Cluster Randomized Trial of a College Health Center Sexual Violence Intervention.
Sexual violence, particularly in the context of drinking, is prevalent on college campuses. This study tested a brief intervention to prevent sexual violence among students receiving care from college health centers. This study was a two-arm, unblinded cluster RCT. On 28 campuses with health/counseling centers (1:1 randomization allocation; 12 intervention and 16 control), from September 2015 to March 2018, a total of 2,291 students seeking care at college health centers completed surveys before the appointment, immediately after, 4 months later, and 12 months later. Intervention college health center staff received training on delivering sexual violence education to all students seeking care. Control sites provided information about drinking responsibly. The primary outcome was students' change in recognition of sexual violence. Additional outcomes included sexual violence disclosure and use of services among students with a history of sexual violence at baseline. Generalized linear mixed models accounting for campus-level clustering assessed intervention effects. Data were analyzed from September 2018 to June 2019. Half (55%) of students seeking care at college health centers reported any history of sexual violence exposure. No between-group differences in primary (β=0.001, 95% CI= -0.04, 0.04) or secondary outcomes emerged between intervention and control students. Post-hoc analyses adjusting for the intensity of intervention delivery (intensity-adjusted) revealed an increase in self-efficacy to use harm reduction strategies (β=0.09, 95% CI=0.01, 0.18) among intervention participants. Among those who reported sexual violence at baseline, intervention students had increased odds of disclosing violence during the visit (AOR=4.47, 95% CI=2.25, 8.89) in intensity-adjusted analyses compared with control. No between-group differences emerged for remaining outcomes. Sexual violence exposure is high among students seeking care in college health centers. A brief provider-delivered sexual violence intervention, when implemented with fidelity, was associated with improved self-efficacy to use harm reduction and increased disclosure of sexual violence during clinical encounters but no increased use of services. More interventions that are stronger in intensity are needed to connect students to sexual violence services. This study is registered at www.clinicaltrials.gov NCT02355470.


Correction: Liu et al. A Predictive Model for the Risk of Posterior Circulation Stroke in Patients with Intracranial Atherosclerosis Based on High Resolution MRI. Diagnostics 2022, 12, 812.
Errors occurred in the number of patients in the posterior circulation ischemic stroke (PCIS) group and non-PCIS group described in the original publication [...].


Flavonoid of Drynaria fortunei protects against acute renal failure.
The flavonoid fraction (FF) from Drynaria fortunei was investigated to determine its biological activity expression in three acute renal failure animal models. Guinea pigs received 100 mg/kg of gentamicin (GM group), 100 mg/kg of GM plus 10 mg/kg of FF (GMFF group), 10 mg/kg of FF (FF group) or saline (saline group) intramuscularly for 14 days. The blood urea nitrogen (BUN) and creatinine levels were found to be significantly higher in the GM group (22.70+/-3.84 mg/dL, 0.68+/-0.05 mg/dL) than in the GMFF group (17.10+/-1.04 mg/dL, 0.58+/-0.09 mg/dL), the FF group (17.40+/-1.01 mg/dL, 0.49+/-0.20 mg/dL) and the saline group (17.50+/-1.22 mg/dL, 0.50+/-0.02 mg/dL). Mice were treated once with 6 mg/kg of mercuric chloride, followed by 10 mg/kg of FF or saline. On days 3, 4 and 5, BUN and creatinine levels were found to be significantly higher in the HgCl2-saline group (74.00+/-39.20 mg/dL, 59.30+/-31.20 mg/dL, 74.00+/-37.30 mg/dL and 0.53+/-0.17 mg/dL, 0.48+/-0.15 mg/dL 0.33+/-0.15 mg/dL) than in the HgCl2-FF group (19.50+/-4.90 mg/dL, 43.00+/-26.30 mg/dL, 38.50+/-13.80 mg/dL and 0.23+/-0.05 mg/dL, 0.30+/-0.12 mg/dL, 0.15+/-0.06 mg/dL).After surgery for 5/6-nephrectomy, ten mice received FF at a dose of 10 mg/kg/day and eight received saline for 42 days. The saline group survived for 12-62 days and the FF group survived for 20-320 days. The FF group had a significantly longer survival time than the saline group (p<0.05). Regeneration of kidney tubular cells and significantly enlarged convoluted tubules were noted in the pathology study of the FF group. In conclusion, the present study suggests that FF prevents nephrotoxicity, improves kidney function and promotes kidney primary epithelial tubular cell regeneration.


Intake of selected micronutrients and risk of colorectal cancer.
The relationship between various micronutrients and colorectal cancer risk was investigated using data from a case-control study conducted between January 1992 and June 1996 in Italy. Cases were 1,953 incident, histologically confirmed colorectal cancers (1,225 of the colon and 728 of the rectum), admitted to the major teaching and general hospitals in the study areas, and 4,154 controls with no history of cancer, admitted to hospitals in the same catchment areas for acute, non-neoplastic diseases unrelated to the digestive tract and requiring no long-term modifications of the diet. Dietary habits were investigated using a validated food-frequency questionnaire. Odds ratio (ORs) were computed after allowance for age, sex and other potential confounding factors, including physical activity, total energy and fibre intake. For most micronutrients, ORs were below unity with increasing quintile of intake. The most consistent protective effects were for carotene, riboflavin and vitamin C (Multivariate ORs from the continuous model, with unit set as the difference between the upper cut-point of the 4th quintile and that of the 1st one, were 0.65, 0.73 and 0.80, respectively). Inverse relationships were observed also for calcium and vitamin D (ORs of 0.85 and 0.93, respectively). When the combined effect of calcium and vitamin D and selected anti-oxidants was considered, the OR reached 0.46 in subjects reporting high calcium/vitamin D and high anti-oxidant intake compared to those reporting low intake of both groups of micronutrients. Most results were apparently stronger for colon cancer and among females. Our results provide further support for a protective effect of several micronutrients on colorectal cancer risk and some indications for a specific and stronger effect of selected anti-oxidants.


An update on novel pharmacological agents for primary sclerosing cholangitis.
Primary sclerosing cholangitis (PSC) is a rare chronic cholestatic disease with heterogeneous phenotypes that may lead to liver transplantation and/or end-stage liver disease. Its multifactorial etiopathogenesis remains uncertain, but gut-liver axis and bile composition and excretion are widely demonstrated to influence the immune-mediated fibrogenic reactive cascade. Different experimental therapeutic options are under investigation, mainly aiming at modulating bile acids excretion, limiting inflammatory-cascade reactions, and changing intestinal microbiota composition; none of them yet demonstrated to prolong transplant-free survival.This review provides a comprehensive description of the experimental drugs recently tested and/or currently under investigation. A bibliographical search was performed in PubMed, MEDLINE, EMBASE, OVID, and clinicaltrial.gov until July 2021. The heterogeneity and poor prevalence of PSC, its uncertain pathophysiology, and the lack of surrogate endpoints are the major challenges in drug discovery. Strategies that synergistically target microbiota, bile acids, and liver fibrosis are needed. In parallel, we must enhance biomarkers discovery to develop surrogate endpoints, as biochemical markers' fluctuations over the time hamper their effectiveness. Magnetic resonance cholangiopancreatography tools that accurately measure bile duct changes represent a potential marker for disease monitoring. A collaboration between academia, research consortia, patient's associations, and industry is required.


A preoperative classification to predict the intrauterine and ectopic pregnancy rates after distal tubal microsurgery.
A simple preoperative classification is described to predict the intrauterine and ectopic pregnancy rates following distal tubal microsurgery. Laser CO2 microsurgical salpingostomies were performed on 76 patients between January 1979 and January 1984. All of the patients underwent a preoperative assessment, which included hysterosalpingogram and laparoscopy, to formulate a preoperative classification based on a point system. The patients were divided into four groups according to tubal damage, with a subsequent intrauterine pregnancy rate of 58.3% in grade I, 36.6% in grade II, 9.5% in grade III, and 0% in grade IV. The patients were divided into four groups according to adhesions, with a subsequent intrauterine pregnancy rate of 38.8% with no adhesion, 32.0% with mild adhesions, 26.6% with moderate adhesions, and 5.5% with severe adhesions. From these results, a preoperative management is proposed for patients being considered for either distal tubal microsurgery or in vitro fertilization.


Automated Breast Ultrasound (ABUS)-based radiomics nomogram: an individualized tool for predicting axillary lymph node tumor burden in patients with early breast cancer.
Preoperative evaluation of axillary lymph node (ALN) status is an essential part of deciding the appropriate treatment. According to ACOSOG Z0011 trials, the new goal of the ALN status evaluation is tumor burden (low burden, < 3 positive ALNs; high burden, ≥ 3 positive ALNs), instead of metastasis or non-metastasis. We aimed to develop a radiomics nomogram integrating clinicopathologic features, ABUS imaging features and radiomics features from ABUS for predicting ALN tumor burden in early breast cancer. A total of 310 patients with breast cancer were enrolled. Radiomics score was generated from the ABUS images. Multivariate logistic regression analysis was used to develop the predicting model, we incorporated the radiomics score, ABUS imaging features and clinicopathologic features, and this was presented with a radiomics nomogram. Besides, we separately constructed an ABUS model to analyze the performance of ABUS imaging features in predicting ALN tumor burden. The performance of the models was assessed through discrimination, calibration curve, and decision curve. The radiomics score, which consisted of 13 selected features, showed moderate discriminative ability (AUC 0.794 and 0.789 in the training and test sets). The ABUS model, comprising diameter, hyperechoic halo, and retraction phenomenon, showed moderate predictive ability (AUC 0.772 and 0.736 in the training and test sets). The ABUS radiomics nomogram, integrating radiomics score with retraction phenomenon and US-reported ALN status, showed an accurate agreement between ALN tumor burden and pathological verification (AUC 0.876 and 0.851 in the training and test sets). The decision curves showed that ABUS radiomics nomogram was clinically useful and more excellent than US-reported ALN status by experienced radiologists. The ABUS radiomics nomogram, with non-invasive, individualized and precise assessment, may assist clinicians to determine the optimal treatment strategy and avoid overtreatment.


Antianginal efficiency of nifedipine with and without a beta-blocker, studied with exercise test. A double-blind, randomized subacute study.
Twenty-one patients, mean age 60.3 years, with stable angina pectoris earlier treated with beta-blockers, were investigated with standardized exercise tests to evaluate the action of nifedipine alone and in combination with a beta-blocker. The first exercise test was performed 3 weeks after treatment with the patient's usual beta-blocker. Following this, the patients were tested twice after a double-blind cross-over 3-week trial with nifedipine and placebo. The patients were subsequently treated for 3 weeks with nifedipine 10 mg 3 times daily or placebo and then performed an exercise test. During the 4th period of 3 weeks the patients took a combination of nifedipine, 10 mg 3 times daily, and their usual beta-blocker and then performed the final exercise test. Nifedipine alone raised the heart rate by 5 beats/min at rest and diminished the systolic blood pressure at rest by 17 mm Hg. During exercise at comparable load the heart rate did not change significantly, but the systolic blood pressure decreased with 22 mm Hg. The exercise tolerance expressed as total work increased on a average by 20%, range-14 - + 194%. Nifedipine in combination with a beta-blocker gave a further decrease in the systolic blood pressure, totally 37 mm Hg at comparable load. The exercise tolerance increased more, totally by an average of 41%. There was a significant correlation between basal values for systolic blood pressure registered during the placebo period at rest and the percentage change in total work. The atrioventricular conduction time did not change significantly compared to placebo during treatment with nifedipine or the combination nifedipine + beta-blocker. No serious side-effects were observed during the study.


Transcriptome analysis of bovine lymphocytes stimulated by Atractylodis macrocephalae Koidz. polysaccharides in vitro.
Our previous studies demonstrated that total polysaccharides isolated from Atractylodis macrocephalae Koidz. (RAMPtp) had a therapeutic effect on bovine subclinical mastitis and an immunomodulatory effect on the lymphocytes from the supramammary lymph node (SMLN) in cows. To investigate the potential molecules involved in the immunomodulation, the present study identified 243 differentially expressed genes (DEGs) in RAMPtp-stimulated SMLN lymphocytes by RNA-seq. GO/KEGG enrichment analyses identified 47 significantly enriched gene ontology (GO) terms and 9 canonical pathways. These findings indicated that RAMPtp might stimulate lymphocytes to modulate productions of cytokines and chemokines through multiple compounds, targets and pathways. In particular, the Jak-STAT signaling pathway might be primarily involved in the immunomodulation. The therapeutic effect of RAMPtp on bovine subclinical mastitis may be attributed to activation of SMLN lymphocytes by injection of the polysaccharides in the area of SMLN in cows.


Head and neck radiology: role of multidetector computed tomography in the evaluation of the tympanic canaliculus.
This study was undertaken to evaluate the potential of multidetector computed tomography (MDCT) for multiplanar visualisation of the tympanic canaliculus both in healthy individuals and in patients affected by chronic inflammatory disease of the middle ear. A preliminary study was performed on three dried skulls by placing a metal landmark inside the tympanic canal lumen with a view to optimising depiction by multiplanar CT. Subsequently, 50 patients were enrolled in a prospective study. Three of the 100 petrous pyramids studied were excluded owing to the presence of jugulotympanic glomus tumour with severe bone changes. The entire course of the tympanic canaliculus was identified in 80/97 petrous pyramids (82.4%), 57 of which were normal (75.4% detection rate) and 40 pathological (90% detection rate). To assess the tympanic canaliculus in the pathological petrous pyramids and evaluate its possible role in the disease process, some qualitative criteria were introduced: canal enlargement, loss of margin sharpness, focal erosion of canal margins and presence of pathological tissue. MDCT represents the only technique allowing evaluation of the tympanic canal in vivo and with multiplanar images in a large number of cases (82.4%).


Periorbital rejuvenation to improve the negative vector with blepharoplasty and fat grafting in the malar area.
Periorbital rejuvenation is not achieved by upper and lower blepharoplasty alone; the presence of malar atrophy and the excessive length of the lower eyelid may change the face's oval shape, with the progressive formation of the negative vector. We describe our technique combining blepharoplasty and malar fat grafting to reverse the negative vector. After thorough anamnesis, we perform the blepharoplasty and canthopexy if necessary. In the upper blepharoplasty, we do not extirpate muscle, and in the lower blepharoplasty, we extirpate the fat pads via the transconjunctival route. In the case of excess skin, we prefer to perform skin pinching without resecting muscle, followed by a canthopexy. We then perform malar fat grafting by using fat obtained with low to moderate-pressure aspiration and centrifugation, injected with criss-cross tunnels in the malar region with a volume of 7 to 12 cm3 of fat on each side. Between 2006 and 2010, we operated on 142 female patients (age range, 45-74 years). The follow-up period was 2 years. In patients with "good fat quality" (n = 129), the results at 24 months were "excellent" in 93.79% of cases, "good" in 3.8%, and "fair" in 2.32%. The medical team's ratings were "excellent" in 97.6% of cases and "good" in 2.3%. In patients with "poor fat quality" (n = 13) at 12 months, a high percentage of the injected fat had been reabsorbed. The application of high-density hyaluronic acid was recommended (16). Periorbital rejuvenation is a part of integral facial rejuvenation and is achieved only if, in addition to the blepharoplasty, the negative vector is also corrected. With the technique of malar fat grafting, we achieve very good remodeling of the oval face shape, correct the negative vector, and shorten the height of the eyelid; the preadipocytes improve the tissue quality, especially in the skin.


Soft tissue reconstruction.
The potential of adipose-derived stem cells (ASCs) in clinical applications of soft tissue regeneration is immense. This chapter discusses the isolation and characterization of human ASCs, expansion in vitro, and relevant in vivo models for adipose tissue engineering.


Quantitative analysis of disulfiram and its metabolites in human blood by gas-liquid chromatography.
A simple method is described that permits the direct quantitative determination of carbon disulphide, free diethyldithiocarbamate and disulphides derived from disulfiram in 1 ml of a patient's blood. It is based on a gas chromatographic determination of carbon disulphide produced from diethyldithiocarbamate and disulfiram using the head-space technique and a flame-photometric detector. The method is compared with a recently described spectrophotometric method.


Recovery from Coronavirus Disease 2019 among Older Adults in Post-Acute Skilled Nursing Facilities.
To examine functional outcomes of post-acute care for coronavirus disease 2019 (COVID-19) in skilled nursing facilities (SNFs). Retrospective cohort. Seventy-three community-dwelling adults ≥65 years of age admitted for post-acute care from 2 SNFs from March 15, 2020, to May 30, 2020. COVID-19 status was determined from chart review. Frailty was measured with a deficit accumulation frailty index (FI), categorized into nonfrail, mild frailty, and moderate-to-severe frailty. The primary outcome was community discharge. Secondary outcomes included change in functional status from SNF admission to discharge, based on modified Barthel index (mBI) and continuous functional scale scored by physical (PT) and occupational therapists (OT). Among 73 admissions (31 COVID-19 negative, 42 COVID-19 positive), mean [standard deviation (SD)] age was 83.5 (8.8) and 42 (57.5%) were female, with mean FI of 0.31 (0.01) with no differences by COVID-19 status. The mean length of SNF stay for rehabilitation was 21.2 days (SD 11.1) for COVID-19 negative with 20 (64.5%) patients discharged to community, compared to 23.0 (SD 12.2) and 31 (73.8%) among patients who tested positive for COVID-19. Among those discharged to the community, all groups improved in mBI, PT, and OT score. Those with moderate-to-severe frailty (FI >0.35) had lower mBI scores on discharge [92.0 (6.7) not frail, 81.0 (15.4) mild frailty, 48.6 (20.4) moderate-to-severe frailty; P = .002], lower PT scores on discharge [54.2 (3.9) nonfrail, 51.5 (8.0) mild frailty, 37.1 (9.7) moderate-to-severe frailty; P = .002], and lower OT score on discharge [52.9 (3.2) nonfrail, 45.8 (9.4) mild frailty, 32.4 (7.4) moderate or worse frailty; P = .001]. Older adults admitted to a SNF for post-acute care with COVID-19 had community discharge rates and functional improvement comparable to a COVID-19 negative group. However, those who are frailer at admission tended to have lower function at discharge.


Timeliness of Care for High-acuity Conditions at Hospital-affiliated Freestanding Emergency Departments.
Hospital-affiliated freestanding emergency departments (FREDs) are rapidly proliferating in some states and have been the subject of recent policy debate. As FREDs' role in acute care delivery is expanding in certain regions, little is known about the quality of care that they provide for their sickest patients. Our aim was to compare timeliness of emergent care at FREDs and hospital-based EDs (HEDs) for patient visits with selected high-acuity and time-sensitive conditions. We performed a retrospective observational analysis of adult patient visit data from 19 FREDs and five HEDs from one health system over a 1-year period. Median times to events and hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated via Cox regression. The median time to electrocardiogram for visits with chest pain was 10 minutes at FREDs and 9 minutes at HEDs (HR = 0.91 [CI = 0.87 to 0.96]). Time to cardiac catheterization lab for visits with ST-segment elevation myocardial infarction (STEMI) was 78 minutes at FREDs, inclusive of transfer time, and 31 minutes at HEDs (HR = 0.41 [CI = 0.24 to 0.71]). Time to computed tomography for visits with stroke was 37 minutes at FREDs and 29 minutes at HEDs (HR = 0.42 [CI = 0.31 to 0.58]). Among visits with sepsis, FREDs had longer times to lactate collection (HR = 0.41 [CI = 0.30 to 0.56]), blood culture collection (HR = 0.24 [CI = 0.11 to 0.51]), and antibiotic administration (HR = 0.61 [CI = 0.26 to 1.42]). Beta agonists were administered for visits with asthma exacerbations in 24 minutes at FREDs and 44 minutes at HEDs (HR = 2.50 [CI = 2.34 to 2.68]), with similar times for anticholinergic and corticosteroid administration. Freestanding EDs provided more timely care than HEDs for visits with asthma exacerbation and less timely care for acute chest pain, stroke, and sepsis, although absolute differences were small. Even though STEMI patients at FREDs required transfer for catheterization, they tended to receive care in line with national guidelines.


Mid dermal elastolysis.
Mid dermal elastolysis is an exceedingly rare condition. Only three cases have been reported previously. The disease manifests as sharply marginated plaques of fine wrinkles of various size that give the skin an aged appearance. It is characterized histologically by a complete absence of mid dermal elastic fibers and lack of any inflammatory infiltrate. Two new cases are reported, and the other cases are reported.


Development and validation of a logistic regression model to distinguish transition zone cancers from benign prostatic hyperplasia on multi-parametric prostate MRI.
To develop a prediction model to distinguish between transition zone (TZ) cancers and benign prostatic hyperplasia (BPH) on multi-parametric prostate magnetic resonance imaging (mp-MRI). This retrospective study enrolled 60 patients with either BPH or TZ cancer, who had undergone 3 T-MRI. We generated ten parameters for T2-weighted images (T2WI), diffusion-weighted images (DWI) and dynamic MRI. Using a t-test and multivariate logistic regression (LR) analysis to evaluate the parameters' accuracy, we developed LR models. We calculated the area under the receiver operating characteristic curve (ROC) of LR models by a leave-one-out cross-validation procedure, and the LR model's performance was compared with radiologists' performance with their opinion and with the Prostate Imaging Reporting and Data System (Pi-RADS v2) score. Multivariate LR analysis showed that only standardized T2WI signal and mean apparent diffusion coefficient (ADC) maintained their independent values (P < 0.001). The validation analysis showed that the AUC of the final LR model was comparable to that of board-certified radiologists, and superior to that of Pi-RADS scores. A standardized T2WI and mean ADC were independent factors for distinguishing between BPH and TZ cancer. The performance of the LR model was comparable to that of experienced radiologists. • It is difficult to diagnose transition zone (TZ) cancer. • We performed quantitative image analysis in multi-parametric MRI. • Standardized-T2WI and mean-ADC were independent factors for diagnosing TZ cancer. • We developed logistic-regression analysis to diagnose TZ cancer accurately. • The performance of the logistic-regression analysis was higher than PIRADSv2.


Total leukocyte count, leukocyte subsets and their indexes in relation to cardiovascular risk in adolescent population.
No studies investigated total leukocytes, their subpopulations and novel indexes based on different ratios of leukocyte subsets concerning cardiovascular risk (CV) risk in late adolescents. Therefore, the aim of the present study was to explore such potential relationships. A total of 156 adolescents were included. CV risk score was calculated by summarizing each risk factor (i.e., female sex, low high density lipoprotein cholesterol (HDL-c), high non-HDL-c, smoking, blood pressure, and fasting glycemia). Adolescents were divided into a low CV risk score (i.e., -2≤ CV risk score ≤1) and moderate/higher CV risk score (i.e., CV risk score ≥ 2). White blood cell count (WBC) and its subsets were analyzed on an automatic device. The indexes were calculated. Total and differential WBC counts except basophil count were higher in moderate/higher CV risk participants. Multivariate binary regression analysis showed that total WBC count independently increased CV risk score by 1.623 times (p=0.001). Neutrophil and eosinophil counts (p=0.027 and p=0.010, respectively) were independently able to increase CV risk score by 1.486 and 1.556 times, respectively. On the contrary, indexes were not independently correlated with CV risk. WBC, neutrophil, and eosinophil count are the independent predictors of increased CV risk in adolescents. The associations may indicate the different pathways that lead to CV disease in adulthood.


dCas9-guided demethylation of the AKT1 promoter improves milk protein synthesis in a bovine mastitis mammary gland epithelial model induced by using Staphylococcus aureus.
Mastitis is among the main factors affecting milk quality and yield. Although DNA methylation is associated with mastitis, its role in mastitis remains unclear. In this study, a bovine mastitis mammary epithelial cells (BMMECs) model was established via Staphylococcus aureus infection of bovine mammary gland epithelial cells (BMECs). Bisulfite sequencing PCR was used to determine the methylation status of the AKT1 promoter in BMMECs. We found that the degree of the AKT1 promoter methylation in BMMECs was significantly greater than that in BMECs, and the expression levels of genes related to milk protein synthesis were significantly decreased. We used the pdCas9-C-Tet1-SgRNA 2.0 system to regulate the methylation status of the AKT1 promoter. High-efficiency sgRNAs were screened and dCas9-guided AKT1 promoter demethylation vectors were constructed. Following transfection with the vectors, the degree of methylation of the AKT1 promoter was significantly reduced in BMMECs, while AKT1 protein levels increased. When the methylation level of the AKT1 promoter decreased, the synthesis of milk proteins and the expression levels of genes related to milk protein synthesis increased significantly. The viability of the BMMECs was enhanced. Taken together, these results indicate that demethylation guided by the pdCas9-C-Tet1-SgRNA 2.0 system on the AKT1 promoter can reactivate the expression of AKT1 and AKT1/mTOR signaling pathway-related proteins by reducing the AKT1 promoter methylation level and promoting the recovery milk protein expression in BMMECs, thereby alleviating the symptoms of mastitis.


Structural, antioxidant, aroma, and sensory characteristics of Maillard reaction products from sweet potato protein hydrolysates as influenced by different ultrasound-assisted enzymatic treatments.
Effects of energy-divergent ultrasound (EDU), energy-gathered ultrasound (EGU), and energy-gathered ultrasound-microwave (EGUM) on structure, antioxidant activities, aroma, and sensory attributes of Maillard reaction products (MRPs) from sweet potato protein hydrolysates (SPPH) were investigated. EGU and EGUM markedly enhanced the Maillard reaction (MR) progress. FTIR results revealed significant peptide structure changes in MRPs as compared to their SPPHs counterparts. EGU-MRPs exhibited the highest percentages in lower MW fractions of 200-3,000 Da, and presented a significantly enhanced ORAC value of 92.10 µg TE/mL (p < 0.05). Besides, EGU-MRPs and EGUM-MRPs showed higher content and quality of aroma compounds than other MRPs, and presented increased umami, sweetness, and sourness attributes, but decreased bitterness (p < 0.05). Their stronger umami taste was highly correlated to 1-naphthalenol, dodecanoic acid, <200, 200-500, 500-1,000 and 1,000-3,000 Da. Thus, EGU and EGUM assisted enzymatic hydrolysis coupled with MR might be promising ways to produce natural flavoring with improved antioxidant activities.


First report of the repellency of 2-tridecanone against ticks.
2-Tridecanone and 2-undecanone are both found naturally in the trichomes of wild tomato plants and are important in plant resistance to herbivory. 2-Undecanone is the U.S. Environmental Protection Agency (EPA)-registered active ingredient in the commercially available arthropod repellent, BioUD(®) . The goal of this study was to examine the tick repellency of 2-tridecanone. Two-choice bioassays were conducted using 8% 2-tridecanone vs. the repellent carrier (absolute ethanol) and compared with two-choice studies using 8% 2-undecanone vs. absolute ethanol. Unfed, host-seeking adult (mixed sex) Amblyomma americanum (L.) (Acari: Ixodidae) and Dermacentor variabilis Say (Acari: Ixodidae) were used to evaluate repellency and time to repellent failure at room temperature. The present study shows in filter paper assays (0.63 mg test compound/cm(2) ) that 2-tridecanone was 87% repellent to A. americanum at 12 h after application, but had no statistically significant repellency at 15 h and 24 h, and was 72% repellent to D. variabilis at 15 h, but had no statistically significant repellency at 24 h. By contrast, 2-undecanone was 74% and 75% repellent to A. americanum and D. variabilis, respectively, at 2 h after application, but no statistically significant repellency was noted at 2.5 h and 3 h. In two-choice assays on cheesecloth, 2-tridecanone at 0.25 mg/cm(2) was 85% repellent to A. americanum 6 h after application, demonstrating its potential use as an arthropod repellent that can be used on clothing without the need for formulation. No statistically significant repellency was found at 9 h or 12 h. The potential use of 2-tridecanone as a tick repellent is discussed.


Giant Ferroelectric Polarization in Ultrathin Ferroelectrics via Boundary-Condition Engineering.
Tailoring and enhancing the functional properties of materials at reduced dimension is critical for continuous advancement of modern electronic devices. Here, the discovery of local surface induced giant spontaneous polarization in ultrathin BiFeO3 ferroelectric films is reported. Using aberration-corrected scanning transmission electron microscopy, it is found that the spontaneous polarization in a 2 nm-thick ultrathin BiFeO3 film is abnormally increased up to ≈90-100 µC cm-2 in the out-of-plane direction and a peculiar rumpled nanodomain structure with very large variation in c/a ratios, which is analogous to morphotropic phase boundaries (MPBs), is formed. By a combination of density functional theory and phase-field calculations, it is shown that it is the unique single atomic Bi2 O3-x layer at the surface that leads to the enhanced polarization and appearance of the MPB-like nanodomain structure. This finding clearly demonstrates a novel route to the enhanced functional properties in the material system with reduced dimension via engineering the surface boundary conditions.


First report on the bacterial community composition, diversity, and functions in Ramsar site of Central Himalayas, Nepal.
Wetland bacterial communities are highly sensitive to altered hydrology and the associated change in water physicochemical and biological properties leading to shifts in community composition and diversity, hence affecting the ecological roles. However, relevant studies are lacking in the wetlands of central Himalayas Nepal. Thus, we aimed to explore the variation of bacterial communities, diversity, and ecologic functions in the wet and dry periods of a wetland (designed as Ramsar site, Ramsar no 2257) by using 16S rRNA gene-based Illumina MiSeq sequencing. We reported a pronounced variation in water physicochemical and biological properties (temperature, pH, Chla, DOC, and TN), bacterial diversity, and community composition. Bacterial communities in the dry season harbored significantly higher alpha diversity, while significantly higher richness and abundance were reflected in the wet season. Our results uncovered the effect of nutrients on bacterial abundance, richness, and community composition. Fourteen percent of the total OTUs were shared in two hydrological periods, and the largest portion of unique OTUs (58%) was observed in the dry season. Planctomycetes and Bacteroidetes dominated the wet season exclusive OTUs; meanwhile, Actinobacteria dominated the dry season exclusive OTUs. Bacteria in these wetlands exhibited divergent ecological functions during the dry and wet seasons. By disclosing the variation of water bacterial communities in different hydrologic periods and their relationship with environmental factors, this first-hand work in the Ramsar site of Nepal will develop a baseline dataset for the scientific community that will assist in understanding the wetland's microbial ecology and biogeography.


A flipped classroom in graduate medical education.
The role of the flipped classroom model in graduate medical education (GME) is not yet defined. We set out to evaluate the feasibility, acceptability and outcomes of a flipped classroom instructional model in an internal medicine curriculum. This pilot study was carried out in an academic medical centre in the USA with 43 second-year internal medicine postgraduate trainees. Trainees watched videos on the pharmacological treatment of type 2 diabetes outside of the classroom, followed by an in-class session in which they engaged in case-based discussions. The intervention was evaluated using surveys and a knowledge test before, immediately after and 6 months after the intervention. The mean number of correct answers for a 10-question knowledge test was 5.25 before the intervention, 8.00 in the immediate post-intervention test, and 7.10 in the 6-month follow-up test (p < 0.001). Six months after the intervention, 57.1% of participants reported prescribing an antidiabetic medication discussed at the session. In a focus group, trainees reported their preference for interactive, case-based learning, concern about the time required for preparation and interest in incorporating real patient cases. Trainees preferred the flipped classroom, which also resulted in increased knowledge and self-reported prescribing changes; however, the required preparatory time may limit its feasibility in GME.


Performance of the Afirma genomic sequencing classifier versus gene expression classifier: An institutional experience.
The use of fine-needle aspiration (FNA) to triage thyroid nodules has resulted in a significant reduction in thyroid surgery. However, approximately one-third of FNA specimens fall into the "indeterminate" category. The Afirma gene expression classifier (GEC) has been used to identify benign nodules with a high sensitivity and negative predictive value. However, the specificity and positive predictive value of the "suspicious" category are low. The updated Afirma genomic sequencing classifier (GSC) has been reported to demonstrate increased specificity while maintaining a high sensitivity and negative predictive value. The authors retrospectively investigated 272 indeterminate thyroid FNA specimens (Bethesda categories III and IV) from nodules measuring >1 cm using the Afirma GEC or GSC tests (July 2012-January 2019). Of the 194 nodules tested using the Afirma GEC, a benign result was obtained in 88 cases (45.4%). In comparison, 52 of 78 FNA samples (66.7%) tested using GSC yielded a benign result (P = .002). In the GEC group, there were 31 cases with oncocytic cytology, 5 of which (16.1%) were benign on Afirma and 26 of which (83.9%) were suspicious on Afirma. In contrast, in the GSC group, there were 10 cases with oncocytic cytology, 8 of which (80%) were benign on Afirma and only 2 of which (20%) were found to be suspicious on Afirma (P < .001). The positive predictive value of the GSC group (57.1%) was higher than that of the GEC group (36.7%); however, there was no statistical significance noted (P = .15). A larger percentage of indeterminate thyroid FNA specimens were classified as benign using the Afirma GSC compared with the Afirma GEC, especially among samples with oncocytic features. The Afirma GSC appears to have a higher benign call rate compared with the Afirma GEC.


Differences in c-myc and pvt-1 amplification in SEWA sarcoma sublines selected for adherent or non-adherent growth.
Conversion of solid sarcomas and carcinomas into ascites tumors depends on the in vivo selection of phenotypically altered tumor cell variants that can grow in the dissociated form. Once selected, they retain this property even after prolonged s.c. growth as solid tumors. From an s.c.-passaged subline of an ascites-converted murine sarcoma (SEWA-AS12), we were able to separate cells adapted to the ascites form of growth from cells that can only grow in the solid form on the basis of their differential adherence to plastic. Both c-myc and pvt-1 were amplified approximately 63- to 77-fold in the nonadherent subline (SEWA-AS12-NA), but only 5- to 8-fold in the adherent subline (SEWA-AS12-ADH). This suggests that c-myc and/or pvt-1 amplification may provide a selective advantage to cells that can grow in the dissociated form.


Longitudinal data of multimorbidity and polypharmacy in older adults in Taiwan from 2000 to 2013.
The objective of the study was to evaluate the prevalences and trends of multimorbidity and polypharmacy in older adults in Taiwan. An observational study was performed using the 2000-2013 database of the Taiwan National Health Insurance Program (analysis in 2018). Participants ≥65 years were included in the study. Multimorbidity was defined as participants having two or more chronic diseases annually. Polypharmacy was defined as the average daily number of prescribed medications ≥5. The prevalences of multimorbidity were 42.4% in 2000 and 56% in 2013. The prevalences of polypharmacy were 22.9% in 2000 and 32.1% in 2013. From 2000 to 2013, multimorbidity and polypharmacy were prevalent among older adults in Taiwan. Public health efforts to intervene the primary prevention for chronic diseases should be considered in older adults.


A wide spectrum of variably periictal MRI abnormalities induced by a single or a cluster of seizures.
Although predominantly reported in patients with status epilepticus, periictal MRI abnormalities have been reported in patients with a single or a cluster of seizures. Clinicians are often presented with a dilemma concerning the features of MRI abnormalities induced by a single or a cluster of seizures, as they may represent the effect of seizure activity rather than its structural cause. A retrospective review of clinical and neuroimaging charts of 14 patients diagnosed with a single or a cluster of seizure-related MR-signal changes from the database of our unit (approximately 300 patients diagnosed with a single or a cluster of seizures underwent brain-MRI within 14 days from a seizure) was conducted. Extensive clinical work-up and follow-up, ranging from 3 months to 5 years, ruled out infection or other possible causes of brain damage. Site, characteristics and reversibility of MRI changes, and association with characteristics of seizures were determined. MRI showed unilateral abnormalities in 14 patients, with hyperintensities on T2-signal (12/14), fluid-attenuated inversion-recovery (FLAIR) (12/14), and restricted diffusion (6/8). Location of abnormality was cortical (4/14), subcortical (6/14), thalamus (2/14), corpus callosum (1/14), and bordering an old encephaloclastic lesion (1/14). Periictal MRI abnormalities and electroclinical findings in 10 patients showed an almost complete topographic concordance, which was not consistent in 4 patients. Reversibility of MRI changes was complete in 11 patients, partially disappeared in 1 patient, and irreversible on MRI in 2 patients. A single or a cluster of seizures cannot only induce transient, variably reversible MRI brain abnormalities, but also irreversible changes. These seizure-induced MRI abnormalities pose a broad differential diagnosis; increased awareness may reduce the risk of misdiagnosis and unnecessary intervention.


Distal intramural spread in adenocarcinoma of the lower third of the rectum treated with total rectal resection and coloanal anastomosis.
This study was designed to evaluate the frequency of microscopic distal intramural spread in rectal adenocarcinoma and its correlation to other histopathologic prognostic factors. We examined 55 patients with adenocarcinomas of the lower one-third of the rectum and measured the extent of distal intramural spread in the submucosa and/or muscular layer in comparison with Dukes Stage, diameter of tumor, distance of distal margin of resection from tumor, depth of infiltration into perirectal adipose tissue, nodal status, neoplastic infiltration of lymphatic vessels, blood vessels, and nervous branches. Distal intramural spread was found in 40 percent of patients, 77 percent of whom had advanced tumors with nodal metastases. Distal intramural spread appeared to be strictly related to tumor size (superior to 40 mm), infiltration of the perirectal adipose tissue, multiple positive lymph nodes, presence of neoplastic emboli in the intramural lymphatic vessels, and neoplastic invasion of the nervous branches. Local recurrence occurred in one Dukes Stage B patient with a positive distal margin of resection and in four patients with a negative distal margin of resection: three Dukes Stage C and one Dukes Stage B patients with neoplastic involvement of the circumferential margin of resection of the mesorectum. These preliminary data suggest that distal intramural spread may carry little importance in determining local recurrence of rectal adenocarcinoma.


The Influence of Environmental Values on Consumer Intentions to Participate in Agritourism-A Model to Extend TPB.
This study examines the influence of environmental values on consumer intentions to participate in agritourism through the theory of planned behaviour (TPB) and value-belief-norm (VBN) theory. It proposes an integrative model by adding two variables, i.e., environmental benefits and the human-nature coordination concept, to the TPB. The study employs a questionnaire survey method and a sample of 640, which was statistically analysed through structural equation modeling (SEM). The results reveal that the "environmental values-attitudes-behavioural intentions" framework has scientific applicability in agritourism. Environmental values, measured through the variables environmental benefits and the human-nature coordination concept, are positively correlated directly or indirectly with agritourism consumption intentions, while attitudes and subjective norms serve as mediators. However, the mediating effect of perceived behavioural control is not statistically significant, indicating making efforts to influence attitudes and subjective norms is more useful for and effective in stimulating the public's intentions towards agritourism. As this study tests the hypotheses with empirical data, it provides practical implications for policy-makers and programme managers.


Sport Science Lab® Screening Protocol: The association between physical fitness Parameters and injury among elite rugby players.
The Sport Science Lab® (SSL®) screening protocol includes novel methods of assessing flexibility, strength, plyometric ability and rugby specific fitness. The objective of this study was to investigate the association between these tests and injury among professional rugby players. Prospective cohort study. Fitness facilities of participating teams. Thirty-nine injury-free, elite, adult (>18 years), male rugby players. The test battery consisted of eleven flexibility-, nine strength- and six plyometric tests and a rugby specific fitness test (RSFT). Injuries were recorded weekly during the 2019 rugby season. Associations between test results and injuries were analysed utilising suitable tests of association i.e., sensitivity, specificity, false positive rate, false negative rate, positive predictive value and negative predictive value and odds ratios (OR) (with confidence intervals (CI)). Bivariate correlations and logistic regression were performed to assess the relationship of the predictor variables to the outcome. Players who achieved the set standard for the RSFT (OR = 3.17; 95% CI = 0.79-12.75), triple horizontal broad jump (OR = 2.40; 95% CI = 0.86-19.61) and lateral depth jumps (OR = 2.40-3.44; 95% CI = 0.53-18.84) were two to three times less likely to sustain an injury during the season. Players with superior rugby specific fitness and cyclic linear- and lateral plyometric ability, may have a decreased risk of sustaining injuries.


Drug addiction: the neurobiology of behaviour gone awry.
Drug addiction manifests as a compulsive drive to take a drug despite serious adverse consequences. This aberrant behaviour has traditionally been viewed as bad "choices" that are made voluntarily by the addict. However, recent studies have shown that repeated drug use leads to long-lasting changes in the brain that undermine voluntary control. This, combined with new knowledge of how environmental, genetic and developmental factors contribute to addiction, should bring about changes in our approach to the prevention and treatment of addiction.


Expression of cyclooxygenase-2 (COX-2) and p53 in neighboring invasive and in situ components of breast tumors.
The aim of the study was to assess the relationship between the expression of COX-2 and p53, hormone receptors and HER-2 in the in situ (DCIS) and invasive components of ductal carcinomas (IDC) of the same breast. The expression of COX-2, p53, and hormone receptors was assessed in 87 cases of IDC with contiguous areas of DCIS. Results showed that there was no difference in COX-2 expression comparing the in situ and invasive components of the tumors. In the in situ component, there was a statistically borderline increase in p53 expression in tumors that also expressed COX-2. ER-positive specimens were more common in the group of tumors that expressed COX-2 in the invasive component. From this study we conclude that the expression of COX-2 was similar in the in situ and invasive components of the breast carcinomas. COX-2 positivity was marginally related with the expression of p53 in the in situ components, and with the ER expression in the invasive components.


Interactions between water activity and temperature on the Aspergillus flavus transcriptome and aflatoxin B1 production.
Effects of Aspergillus flavus colonization of maize kernels under different water activities (aw; 0.99 and 0.91) and temperatures (30, 37°C) on (a) aflatoxin B1 (AFB1) production and (b) the transcriptome using RNAseq were examined. There was no significant difference (p=0.05) in AFB1 production at 30 and 37°C and 0.99 aw. However, there was a significant (p=0.05) increase in AFB1 at 0.91 aw at 37°C when compared with 30°C/0.99 aw. Environmental stress effects using gene ontology enrichment analysis of the RNA-seq results for increasing temperature at 0.99 and 0.91 aw showed differential expression of 2224 and 481 genes, respectively. With decreasing water availability, 4307 were affected at 30°C and 702 genes at 37°C. Increasing temperature from 30 to 37°C at both aw levels resulted in 12 biological processes being upregulated and 9 significantly downregulated. Decreasing aw at both temperatures resulted in 22 biological processes significantly upregulated and 25 downregulated. The interacting environmental factors influenced functioning of the secondary metabolite gene clusters for aflatoxins and cyclopiazonic acid (CPA). An elevated number of genes were co-regulated by both aw and temperature. An interaction effect for 4 of the 25 AFB1 genes, including regulatory and transcription activators occurred. For CPA, all 5 biosynthetic genes were affected by aw stress, regardless of temperature. The molecular regulation of A. flavus in maize is discussed.


[Extracorporeal membrane oxygenation and severe traumatic brain injury. Is the ECMO-therapy in traumatic lung failure and severe traumatic brain injury really contraindicated?].
Veno-venous extracorporeal membrane oxygenation (ECMO) may be lifesaving in multiple injured patients with acute respiratory distress syndrome (ARDS) due to chest trauma. To prevent circuit thrombosis or thromboembolic complications during ECMO systemic anticoagulation is recommended. Therefore, ECMO treatment is contraindicated in patients with intracranial bleeding. The management of veno-venous ECMO without systemic anticoagulation in a patient suffering from traumatic lung failure and severe traumatic brain injury is reported.


Benzotriazolium picrate.
In the crystal structure of the title compound, C(6)H(6)N(3) (+)·C(6)H(2)N(3)O(7) (-), anions and cations are linked into chains along [010] by inter-molecular N-H⋯O hydrogen bonds. These chains are further stabilized by weak C-H⋯O hydrogen bonds and π-π stacking inter-actions with a centroid-centroid distance of 3.908 (1) Å.


The relation between annular disruption on computed tomography scan and pressure-controlled diskography.
To analyze the relation between annular disruption determined by computed tomography (CT) scan and diskographic findings using pressure-controlled manometric diskography. Cross-sectional using prospectively gathered data. Ambulatory spine intervention unit. Two hundred seventy-nine disks from 86 patients (55 men, 31 women) who were referred for diskography of suspected chronic diskogenic low back pain. Not applicable. The grade of annular disruption was rated using CT diskography and fluoroscopic imaging as follows: 0 (no disruption); 1 (extension into the inner third of the annulus); 2 (extension into the middle third of the annulus); 3 (extension into the outer third of the annulus); 4 (circumferential extension with a >30 degrees arc at the disk center); and 5 (contrast media leakage into the outer space). Diskography was performed via a pressure-controlled manometric technique using an injection rate of .05 mL/s and a restricted total volume of 3.5 mL. Pain was rated on a 0 to 10 numeric rating scale (NRS). Criteria for symptomatic disks included provocation of patient concordant pain (NRS score, > or =6/10) at 50psi or less above opening pressure, with 3.5 mL or less of total volume. Symptomatic disks were classified as "low pressure sensitive" or "high pressure sensitive" based on the pressure level that evoked pain. Disks classified as low pressure sensitive required an NRS score of 6 out of 10 or higher at 15 psi or less above opening pressure. Disks classified as high pressure sensitive required an NRS score of 6 out of 10 or higher at pressures within a range of 15 to 50 psi. The numbers of disks at each annular disruption grade were 19 (6.8%) at grade 0, 29 (10.4%) at grade 1, 35 (12.5%) at grade 2, 42 (15.1%) at grade 3, 69 (24.7%) at grade 4, and 85 (30.5%) at grade 5. A total of 93 disks met the criteria for a symptomatic disk. The extent of annular disruption and the rate of symptomatic disks correlated significantly (P<.001). The highest symptomatic disk rate was observed in grade 4 disks. Of 93 symptomatic disks, 88 (94.6%) showed annular disruption of grade 3 or greater. Disks with grades 0 to 2 and grades 3 to 5 annular disruption differed significantly when the mean NRS relative to intradiskal pressure was compared (P<.001). Comparing the disk type of symptomatic disks at each annular disruption grade, there was a decreasing trend of low pressure sensitive disks relative to the extent of annular disruption (62.5% at grade 3, 39.4% at grade 4, 34.2% at grade 5). Annular disruption reaching the outer annulus fibrosus is a key factor in pain generation. Disk morphology, including annular disruptions extending beyond the outer annulus, may permit increased diskography specificity.


Expression of PD-L1 and CTLA-4 in female urethral carcinoma.
Although the tumors are often easily detected, a considerable number of patients with female urethral carcinoma are diagnosed in an advance stage. Thus, no evidence-based therapeutic approach has been established. We herein report our experience in the treatment of three female patients with urethral carcinoma. We also examined the expression of PD-L1 and CTLA-4. Three female patients pathologically diagnosed with urethral carcinoma, including urothelial carcinoma, squamous cell carcinoma, and adenocarcinoma, between 2013 and 2017 were analyzed in this study. Two patients underwent urethrectomy with cystostomy. Immunohistochemistry was performed to assess the levels of PD-L1 and CTLA-4 expression in patients with urethral carcinoma. Eleven control cases of urethral carcinoma tissue were also stained. This study revealed the expression of PD-L1 and CTLA-4 in female urethral carcinomas.


Enhancement of the anticonvulsant effect of fluoxetine following blockade of 5-HT1A receptors.
Serotonin reuptake inhibitors, such as fluoxetine, have been shown to exert anticonvulsant effects in several animal models of epilepsy. In view of recent studies showing that 5-HT1A receptor antagonists (somatodendritic autoreceptor antagonists) enhance the increase in extracellular 5-hydroxytryptamine (5-HT, serotonin) produced by serotonin reuptake inhibitors, it was of interest to determine if these antagonists also enhance the anticonvulsant effect of fluoxetine in Genetically Epilepsy-Prone Rats (GEPRs). The 5-HT1A receptor antagonists (-)-pindolol and LY 206130 (1-[1-H-indol-4-yloxy]-3-[cyclohexylamino]-2-propanol maleate) were examined in the present study and both enhanced the anticonvulsant action of fluoxetine in severe seizure GEPRs (GEPR-9s). The latter effect of LY 206130 was found to be dose- and 5-HT-dependent. These findings provide further evidence that the increase in extracellular serotonin observed after administering fluoxetine in combination with a 5-HT1A receptor antagonist is physiologically important and that the anticonvulsant effect of fluoxetine in the GEPR is mediated through an increase in extracellular 5-HT.


Detection of GM2-gangliosidosis (Tay-Sachs and Sandhoff disease) gene carriers by serum hexosaminidase assay.
With a view to the biochemical detection of homo- and heterozygous carriers of GM2-gangliosidosis, serum hexosaminidase activities were investigated in patients from Tay-Sachs and from Sandhoff disease, respectively, in their relatives, and in normal controls. Two related methods for the differential determination of hexosaminidase A and B activities were tested. Homozygous carriers (patients) were detected by both methods in a similar manner. As regards the identification of heterozygous carriers more conclusive results were attained by the "heat inactivation method" (O'Brien, J.S., Okada, S., Chen, A. and Fillerup, D.L. (1970) New Engl. J. Med 283, 15).


Accurate measurement of strain at interfaces in 4D-STEM: A comparison of various methods.
Strain analysis by nano-beam electron diffraction allows for measurements of strain with nanometre resolution in a large field of view. This is done by evaluating distances between diffraction discs in diffraction patterns acquired while a focussed electron beam is scanned across the sample in a transmission electron microscope. The bottleneck of this method is a precise determination of diffraction disc positions, which suffers from the inner structure of the discs caused by dynamical diffraction. Electron beam precession is a tool that solves this problem but it is not commonly available in every microscope. Without precession significant progress has been reported recently by using patterned condenser apertures. The pattern of the aperture is reproduced in patterns of the diffraction discs allowing for a more precise position determination. In this report the accuracy of measured strain profiles using patterned apertures is investigated by evaluation of realistic simulations. This is done especially at interfaces between regions with different lattice plane spacing. It is found by evaluation of the simulations that measured strain profiles are more blurred and hence the accuracy at the interface is worse the more patterns are imprinted to the condenser aperture. An explanation of this effect is given and as a proof of principle a solution to this problem is provided applying geometric phase analysis ptychography.


MR-proANP, a cardiovascular biomarker to predict late-onset preeclampsia and intrauterine growth restricted fetuses.
Midregional pro-atrial natriuretic peptide (MR-proANP) is a cardiac biomarker and the maternal serum levels could predict late-onset preeclampsia (PE) or intrauterine growth restriction (IUGR) at third trimester of pregnancy. We measured MR-proANP between 32 and 37 weeks of pregnancy prospectively: 32 patients suffered from PE and 22 developed IUGR. 676 patients exhibited no pregnancy complications. The median MR-proANP showed significantly higher results in PE (64.9 pmol/l (interquartile range (IQR) 36.3-105.2) and IUGR (59.7 pmol/l (IQR 39.7-163.0) groups compared to controls (38.7 pmol/l (IQR 29.7-49.2). Linear regression analysis showed association between PE and MR-proANP levels (Exp(ß) = 1.56; 95% CI: 1.34-1.81). AUC showed a predictive value for PE (AUC: 0.72) and IUGR (AUC: 0.71). Measuring MR-proANP in maternal serum between 32 and 37 weeks of pregnancy could help predicting IUGR and PE diagnosed after 34 week in pregnancy. Thus, we assume that MR-proANP may be an additional biomarker which mirrors the maternal cardiosvascular status next to sFlt-1/PLGF representing the angiogenic status.


Enlarged tumour-draining lymph node with immune-activated profile predict favourable survival in non-metastatic colorectal cancer.
The tumour-draining lymph node (TDLN) plays a pivotal role in the suppression of malignant tumour, however, the immunological profile and prognostic differences between large TDLN (L-TDLN) and small TDLN (S-TDLN) in colorectal cancer (CRC) remain unclear. We conducted a study using data from the Chinese National Cancer Center (CNCC) database, identifying 837 CRC patients with non-metastatic TDLN, and categorised them into L-TDLN and S-TDLN groups. The long-term survival outcomes and adjuvant therapy efficacy were compared between the two groups. Furthermore, we evaluated the differences in immune activation status and immune cell subsets between patients in L-TDLN and S-TDLN groups by RNA sequencing and immunohistochemical (IHC) staining. Patients with L-TDLN demonstrated better long-term outcomes compared to those with S-TDLN. Among patients with L-TDLN, there was no significant difference in long-term outcomes between those who received adjuvant chemotherapy and those who did not. The RNA sequencing data revealed a wealth of immune-activating pathways explored in L-TDLN. Furthermore, IHC analysis demonstrated higher numbers of CD3+ and CD8 + T cells in L-TDLN and the corresponding CRC lesions, as compared to patients with S-TDLN. Enlarged TDLN exhibited an activated anti-tumour immune profile and may serve as an indicator for favourable survival in non-metastatic CRC.


The effect of eugenol on nerve transmission.
Because of its long-time use as a sedative or anodyne in dental procedures, eugenol was studied to determine its effect on evoked nerve impulse transmission. The sciatic nerve of the bullfrog was stimulated in a nerve chamber, and the compound action potential was visualized on and recorded from an oscilloscope screen. It was determined that eugenol concentrations ranging from 100 per cent to 0.01 per cent extinguished the impulse-transmission capabilities of the nerve within 3 hours. No reversal was observed within this time frame.


Threonyl-transfer ribonucleic acid synthetase from Escherichia coli: subunit structure and genetic analysis of the structural gene by means of a mutated enzyme and of a specialized transducing lambda bacteriophage.
Threonyl-transfer ribonucleic acid synthetase (ThrRS) has been purified from a strain of Escherichia coli that shows a ninefold overproduction of this enzyme. Determination of the molecular weight of the purified, native enzyme by gel chromatography and by polyacrylamide gel electrophoresis at different gel concentrations yielded apparent molecular weight values of 150,000 and 161,000, respectively. Polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate yields a single protein band of 76,000-dalton size. From these results an alpha(2) subunit structure can be inferred. A mutant with a structurally altered ThrRS, which had been obtained by selection for resistance against the antibiotic borrelidin, was used to map the position of the ThrRS structural gene (thrS) by P1 transductions. It was found that thrS is located in the immediate neighborhood of pheS and pheT, which are the structural genes for the alpha and beta subunits of phenylalanyl-transfer ribonucleic acid (tRNA) synthetase, the gene order being aroD-pheT-pheS-thrS. A lambda phage that was previously shown to specifically transduce pheS, pheT, and also the structural gene for the translation initiation factor IF3 can complement the defect of the altered ThrRS of the borrelidin-resistant strain. This phage also stimulates the synthesis of the 76,000, molecular-weight polypeptide of ThrRS in ultraviolet light-irradiated. E. coli cells. These results indicate that the genes for ThrRS, alpha and beta subunits of phenylalanyl-tRNA synthetase, and initiation factor IF3 are immediately adjacent on the E. coli chromosome.


Artificial intelligence for quality assurance in radiotherapy.
In radiotherapy, patient-specific quality assurance is very time-consuming and causes machine downtime. It consists of testing (using measurement with a phantom and detector) if a modulated plan is correctly delivered by a treatment unit. Artificial intelligence and in particular machine learning algorithms were mentioned in recent reports as promising solutions to reduce or eliminate the patient-specific quality assurance workload. Several teams successfully experienced a virtual patient-specific quality assurance by training a machine learning tool to predict the results. Training data are generally composed of previous treatment plans and associated patient-specific quality assurance results. However, other training data types were recently introduced such as actual positions and velocities of multileaf collimators, metrics of the plan's complexity, and gravity vectors. Different types of machine learning algorithms were investigated (Poisson regression algorithms, convolutional neural networks, support vector classifiers) with sometimes promising results. These tools are being used for treatment units' quality assurance as well, in particular to analyse the results of imaging devices. Most of these reports were feasibility studies. Using machine learning in clinical routines as a tool that could fully replace quality assurance tests conducted by physics teams has yet to be implemented.


Impact of early NK cell recovery on development of GvHD and CMV reactivation in dose-reduced regimen prior to allogeneic PBSCT.
Dose-reduced allogeneic peripheral blood stem cell transplantation (PBSCT) is a therapeutic approach for patients with haematological malignancies who are not eligible for conventional allogeneic PBSCT. We analysed early development of lymphocyte subpopulations and the occurrence of cytomegalovirus (CMV) reactivation and acute graft-versus-host reaction (GvHD) in patients undergoing the protocol according to Slavin vs conventionally treated patients. Lymphocyte status prior to conditioning and at day +30 after allogeneic PBSCT was determined in 24 out of 51 patients who received conventional allogeneic PBSCT (eg cyclophosphamide plus total body irradiation) and compared with 27 patients being treated according to the Slavin protocol (fludarabine, busulphan and ATG). There is a significant delay in CD4 (T helper) cell development and consecutive lower CD4/CD8 ratios and a better reconstitution of CD8 (T cytotoxic) and NK (natural killer) cells after the Slavin protocol. Patients undergoing this protocol and no, or only grade I, acute GvHD show an even better NK cell reconstitution compared to patients with grade II-IV GvHD. A low CD4/CD8 ratio represents a CMV risk factor only in conventionally treated patients with grade 0-I GvHD, while after preparative regimen according to the Slavin protocol, the NK/CD8 ratio might be a marker for the prediction of CMV reactivation in addition to CMV risk status.


Rate of stroke death after depression: a 40-year longitudinal study extension of Chichester/Salisbury Catchment area study.
This study examined clinically diagnosed depression as a risk factor for incidence of death by stroke in a prospective clinically based design study. Risk for stroke was examined separately by sex in a long-term follow-up study spanning 40 years. Patients who were diagnosed with depression in the Chichester (population 100,000)/Salisbury (population 85,000) Catchment Area Study were followed up for 40 years. Death certificates were used to determine the cause of death in the cohort. Death rates in the general population, adjusted for age, gender, and year, were used as a control. Clinical depression was found to be a risk factor for subsequent death from stroke in men but not in women. Death by stroke was a statistically significant cause of death in the men with diagnoses of endogenous depression but not in those men diagnosed with reactive depression. The strength of the relationship of depression with stroke increased over time. These findings suggest that the identification of depressive symptoms at younger ages may have an impact on the primary prevention of stroke in later life. The notion that depression has stronger effects over a long period is consistent with a view that severe clinical depression and physical illness occur concurrently, one exacerbating the other, and health is degraded through slow-acting, cumulative processes. Data were unavailable for the type of stroke or the health-risk behaviors (smoking, diet, and so forth) in the cohort which constituted a limitation of the study. Neither is it known what proportion of the cohort suffered a nonlethal stroke nor to what extent the treatment of clinical depression militates against suffering a lethal stroke.


Impact of microsatellite instability (MSI) on survival in high grade endometrial carcinoma.
Although microstellite instability (MSI) is a prognostic marker in colorectal cancer, it's relation with prognosis in the endometrial cancer is controversial. The goal of this study is to identify the correlation between MSI and clinicopathologic markers along with survival in high grade endometrial carcinoma EC. Between 1995 and 2004, we identified 119 patients (57 type-I, and 62 type-II) diagnosed with high grade EC and underwent hysterectomy. Sections were immunostained using antibodies against MLH1, MSH2, and MSH6. Semi-quantitative scoring of immunoreactivity was based on percentage of tumor staining and staining intensity. Statistical analysis and survival were assessed using the Kaplan-Meier method and Cox regression. Tumors were considered microsatellite unstable (MSI) when at least 2/3 markers tested negative on IHC. Overall, there was no statistically significant difference in survival between patients with MSI tumors and those with microsatellite stable tumors (MSS) (p value=0.70). However, MSI tumors which tested negative for all three markers had markedly poor survival (median survival 3 months vs 71 months, p=0.04) when compared to MSS tumors. The risk of death was 13.2 times greater among women with MSI tumors (with 3 negative markers) compared to women with MSS tumors (OR=13.20 95% CI 3.50-49.76). Although this study has its limitation due to the small sample size, it raises the question of the prognostic significance of MSI in high grade endometrial carcinoma. It also points to the importance of evaluating three mismatch repair genes (MLH1, MSH2, and MSH6) as a prognostic indicator.


Efficacy and safety of saxagliptin compared with acarbose in Chinese patients with type 2 diabetes mellitus uncontrolled on metformin monotherapy: Results of a Phase IV open-label randomized controlled study (the SMART study).
To investigate the efficacy, safety and tolerability of saxagliptin compared with acarbose in Chinese patients with type 2 diabetes mellitus inadequately controlled with metformin monotherapy. SMART was a 24-week, multicentre, randomized, parallel-group, open-label Phase IV study conducted at 35 sites in China (September 24, 2014 to September 29, 2015). The primary outcome was absolute change from baseline in HbA1c at Week 24. Secondary outcomes assessed at Week 24 included the proportion of patients achieving HbA1c < 7.0%, the proportion of patients with gastrointestinal adverse events (GI AEs), and the proportion of patients achieving HbA1c < 7.0% without GI AEs. Safety and tolerability were also assessed in all patients who received ≥1 dose of study medication. Four-hundred and eighty-eight patients were randomized (1:1) to saxagliptin or acarbose via a central randomization system (interactive voice/web response system); 241 and 244 patients received saxagliptin and acarbose, respectively, and 238 and 243 of these had ≥1 pre- and ≥1 post-baseline efficacy values recorded. Saxagliptin was non-inferior to acarbose for glycaemic control [Week 24 HbA1c change: -0.82% and -0.78%, respectively; difference (95% confidence interval): -0.04 (-0.22, 0.13)%], with similar proportions of patients in both treatment groups achieving HbA1c < 7.0%. However, fewer GI AEs were reported with saxagliptin compared with acarbose, and a greater number of patients who received saxagliptin achieved HbA1c < 7.0% without GI AEs compared with those receiving acarbose. Both therapies had similar efficacy profiles. However, saxagliptin was associated with fewer GI AEs, suggesting it might be preferential for clinical practice. NCT02243176, clinicaltrials.gov.


Lack of effect of phototherapy on plasma cyclic-AMP in newborn infants.
The effect of phototherapy on plasma cyclic-AMP in newborn infants has been studied. Our results suggest that phototherapy does not produce appreciable changes in plasma cyclic-AMP levels.


Replacement of Less-Preferred Dipolar Aprotic and Ethereal Solvents in Synthetic Organic Chemistry with More Sustainable Alternatives.
Dipolar aprotic and ethereal solvents comprise just over 40% of all organic solvents utilized in synthetic organic, medicinal, and process chemistry. Unfortunately, many of the common "go-to" solvents are considered to be "less-preferable" for a number of environmental, health, and safety (EHS) reasons such as toxicity, mutagenicity, carcinogenicity, or for practical handling reasons such as flammability and volatility. Recent legislative changes have initiated the implementation of restrictions on the use of many of the commonly employed dipolar aprotic solvents such as dimethylformamide (DMF) and N-methyl-2-pyrrolidinone (NMP), and for ethers such as 1,4-dioxane. Thus, with growing legislative, EHS, and societal pressures, the need to identify and implement the use of alternative solvents that are greener, safer, and more sustainable has never been greater. Within this review, the ubiquitous nature of dipolar aprotic and ethereal solvents is discussed with respect to the physicochemical properties that have made them so appealing to synthetic chemists. An overview of the current legislative restrictions being imposed on the use of dipolar aprotic and ethereal solvents is discussed. A variety of alternative, safer, and more sustainable solvents that have garnered attention over the past decade are then examined, and case studies and examples where less-preferable solvents have been successfully replaced with a safer and more sustainable alternative are highlighted. Finally, a general overview and guidance for solvent selection and replacement are included in the Supporting Information of this review.


Timing of Nonurgent Transesophageal Echocardiography and The Risk of Embolic Events Among Patients Admitted With Infective Endocarditis. A Review of the National Inpatient Sample.
In patients hospitalized for infective endocarditis (IE), timing of nonurgent transesophageal echocardiography (TEE) to reduce embolic events (EE) is unclear. In a retrospective cohort from the 2016 to 2018 combined National Inpatient Sample (NIS), Low-risk adults with IE who underwent nonurgent (>48 hours) TEE were stratified into 3 cohorts based on the timing of the first TEE: early-TEE (3-5 days), intermediate-TEE (5-7 days) and late-TEE (>7). The primary outcome was a composite of an embolic event. Each day before TEE led to 3% increased odds of composite-embolic-events (P < 0.001), 1.21-day extra LOS (P < 0.001) and 14,186 USD increased total charge (P < 0.001). Early compared to late TEE led to reduced LOS by 10 days (P < 0.001) and total cost by 102,273 USD (P < 0.001), odds reduction of 27% in embolic strokes, 21% in septic arterial embolization and 50% reduction in preoperative time (P < 0.001). Among patients hospitalized for suspected IE, the time to TEE was correlated with increased odds of all EE, prolonged preoperative time for valve surgery, LOS, and total charge. Early TEE compared to late TEE led to the largest reduction in length of stay and total cost.


The role of H3K36 methylation and associated methyltransferases in chromosome-specific gene regulation.
In Drosophila, two chromosomes require special mechanisms to balance their transcriptional output to the rest of the genome. These are the male-specific lethal complex targeting the male X chromosome and Painting of fourth targeting chromosome 4. Here, we explore the role of histone H3 methylated at lysine-36 (H3K36) and the associated methyltransferases—Set2, NSD, and Ash1—in these two chromosome-specific systems. We show that the loss of Set2 impairs the MSL complex–mediated dosage compensation; however, the effect is not recapitulated by H3K36 replacement and indicates an alternative target of Set2. Unexpectedly, balanced transcriptional output from the fourth chromosome requires intact H3K36 and depends on the additive functions of NSD and Ash1. We conclude that H3K36 methylation and the associated methyltransferases are important factors to balance transcriptional output of the male X chromosome and the fourth chromosome. Furthermore, our study highlights the pleiotropic effects of these enzymes.


Steroids for the treatment of viral encephalitis: a systematic literature review and meta-analysis.
Specific antiviral treatment is only available for a small subset of viral encephalitis (VE). Adjunctive steroids are used, but there is scant evidence evaluating its utility. We present a systematic review and meta-analysis on the outcome of steroid use in VE. We conducted a systematic literature review and reported it according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standards. Two observational studies from unpublished or partially published data were added. For the meta-analysis, we employed the metaphor package of the statistical software R-4.3.1. We screened 378 studies and included 50. 155 patients were added from the Houston and Linz cohorts. Individual data were available for 281 persons, 120 (43%) of whom received steroids. The most common pathogens were herpes simplex virus 1, West Nile virus, and measles. Study designs and patient outcomes were heterogeneous. Only three of the trials report an advantage of steroid therapy. Steroid-induced side effects were scarce. Ten cohorts were included into the meta-analysis. For the pooled data, the null hypothesis could not be rejected (p = 0.245) using a random effects model, i.e., a benefit of steroid treatment on survival in VE could not be shown. Steroids as potent anti-inflammatory agents may act through a reduction of secondary inflammation-mediated damage. Our data do not support the use of steroids in VE. However, multiple shortcomings apply. Standardized controlled trials are needed to investigate optimal dosing and timing of steroid administration and to explore potential subgroups that could benefit.


Pulsatile luteinizing hormone release and ovarian steroid levels in female-to-male transsexuals compared to heterosexual women.
It has been suggested that there is a difference in the interaction between sex steroids and gonadotropin secretion between transsexual and heterosexual women. In this study we tested whether there is a difference in the pulsatile release characteristics of luteinizing hormone (LH) and in ovarian steroid concentrations between 16 female-to-male (f-to-m) transsexuals and eight eugonadal heterosexual women during the early follicular phase of the menstrual cycle. Blood samples for LH determination were collected every 10 min for 7 hr in the transsexual group, and every 10 min for 6 hr in the heterosexual group. There were no significant differences between the transsexual and heterosexual group in mean serum LH concentration (6.9 +/- 2.4 U/l vs. 7.5 +/- 2.6 U/l), mean LH nadir interval (77 +/- 37 min vs. 70 +/- 16 min), and mean LH pulse amplitude (2.9 +/- 1.1 U/l vs. 3.0 +/- 1.1 U/l). Serum estrone, 17-beta-estradiol, testosterone, progesterone and FSH concentrations also did not differ between the two groups. There also was not a higher prevalence of polycystic ovarian disease in our f-to-m transsexual group than in the general population.


Reflections on the unexpected laboratory finding of hemorheological alterations observed in some haematological disorders.
Hyperviscosity syndrome is a clinical condition characterized by the slowing of blood flow through the vessels and it may be associated with several diseases. The nosographic classification of primary hyperviscosity conditions (Wells classification 1970) divided the primary hyperviscosity syndromes in polycythaemic, sclerocytemic and sieric. Recent and personal laboratory observations have highlighted an unexpected behaviour of the erythrocyte deformability observed in some haematological disorders such as polycythemia vera, multiple myeloma and monoclonal gammopathy of undetermined significance. The interest of this observation depends on the fact that up to now, according to the Wells classification, the hemorheological alteration present in PV was related to the increase of RBC mass while that present in MM and MGUS was attributable to the abnormality of plasma or serum viscosity only. Through an extensive research among the literature, using MEDLINE/PubMed to identify all published reports on the hyperviscosity syndromes, issues that until now have been dealt with separately will therefore be analyzed in a unique paper, allowing a global view. The aim of this paper is to provide some suggestions for reflection and emphasizing the need of a nosographic framework of hyperviscosity that, probably, deserves to be reviewed.


Profiles of phenolic compounds in modern and old common wheat varieties determined by liquid chromatography coupled with time-of-flight mass spectrometry.
The health-promoting properties of common wheat (Triticum aestivum L.) have been largely attributed to the presence of unique phytochemicals of whole grains. The aim of this study was to profile the phenolic content of 16 old and 6 modern Italian wheat varieties, cropped in the same location and growing season. High variability was observed among the investigated wheat genotypes, both in the free and bound phenolic extracts. The total polyphenol content ranged from 885.5 to 1715.9 μmol GAE/100 g of grain and, on average, the bound fraction contributed for 72.0% to the total phenolic content. As regards the flavonoid content, the free fraction ranged from 50.7 to 106.1 μmol CE/100 g of grain and the bound fraction from 78.3 to 148.9 μmol CE/100 g of grain. Moreover, the interpretation of the mass spectra allowed the characterization of 34 phenolic compounds (104 including isomer forms) belonging to the phenolic acid, flavonoid, coumarin, stilbene, proanthocyanidin and lignan chemical classes. HPLC-ESI-TOF-MS analysis highlighted remarkable differences in the phytochemical fingerprints of old and modern wheat varieties. Six ancient wheat genotypes (Bianco Nostrale, Frassineto, Gentil Rosso, Gentil Rosso Mutico, Marzuolo d'Aqui, Verna) showed phenolic profiles with a number of total compounds and isomer forms much higher than that identified in the modern cultivars. The present findings confirm that ancient wheat may represent a valuable source of biodiversity, especially as regards phenolic compounds. The investigated old wheat genotypes may be successfully used in breeding programs for developing bread wheat varieties with added value in terms of health-promoting phytochemicals.


A new case of neuropeptide coexpression (RGamide and LWamides) in Hydra, found by whole-mount, two-color double-labeling in situ hybridization.
The freshwater polyp Hydra has a primitive nervous system that expresses at least six different neuropeptide genes: (1) three genes, coding for the preprohormones-A, -B, and -C that each gives rise to a variety of peptides with the C-terminal sequence Arg-Phe-NH(2) (the Hydra-RFamides); (2) one gene, coding for a preprohormone that gives rise to five peptides with the C-terminal sequence Leu-Trp-NH(2) (the Hydra-LWamides); (3) one gene, coding for a preprohormone that produces a peptide with the C-terminal sequence Lys-Val-NH(2) (Hydra-KVamide, also called Hym-176); and (4) one gene, coding for a preprohormone that gives rise to a peptide with the C-terminal sequence Arg-Gly NH(2) (Hydra-RGamide, also called Hym-355). In a previous paper, we described that a population of neurons in the peduncle (a region just above the foot) of Hydra coexpresses the preprohormone-A and KVamide genes, whereas neurons in the other regions only express either the preprohormone-A, -B, -C, LWamide, or the KVamide genes. Here, we investigated the RGamide gene expression, using whole-mount, two-color double-labeling in situ hybridization, and found that neurons in the basal disk (foot), gastric region, hypostome (a region around the mouth), and tentacles coexpress this gene together with the LWamide gene. A small population of neurons in the hypostome and upper gastric region expresses only the LWamide gene. No coexpression of the RGamide gene with any of the other neuropeptide genes was observed. This is the second example of coexpression of two neuropeptide genes in cnidarians. It demonstrates that many neurons in the primitive nervous systems of cnidarians use combinations ("cocktails") of neuropeptides for their signaling. It also shows that Hydra has at least seven neurochemically different populations of neurons.


Hemispheric lateralization of bilaterally presented homologous visual and auditory stimuli in normal adults, normal children, and children with central auditory dysfunction.
Two experiments were conducted to examine the performance of normal adults, normal children, and children diagnosed with central auditory dysfunction presumed to involve the interhemispheric pathways on a dichotic digits test in common clinical use for the diagnosis of central auditory processing disorder (CAPD) and its corresponding visual analog. Results of the first experiment revealed a significant right ear advantage (REA) for the dichotic listening task and a left-visual-field advantage (LVFA) for the corresponding visual analog in normal adults and children. In the second experiment, results revealed a significantly larger REA in the children with CAPD as compared to the normal children. Results also revealed a reversed cerebral asymmetry (RVFA) for the children with CAPD on the visual task. Significant cross-modal correlations suggest that the two tasks may reflect, at least in part, similar interhemispheric processing mechanisms in children. Findings are discussed in relation to differential diagnosis and modality-specificity of CAPD.


Radiopharmaceutical research and production in Brazil: a 30-year history of participation in the nuclear medicine scenario.
This article describes the 30-y history of nuclear medicine in Brazil, including reactors, production of radiopharmaceuticals, and trends.


Comparison of the sensitivity of four rapid assays for the detection of antibodies to HIV-1/HIV-2 during seroconversion.
To compare the sensitivity of four rapid assays for the detection of antibodies against HIV-1 during early seroconversion. Four rapid assays for the detection of antibodies to HIV-1/HIV-2 (SUDS HIV 1 + 2, TestPack HIV-1/HIV-2, HIV-SPOT and CAPILLUS HIV-1/HIV-2) were evaluated on 38 sera derived from 14 HIV-1 seroconverters, formerly tested with Abbott second- and third-generation HIV-1/HIV-2 enzyme immunoassay (EIA) and Diagnostic Biotechnology HIV blot 2.2. EIA-negative sera had also been investigated by HIV-1 antigen testing and polymerase chain reaction (PCR) analysis detecting HIV-1 proviral DNA. On 16 sera which were Abbott second-generation EIA negative, the SUDS assay rated highest with six positive results. Four sera were TestPack positive. No specimens in this group were HIV-SPOT positive or CAPILLUS positive. Of the remaining 22 sera (Abbott second- and third-generation EIA positive), all but two were positive in all tests. The study revealed differences in the sensitivities of the rapid assays in the early phase of seroconversion. The most sensitive assay, SUDS, was even more sensitive than the Abbott third-generation EIA, while TestPack and the EIA were equally sensitive. Based on these findings, we suggest the inclusion of these assays in the supplemental testing for detection of antibodies to HIV.


WITHDRAWN: Ghrelin in obesity and endocrine diseases.
The Publisher regrets that this article is an accidental duplication of an article that has already been published, doi:10.1016/j.mce.2011.02.011. The duplicate article has therefore been withdrawn.


Myxobacteria and their products: current trends and future perspectives in industrial applications.
Myxobacteria belong to a group of bacteria that are known for their well-developed communication system and synchronized or coordinated movement. This typical behavior of myxobacteria is mediated through secondary metabolites. They are capable of producing secondary metabolites belonging to several chemical classes with unique and wide spectrum of bioactivities. It is predominantly significant that myxobacteria specialize in mechanisms of action that are very rare with other producers. Most of the metabolites have been explored for their medical and pharmaceutical values while a lot of them are still unexplored. This review is an attempt to understand the role of potential metabolites produced by myxobacteria in different applications. Different myxobacterial metabolites have demonstrated antibacterial, antifungal, and antiviral properties along with cytotoxic activity against various cell lines. Beside their metabolites, these myxobacteria have also been discussed for better exploitation and implementation in different industrial sectors.


Transfer of latissimus dorsi muscle for the functional reconstruction of quadriceps femoris muscle following oncological resection of sarcoma in the thigh.
Wide resection of tumours in the anterior compartment of the thigh frequently requires en bloc removal of the quadriceps femoris muscle. Such resection can result in significantly decreased muscle power of knee extension. Functional muscle transfer is a beneficial tool for the reconstruction process. Until now, however, there have been few reports on the outcome of quadriceps muscle reconstruction using free innervated muscle transfer. We reviewed 14 patients (seven women and seven men, mean age 53 years). The extent of tumour invasion required resection of the entire quadriceps in four cases, of three heads in six cases and of two heads in the remaining four cases. Local recurrence occurred in one patient only, and there were no major complications. In the four patients with entire resection of the quadriceps, the postoperative muscle manual test (MMT) result was 0-1 (mean, 0.5), but this recovered to between 2 and 3 (mean 2.3) after a mean follow-up of 70 months. In the six cases with resection of three heads, the MMT test result was 2 and active knee extension recovered almost fully. Transfer of free, functional latissimus dorsi muscle is best indicated for cases in which the entire quadriceps or three heads are resected. Active knee extension can be expected to improve to an MMT score of 2 after reinnervation of the transferred muscle. Microsurgical reconstruction following resection of soft-tissue sarcoma provides adequate functional and coverage reconstruction, together with better local control by allowing wider surgical margins.


Efficient diterpene production in yeast by engineering Erg20p into a geranylgeranyl diphosphate synthase.
Terpenes have numerous applications, ranging from pharmaceuticals to fragrances and biofuels. With increasing interest in producing terpenes sustainably and economically, there has been significant progress in recent years in developing methods for their production in microorganisms. In Saccharomyces cerevisiae, production of the 20-carbon diterpenes has so far proven to be significantly less efficient than production of their 15-carbon sesquiterpene counterparts. In this report, we identify the modular structure of geranylgeranyl diphosphate synthesis in yeast to be a major limitation in diterpene yields, and we engineer the yeast farnesyl diphosphate synthase Erg20p to produce geranylgeranyl diphosphate. Using a combination of protein and genetic engineering, we achieve significant improvements in the production of sclareol and several other isoprenoids, including cis-abienol, abietadiene and β-carotene. We also report the development of yeast strains carrying the engineered Erg20p, which support efficient isoprenoid production and can be used as a dedicated chassis for diterpene production or biosynthetic pathway elucidation. The design developed here can be applied to the production of any GGPP-derived isoprenoid and is compatible with other yeast terpene production platforms.


The impact of supportive intervention after second trimester termination of pregnancy for fetal abnormality.
The reactions of women who had had a termination of pregnancy for fetal abnormality in the second trimester have been studied retrospectively using a semi-structured questionnaire. The severity of the grief reaction was measured and the outcome at 6 months was compared with the findings from a previous study in South Wales which had led to the introduction of skilled support from genetic fieldworkers and formal genetic counselling after the termination. Of the 69 women interviewed, 55 (80 per cent) experienced an acute grief reaction and 17 (25 per cent) had not resolved their grief 6 months after the termination, compared with 37 (77 per cent) and 22 (46 per cent) out of 48 respectively in the previous study. Fifty-seven (83 per cent) women had found the fieldworker's intervention useful or very useful, some describing her support as essential. An association between poor resolution of the grief reaction with increasing maternal age and with poor perceived support from partners was noted. Improved follow-up support and counselling have lessened the adverse emotional consequences and support should therefore be offered to all women undergoing termination for fetal malformation.


Promotion of early and exclusive breastfeeding in neonatal care units in rural Rwanda: a pre- and post-intervention study.
Early initiation of breastfeeding after birth and exclusive breastfeeding for the first six months improves child survival, nutrition and health outcomes. However, only 42% of newborns worldwide are breastfed within the first hour of life. Small and sick newborns are at greater risk of not receiving breastmilk and often require additional support for feeding. This study compares breastfeeding practices in Rwandan neonatal care units (NCUs) before and after the implementation of a package of interventions aimed to improve breastfeeding. This pre-post intervention study was conducted at two district hospital NCUs in rural Rwanda from October-December 2017 (pre-intervention) and September 2018-March 2019 (post-intervention). Only newborns admitted before their second day of life (DOL) were included. Data were extracted from patient charts for clinical and demographic characteristics, feeding, and patient outcomes. Exclusive breastfeeding at discharge was based on last recorded infant feeding on the day of discharge. Logistic regression analysis was used to evaluate factors associated with exclusive breastfeeding at discharge. Pre-intervention, 255 newborns were admitted in the NCUs and 793 were admitted in post-intervention. Exclusive breastfeeding on the day of birth (DOL0) increased from 5.4% (12/255) to 35.9% (249/793). At discharge, exclusive breastfeeding increased from 69.6% (149/214) to 87.0% (618/710). The mortality rate decreased from 16.1% (41/255) to 10.5% (83/793). Factors associated with greater odds of exclusive breastfeeding at discharge included admission during the post-intervention period (aOR 4.91; 95% CI 1.99, 12.11), and admission for infection (aOR 2.99; 95% CI 1.13, 7.93). Home deliveries (aOR 0.15; 95% CI 0.05, 0.47), preterm delivery (aOR 0.36; 95% CI 0.15, 0.87) and delayed first breastmilk feed (aOR 0.04 for DOL3 vs. DOL0; 95% CI 0.01, 0.35) reduced odds of exclusive breastfeeding at discharge. Expansion and adoption of evidenced-based guidelines, using innovative approaches, aimed at the unique needs of small and sick newborns may help to improve earlier initiation of breastfeeding, decrease mortality, and improve exclusive breastfeeding on discharge from hospital among small and sick newborns. These interventions should be replicated in similar settings to determine their effectiveness.


Pten, Pi3K and PtdIns(3,4,5)P 3 dynamics modulate pulsatile actin branching in Drosophila retina morphogenesis.
Epithelial remodeling of the Drosophila retina depends on the pulsatile contraction and expansion of apical contacts between the cells that form its hexagonal lattice. Phosphoinositide PI(3,4,5)P 3 (PIP 3 ) accumulates around tricellular adherens junctions (tAJs) during contact expansion and dissipates during contraction, but with unknown function. Here we found that manipulations of Pten or Pi3K that either decreased or increased PIP 3 resulted in shortened contacts and a disordered lattice, indicating a requirement for PIP 3 dynamics and turnover. These phenotypes are caused by a loss of protrusive branched actin, resulting from impaired activity of the Rac1 Rho GTPase and the WAVE regulatory complex (WRC). We additionally found that during contact expansion, Pi3K moves into tAJs to promote the cyclical increase of PIP 3 in a spatially and temporally precise manner. Thus, dynamic regulation of PIP 3 by Pten and Pi3K controls the protrusive phase of junctional remodeling, which is essential for planar epithelial morphogenesis.


Prognostic Value of Feature-Tracking Right Ventricular Longitudinal Strain in Severe Functional Tricuspid Regurgitation: A Multicenter Study.
This study sought to evaluate the prognostic value of cardiac magnetic resonance (CMR) feature-tracking-derived right ventricular (RV) free wall longitudinal strain (RVFWLS) in a large multicenter population of patients with severe functional tricuspid regurgitation. Tricuspid regurgitation imposes a volume overload on the RV that can lead to progressive RV dilation and dysfunction. Overt RV dysfunction is associated with poor prognosis and increased operative risk. Abnormalities of myocardial strain may provide the earliest evidence of ventricular dysfunction. CMR feature-tracking techniques now allow assessment of strain from routine cine images, without specialized pulse sequences. Whether abnormalities of RV strain measured using CMR feature tracking have prognostic value in patients with tricuspid regurgitation is unknown. Consecutive patients with severe functional tricuspid regurgitation undergoing CMR at 4 U.S. medical centers were included in this study. Feature-tracking RVFWLS was calculated from 4-chamber cine views. The primary endpoint was all-cause death. Cox proportional hazards regression modeling was used to examine the independent association between RVFWLS and death. The incremental prognostic value of RVFWLS was assessed in nested models. Of the 544 patients in this study, 128 died during a median follow-up of 6 years. By Kaplan-Meier analysis, patients with RVFWLS ≥median (-16%) had significantly reduced event-free survival compared with those with RVFWLS <median (log-rank p < 0.001). By Cox multivariable regression modeling, RVFWLS was associated with increased risk-of-death after adjustment for clinical and imaging risk factors, including RV size and ejection fraction (hazard ratio: 1.14 per %; p < 0.001). Addition of RVFWLS in this model resulted in significant improvement in the global chi-square (31 to 78; p < 0.001). CMR feature-tracking-derived RVFWLS is an independent predictor of mortality in patients with severe functional tricuspid regurgitation, incremental to common clinical and imaging risk factors.