used for education in undergraduate dental education. 3D prototype CBCT-based haptic patient models can be used in undergraduate and postgraduate education. Students can simulate routine standard oral surgical procedures with supervision under 'dry conditions'. Residents can simulate advanced and complex cases before performing the real operation.


Elevated progesterone during ovarian stimulation for IVF.
There is an ongoing debate regarding the impact of premature progesterone rise on the IVF outcome. The objective of this review is to assess evidence of poorer ongoing pregnancy rate in IVF cycles with elevated serum progesterone at the end of follicular phase in ovarian stimulation. It also explores the origin of the progesterone rise, potential modifying factors and possible methods to prevent its rise during ovarian stimulation. This review draws on information already published from monitoring progesterone concentrations at the end of follicular phase in ovarian stimulation. The databases of Medline and PubMed were searched to identify relevant publications. Good-quality evidence supports the negative impact on endometrial receptivity of elevated progesterone concentrations at the end of the follicular phase in ovarian stimulation. Future trials should document the cause and origin of premature progesterone in stimulated IVF cycles. There is an ongoing debate regarding the impact of premature progesterone rise on the IVF outcome. The objective of this review is to assess evidence of poorer ongoing pregnancy rate in IVF cycles with elevated serum progesterone at the end of follicular phase in ovarian stimulation. It also explores the origin of the progesterone rise, potential modifying factors and possible methods to prevent its rise during ovarian stimulation. This review draws on information already published from monitoring progesterone concentrations at the end of follicular phase in ovarian stimulation. The databases of Medline and PubMed were searched to identify relevant publications. Good-quality evidence supports the negative impact on endometrial receptivity of elevated progesterone concentrations at the end of follicular phase in ovarian stimulation. Future trials should document the cause and origin of premature progesterone in stimulated IVF cycles.


Absolute stereochemistry of immunosuppressive macrolide brasilinolide A and its new congener brasilinolide C.
Brasilinolide A (2) is a 32-membered polyhydroxyl macrolide with immunosuppressive activity isolated from a pathogenic actinomycete, Nocardia brasiliensis IFM0406. The absolute configurations at 26 chiral centers of 2 and its new congener, brasilinolide C (1), were determined on the basis of the spectral data of 1 and degradation products derived from 1 and 2.


Prevalence and factors associated with incomplete immunization among children aged 12 to 35 months in Eswatini: analysis of the Eswatini multiple indicator cluster survey.
incomplete childhood immunization is a significant public health challenge as children continue to succumb to vaccine-preventable diseases in most developing countries. Studies on childhood immunization conducted in Eswatini are sparse. Therefore, the present study assessed the prevalence of incomplete childhood immunization in Eswatini and further explored associated factors among children aged 12 to 35 months. using data from Eswatini multiple indicator cluster survey 5 (EMICS5), a cross-sectional analysis with 978 children aged 12 to 35 months was conducted. This is the latest available data in the public domain. The survey was conducted from July 2014 to October 2014. The primary outcome variable was incomplete immunization. Univariate and multivariate logistic regressions were used to examine the association between selected variables and incomplete immunization. the mean age of the children was 23.45±6.92 months, 50.2% were boys, and 74.1% lived in rural areas. The prevalence of incomplete immunization was 31.5%. Increased child´s age, being a girl, increased caregiver´s age, and increased number of children under-five years in the household and residing in the Manzini or Hhohho region were significantly associated with incomplete immunization. the EMICS 5 revealed a high prevalence of incomplete immunization in Eswatini. Health promotion activities such as empowering women and caregivers of children through health education about child health should be emphasized. Where feasible, outreach services and door-to-door immunization should be strengthened to improve immunization coverage in the country and cover dropouts.


Estimation of human body built in Egyptians.
Identification of an unknown body and prediction of growth from specific body measurements are very important tasks in the fields of physical anthropology and forensic medicine. Height and weight are two factors among others required to establish individuality of an unidentified body. In the present work, an attempt has been made to calculate the stature and weight from percutaneous tibial length and bimalleolar breadth. The study was carried out on 1000 living Egyptian individuals comprising 500 males and 500 females; their age was between 19 and 21 years. A significant positive correlation between stature and tibial length in both sexes was recorded. The coefficient of determination showed that 56% of variation in stature was due to tibial length and bimalleolar breadth in males, while in females the coefficient of determination was 23%. On the other hand, the coefficient of determination for weight showed that 11% of variability in weight was due to tibial length and bimalleolar breadth in males, while in females it was 5%. Linear regression analysis was done for all variables in all cases. The regression equation formulae are helpful in the estimation of stature and weight of the deceased from tibial length and bimalleolar breadth when leg or foot is the only portion available for autopsy examination.


Surgical Management and Oncologic Outcomes for Local Retroperitoneal Recurrence of Renal Cell Carcinoma After Radical Nephrectomy.
Local retroperitoneal recurrence (RPR) after racial nephrectomy (RN) of renal cell carcinoma (RCC) remains a therapeutic challenge and has a poor prognosis. We aimed to compare the oncological outcomes of patients with RPR treated with RPR surgery or targeted therapy alone and assess the prognostic factors of these patients. This is a retrospective multi-center study of patients with RPR after prior RN treated with or without surgical treatment from 2008 to 2020. RPR of RCC is defined as an ipsilateral recurrence confined to the renal fossa, adrenal gland or retroperitoneal lymph nodes after prior nephrectomy, which was diagnosed by cross-sectional imaging. Clinical and pathological features, perioperative complications were reported using descriptive statistics. Cancer-specific survival (CSS) was evaluated by Kaplan-Meier method and studied using Cox proportional hazards model. Median follow-up period was 35 months (IQR 20-61) for the RPR surgery group and 23 months (IQR 9-40.5) for the targeted therapy group. No patients had distant metastatic disease at the time of RPR diagnosis. Treatment with RPR surgery resulted in significantly longer CSS than targeted therapy alone (P < .001). In multivariable analysis, high Fuhrman grade, size of RPR tumor, mixed type of RPR, multiple recurrence lesions and the absence of RPR surgery were associated with a significantly increased risk of death from RCC. Aggressive surgical resection of RPR after RN represents a potentially curative treatment for selected RCC patients without synchronous metastases, resulting in significantly longer CSS than targeted therapy alone.


Insertion of the plant photosystem I subunit G into the thylakoid membrane.
Subunit G of photosystem I is a nuclear-encoded protein, predicted to form two transmembrane alpha-helices separated by a loop region. We use in vitro import assays to show that the positively charged loop domain faces the stroma, whilst the N- and C-termini most likely face the lumen. PSI-G constructs in which a His- or Strep-tag is placed at the C-terminus or in the loop region insert with the same topology as wild-type photosystem I subunit G (PSI-G). However, the presence of the tags in the loop make the membrane-inserted protein significantly more sensitive to trypsin, apparently by disrupting the interaction between the loop and the PSI core. Knock-out plants lacking PSI-G were transformed with constructs encoding the C-terminal and loop-tagged PSI-G proteins. Experiments on thylakoids from the transgenic lines show that the C-terminally tagged versions of PSI-G adopt the same topology as wild-type PSI-G, whereas the loop-tagged versions affect the sensitivity of the loop region to trypsin, thus confirming the in vitro observations. Furthermore, purification of PSI complexes from transgenic plants revealed that all the tagged versions of PSI-G are incorporated and retained in the PSI complex, although the C-terminally tagged variants of PSI-G were preferentially retained. This suggests that the loop region of PSI-G is important for proper integration into the PSI core. Our experiments demonstrate that it is possible to produce His- and Strep-tagged PSI in plants, and provide further evidence that the topology of membrane proteins is dictated by the distribution of positive charges, which resist translocation across membranes.


Prenatal diagnosis of intracranial immature teratoma in the third trimester using 2D and 3D sonography.
Intracranial tumors are uncommon and represent 0.5-1.5 % of all pediatric tumors. Teratoma is the most frequent intracranial tumor found at birth. Large teratomas are extremely rare and have a guarded prognosis since they grow fast and cause brain tissue destruction. A 31-week primigravida was referred to our hospital for investigation of an intracranial mass seen in the fetus. Two-dimensional ultrasound showed a large heterogeneous solid mass with calcifications inside, measuring 5.3 × 4.8 cm. It was in the right cerebral hemisphere at the level of the middle and posterior fossa, thereby shifting the midline and causing severe ventriculomegaly that measured 3.5 cm at the level of the lateral ventricle. Three-dimensional ultrasound (3DUS) in multiplanar mode allowed us to assess the anatomical relationships between the mass and the midline structures. The neurosurgical team, who had suspected that the case was inoperable, was thus able to gain a better understanding of the case. Transfontanellar ultrasound was performed on the day after the birth and confirmed the previous findings. Moreover, a biopsy confirmed the histology of the mass: it was an immature teratoma. The infant died on the 24th day of life after a large expansion of head circumference. Intracranial teratomas are extremely severe because of their quick growth and mass effect, often leading to neonatal death within days. 3DUS is a new prenatal diagnostic method that makes it possible to assess the anatomical relationships between the mass and the intracranial structures, thus enabling better preoperative planning.


Use of bovine albumin-glutaraldehyde glue in cardiovascular surgery.
As with any new surgical device, effectiveness requires both an understanding of its characteristics and proper technique of application. This report details application techniques from the author's experience for the use of bovine albumin-glutaraldehyde glue in a variety of cardiovascular surgical cases.


Myosin heavy chain expression in human muscle cocultured with mouse spinal cord.
Monoclonal antibodies which specifically recognise the neonatal or adult fast (type 2A and 2B) or slow myosin heavy chain (MHC) were used to investigate the myosin composition of human muscle which had regenerated in culture in the presence or absence of embryonic mouse spinal cord tissue. Adult fast MHC was found in an average of 75% of the cultured fibres, irrespective of the time in culture, the source of the muscle, the presence of neurones or modifications to the growth medium. It was not found alone but was always in association with the neonatal and/or slow myosin isoforms. The expression of fast MHC in human muscle therefore differs from that in mouse muscle in this culture system (Ecob-Prince et al. 1986), but is still strong evidence for the development of at least one aspect of an adult phenotype in culture.


Acute type-A dissection of the aorta: which diagnostic modes remain for surgical indication?
The natural course of acute type-A dissection of the aorta (AADA) implies a mortality of 50% within the initial 2 days. Preoperative diagnostic tests have to be expeditious while avoiding hypertension and direct manipulation of the aneurysm to prevent aortic rupture. Since 1979, 51 patients have been operated upon for AADA. The diagnosis was established by one or more of the following methods: transthoracic echocardiography (TTE); transesophageal echocardiography (TEE); conventional angiography (CA); intravenous digital subtraction angiography (DSA); and computed tomography with bolus injection of contrast medium (CT). TTE (n = 26) showed a dissection in 72%, suggested an intimal flap in 25%, and missed the diagnosis in 1 case. CT (n = 15) and DSA (n = 10) failed to indicate dissection in 1 case each. CA (n = 27) demonstrated dissection in every case but was the most time-consuming and stressful method. Since the introduction of combined transthoracic and transesophageal echocardiography, no other diagnostic methods have been used. On the basis of this experience, we propose the following diagnostic plan: 1. in AADA, the demonstration of an intimal flap in the ascending aorta by TTE/TEE is an indication for immediate surgery without further diagnostic measures (10 patients: no false-positive findings); 2. if a dissection is suggested by TTE/TEE, then DSA is performed if the supra-aortic branches are suspected to be compromised; CT is preferred if an extrapericardial aortic rupture is suspected; 3. the time-consuming and stressful diagnostic approach of conventional angiography is no longer indicated.


Early experience with the automatic implantable cardioverter defibrillator in sudden death survivors.
Medical management of life-threatening ventricular arrhythmias is difficult because of the toxicity and limited efficacy of antiarrhythmic drugs. The automatic implantable cardioverter defibrillator (AICD) offers protection against malignant ventricular arrhythmias and allows some patients to be managed without antiarrhythmic drugs. We reviewed our experience with the AICD to determine its safety and efficacy. Since June 1987, 24 patients (mean age 63 years) who survived out-of-hospital ventricular fibrillation or hemodynamically unstable ventricular tachycardia not associated with acute myocardial infarction had implantation of an AICD. None had inducible monomorphic ventricular tachycardia associated with ventricular aneurysm. Twenty-three had abnormal left ventricular function (mean ejection fraction 0.32). There were no operative deaths and three complications. At last follow-up (mean 8.9 months) 23 patients were alive. Eight patients had one or more AICD discharges associated with symptomatic or monitored cardiac arrest. AICD implantation can be performed with low risk and appears to be an effective alternative to antiarrhythmic therapy with toxic drugs.


Psychrophile spoilers dominate the bacterial microbiome in musculature samples of slaughter pigs.
The aim of this study was to disentangle the microbial diversity on porcine musculature. The hypervariable V1-V2 region of the 16S rRNA gene was amplified from DNA samples of clinically healthy slaughter pigs (n=8). Pyrosequencing yielded 37,000 quality-controlled reads and a diverse microbiome with 54-159 OTUs per sample was detected. Interestingly, 6 out of 8 samples were strongly dominated by 1-2 highly abundant OTUs (best hits of highly abundant OTUs: Serratia proteamaculans, Pseudomonas syringae, Aeromonas allosaccharophila, Brochothrix thermosphacta, Acidiphilium cryptum and Escherichia coli). In 1g musculature scraping, 3.20E+06 16S rRNA gene copies and 4.45E+01 Enterobacteriaceae rRNA gene copies were detected with qPCR. We conclude that i.) next-generation sequencing technologies help encompass the full content of complex, bacterial contamination, ii.) psychrophile spoilers dominated the microbiota and iii.) E. coli is an effective marker species for pork contamination, as it was one of very few abundant species being present in all samples.


Simvastatin therapy for hypercholesterolemic patients with nephrotic syndrome or significant proteinuria.
Experimental evidence suggests that lipid lowering therapy could slow the progression of renal disease in humans. We have conducted a double-blind, placebo controlled trial of the HMG CoA reductase inhibitor simvastatin in patients with the nephrotic syndrome or significant proteinuria (> 1 g/day) and hypercholesterolemia (> or = 6.5 mmol/liter). Patients were placed on a lipid lowering diet for at least 10 weeks before randomization. After a four-week placebo run-in, 30 adults were randomized to simvastatin or placebo therapy (10 mg/day, increasing to 20 to 40 mg/day as required) for 24 weeks. There were seven dropouts, none of whom were "definitely" related to drug therapy. Total and LDL cholesterol levels fell by a mean of 33 and 31%, respectively, in simvastatin treated patients, compared with only 5 and 1% in patients on placebo (P < 0.001, P = 0.002, respectively). Apolipoprotein B100 levels fell by a mean of 31% in the simvastatin group but rose 0.3% in the placebo group (P = 0.014). There were no significant changes in HDL levels. There were no significant differences between the groups in their urine protein levels, their rise in plasma creatinine, or decline in plasma inulin clearance. Simvastatin is a safe, effective therapy for hypercholesterolemia in proteinuric states. A much larger trial is needed to show if potent lipid-lowering therapy slows progression of hypercholesterolemic proteinuric diseases.


A pharmacological study of the inhibition of ventral group Ia-excited spinal interneurones.
In cats anaesthetized with pentobarbitone a pharmacological investigation was made of the inhibition by volleys in afferent fibres and ventral roots of physiologically identified Ia interneurones in the ventral horn. The recurrent inhibition of Ia interneurones by Renshaw cells, and the "mutual" inhibition between Ia interneurones, were suppressed by electrophoretic strychnine and are presumably mediated by glycine. Short latency and duration inhibitions by impulses in muscle and cutaneous afferents were also suppressed by strychnine. Electrophoretic GABA inhibited the firing of Ia interneurones and the effects of bicuculline methochloride suggested that this amino acid mediates longer latency and duration inhibition produced by afferent impulses of muscle and cutaneous origin.


Correction to: Glioblastoma multiforme: another potential application for 68Ga-PSMA PET/CT as a guide for targeted therapy.
The author names of the original version of this article were inadvertently interchanged. Correct author names are presented here.


iDRBP_MMC: Identifying DNA-Binding Proteins and RNA-Binding Proteins Based on Multi-Label Learning Model and Motif-Based Convolutional Neural Network.
DNA-binding protein (DBP) and RNA-binding protein (RBP) are playing crucial roles in gene expression. Accurate identification of them is of great significance, and accurately computational predictors are highly required. In previous studies, DBP recognition and RBP recognition were treated as two separate tasks. Because the functional and structural similarities between DBPs and RBPs are high, the DBP predictors tend to predict RBPs as DBPs, while the RBP predictors tend to predict the DBPs as the RBPs, leading to high cross-prediction rate and low prediction precision. Here we introduced a multi-label learning model based on the motif-based convolutional neural network, and a sequence-based computational method called iDRBP_MMC was proposed to solve the cross-prediction problem so as to improve the predictive performance of DBPs and RBPs. The results on four test datasets showed that it outperformed other state-of-the-art DBP predictors and RBP predictors. When applied to analyze the tomato genome, the results reveal the ability of iDRBP_MMC for large-scale data analysis. Moreover, iDRBP_MMC can identify the proteins binding to both DNA and RNA, which is beyond the scope of existing DBP predictors or RBP predictors. The web-server of iDRBP_MMC is freely available at http://bliulab.net/iDRBP_MMC.


[Ectopic intestinal varices in cirrhotic patients; an infrequent cause of severe intestinal bleeding].
We report on a cirrhotic patient, with history of colecistectomy, admitted for acute digestive bleeding. Esogastric causes were excluded by endoscopy; due to continuous hemorrhage, the patient was operated in the next 20 hours. The cause was established during the operation; solitary omfalo-enteric varices, with active vascular fistula. Preoperative etiology of acute intestinal bleeding may be difficult to establish, sometimes even during the surgical intervention. We comment upon rare causes of acute intestinal bleeding, mainly ectopic varices determined by portal hypertension.


Successful management of right coronary air embolus after intracoronary administration of verapamil.
A case of a 50 year-old male with a coronary air embolism is described. The case was successfully treated with intracoronary administration of verapamil.


Tibor Jack Greenwalt: Father of Transfusion Medicine.
Tibor J. Greenwalt (1914-2005) was, as much as anyone, the Father of Transfusion Medicine. He was founder of the Blood Center of Wisconsin, the first member of the American Association of Blood Banks, founding editor of Transfusion, chair of the National Research Council's Committee on Blood and Transfusion, national medical director of the American Red Cross Blood Services, and president of the International Society of Blood Transfusion. He wrote 200 papers and 25 books, describing erythroblastosis fetalis as an immune hemolytic anemia, new blood groups and antigens, the effects of hepatitis testing on blood safety, better ways to store red cell, and much more. He worked until days before his death at age 91, ending a 63-year career with 5 papers in press.


Respiratory diseases and allergic sensitization in swine breeders: a population-based cross-sectional study.
The daily occupation as a swine breeder involves exposure to several bacterial components and organic dusts and inhalation of a large amount of allergens. To investigate the risk of respiratory diseases and atopy in swine breeders compared with the general population living in the same area. A population-based cross-sectional study was conducted in an agricultural area of northern Italy that enrolled a random sample of resident male breeders and non-breeders. Demographic features, comorbidities, and presence of allergic respiratory disease were retrieved through interview. Prick tests for common allergens were performed. An evaluation of pollen and mold in air samples taken inside and outside some swine confinement buildings also was performed. One hundred one male breeders (78 native-born, mean age ± SD 43.0 ± 11.1 years) and 82 non-breeders (43.0 ± 11.1 years) were enrolled. When restricting the analysis to native-born subjects, breeders vs non-breeders showed a lower prevalence of respiratory allergy (12.8% vs 31.1%, respectively, P = .002), asthma (6.4% vs 15.8%, P = .059), rhinitis (16.7% vs 51.2%, P < .001), persistent cough (5.1% vs 15.9%, P = .028), and sensitization to grass (7.7% vs 25.6%, P = .002). There was no difference in prick test positivity, polysensitization, nasal cytologic pattern, forced expiratory volume in 1 second, and the ratio of forced expiratory volume in 1 second to forced vital capacity between breeders and non-breeders. Air concentration of molds and pollens was lower inside than outside the swine buildings investigated, particularly when the pigs were inside vs outside the buildings. This study suggests that swine breeding does not increase, and might decrease, the risk of pollen sensitization and allergic disease.


Effects of related sensory inputs on motor performances in man studied through changes in perceived heaviness.
1. The perception of the heaviness of lifted objects was studied using a weight-matching task when sensory inputs from parts related to the lifting task were altered.2. A weight lifted by flexing the index finger feels heavier when the thumb is anaesthetized and lighter when the thumb is electrically stimulated. A weight lifted by flexing the distal joint of the thumb feels heavier when the sensory input from the skin and joint of the thumb is abolished by anaesthesia. It also feels heavier when the index (but not the little) finger is anaesthetized, and lighter when the index (but not the little) finger is electrically stimulated.3. A weight lifted by extending the thumb feels lighter when the sensory input from the thumb is abolished.4. The perceived heaviness of a weight lifted by flexing the thumb is increased during anaesthesia of the thumb when the flexor of the thumb is the prime mover but not when it is acting simply as a postural fixator to support the weight.5. The sensation of the heaviness of lifted objects derives from the effort or centrally generated voluntary motor command employed in the lift. Our results indicate that the motor commands to either thumb or index finger flexors are facilitated by sensory inputs arising from a wide sensory field usually involved in co-operative motor performances carried out by both muscle groups together.


Electrogram polarity reversal as an additional indicator of breakthroughs from the left atrium to the pulmonary veins.
We assessed the anatomical distribution and electrogram characteristics of breakthrough from the left atrium (LA) to the pulmonary veins (PVs). Localization of LA-PV breakthrough is an important technique for PV ablation in patients with atrial fibrillation (AF). A total of 157 patients with paroxysmal AF underwent PV disconnection guided by mapping with a circumferential 10-electrode catheter. Radiofrequency (RF) current was delivered ostially at the site(s) of earliest activation (113 patients) or electrogram polarity reversal defined by opposite polarity across adjacent bipoles (44 patients). Breakthrough sites were proved by changes in pulmonary vein potential activation sequence occurring as a result of localized RF delivery and were classified into four segments around the ostium (top, bottom, anterior, posterior). Results of mapping and ablation were compared between the two groups. A total of 99% of 411 targeted PVs were successfully disconnected in both groups. Breakthroughs were most frequent at the bottom of superior PVs (85% prevalence) and the top of inferior PVs (75% prevalence). A wide activation front (>5 synchronous bipoles) indicating broad breakthrough was observed in 18% of PVs. Polarity reversal occurred with 88% sensitivity and 91% specificity at breakthrough sites. Polarity reversal was restricted to fewer bipoles (2.0 +/- 0.4 bipoles vs. 3.4 +/- 2.0 bipoles, p < 0.01) compared with earliest activation. Shorter RF application time was required to disconnect PVs with wide synchronous activation using polarity reversal compared with using conventional earliest activity (10.3 +/- 3.0 min vs. 12.3 +/- 3.4 min, p < 0.05). Bipolar electrogram polarity reversal allows more precise localization of breakthrough compared with the earliest activation, particularly in cases of wide synchronous PV activation.