Segmentation of trabecular bone microdamage in Xray microCT images using a two-step deep learning method.
One of the current approaches to improve our understanding of osteoporosis is to study the development of bone microdamage under mechanical loading. The current practice for evaluating bone microdamage is to quantify damage volume from images of bone samples stained with a contrast agent, often composed of toxic heavy metals and requiring long tissue preparation. This work aims to evaluate the potential of linear microcracks detection and segmentation in trabecular bone samples using well-known deep learning models, namely YOLOv4 and Unet, applied on microCT images. Six trabecular bovine bone cylinders underwent compression until ultimate stress and were subsequently imaged with a microCT at a resolution of 1.95 μm. Two of these samples (samples 1 and 2) were then stained using barium sulfate (BaSO4) and imaged again. The unstained samples (samples 3-6) were used to train two neural networks YOLOv4 to detect regions with microdamage further combined with Unet to segment the microdamage at the pixel level in the detected regions. Four different model versions of YOLOv4 were compared using the average Intersection over Union (IoU) and the mean average precision (mAP). The performance of Unet was also measured using two segmentation metrics, the Dice Score and the Intersection over Union (IoU). A qualitative comparison was finally done between the deep learning and the contrast agent approaches. Among the four versions of YOLOv4, the YOLOv4p5 model resulted in the best performance with an average IoU of 45,32% and 51,12% and a mAP of 28.79% and 46.22%, respectively for samples 1 and 2. The segmentation performance of Unet provided better IoU and DICE score on sample 2 compared to sample 1. The poorer performance of the test on sample 1 could be explained by its poorer contrast to noise ratio (CNR). Indeed, sample 1 resulted in a CNR of 7,96, which was worse than the average CNR in the training samples, while sample 2 resulted in a CNR of 10,08. The qualitative comparison between the contrast agent and the deep learning segmentation showed that two different regions were segmented by the two techniques. Deep learning is segmenting the region inside the cracks while the contrast agent segments the region around it or even regions with no visible damage. The combination of YOLOv4 for microdamage detection with Unet for damage segmentation showed a potential for the detection and segmentation of microdamage in trabecular bone. The accuracy of both neural networks achieved in this work is acceptable considering it is their first application in this specific field and the amount of data was limited. Even if the errors from both neural networks are accumulated, the two-steps approach is faster than the semantic segmentation of the whole volume.


Fast generation of three-atom singlet state by transitionless quantum driving.
Motivated by "transitionless quantum driving", we construct shortcuts to adiabatic passage in a three-atom system to create a singlet state with the help of quantum zeno dynamics and non-resonant lasers. The influence of various decoherence processes is discussed by numerical simulation and the results reveal that the scheme is fast and robust against decoherence and operational imperfection. We also investigate how to select the experimental parameters to control the cavity dissipation and atomic spontaneous emission which will have an application value in experiment.


Metalloestrogenic effects of cadmium are absent in long-term estrogen-deprived MCF-7 cells: Evidence for the involvement of constitutively activated estrogen receptor α and very low expression of G protein-coupled estrogen receptor 1.
Cadmium (Cd) has estrogen-like activities in breast cancer; it acts as a metalloestrogen in humans. Prospective cohort studies of Cd and breast cancer risk suggest a significant relationship between increased Cd intake and cancer incidence, with more pronounced effects for estrogen receptor α (ERα)-positive breast cancers. However, a recent systematic review with the highest level of evidence demonstrated no such relationship in post-menopausal women. Thus, the reported effects of Cd in pre- and post-menopausal ERα-positive breast cancers are inconsistent. MCF-7 human breast cancer cells normally exhibit growth through estradiol-triggered ERα signaling; however, the MCF-7 cells cultured in estrogen-deprived conditions for a long time (∼ 6 months) eventually result in LTED cells that can be used to utilize to study the proliferation of ERα-positive breast cancer cells obtained from post-menopausal women. Our results showed that unlike MCF-7 cells, LTED cells showed estradiol-independent growth because of constitutively activated ERα. Moreover, Cd (∼10 nM) stimulated ERα signaling in MCF-7 cells and ERα-expressing LTED cells, but not in LTED cells; in ERα-expressing LTED cells, this effect was reversed by ICI 182,780 (an ERα antagonist). Furthermore, in comparison with MCF-7 cells, the LTED cells expressed very low levels of G protein-coupled estrogen receptor 1 (GPER1), a membrane ER capable of stimulating the estrogenic activity of Cd. These findings suggest that the estrogenic action of Cd may be suppressed in LTED cells, and potentially in post-menopausal breast cancer.


The risk of imported malaria in security forces personnel returning from overseas missions in the context of prevention of re-introduction of malaria to Sri Lanka.
Sri Lanka is a malaria-free country. However it remains surrounded by countries with endemic malaria transmission. Since the last indigenous case of malaria was reported in October 2012, only imported malaria cases have been diagnosed with 36 cases detected in 2015, which includes 17 cases each of Plasmodium vivax and Plasmodium falciparum and two cases of Plasmodium ovale. This study investigated the knowledge and practices regarding malaria chemoprophylaxis among all the Sri Lankan security forces personnel returning from peacekeeping missions in malaria endemic countries over a 7 month period. Adherence to other malaria prevention measures, occurrence of adverse events and incident cases of malaria were also recorded maintaining the anonymity of the respondents. Potential associations for non-compliance were studied. Interviews were carried out with 559 security forces personnel returning home from foreign deployments in malaria-endemic regions (males: 550, 98.4 %). The majority (553, 98.9 %) was well aware of the need for chemoprophylaxis during the overseas stay and its regular use as prescribed. The overall adherence to chemoprophylaxis was good with 78.7 % (440/559) reporting regular, as prescribed, use. Having better educational qualifications, being female, being prescribed mefloquine, having fever during deployment and belonging to a security force other than the army were significantly associated with poor compliance (p < 0.05). The study reveals that knowledge regarding malaria chemoprophylaxis among Sri Lankan security forces personnel serving abroad was good, a fact that may have contributed to absence/extremely low incidence of malaria during deployment.


Poly(ethylene glycol)-b-poly(epsilon-caprolactone) nanoparticles as a platform for the improved oral delivery of cannabidiol.
Cannabidiol (CBD), a non-psychoactive constituent of Cannabis, has proven neuroprotective, anti-inflammatory and antioxidant properties though his therapeutic use, especially by the oral route, is still challenged by the poor aqueous solubility that results in low oral bioavailability. In this work, we investigate the encapsulation of CBD within nanoparticles of a highly hydrophobic poly(ethylene glycol)-b-poly(epsilon-caprolactone) block copolymer produced by a simple and reproducible nanoprecipitation method. The encapsulation efficiency is ~ 100% and the CBD loading 11% w/w (high performance liquid chromatography). CBD-loaded nanoparticles show a monomodal size distribution with sizes of up to 100 nm (dynamic light scattering), a spherical morphology, and the absence of CBD crystals (high resolution-scanning electron microscopy and cryogenic-transmission electron microscopy) which is in line with a very efficient nanoencapsulation. Then, the CBD release profile from the nanoparticles is assessed under gastric- and intestine-like conditions. At pH 1.2, only 10% of the payload is released after 1 h. Conversely, at pH 6.8, a release of 80% is recorded after 2 h. Finally, the oral pharmacokinetics is investigated in rats and compared to a free CBD suspension. CBD-loaded nanoparticles lead to a statistically significant ~ 20-fold increase of the maximum drug concentration in plasma (Cmax) and a shortening of the time to the Cmax (tmax) from 4 to 0.3 h, indicating a more complete and faster absorption than in free form. Moreover, the area-under-the-curve (AUC), a measure of oral bioavailability, increased by 14 times. Overall results highlight the promise of this simple, reproducible, and scalable nanotechnology strategy to improve the oral performance of CBD with respect to common oily formulations and/or lipid-based drug delivery systems associated with systemic adverse effects.


The connection between young women's body esteem and sexual assertiveness.
Healthy sexuality includes having positive feelings about one's body and developing positive romantic relationships. Previous research predicts that women dissatisfied with their bodies may be less likely to enforce their rights of sexual autonomy (i.e., sexual assertiveness). We assessed whether the body esteem of young women was related to their reports of sexual assertiveness. Young women from local colleges (N = 127) completed a questionnaire that included demographics, self reported weight and height, sexual history, along with body esteem and sexual assertiveness. Overall, body esteem was related to sexual assertiveness regarding condom use when controlling for other variables. Women with less body esteem were less likely to insist that their partner use a condom. Individual components of body esteem did not independently predict insistence of condom use. Body esteem was not related to initiation of sex or refusal of unwanted sex. The current study found relationships between body esteem and sexual assertiveness regarding STI prevention behaviors. Given these findings, implications for STI prevention programs are discussed.


Intrinsic laryngeal muscle activity in response to autonomic nervous system activation.
To determine whether the intrinsic laryngeal muscles exhibit a response to induced autonomic nervous system (ANS) activation, and to characterize responses that may occur. Prospective within-subjects study. A cold pressor (CP) task was used to trigger a whole-body ANS response in eight vocally normal adult females. Surface electromyography of the trapezius muscle and bipolar hook-wire electromyography of intrinsic laryngeal muscles, as well as cardiovascular measures of heart rate (HR) and blood pressure (systolic [SBP] and diastolic [DBP]), were used to characterize participants' response to CP exposure compared to at-rest baseline. Cardiovascular response to the CP task was confirmed for subjects via HR or blood pressure measures. Post hoc Bonferroni analysis confirmed statistically significant increases in HR (P = .027), SBP (P < .001), and DBP (P < .001) during the CP task as compared to baseline. Concurrent increases in muscle activity were generally observed in trapezius, posterior cricoarytenoid, bilateral thyroarytenoid/lateral cricoarytenoid muscle complex, and bilateral cricothyroid muscles for each subject. Three individuals elected to repeat the CP task and displayed the same pattern of laryngeal response as observed in their first exposure. Results for repeated baseline measures obtained after the cessation of the CP task were compared to pre-CP baseline. Overall laryngeal activation remained even after the cardiovascular response was attenuated. Results are consistent with the suggestion that human laryngeal muscles exhibit an elevated level of activation concurrent with ANS activation, and endorse the putative link between laryngeal muscle tension and acute stress. Findings are replicable within a subset of three individuals.


A mathematical analysis of the disk-sphere transition of the human red cell.
By means of analytical calculations, an attempt is made to approximate the profile of the human red cell during the 'disk-sphere' transition induced by variation of the tonicity of the medium.


A survey of horse owners in Great Britain regarding horses in their care. Part 2: Risk factors for recurrent airway obstruction.
Recurrent airway obstruction (RAO) is a commonly encountered respiratory condition of horses. Despite this, the epidemiology of this predominately manageable and reversible disease in Great Britain has been largely ignored. To estimate the prevalence of RAO in the general horse population of Great Britain and to investigate possible risk factors for RAO associated with management or early life. Horse owners were surveyed using a self-administered postal questionnaire that contained a risk-screening questionnaire (RSQ) designed to identify horses with RAO. These owners were randomly selected, following geographical stratification, using 2-stage cluster sampling of veterinary practices and their clients. Multilevel, multivariable logistic regression models were used to investigate risk factors for RAO in the selected horse population. The estimated true prevalence of RAO in the selected horse population was 14.0% (95%CI 10.7-17.4%). Risk factors for RAO identified in a general horse management logistic regression model included increasing age and exposure to an urbanised environment. Recurrent airway obstruction has long been associated with mature horses while the association with an urbanised environment could be related to different management practices in these areas or possibly air pollution could be involved. The second model associated exposure to hay and respiratory infection in early life with a horse having RAO in later life. Challenges to the respiratory system in early life may be involved in the development of this disease. Recurrent airway obstruction is a significant health problem in the horse population of Great Britain. This form of epidemiological investigation highlights potential risk factors for the disease.


Addressing the burden of cervical cancer through IAEA global brachytherapy initiatives.
Brachytherapy (BT) is an essential component of definitive therapy for locally advanced cervical cancer. Despite the advantages of the dose distribution with BT in cervical cancer, there is paucity of specific skills required for good-quality BT applications. Furthermore, replacing BT with other modern external beam techniques as a boost can lead to suboptimal results in cervix cancer. Review of available IAEA resources, research and cooperation programs available from the IAEA was completed. These opportunities can be used to address challenges in Brachytherapy. The International Atomic Energy Agency (IAEA) provides support for BT through various means that includes education and training, both long term, short term and continuing medical education of professionals, providing expert visits to support implementation, development of curricula for professionals, e-learning through the human health campus, contouring workshops, 2D to 3D BT training, and virtual tumor boards. In addition, the IAEA provides support for implementing quality assurance in radiotherapy to its member states and provides guidelines for comprehensive audits in radiation therapy (QUATRO), and produces safety standards and training in radiation safety. In addition, mapping BT resources, making the case for investment and support for setting up BT services and radiotherapy centers are also available. The IAEA Dosimetry Laboratory provides calibration services to Secondary Standards Dosimetry Laboratories for well chambers used to confirm the reference air kerma rate of Co60 and Ir192 high-dose-rate BT sources, as well as for Cs137 low-dose-rate sources. Furthermore, the IAEA supports research and development in radiotherapy (and BT) through coordinated research activities that include controlled randomized clinical trials, Patterns of Care studies among others. Partnerships with professional organizations and funding bodies, as well as through the United Nations Joint Global Programme on Cervical Cancer Prevention and Control support radiotherapy activities, including BT in countries worldwide. The IAEA supports brachytherapy implementation, training and research and provides resources to professionals in the area.


Genetic and Environmental Influences on Literacy and Numeracy Performance in Australian School Children in Grades 3, 5, 7, and 9.
We examined the extent to which genes and the environment contributed to variation in and covariation among reading, spelling, grammar and punctuation, writing, and numeracy in Australian school children in Grades 3, 5, 7, and 9. Heritability was generally high: reading .58-.71 (excepting Grade 5 girls), spelling .68-.78; grammar and punctuation .52-.66, writing .39-.52, and numeracy .39-.79. Boys' performance varied more than girls in spelling and numeracy, and the common environment was a greater influence in girls than boys in Grade 3 numeracy and Grade 5 reading. Independent pathway models showed similar genetic and environmental structures at each grade with approximately one third to one half of the variation in each domain due to genes that influenced all domains. The covariation among the domains was largely mediated by genes. Results suggest substantial uniformity in the environmental factors influencing these academic domains.


Association between nutritional status and subjective health status in chronically ill children attending special schools.
In hospitalized children with a chronic disease, malnutrition was associated with a lower subjective health status. In outpatient children with a chronic disease attending special schools, this association has never been studied. The aim of this study was to assess the association between nutritional status and subjective health status in chronically ill children attending special schools. Overall, 642 children, median age 9.8 years (IQR 7.7-11.5), 60 % male, 72 % Caucasian, were included in this prospective study in nine special schools for chronically ill children in the Netherlands. Overall malnutrition was assessed as: acute malnutrition (<-2 SDS for weight for height (WFH)) and chronic malnutrition (<-2 SDS for height for age). The malnutrition risk was assessed with the nutritional risk-screening tool STRONGkids. Subjective health status was assessed with EQ-5D. Overall, 16 % of the children had overall malnutrition: 3 % acute and 13 % chronic malnutrition. Nurses reported 'some/severe problems' on the health status dimensions mobility (15 %), self-care (17 %), usual activities (19 %), pain/discomfort (22 %), and anxiety/depression (22 %) in chronically ill children. Their mean visual analogue scale score (VAS) was 73.0 (SD 11.1). Malnutrition, medication usage, and younger age explained 38 % of the variance of the VAS score. The presence of overall malnutrition in chronically ill children attending special schools was associated with lower subjective health status, especially in younger children and in those with chronic medication usage. Therefore, it is important to develop and use profile-screening tools to identify these children.


Protection from natural infections with enterotoxigenic Escherichia coli: longitudinal study.
Enterotoxigenic Escherichia coli (ETEC) are an important cause of diarrhoea and diarrhoeal deaths in children living in developing countries and of travellers' diarrhoea. During the past 25 years, vaccine development efforts have been focused on induction of protective immunity against surface colonisation factors (CFs) and the heat-labile enterotoxin. Although vaccines that induce immunity to heat-labile toxin offer protection against diarrhoea from ETEC that produce this toxin, the benefit of including CF antigens remains uncertain. We aimed to estimate the protection that natural ETEC infections induce against new infections. In Guinea-Bissau, we followed up 200 neonates until up to age 2 years, most of whom were breastfed throughout the study. We collected stool specimens from the children every week irrespective of whether they had diarrhoea. As a measure of protection, we used Cox regression models to estimate the change in infection rates after a primary ETEC infection. We thus estimated the protection attributable to CFs, toxins, and to any other factors that could be shared by ETEC with the same toxin-CF profile. ETEC infections induced a 47% (95% CI 12 to 69) protection against new infections with ETEC that had the same toxin-CF profile; the corresponding estimate attributable to CFs was -1% (-40 to 27). Infection with heat-labile toxin-positive ETEC conferred a 45% (-1 to 70) protection against symptomatic infections with ETEC positive for this toxin. For breastfed children living in endemic areas, other antigens are substantially more important than CFs for induction of protective immunity against ETEC infection.


Self-reported history of concussions is associated with risk factors for suicide completion among high school students.
Suicide is the third leading cause of death among adolescents. While research has found concussions to be a risk factor for suicide in adults, this relationship is not well studied in nationally representative samples of youth. This study examines the relationship between self-reported history of sports-related concussion and five risk factors for suicide completion. Data were obtained from the 2017 Youth Risk Behavior Surveillance Survey (n=13,353). Multivariate logistic regression models assessed the relationship between self-reported, sports-related concussion and five risk factors for suicide completion. Analyses controlled for sex, race/ethnicity, grade, bullying victimization, and sexual orientation. Subsample analyses were conducted stratified by sex. Interaction models examined biological sex as a possible effect modifier. Overall, 15.0% of high school students reported a sports-related concussion in the past 12-months. Self-reported, sports-related concussion was significantly associated with greater odds of feeling sad/hopeless (Adj OR: 1.20; 95% CI:1.02-1.42), suicidal ideations (Adj OR: 1.25; 95% CI:1.02-1.55), suicide attempt (Adj OR: 1.60; 95% CI:1.31-1.96), and suicide attempt treated by a doctor/nurse (Adj OR: 2.35; 95% CI:1.68-3.29), adjusting for covariates. Stratified analyses demonstrated differences by sex, however, no direct evidence of effect modification was observed in interaction models. Data are cross-sectional, prohibiting causal inferences. Measures were assessed via self-report. No pre-concussion measures of mental health. Self-reported sports-related concussion was associated with risk factors for suicide completion. No direct evidence of effect modification was observed but stratified analyses suggest biological sex may impact the observed relationship.


The watershed between right and left hepatic artery territories: findings on CT scans after transcatheter oily chemoembolization of hepatic tumors. A preliminary report.
The goals of this study were to delineate the boundary between the right and left hepatic artery territories by computed tomography (CT), to compare this boundary with the middle scissura of Couinaud's segmental anatomy, and to discuss the clinical implications of these findings. The 18 patients who underwent transcatheter oily chemoembolization (TOCE) of liver tumors via the right or left hepatic artery, were examined with an immediate postembolization CT scan. We measured the orientation of the watershed line between the right and left hepatic artery territories and the orientation of the middle scissura on other available sectional imaging modalities, and then compared the middle scissura with the arterial watershed line. A part of segment IV was fed by the right hepatic artery in two of 18 (11.1%) patients. Moreover, one of 4 segment IV lesions was embolized via right hepatic artery infusion. Thus, in 11.1% of cases there was no coincidence between the arterial watershed line and the middle scissura. Some segment IV lesions may be fed and therefore embolized only via right hepatic artery infusion in TOCE for liver tumor.


Comparison of Antiretroviral Therapies in Pregnant Women Living With Human Immunodeficiency Virus and Hepatitis B Virus: A Randomized Controlled Trial.
To describe the anti-hepatitis B virus (HBV) efficacy, HBeAg serologic changes, HBV perinatal transmission, and safety in pregnant women who are living with human immunodeficiency virus (HIV) and HBV co-infection who were randomized to various antiretroviral therapy (ART) regimens. The PROMISE (Promoting Maternal and Infant Survival Everywhere) trial was a multicenter randomized trial for ART-naive pregnant women with HIV infection. Women with HIV and HBV co-infection at 14 or more weeks of gestation were randomized to one of three ART arms: one without HBV treatment (group 1) and two HBV treatment arms with single (group 2) or dual anti-HBV activity (group 3). The primary HBV outcome was HBV viral load antepartum change from baseline (enrollment) to 8 weeks; safety assessments included alanine aminotransferase (ALT) level, aspartate aminotransferase (AST) level, and anemia (hemoglobin less than 10 g/dL). Primary comparison was for the HBV-active treatment arms. Pairwise comparisons applied t test and the Fisher exact tests. Of 3,543 women, 3.9% were HBsAg-positive; 42 were randomized to group 1, 48 to group 2, and 48 to group 3. Median gestational age at enrollment was 27 weeks. Among HBV-viremic women, mean antepartum HBV viral load change at week 8 was -0.26 log 10 international units/mL in group 1, -1.86 in group 2, and -1.89 in group 3. In those who were HBeAg-positive, HBeAg loss occurred in 44.4% at delivery. Two perinatal HBV transmissions occurred in group 2. During the antepartum period, one woman (2.4%) in group 1 had grade 3 or 4 ALT or AST elevations, two women (4.2%) in group 2, and three women (6.3%) in group 3. Over a short period of time, HBV DNA suppression was not different with one or two HBV-active agents. HbeAg loss occurred in a substantial proportion of participants. Perinatal transmission of HBV infection was low. Hepatitis B virus-active ART was well-tolerated in pregnancy, with few grade 3 or 4 ALT or AST elevations. ClinicalTrials.gov , NCT01061151.


MicroRNA-3613-5p Promotes Lung Adenocarcinoma Cell Proliferation through a RELA and AKT/MAPK Positive Feedback Loop.
Aberrant activation of nuclear factor κB (NF-κB)/RELA is often found in lung adenocarcinoma (LUAD). In this study, we determined that microRNA-3613-5p (miR-3613-5p) plays a crucial role in RELA-mediated post-transcriptional regulation of LUAD cell proliferation. Expression of miR-3613-5p in clinical LUAD specimens is associated with poor prognosis in LUAD. Upregulation of miR-3613-5p promotes LUAD cell proliferation in vitro and in vivo. Our results suggested a mechanism whereby miR-3613-5p expression is induced by RELA through its direct interaction with JUN, thereby stimulating the AKT/mitogen-activated protein kinase (MAPK) pathway by directly targeting NR5A2. In addition, we also found that phosphorylation of AKT1 and MAPK3/1 co-transactivates RELA, thus constituting a RELA/JUN/miR-3613-5p/NR5A2/AKT1/MAPK3/1 positive feedback loop, leading to persistent NF-κB activation. Our findings also revealed that miR-3613-5p plays an oncogenic role in LUAD by promoting cell proliferation and acting as a key regulator of the positive feedback loop underlying the link between the NF-κB/RELA and AKT/MAPK pathways.


Plant-herbivore interactions: Examination of potential effects of bison saliva on regrowth of Bouteloua gracilis (H.B.K.) lag.
Laboratory experiments were performed to determine whether regrowth of blue grama was affected by potential growth-promoting substances in saliva of North American bison. We observed no statistically significant effects of foliar application of whole bison saliva on net photosynthesis (PN), root respiration (RR), allocation patterns of photosynthetically fixed 14C, or regrowth rates over a 10-day period following clipping to various heights. In a 10-week experiment, there were no significant effects of saliva on leaf, crown or root growth or tiller production in plants clipped to heights of 6, 4 or 2 cm above crowns. Similarly, nitrogen-stressed plants failed to show significant changes in growth rates or tillering in response to saliva over a 3-week period. Clipped blue grama plants did exhibit significant compensatory growth responses, including higher PN rates from 3-10 days following clipping and allocation of a higher proportion of current photosynthate to synthesis of new leaf tissue with increasing severity of defoliation. Nevertheless, unclipped plants invariably outproduced clipped plants following defoliation.


Asymmetry of long-latency auditory evoked potentials in LGI1-related autosomal dominant lateral temporal lobe epilepsy.
To investigate auditory processing with cortical long-latency auditory evoked potentials (AEPs) in patients with autosomal dominant lateral temporal lobe epilepsy (ADTLE). Eight patients with LGI1-related ADTLE belonging to a family with predominantly aphasic seizures were studied. Sixty-five individuals without epilepsy served as controls. AEPs (N1-P2 amplitudes) to binaural tones were recorded over the left and the right hemispheres. Brainstem auditory evoked potentials (BAEPs) to monaural rarefaction clicks also were analyzed. Group differences were statistically assessed with Student's t test and repeated-measures analysis of variance. Left N1-P2 AEP amplitudes were moderately reduced in ADTLE patients (p = 0.005). No group differences in BAEP were found, indicating unaffected cochlear system and auditory brainstem pathways. A moderate, but highly significant reduction in N1-P2 AEP amplitudes over the left hemisphere was demonstrated in patients with ADTLE. This finding corresponds to the cardinal symptom of aphasia in this family, and also to the generally prevailing left-sided EEG abnormalities in this condition. The background for this electrophysiologic lateralization in LGI1-related epilepsy is unknown. It may be related to a specific function of LGI1 in the dominant hemisphere.


Preservation of renal haemodynamic response to an oral protein load in non-insulin-dependent diabetes mellitus.
Glomerular Filtration Rate (GFR) and Effective Renal Plasma Flow (ERPF) were determined, for 2 h prior to and 3 h following the ingestion of a 1.2 g kg-1 meat meal, in seven normotensive normoalbuminuric Type 2 diabetic patients exhibiting good glycaemic control (fasting plasma glucose (mean +/- SD): 7.2 +/- 2.0 mmol l-1; glycosylated haemoglobin: 8.1 +/- 1.7%) and in nine normal subjects selected for similar basal GFR values. Baseline GFR and ERPF (corrected to 1.73 m2 surface area) were 83 +/- 10 and 410 +/- 76 ml min-1 for the Type 2 diabetic patients and 86 +/- 11 and 405 +/- 113 ml min-1 for the normals. GFR increased by 38 +/- 8 and 32 +/- 15% in the diabetic patients and normals, to 108 +/- 25 and 105 +/- 26 ml min-1 (p < 0.01 vs baseline). Peak ERPF was 501 +/- 127 and 476 +/- 119 ml min-1 for the two respective groups (p < 0.01 vs baseline). Filtration fractions at peak GFR and EPRF values were unchanged from baseline for either groups. Fractional clearance of albumin for the Type 2 diabetic patients was unaltered by protein ingestion. Therefore, protein ingestion in Type 2 diabetes, as in normals, results in an acute elevation of GFR. Absolute and incremental changes in GFR were identical for the two groups. These data demonstrate a preserved capacity for renal vasodilatation in Type 2 diabetic patients despite their greater chronological age.


End-systolic radius to thickness ratio: an echocardiographic index of regional performance during reversible myocardial ischemia in the conscious dog.
Regional myocardial dysfunction induced by ischemia is associated with less thickening and a larger ventricular radius at end-systole. Thus, end-systolic radius to thickness ratio measured by echocardiography may provide an accurate index of regional left ventricular function that is totally independent of cardiac motion. To test this hypothesis, a total of 14 transient (less than or equal to 10 minutes) coronary artery occlusions (8 left anterior descending, 6 left circumflex) followed by up to 24 hours of reperfusion were performed in six chronically instrumented conscious dogs providing multiple grades of regional ventricular dysfunction. Regional myocardial thickening fraction was determined with epicardial pulsed Doppler probes and served as an independent standard for comparison with simultaneous echocardiographic measurements. End-systolic radius to thickness ratio and radial shortening fraction were derived from the two-dimensional echocardiographic short-axis view along 12 equidistant radii. In the ischemic zone, percent thickening fraction averaged 22 +/- 5% during baseline, decreased to -4 +/- 4% during occlusion with gradual return to baseline after reperfusion. End-systolic radius to thickness ratio averaged 1.39 +/- 0.25 before coronary occlusion and increased to 2.97 +/- 0.48 during occlusion with a gradual return to baseline values. A significant correlation was found between Doppler-determined thickening fraction measurements and echocardiographic end-systolic radius to thickness ratio as well as radial shortening fraction for absolute values (r = -0.83 and 0.75, respectively; n = 65) and percent change from baseline (r = -0.86 and 0.78, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)


Treatment response for late-life generalized anxiety disorder: moving beyond symptom-based measures.
Response to treatment of late-life generalized anxiety disorder has been defined by a variety of methods, all based on statistically significant reductions in symptom severity. However, it is unknown whether these improvements in symptom severity are associated with meaningful differences in everyday functioning. The current study used four methods to define response to treatment for 115 primary-care patients 60 years and older, with a principal or coprincipal diagnosis of generalized anxiety disorder. The methods examined included percentage of improvement, reliable change index, and minimal clinically significant differences. Agreement among classification methods and their associations with general and mental health-related quality of life were assessed. Results indicated moderate agreement among symptom-based classification methods and significant associations with measures of quality of life.


Energy metabolism in astrocytes: high rate of oxidative metabolism and spatiotemporal dependence on glycolysis/glycogenolysis.
Astrocytic energy demand is stimulated by K(+) and glutamate uptake, signaling processes, responses to neurotransmitters, Ca(2+) fluxes, and filopodial motility. Astrocytes derive energy from glycolytic and oxidative pathways, but respiration, with its high-energy yield, provides most adenosine 5' triphosphate (ATP). The proportion of cortical oxidative metabolism attributed to astrocytes ( approximately 30%) in in vivo nuclear magnetic resonance (NMR) spectroscopic and autoradiographic studies corresponds to their volume fraction, indicating similar oxidation rates in astrocytes and neurons. Astrocyte-selective expression of pyruvate carboxylase (PC) enables synthesis of glutamate from glucose, accounting for two-thirds of astrocytic glucose degradation via combined pyruvate carboxylation and dehydrogenation. Together, glutamate synthesis and oxidation, including neurotransmitter turnover, generate almost as much energy as direct glucose oxidation. Glycolysis and glycogenolysis are essential for astrocytic responses to increasing energy demand because astrocytic filopodial and lamellipodial extensions, which account for 80% of their surface area, are too narrow to accommodate mitochondria; these processes depend on glycolysis, glycogenolysis, and probably diffusion of ATP and phosphocreatine formed via mitochondrial metabolism to satisfy their energy demands. High glycogen turnover in astrocytic processes may stimulate glucose demand and lactate production because less ATP is generated when glucose is metabolized via glycogen, thereby contributing to the decreased oxygen to glucose utilization ratio during brain activation. Generated lactate can spread from activated astrocytes via low-affinity monocarboxylate transporters and gap junctions, but its subsequent fate is unknown. Astrocytic metabolic compartmentation arises from their complex ultrastructure; astrocytes have high oxidative rates plus dependence on glycolysis and glycogenolysis, and their energetics is underestimated if based solely on glutamate cycling.


A 119Sn Mössbauer spectroscopic study on the interaction of dimethyltin (IV) derivatives with rat hemoglobin, and of related model systems in aqueous solution.
In the context of a study of the molecular basis of the antileukemia (murine) activity of diorganotin (IV) compounds, the interaction with rat hemoglobin (selected as a model protein) of the representative terms dimethyltin dichloride, dimethyltin glycylglycinate (Me2SnGlyGly), and dimethyltin L-cysteinate (Me2Sn-Cys) has been investigated by 119Sn Mössbauer spectroscopy. In order to possibly determine the reaction pathway, aqueous model systems in Hepes buffer at pH 7.4 were also considered. The structural characteristics of reactants and products were advanced on the basis of semiempirical calculations of Mössbauer nuclear quadrupole splitting parameters, delta E, by the point-charge model approach. In aqueous Hepes at pH 7.4, evidence was obtained for the formation of the five-coordinated species, trigonal bipyramidal type (tbp), Me2Sn(OH)2.Hepes(II), Me2Sn(OH)(GlyGly).Hepes(III), and Me2Sn(OH)Cys(IV) (see Fig. 1). Equatorial groups or atoms would be the Me radicals, as well as OH, N(peptide), and S(thiol), respectively. Hepes would coordinate to tin in axial position through the tertiary amino nitrogen, while cysteine would behave as a bidentate chelating agent, with an axially located amino group. Species (II), (III), and (IV) react with cysteine in aqueous Hepes at pH 7.4, yielding Me2Sn(OH)Cys(IV), as well as Me2SnCys2(V), where tin would be embedded into a tbp structure due to one cysteine probably chelating (equatorial S thiol and axial amino nitrogen), and one monodentate through S thiol. Species (II), (III), and (IV) react analogously with rat hemoglobin, primarily through the S thiol of a cysteine side chain, yielding pellets where the environment of tin could be tetrahedral, such as in Me2Sn(OH)(S thiol), (VI), and tetrahedral (IX) or tbp (V) in Me2Sn(Cys)(S thiol), where Cys would act either as chelating or monodentate. Further reaction of (VI) and (IX) could involve imidazole nitrogen atoms, N het, of histidine side chains, forming tetrahedral Me2Sn(S thiol)(N het), (VIII), or tbp Me2Sn(OH)(S thiol)(N het), (VII), and Me2Sn(Cys)(S thiol)(N het), (V) (see Figs. 1 and 5).


Renal findings in rheumatoid arthritis: clinical aspects of 132 necropsies.
Renal abnormalities in 132 necropsied patients with rheumatoid arthritis were studied. Clinical findings before death included extra-articular manifestations of the disease (86% of patients), systemic vasculitis (6%), and uraemia (23%). Necropsy findings included nephrosclerosis (90%), systemic vasculitis (14%) with kidney involvement in 8%, amyloidosis (11%), membranous glomerulopathy (8%), and focal glomerular disease (8%). Association with clinical data suggests that both rheumatoid and non-rheumatoid disease may play a part in the cause of these abnormalities.


Nitric oxide inhibits prooxidant actions of uric acid during copper-mediated LDL oxidation.
Interactions between uric acid and physiologically relevant fluxes of nitric oxide ((?)NO) during copper-mediated low-density lipoprotein (LDL) oxidation were evaluated. In the absence of (?)NO, a dual pro- and antioxidant action of uric acid was evident: low concentrations of uric acid enhanced lipid oxidation and alpha-tocopherol consumption, while its protective role was observed at higher concentrations. The prooxidant effects of uric acid were mostly related to its copper-reducing ability to form Cu(+), an initiator of lipid oxidation processes. While the prooxidant action of uric acid was completely inhibited by (?)NO, the antioxidant action of (?)NO was slightly counterbalanced by uric acid. Enhancement of alpha-tocopherol consumption by uric acid was inhibited in the presence of (?)NO while additive antioxidant effects between (?)NO and uric acid were observed in conditions where uric acid spared alpha-tocopherol. Altogether, these results suggest that in the artery wall, the (?)NO/uric acid pair may exert antioxidant actions on LDL, even if increased amounts of redox active copper were available at conditions favoring prooxidant activities of uric acid.


Dermorphin and deltorphin heptapeptide analogues: replacement of Phe residue by Dmp greatly improves opioid receptor affinity and selectivity.
The usefulness of 2,6-dimethylphenylalanine (Dmp) as a Phe surrogate in two opioid peptides, dermorphin (DM) and deltorphin II (DT), was investigated. Compared to DM, [L-Dmp(3)]DM (1) showed a 170-fold increase in mu affinity and only a 4-fold increase in delta affinity, resulting in a 40-fold improvement in mu receptor selectivity. Compared to DT, [L-Dmp(3)]DT (3) showed a 22-fold increase in delta affinity and somewhat of a loss in mu affinity, and consequently a marked (75-fold) improvement in delta receptor selectivity. The D-Dmp replacement, however, resulted in a great loss in receptor selectivity in each of the peptides. The specific receptor interactions of 1 and 3 were confirmed by in vitro bioassays. Analogues 1 and 3 seem to be useful as pharmacological tools for the study of opioid systems.


Criteria Restricting Inappropriate Meropenem Empiricism (CRIME): a quasi-experimental carbapenem restriction pilot at a large academic medical centre.
The broad-spectrum activity of carbapenems makes them appealing for empirical use; however, they are associated with development of Clostridioides difficile infection (CDI) and multidrug resistance. Selective carbapenem use is vital in maintaining their effectiveness. We examined the impact of meropenem restriction criteria on utilisation and patient outcomes. This quasi-experimental study was conducted at a single academic medical centre after medication use evaluation found frequent inappropriate meropenem utilisation. Antimicrobial stewardship-led restriction criteria were developed and implemented in February 2022. Investigators aimed to determine how restriction criteria affected meropenem utilisation across 8 weeks in the pre- (February-April 2020) versus post-implementation period (February-April 2022). The primary outcome was inappropriateness of meropenem utilisation. Secondary outcomes included days of therapy per 1000 patient-days (DOT/1000 PD), hospital length of stay (LOS), CDI Standardized Infection Ratio (SIR), and acquisition cost. Across the 8-week timeframes, reductions in inappropriate meropenem use (64.5% vs. 12.8%; P < 0.001), duration of therapy [5.8 (3.2-7.3) vs. 2.4 (1.0-5.5) days; P < 0.001] and utilisation (30.5 vs. 8.3 DOT/1000 PD; P < 0.001) pre- versus post-implementation were observed. Total meropenem orders decreased by 65% (P < 0.001). Median hospital LOS also decreased between periods [11.9 (7.8-20.4) vs. 9.2 (5.4-15.2) days], although not statistically significant (P = 0.051). There was no difference in CDI SIR (0.1 vs. 0.1; P = 0.99). Projected annual cost savings were ∼US$57 300. Implementation of antimicrobial stewardship-initiated restriction criteria can reduce inappropriate meropenem utilisation, overall number of orders, and total duration of therapy.


Effects of a citrate buffer system on the solid-state chemical stability of lyophilized quinapril preparations.
The objective of this study was to examine the effect of a citric acid-citrate buffer system on the chemical instability of lyophilized amorphous samples of quinapril hydrochloride (QHCI). Molecular dispersions of QHCI and citric acid were prepared by colyophilization from their corresponding aqueous solutions with a molar ratio of QHCI to citric acid from 1:1 to 6:1 and solution pH from 2.49 to 3.05. Solid samples were subjected to a temperature of 80 degrees C and were analyzed for degradation using high-performance liquid chromatography. The glass transition temperature, Tg, of all samples was measured by differential scanning calorimetry. Samples were first examined by varying the Tg and maintaining the initial solution pH constant. At pH 2.49 the rate of reaction was found to be less dependent on the sample Tg, whereas at pH > or = 2.75 the rate decreased with an increase in Tg. In a second set of experiments at a constant Tg of approximately 70 degrees C, the reaction rate increased as the pH increased. The overall solid-state chemical reactivity of amorphous quinapril depends on the relative amount of QHCI and Q+-, the zwitterionic form of quinapril. At high proportions of Q+- (higher pH values) the reaction rate seems to be strongly influenced by the Tg of the mixture, and hence the molecular mobility, whereas at higher proportions of QHCI (lower pH) the reaction rate is less sensitive to Tg, presumably because of different mechanistic rate determining steps for the two sets of conditions.


A new mathematical approach for solving carrier-facilitated steady-state diffusion problems.
A new mathematical treatment is presented which simplifies the solution of carrier-diffusion problems. The method is generally applicable and is illustrated and tested for a specific, commonly occurring situation: facilitated diffusion of a single substrate through flat layers. Results predicted for total substrate flux are in excellent agreement with control computer calculations. The method also can be used to obtain concentration profiles for each species; here the results are good only if conditions at the boundaries are predicted correctly.


A study of wide unfocused wavefront for convex-array ultrasound imaging.
Ultrafast ultrasound imaging modalities have attracted a lot of attention in the ultrasound community. It breaks the compromise between the frame rate and the region of interest by insonifying the whole medium with wide unfocused waves. Coherent compounding can be performed to enhance the image quality at a cost of frame rate. Ultrafast imaging has wide clinical applications, such as vector Doppler imaging and shear elastography. On the other hand, the use of unfocused waves is still marginal with convex-array transducers. For convex array, plane wave imaging is limited by the complicated transmission delay calculation, limited field-of-view, and inefficient coherent compounding. In this article, we study three wide unfocused wavefronts, namely, lateral virtual-source defined diverging wave imaging (latDWI), tilt virtual-source defined diverging wave imaging (tiltDWI), and Archimedean-spiral-based imaging (AMI) for convex-array imaging using the full-aperture transmission. The analytical monochromatic wave solutions to this three imaging are given. The mainlobe width and grating lobe position are given explicitly. Theoretical -6 dB beamwidth and synthetic transmit field response are studied. Simulation studies are carried on with the point targets and hypoechoic cysts. Time-of-flight formulas are given explicitly for beamforming. The conclusions are in good agreement with the theory: latDWI provides the finest lateral resolution but generates the severest axial lobe level for scatterers with large obliquities (i.e., for scatterers located at the image border) which degrades the image contrast. This effect gets worsen as the compound number increases. The tiltDWI and AMI give a very close performance on resolution and image contrast. AMI displays better contrast with a small compound number.


Long-Term Treatment Patterns Among Patients With Psoriasis Treated With Ixekizumab or Adalimumab: A Real-World Study.
There is a paucity of long-term real-world evidence comparing the effectiveness of ixekizumab (IXE) and adalimumab (ADA). We compared real-world treatment patterns of IXE-treated and ADA-treated patients with psoriasis over 24 months in the United States. A retrospective observational study was conducted using IBM Watson Health MarketScan® databases. Adult patients with psoriasis having ≥1 claim for IXE or ADA from March 1, 2016 – October 31, 2019 were identified. Inverse probability of treatment weighting (IPTW) was used to address cohort imbalances. Cox proportional hazards models were used to estimate the risks of non-persistence, discontinuation, and switching. Logistic regression was used to estimate odds of high adherence. Persistence, adherence, discontinuation, reinitiation, and dosing and switching rates were also analyzed. The final cohorts comprised 475 IXE users and 3159 ADA users over 24 months. IXE users demonstrated higher adherence (36.3% vs 28.8%; P<0.001) and persistence rates (35.2% vs 28.8%; P=0.004), and a lower discontinuation rate (59.1% vs 65.3%; P=0.007) compared to ADA users. IXE users had a higher likelihood of being treatment-adherent compared to ADA users (OR=1.52, 95% CI: 1.24–1.87), a lower risk of non-persistence (HR=0.84, 95% CI: 0.75–0.95), and a lower risk of discontinuation (HR=0.83, 95% CI: 0.74–0.94), respectively. Switching rates were similar in both groups (31.2% vs 30.0%; P=0.608). IXE users had better treatment adherence and persistence, and a lower risk of discontinuation compared to ADA users over 24 months. There was no difference in the risk of switching between IXE and ADA. J Drugs Dermatol. 2022;21(4):399-407. doi:10.36849/JDD.6336.


Review of COVID-19 and male genital tract.
COVID-19 pandemic leads to health challenges globally, and its diverse aspects need to be uncovered. Multi-organ injuries have been reported by describing potential SARS-CoV-2 entrance routes: ACE2 and TMPRSS2. Since these cell surface receptors' expression has been disclosed within the male reproductive system, its susceptibility to being infected by SARS-CoV-2 has been summarised through this literature review. Expression of ACE2 and TMPRSS2 at RNA or protein level has been reported across various investigations indicates that the male genitalia potentially is vulnerable to SARS-CoV-2 infection. Presence of SARS-CoV-2 within semen samples and following direct viral damage, secondary inflammatory response causing orchitis or testicular discomfort and finally the amount of viral load leading testicular damage and immune response activation are among probable underlying mechanisms. Therefore, genital examination and laboratory tests should be considered to address the male reproductive tract complications and fertility issues.


Bacterioplankton assembly and interspecies interactions follow trajectories of Gymnodinium-diatom bloom.
The underlying mechanisms of bacterioplankton community assembly and interspecies interactions during harmful algal blooms remain largely unclear. Using 16S rRNA gene amplicon sequencing, we analyzed the bacterioplankton communities over the continuous course of saxitoxin-producing Gymnodinium catenatum blooms and two diatom (i.e., Skeletonema costatum and Chaetoceros curvisetus) blooms in an anthropogenically controlled and eutrophic bay, East China Sea. The succession of bacterioplankton communities correlated with changes in the dynamics of algal species. Deterministic versus stochastic bacterioplankton community assemblage processes were quantified, demonstrating that stochastic processes increased when algal blooms happened. The occurrence of algal blooms caused weaker bacterioplankton interspecies interactions and higher degrees of cooperative activities, changed keystone taxa and diminished the stability of bacterial communities. These findings consequently have important implications for our understanding of bacterioplankton community ecology during algal blooms.


Idiopathic spinal cord herniation. Report of two cases and review of the literature.
The authors experienced unique cases of spinal cord herniation. Only eight cases of spinal cord herniation have been reported formerly. The authors report two cases of spinal cord herniation accompanied with double structure of dura mater (duplicated dura mater). The causes of their condition are discussed in this report.


New direction for environmental water management.
Japan experienced severe environmental problems including water pollution and damages to aquatic organisms and fishery industry through and after the high economic growth period in the 1960s. One of the countermeasures to address these problems was the Total Pollutant Load Control System (TPLCS), which has been implemented with the aim of reducing the total amount of pollutant loads, specifically targeting Chemical Oxygen Demand (COD), total nitrogen and total phosphorus. The TPLCS has significantly improved the quality of the coastal sea water. However, while the accumulated pollutant loads from the past industrialization have still remained, new environmental concerns have arisen. Our new environmental policies are thus to deal with conservation of biological diversity and other related marine environmental issues. Japan has entered a new phase of environmental management, setting the new direction and framework toward a beautiful, bio-diverse, bustling-with-people and bountiful sea.


Synthesis, mechanistic studies, and anti-proliferative activity of glutathione/glutathione S-transferase-activated nitric oxide prodrugs.
Nitric oxide (NO) prodrugs such as O(2)-(2,4-dinitrophenyl) 1-[(4-ethoxycarbonyl)piperazin-1-yl]diazen-1-ium-1,2-diolate (JS-K) are a growing class of promising NO-based therapeutics. Nitric oxide release from the anti-cancer lead compound, JS-K, is proposed to occur through a nucleophilic aromatic substitution by glutathione (GSH) catalyzed by glutathione S-transferase (GST) to form a diazeniumdiolate anion that spontaneously releases NO. In this study, a number of structural analogues of JS-K were synthesized and their chemical and biological properties were compared with those of JS-K. The homopiperazine analogue of JS-K showed anti-cancer activity that is comparable with that of JS-K but with a diminished reactivity towards both GSH and GSH/GST; both the aforementioned compounds displayed no cytotoxic activity towards normal renal epithelial cell line at concentrations where they significantly diminished the proliferation of a panel of renal cancer cell lines. These properties may prove advantageous in the further development of this class of nitric oxide prodrugs as cancer therapeutic agents.


Cetuximab enhances the anti-tumor function of macrophages in an IL-6 dependent manner.
Cetuximab improves the survival of patients with advanced colorectal cancer (CRC). However, how cetuximab affects the tumor microenvironment has not been sufficiently understood. This study was to investigate whether cetuximab could inhibit the pro-tumor function of tumor-associated macrophages (TAMs) by suppressing the EGFR/IL-6 pathway. The azoxymethane/dextran sodium sulfate (AOM/DSS) and tumor xenograft mouse models were used to assess the effect of cetuximab on TAMs. Flow cytometry, Western blotting, RT-qPCR, and ELISA were used to assess the prevalence of M2 and M1 phenotypes. Publicly available datasets of CRC patients were used to assess the relevance of EGFR and IL-6 expression as prognostic indicators. The two mouse models showed that cetuximab could attenuate the pro-tumor function of TAMs and decrease tumor burden. Cetuximab repolarized TAMs from M2-like to M1-like phenotypes, mainly by suppressing the IL-6 expression through NFκB and STAT3 pathways. Analysis of public scRNA-seq data indicated EGFR was mainly expressed on the surface of macrophage infiltration into tumor microenvironment. The public transcriptomics datasets showed that the expression level of IL-6 was positively correlated with EGFR in CRC patients, and PROGgeneV2 analysis indicated that IL-6 and CD206 both predicted poor recurrence-free and overall survival of CRC patients. Furthermore, the inhibition efficacy of cetuximab was significantly attenuated in IL-6 knockout CRC mice model. These results indicate a new macrophage-based molecular mechanism explaining the effect of cetuximab in treatment of colorectal cancer.


One-year real-life efficacy of sitagliptin revealed importance of concomitant pioglitazone use in Japanese patients with type 2 diabetes mellitus.
Dipeptidyl-peptidase 4 inhibitors have become one of the most popular antidiabetic drugs. However, what kind of combinations with other drugs were advantageous was not known. Here, we tried to elucidate it in a real-life clinical setting. We retrospectively studied efficacies of sitagliptin in 87 Japanese patients with type 2 diabetes mellitus for 52 weeks. We divided subjects into excellent, effective and unresponsive subgroups according to glycemic responses to sitagliptin. In the excellent and effective groups the minimum HbA1c values were attained at 16 weeks while HbA1c levels in the unresponsive group kept increasing during the study period. There was a significant difference in the baseline HbA1c values between the excellent and unresponsive groups (p=0.02). Interestingly, the mean doses of pioglitazone were highest in the excellent group and lowest in the unresponsive group (p=0.02). When we compared the effective and unresponsive groups, the mean doses of sulfonylureas were constantly higher in the effective group than in the unresponsive group (p=0.05). These data suggest that the baseline HbA1c value can be a factor that predicts the extent of HbA1c reduction and reveal a possibility that the concomitant use of pioglitazone augments glycemic responsiveness to sitagliptin.


The impact of negative and positive affectivity on the relationship between work-related psychological factors and work engagement in Japanese workers: a comparison of psychological distress.
A previous study has shown that Japanese individuals generally exhibit behavior that suppresses the expression of positive emotions, which are strongly affected by affectivity traits. In the present study, to clarify the relationship between affectivity traits and work engagement (WE) or work-related psychosocial factors among Japanese workers, we compared it to the association between psychological distress and these same factors. A total of 1,000 full-time Japanese regular workers responded to an online survey that measured demographic variables, negative and positive affectivity, job demands and resources, WE, and psychological distress. A hierarchical multiple regression analysis was conducted separately, which used WE and psychological distress as dependent variables. The proportion of variance explained by negative and positive affectivity was lower for WE than for psychological distress. However, the proportion of variance defined by job demands and resources was higher for WE than for psychological distress. The proportion of variance explained by all variables for negative and positive affectivity and job demands and resources, and their interactions was approximately equal for WE and psychological distress. These results emphasize when researchers aim to evaluate the change of psychosocial factors in the workplace, such as improving the workplace environment among Japanese workers, it might be beneficial to measure positive indicators in addition to negative indicators. Furthermore, enriching job resources would be effective in improving WE and alleviating psychological distress.


[Cutaneous foreign body granulomas following cervico-facial arterial embolization: Three cases].
Foreign body granuloma is an inflammatory tissue reaction to exogenous material. Classically it appears on the face after aesthetic procedures. Herein we report for the first time three cases of facial granulomatous reactions to microbeads after arterial cervico-facial embolization. Three patients underwent embolization of the facial arteries using Embogold® microbeads in a setting of epistaxis or tumoral hemostasis. Within 10 to 45 days painful, inflammatory, subcutaneous nodules appeared on the homolateral side of the face. Histological samples showed an inflammatory response with giant cells as well as the presence of microbeads in the skin. A favorable outcome was achieved with colchicine in one patient and with surgery in another; the third patient was lost to follow-up. The embolizing microspheres produced a local inflammatory reaction, with destruction of the vascular wall and bead migration to facial tissue leading to a granulomatous reaction. The occurrence of three cases within a period of few weeks, with several different operators and batches of products, is surprising considering the long-standing use of the product. There was no common comorbidity in the patients and no suggestion of trauma. Retrospective analysis of the product batches was normal. Gold staining could play a role in severe inflammatory response to Embogold® particles. These three cases illustrate the value of discussing potential foreign body granulomatous reaction in cases of facial nodules following cervico-facial embolization. Colchicine may offer a valuable therapeutic alternative.


The effects of RKIP gene expression on the biological characteristics of human triple-negative breast cancer cells in vitro.
The purpose of this study was to investigate the effect of Raf kinase inhibitor protein (RKIP) on the growth, proliferation, invasion and metastasis of triple-negative breast cancer (TNBC) cells to provide experimental evidence for developing future therapies against human TNBC. The pcDNA3.1-RKIP eukaryotic expression vector was constructed and transfected into the TNBC cell line MDA-MB-231. The alterations of the biological characteristics of RKIP-transfected MDA-MB-231 cells were analyzed using the following approaches: a growth curve, a 3-(4,5-dimethylthiazol-2-Yl)-2,5-diphenyltetrazolium bromide (MTT) assay, bromodeoxyuridine (BrdU) staining and a cell migration assay. The effects of the RKIP gene on MMP-1 and MMP-2 expression were also examined. The pcDNA3.1 empty vector-transfected and mock-transfected MDA-MB-231 cells were used as control groups. Compared with the empty vector-transfected and mock-transfected cells, the cell growth of RKIP-transfected MDA-MB-231 cells was significantly reduced. The empty vector-transfected group was not significantly different compared with the mock-transfected MDA-MB-231 cells. The results of the MTT and BrdU assays demonstrated that the proliferation of pcDNA3.1-RKIP-transfected cells was significantly reduced compared to the control cells (P < 0.05). The result of the cell migration assay suggested that the cross-membrane migration rate of the pcDNA3.1-RKIP-transfected cells was significantly lower than that of the control MDA-MB-231 cells (P < 0.05). We also demonstrated that RKIP may inhibit MMP-1 and MMP-2 expression in MDA-MB-231 cells. The RKIP gene may play a role in inhibiting cellular proliferation. The RKIP gene may also have some inhibitory effects on the invasiveness and metastatic capability of human TNBC cells.


Reactive oxygen species and related haem pathway components as possible epigenetic modifiers in neurobehavioural pathology.
The neuroendocrine response to stress utilizes several bio-communicative pathways which also play a role in neurodevelopmental plasticity. The mechanism of action of steroidal compounds includes DNA alteration by reactive oxygen species (ROS) arising through redox cycling of reactive hormone derivatives. ROS and reactive nitrogen species play a significant role in signaling networks affecting gene transcriptional regulation during normal as well as stress-induced responses. ROS-associated synaptic and regulatory region plasticity may have been important for normal brain evolution, but probably simultaneously lowered the threshold for inducing neuropathology. A shift from 'plasticity' to 'instability' is likely to be associated with the emergence of complex effects depending on the timing, duration and intensity of the ROS insult, and is suggested to include heritable epigenetic chromatin/regulatory region remodeling differentially influencing expression levels of significant neuropsychiatric genes and their variant alleles. Neurobehavioural disorder clinical manifestations have been linked with ROS effects. The concepts discussed here relate to ROS-associated instability of DNA regulatory region sequences and a proposal that it may play an important modifying role in brain and neuro-behaviourally related gene expression. Genes encoding key steps in mitochondrial, haem, iron and bilirubin ROS metabolic pathways have been used as examples to illustrate how ROS-modified regulatory networks could possibly alter the context within which (even ostensibly unrelated) neuropsychiatric gene candidates may sometimes be recruited. Furthermore, reactions of certain radicals release sufficient energy to generate UV-photons. DNA conformational changes accompanied by changes in photon emission suggest that functional neuroimaging findings probably reflect interaction on the level of ROS/biophoton/genome regulatory region domains rather than the signatures of individual neurobehavioural disorder candidate genes.


Giant cell arteritis: diagnosis and therapeutic management.
Giant cell arteritis (GCA) is the most common systemic vasculitis in the elderly in Western countries. Anemia and very high erythrocyte sedimentation rates are associated with lower incidence of severe ischemic events. Temporal artery biopsy is the gold standard in the diagnosis of GCA. A threshold size of 1 cm of post-formalin fixed segment of the temporal artery was associated with increased diagnostic yield of GCA. Other tools such as ultrasound, MRI, and fluorodeoxyglucose positron emission tomography are useful in the diagnosis of GCA. Corticosteroids are the cornerstone treatment of GCA. Studies using other drugs have yielded contradictory results.


Transport and phosphorylation of hexoses in normal and Rous sarcoma virus-transformed chick embryo fibroblasts.
Effects of transformation by Rous sarcoma virus on sugar uptake and activity and the subcellular distribution of hexokinase isozymes in chick embryo fibroblasts were examined. Transformation caused a several-fold increase in the maximum velocity for uptake of 2-deoxyglucose without a significant change in Km. Cytochalasin B (CB), was used to differentiate between the effects of transformation on facilitated diffusion and the nonsaturable (CB-insensitive) mode. Transformation was found to stimulate 2-deoxyglucose transport by both mechanisms, but the increase in transport by the CB-insensitive mode was greater. Transformation enhances the activity of hexokinase, the enhancement being confined to the particulate fraction of the enzyme. Heat-inactivation and electrophoretic mobility studies showed that although hexokinase Type I is the major form in both normal and transformed fibroblasts, there is a significant increase in the proportion of the Type II isozyme in the transformed cells.


Quantifying the Severity of a Delirium Episode Throughout Hospitalization: the Combined Importance of Intensity and Duration.
The ability to determine which episodes of delirium are likely to lead to poor clinical outcomes has remained a major area of challenge. To quantify delirium severity and course over an entire hospitalization using several measures, and to evaluate their predictive validity for 30- and 90-day outcomes post-discharge. Two prospective cohort studies. Analysis was conducted in two independent cohorts of adult patients aged ≥70. Nine delirium episode severity measures were examined: (1) measures reflecting delirium intensity (peak Confusion Assessment Method-Severity [CAM-S] and mean CAM-S score), (2) a measure reflecting delirium intensity and duration (sum of all CAM-S scores, sum of all CAM-S scores on delirium days only, peak CAM-S score x days with delirium), (3) measures requiring information on delirium duration and delirium at discharge (total number of delirium days, percentage of delirium days, delirium at discharge), and (4) a measure of cognitive change. Associations of the delirium episode severity measures with 30- and 90-day post-hospital outcomes (death, nursing home placement, and readmission) relevant to delirium were examined. The delirium episode severity measure that required information on both delirium intensity and duration (sum of all CAM-S scores) was the most strongly associated with 30- and 90-day post-hospital outcomes. Using this measure, the relative risk [95 % confidence interval] for death at 30-days increased across levels of sum of all CAM-S scores from 1.0 (referent) to 2.1 [0.8, 5.4] for 'low,' to 2.9 [1.2, 7.1] for 'moderate,' to 6.4 [2.9, 14.0] for 'high' (p for trend <.01). The delirium episode severity measure that included both intensity and duration had the strongest association with important post-hospital outcomes.


Motor overflow in schizophrenia.
The occurrence of motor dysfunction as a sign of schizophrenia, in addition to being a side effect of medication, has received considerable support in recent years. The current study aimed to systematically investigate both the presence and pattern of one such motor dysfunction, motor overflow. It was hypothesised that patients with schizophrenia would show significantly greater motor overflow than controls, and that the pattern of motor overflow occurrence would also vary significantly between the groups. A finger flexion task was used to examine the presence and pattern of motor overflow. Subjects were asked to maintain target forces, using either their index or small finger, representing 25, 50 or 75% of the maximum strength capacity for whichever finger was performing the task. Patients were found to exhibit significantly greater motor overflow than controls. There were also significant findings with respect to the patterns of motor overflow produced, specifically in regards to fine motor control and performance variability. In summary, patients differed significantly from controls in both the degree and pattern of overflow exhibited.


Pre-surgical CT/FEA for craniofacial distraction: I. Methodology, development, and validation of the cranial finite element model.
Recently, surgeons have begun to treat serious congenital craniofacial deformities including craniosynostoses with mechanical devices that gradually distract the skull. As a prospective means of treatment planning for such complex deformities, FE models derived from routine preoperative CT scans (CT/FEA) would provide ideal patient specific engineering analyses. The purpose of this study was to assess the dimensional and predictive accuracy of the CT/FEA process through the development of a 3D model of a dry human calvarium subjected to two-point distraction ex vivo. Comparative skull measurements revealed that CT/FEA construction error did not exceed 1% for transcranial dimensions, and the thickness error did not exceed 8.66% or 0.31 mm. CT/FEA strain predictions for the central region of the skull, between the distraction posts, were not statistically different from homologous gage values at P < 0.05. Peripherally, however, the strain fields were less well behaved and the FE predictions showed only general qualitative agreement with gage recordings.


Correlation between different Chinese medicine syndromes and changes in microcirculation in septic shock patients.
To investigate the correlation between different Chinese medicine (CM) syndromes and variations in microcirculation in septic shock patients. seventy Septic shock patients were divided into four groups: heat damaging qi-yin group (HDQY, 23 cases); yin exhaustion and yang collapse group (YEYC, 26 cases); excessive heat in Fu organ group (EHFO, 10 cases); and heat damaging nutrient-blood group (HDNB, 11 cases). Sublingual microcirculation parameters were observed by sidestream dark-field (SDF) imaging and scored by Acute Physiology and Chronic Health Evaluation II (APACHE II) and the Sequential Organ Failure Assessment (SOFA), and parameters of microcirculation perfusion variations and prognoses were analyzed. Compared with those with qi-yin heat damage, perfused vessel density (PVD) in other groups decreased dramatically (P<0.05), and APACHE II scores increased significantly (P<0.05). In addition, the recovery time was prolonged substantially (P<0.05), and the mixed venous oxygen saturation (SVO2) decreased (P<0.05). Blood lactic acid increased significantly (P<0.05), and the mixed SVO decreased (P<0.05), in the YEYC group. Compared with the thermal injury camp blood group, sublingual microcirculation parameter variations showed no obvious difference in the YEYC and EHFO groups (P>0.05). There were significant positive correlations between CM syndromes and APACHE II scoring in different groups (r=0.512, P<0.05). There were negative correlations between PVD and APACHE II scoring (r=-0.378, P=0.043), the proportion of perfused vessels (PPV) and APACHE II scoring (r=-0.472, P=0.008), as well as between the microvascular flow index (MFI) and APACHE II scoring (r=-0.424, P=0.023) in different patients. Sublingual microcirculation may serve as a clinical diagnostic parameter of the patient condition, as well as being a prognostic indicator.


Cardiac arrhythmias: management of atrial fibrillation in the critically ill patient.
This article reviews the most relevant information for the hospitalist or intensivist managing patients who have atrial fibrillation (AF) in the acute or critical care setting. Emphasis is placed on clinically useful information, and evidence-based strategies for managing acute and chronic AF.


Expression analysis of an α-1, 3-galactosyltransferase, an enzyme that creates xenotransplantation-related α-Gal epitope, in pig preimplantation embryos.
α-1,3-Galactosyltransferase (α-GalT), an enzyme creating Galα1-3Gal (α-Gal) epitope on the cell surface in some mammalian species such as pigs, is known to be a key factor that causes hyperacute rejection upon transplantation from pigs to humans. To establish the RNA interference-based suppression of endogenous α-GalT messenger RNA (mRNA) synthesis in porcine preimplantation embryos, we determined the suitable embryonic stage at which stage such approach is possible by using the semi-quantitative RT-PCR (qRT-PCR) and the cytochemical method using a fluorescence-labeled Bandeiraea simplicifolia Isolectin B(4) (BS-I-B(4) ). Staining with BS-I-B(4) demonstrated that α-Gal epitope expression was first recognized at the 8-cell stage, and increased up to the hatched blastocyst stage. Single embryo-based qRT-PCR also confirmed this pattern. These results indicate that creation of α-Gal epitope is proceeded by de novo synthesis of α-GalT mRNA in porcine preimplantation embryos with peaking at the blastocyst stage.


Workplace Violence in the Hospital: Strategies for Meaningful Change.
Workplace violence is not a unique problem to organizations. Evidence-based toolkits and strategies are available to help provide a guiding framework for the reduction of workplace violence events. As times and stressors (both personal and environmental) change, hospitals must keep constant attention on how to address and implement initiatives to keep staff safe. This manuscript addresses steps taken at 1 hospital to meet this challenge. Although a workplace violence committee had been in place for some time, it was identified that not all of the key players were included. Membership was evaluated, and executive-level support was provided. A review of literature was conducted and identified top priorities upon which to focus efforts. Subcommittees were formed to be responsible for these categories of work and to report back to the committee. Data points and a dashboard were created to monitor trends and effectiveness, especially regarding combating the culture of underreporting. Processes and resources were formalized and made easily accessible to staff. Case studies and direct feedback from staff have been impactful and helped identify additional barriers. Evaluation will continue to occur using process-improvement methodology along with technological assistance. Workplace violence is not part of the job. Ongoing work is needed to continue to move the needle and make hospitals a safer place to work. Engagement from all levels of the organization is necessary to have a successful program.


The Cataract National Dataset Electronic Multi-centre Audit of 55,567 operations: anaesthetic techniques and complications.
The primary aim of this study was to detail anaesthetic techniques and complications for cataract surgery in the UK. The Cataract National Dataset was extracted from 12 National Health Service Trusts that used the same electronic patient record system between November 2001 and July 2006 on a total of 55,567 cataract operations. Anaesthesia was administered by an ophthalmologist in 56.7% of the cases, a career anaesthetist in 42.1% of the cases, a clinical assistant anaesthetist in 0.3% of the cases, and staff were not recorded in 0.9% of the cases. Local anaesthesia (LA) was used in 95.5%, with topical anaesthesia alone in 22.3% (range by site, 0-99.8%), topical and intracameral in 4.7% (range, 0-24.1%), subtenons in 46.9% (range, 0-81.8%), peribulbar in 19.5% (range, 0-63.4%), and retrobulbar in 0.5% (range, 0-5.3%). One or more minor complications occurred in 4.3% of 38,058 local blocks administered by either sharp needle or subtenons (blunt) cannula. Minor complications were 2.3 times more common with subtenons blocks (P<0.001). Serious complications, defined as sight or life threatening occurred in 25 eyes, 0.066%, undergoing sharp needle or subtenons cannula blocks. Sharp needle techniques had a 2.5-fold increased risk of serious complications compared with subtenons cannula techniques (P=0.026). Subtenons anaesthesia was the most widely used anaesthetic technique for cataract surgery but wide variation existed by site. There was a low rate of reported LA complications. There was a statistically significant increased risk of serious complications with sharp needle anaesthesia compared with subtenons technique.


In vitro translation of distinct mRNAs coding for the precursors of porcine LH subunits.
Conditions are described to characterize and estimate the precursors of porcine LH alpha and beta subunits and indirectly their specific mRNAs. Poly(A) RNAs extracted from castrated male pig anterior pituitaries were translated in a wheat-germ system in the presence of [35S] cysteine and [35S] methionine. The translation products were precipitated by antisera directed against reduced and carboxymethylated LH alpha and beta subunits and analyzed by high resolution electrophoresis. It is shown that the precursors of pLH alpha and beta subunits are located in two distinct congruent to 15 K proteins and represent--on the basis of the incorporation of the [35S] labeled aminoacids into proteins--congruent to 0.12% and 0.05% respectively of the total translation products. It is suggested that in the pig, as in other species, the LH alpha and beta subunits are encoded by two distinct mRNAs, and at variance with other species the leader sequence of LH alpha mRNA is longer than that of LH beta mRNA.


Personalized Medicine in Cancer Pain Management.
Previous studies have documented pain as an important concern for quality of life (QoL) and one of the most challenging manifestations for cancer patients. Thus, cancer pain management (CPM) plays a key role in treating pain related to cancer. The aim of this systematic review was to investigate CPM, with an emphasis on personalized medicine, and introduce new pharmacogenomics-based procedures for detecting and treating cancer pain patients. This study systematically reviewed PubMed from 1990 to 2023 using keywords such as cancer, pain, and personalized medicine. A total of 597 publications were found, and after multiple filtering processes, 75 papers were included. In silico analyses were performed using the GeneCards, STRING-MODEL, miRTargetLink2, and PharmGKB databases. The results reveal that recent reports have mainly focused on personalized medicine strategies for CPM, and pharmacogenomics-based data are rapidly being introduced. The literature review of the 75 highly relevant publications, combined with the bioinformatics results, identified a list of 57 evidence-based genes as the primary gene list for further personalized medicine approaches. The most frequently mentioned genes were CYP2D6, COMT, and OPRM1. Moreover, among the 127 variants identified through both the literature review and data mining in the PharmGKB database, 21 variants remain as potential candidates for whole-exome sequencing (WES) analysis. Interestingly, hsa-miR-34a-5p and hsa-miR-146a-5p were suggested as putative circulating biomarkers for cancer pain prognosis and diagnosis. In conclusion, this study highlights personalized medicine as the most promising strategy in CPM, utilizing pharmacogenomics-based approaches to alleviate cancer pain.


Daytime melatonin infusions induce sleep in pigeons without altering subsequent amounts of nocturnal sleep.
Daily infusions of melatonin restore sleep suppressed by continuous bright light in pigeons. To test whether melatonin could also induce sleep in pigeons on a 12:12 h light-dark cycle (LD), pigeons received 12-h intravenous melatonin infusions during the day. Melatonin induced sleep during the day, increased EEG slow wave activity, and decreased body temperature and locomotor activity. None of these variables were altered during the night following infusions. The induction of extended daytime sleep by melatonin infusions indicates that melatonin is a principal factor in the regulation of sleep in pigeons.


[Contribution of the PCPT trial to finasteride treatment of micturition disorders due to benign prostatic hyperplasia].
Two landmark multi-centre trials, MTOPS and PCPT, have shown that finasteride is an effective treatment of micturitional disorders due to benign prostatic hyperplasia, reducing the clinical progression of BPH. The MTOPS trial showed for the first time the medium term benefit which patients could obtain with combined treatment in reducing the risks of the symptoms aggravating, urinary retention, surgery, renal failure, infection and incontinence. The PCPT trial showed finasteride to be beneficial in reducing the clinical progression of BPH. These trials defined risk factors for progression: PSA concentration over 1.6 ng/ml, prostate volume over 31 ml, urine output less than 10.6 ml/sec, age over 62 years old and post-micturitional residual volume of more than 39 ml. A 19% reduction in prostatic volume was also seen at 4.5 years on finastéride compared to a 24% increase on placebo. According to recommendations, the use of combined treatment is reserved for patients with moderate to severe urinary disorders after failure of first line monotherapy.


ASSESSMENT OF THE LATE EFFECTS ON BONES AND ON BODY COMPOSITION OF CHILDREN AND ADOLESCENTS TREATED FOR ACUTE LYMPHOCYTIC LEUKEMIA ACCORDING TO BRAZILIAN PROTOCOLS.
To evaluate the impact of therapy on bone mineral density (BMD) and body composition in survivors of acute lymphoblastic leukemia (ALL) treated in accordance with Brazilian protocols by the Brazilian Cooperative Group of Treatment of Lymphoblastic Leukemia in Childhood (GBTLI) LLA-93 and LLA-99. A cross-sectional study with 101 patients was performed. BMD and body composition were evaluated using bone densitometry and were interpreted according to the age group and the reference population. Values between -1.1 and -1.9 in the group of children under 20 years were considered as risk group for low BMD z-scores. BMD values were compared to clinical characteristics, treatment received and body composition. A chi-square test, Fisher's exact test, likelihood ratio and Student's t-test were applied, with a 5% significance level. The patients presented a frequency of fractures of 2%, of osteonecrosis, 2%, and of low BMD, 2.9%. In the group of 79 patients under 20 years of age, three had low BMD. The 16 that presented risk for low BMD, demonstrated lower valutes in lumbar vertebrae L1-L4 (p=0.01) and whole body (p=0.005), and smaller values of lean body mass (p=0.03). In the group of 22 patients over 20 years of age, ten had osteopenia. The low impact of treatment on BMD of this study confirms the concept that the bone mass gain occurs with increasing age and that the treatment does not influence the process. The population at risk for low BMD values presented lower bone mass values and could benefit from a long-term monitoring for possible bone toxicity.


Putting square pegs in round holes: Why traditional pharmacokinetic principles cannot universally be applied to iron-carbohydrate complexes.
Intravenous iron-carbohydrate complexes are nanomedicines that are commonly used to treat iron deficiency and iron deficiency anemia of various etiologies. Many challenges remain regarding these complex drugs in the context of fully understanding their pharmacokinetic parameters. Firstly, the measurement of the intact iron nanoparticles versus endogenous iron concentration fundamentally limits the availability of data for computational modeling. Secondly, the models need to include several parameters to describe the iron metabolism which is not completely defined and those identified (e.g. ferritin) exhibit considerable interpatient variability. Additionally, modeling is further complicated by the lack of traditional receptor/enzyme interactions. The known parameters of bioavailability, distribution, metabolism, and excretion for iron-carbohydrate nanomedicines will be reviewed and future challenges that currently prevent the direct application of physiologically-based pharmacokinetic or other computational modeling techniques will be discussed.


The host species affects the microbial community in the goat rumen.
This study was carried out to determine whether bacterial and ciliate populations in goat rumen vary significantly between different goat species living in the same environment. Bacterial and ciliate communities in the rumen of three goat species were analysed at the molecular level using denaturing gradient gel electrophoresis. The microbial community varied considerably among goats living in the same environment. Interspecies variation in the bacterial population was noticeably greater than intraspecies variation. In contrast, there was considerable variation in the ciliate population among goats within the same species, and intraspecies similarities were no greater than those observed across species. Because environmental factors and diets were identical for all goats, differences in bacterial populations reflect species-specific differences in rumen microbes. Factors related to the host species have an important effect on determining the bacterial composition in the goat rumen.


Moving toward a theory of normative influences: how perceived benefits and similarity moderate the impact of descriptive norms on behaviors.
In recent years researchers have focused attention on understanding the role of normative factors in influencing behaviors. Although there is some evidence to support the idea that restructuring normative beliefs can result in behavior change, the norms literature is largely silent about how or why this influence occurs. The theory of normative social behavior describes the moderators of the descriptive norm-behavior relationship. Through a 2 (descriptive norms: high or low) x 2 (perceived benefits: high or low) x 2 (similarity: high or low) between-subjects experiment (N = 174), we tested whether these cognitive mechanisms moderated the norms-behavior link. Results indicated that descriptive norms do not exert a direct influence on behavior. Rather, perceived benefits moderated the relationship between descriptive norms and behavioral intention and perceived similarity moderated the relation between descriptive norms and self-efficacy.


The impact of brain lesions on sexual dysfunction in patients with multiple sclerosis: A systematic review of magnetic resonance imaging studies.
Sexual dysfunction is common but underestimated clinical symptom in MS patients. A growing body of evidence has been suggested the link between brain lesions and sexual dysfunction (SD) in patients with multiple sclerosis (MS). However, the clinical research investigating this relationship have shown inconsistent results. Here, we aimed to systematically review the magnetic resonance imaging (MRI) studies evaluating the association between the brain lesions and SD in MS patients. This study was provided according to the recommendations of the preferred reporting items for systematic reviews and meta-analyses statement. A comprehensive systematic search of online databases was performed to find eligible studies up to December 2020. The quality of studies was methodologically assessed using Newcastle-Ottawa Scale score. We identified eight articles regarding MS brain lesions and SD through the search strategy. Seven studies showed significant associations between SD and brain lesions. Three studies investigated the brain stem, two studies the insular and occipital region, one study the frontal lobe, prefrontal cortex, and temporal lobe and one study the parietal area. The results of this systematic review showed that lesions in different brain areas are correlated with SD in MS patients. Plaques in the occipital and hippocampus areas, as well as left insula appear to be related to dysfunction of sexual arousability or lubrication/erection in MS patients. Orgasmic dysfunction in MS patients may be associated with brain lesions in pons, left temporal periventricular, and right occipital areas.


Aprotinin does not prolong the Sonoclot aprotinin-insensitive activated clotting time.
To determine whether a new Sonoclot-based, aprotinin-insensitive activated clotting time (aiACT) assay yields stable results over a broad range of aprotinin concentrations. Prospective trial conducted on in vitro blood samples. Tertiary-care teaching medical center. 19 healthy adult volunteers. Whole blood samples were collected from volunteers. Heparin (2 U/mL) and escalating concentrations of aprotinin of 160 to 500 kallikrein inhibitory units (KIU)/mL were added in vitro. Celite ACT, kaolin ACT, and aiACT assays were completed. The aiACT showed stable activated clotting time (ACT) results on heparinized, noncitrated blood with added aprotinin (P = nonsignificant). In contrast, celite ACT and kaolin ACT were greatly prolonged when aprotinin was added to heparinized, noncitrated, and citrated blood (P < 0.05). The aiACT had consistent results at all aprotinin concentrations (P = nonsignificant). Aprotinin (160, 320, and 500 KIU/mL) significantly prolongs the ACT value with celite and kaolin activators but not with the aprotinin-insensitive activator.


Late breaking trials of 2015 in structural heart disease and peripheral artery disease: Commentary covering ACC, EuroPCR, SCAI, TCT, VIVA, ESC, and AHA.
With the large number of late breaking clinical trials presented at major meetings, it is often difficult to stay current with advances in interventional cardiology. Therefore, the SCAI Publications Committee summarizes and provides editorial commentary on the most important structural heart and peripheral artery disease late-breaking trials from 2015. © 2016 Wiley Periodicals, Inc.


Protein kinase NII. Interaction with RNA polymerase II and contribution to immunological cross-reactivity of RNA polymerases I and II.
The interaction between antibodies directed against RNA polymerase I purified from Morris hepatoma 3924A and homologous RNA polymerase II was investigated. The activity of partially purified polymerase II was inhibited by the antibodies. In contrast, the reaction catalyzed by the purified enzyme was not affected. Partially purified polymerase II preparations contained a protein kinase activity. Sucrose gradient centrifugation in the presence of 0.3 M KCl resulted in complete separation of RNA polymerase II from protein kinase as well as in complete loss of sensitivity to the anti-RNA polymerase I antibodies. The protein kinase possessed reaction characteristics similar to those of the NII protein kinase (Rose, K.M., Bell, L.E., Siefken, D.A. and Jacob, S.T. (1981) J. Biol. Chem. 256, 7468-7477) which is associated with hepatoma RNA polymerase I (Rose, K.M., Stetler, D.A. and Jacob, S.T. (1981) Proc. Natl. Acad. Sci. U.S.A. 78, 2833-2837). The activities of both kinases were inhibited to the same extent by anti-RNA polymerase I antibodies and polypeptides of Mr 42 000 and 25 000, present in both kinase preparations, formed immune complexes with the antisera. Readdition of protein kinase NII to purified polymerase II resulted in phosphorylation of the polymerase and a concomitant enhancement of RNA synthesis. After addition of the kinase, RNA polymerase II activity was again sensitive to anti-RNA polymerase I antibodies. Upon reacting with protein kinase NII, RNA polymerase II polypeptides could be detected in immune complexes with anti-RNA polymerase I antibodies. These data indicate that protein kinase NII is associated with RNA polymerase II during early stages of purification and is at least partially responsible for the immunological cross-reactivity of RNA polymerases I and II.


An aberrant link between gamma oscillation and functional connectivity in Aβ1-42-mediated memory deficits in rats.
Alzheimer's disease (AD) is a neurodegenerative disease that gradually induces cognitive deficits in the elderly. Impairment of working memory was typically observed in AD. As amyloid-β peptide (Aβ) is a causative factor for the cognitive impairments in AD, developing a mechanistic understanding of the contribution of Aβ to cognitive impairments may yield insights into the pathophysiology of AD. Gamma oscillations as well as functional connectivity have been recognized to play important roles in various cognitive functions. Gamma oscillation is hypothesized as the results of the coordinated interaction of neural network. However, the temporal link between gamma oscillation and functional connectivity in working memory has remained largely unexplored. Moreover, whether Aβ-induced working memory deficit is due to the abnormal link between gamma oscillation and functional connectivity? Therefore, in the present study, local field potentials (LFPs) were recorded via multi-electrodes implanted in rat prefrontal cortex (PFC) for the control group and Aβ-injected group (Aβ group) when they performed a Y-maze working memory task. Gamma oscillations and functional connectivity among LFPs were respectively estimated. Compared with the control group, the Aβ group showed significantly weaker oscillations and functional connectivity among LFPs. Moreover, the time gap between gamma oscillation and functional connectivity was examined. The precise temporal link between the gamma oscillation and functional connectivity in the control group and the Aβ-induced abnormal link in the Aβ group were noticed. Our results indicate that the link between gamma oscillation and functional connectivity may provide a potential mechanism for the Aβ1-42-induced working memory deficits.


Bilateral femoral nerve compression and compartment syndrome resulting from influenza A-induced rhabdomyolysis: a case report.
Bilateral femoral nerve compression neuropathy caused by primary iliopsoas muscle pathology is rare. We report a case of extensive compartment syndrome of the right arm and both legs associated with bilateral femoral nerve palsy resulting from severe muscle swelling secondary to influenza A infection. Our objective is to alert physicians to the possible development of compartment syndrome in patients with influenza and severe myalgia. We also reviewed the literature on the pathophysiology and management of femoral nerve compression neuropathy.


Simultaneous intracoronary pressure and Doppler guidewires to assess coronary stenosis: if one is enough, are two too much?
We report a potential source of erroneous estimation of stenosis severity by pressure guidewire assessment. Simultaneous introduction of pressure and Doppler guidewires can lead to an overestimation of stenosis pressure gradient in the evaluation of intermediate stenosis.


Hepatitis C: incidence and knowledge among Brazilian dentists.
To evaluate the incidence of Hepatitis C among dentists from the city of Piracicaba-SP--Brazil, and also to analyze the knowledge of this disease among these health care workers. Two hundred and sixty-seven dentists completed a questionnaire and supplied a sample of blood for serologic testing for hepatitis C virus (HCV). Only one participant was positive for HCV, representing 0.4% of total. There was a lack of knowledge of this disease among dentists. There is an occupational risk of infection for HCV in dentistry and there is a need to make professionals aware of it.


[Induced variability of the lipase producing fungus Rhizopus microsporus].
The most effective way for inducing mutants of Rhizopus microsporus with an elevated lipolytic activity is the combined action of nitrosomethyl urea and UV. Variants with the lipolytic activity of 3600--3700 units per 1 ml have been produced, thus being by 72--75% more effective than the parent culture.