Changes in vaginal anatomy and sexual function after vaginal surgery.
The study's objectives were to determine changes in vaginal length and caliber after vaginal surgery and to correlate changes with sexual function. This prospective study measured vaginal length and caliber before and immediately after vaginal surgery and at 5- to 8-week follow-up. A sexual function questionnaire was administered preoperatively and 6 months postoperatively. Ninety-two women were enrolled (mean age, 64 years); 44 (47.8%) were sexually active. The most common procedure was Mayo-McCall culdoplasty in 85 women (92.4%). Fourteen (15.2%) had intentional vaginal shortening and narrowing (coning). Mean vaginal length changed from 10.4 cm preoperatively to 8.7 cm at 5- to 8-week follow-up in women not having coning. Mean vaginal caliber changed from 3.2 to 2.8 cm. Preoperative and postoperative sexual function questionnaire scores did not correlate with vaginal measurements. Vaginal shortening and narrowing occurred after vaginal surgery; sexual function was unchanged.


Lentinan reduces tumor progression by enhancing gemcitabine chemotherapy in urothelial bladder cancer.
It has been shown that chemotherapy has limited antitumor activity against advanced urothelial bladder cancer (UBC). Consequently, there is an urgent need to develop effective therapeutic methods for patients with advanced UBC. In the present study, the inhibitory effects of lentinan alone, gemcitabine alone, or lentinan combined with gemcitabine on the proliferation of the UBC cell line, T24, were investigated. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay, annexin V fluorescein isothiocyanate/propidium iodide staining, and flow cytometry were used to determine the proliferation and apoptosis of T24 cells in each treatment group. Survival-related protein expression was analyzed by western blotting. Increased concentrations of lentinan, or lentinan combined with gemcitabine, positively correlated with decreased T24 cell proliferation. Lentinan combined with gemcitabine chemotherapy significantly inhibited UBC cell proliferation. Gemcitabine has the ability to induce T24 cell apoptosis, and this effect is enhanced when it is combined with lentinan.


A Rapid and Accurate 1HNMR Method for the Identification and Quantification of Major Constituents in Qishen Yiqi Dripping Pills.
Qishen Yiqi dripping pills (QSYQ), composed of four herbal medicines-Salvia miltiorrhiza, Astragalus membranaceus, Panax notoginseng, and Dalbergiaodorifera-are widely used to treat ischemic cerebrovascular and hemorrhagic cerebrovascular conditions. In this study, a rapid and accurate proton NMR (1HNMR) spectroscopy method was established to control the quality of QSYQ and ensure their clinical efficacy. Firstly, different types of metabolites were identified based on the proton signal peaks of chemical shifts, coupling constants, and related information provided through two-dimensional NMR spectroscopy. Secondly, a quantitative 1HNMR method was established for the simultaneous determination of major constituents in QSYQ samples. In addition, an HPLC method was performed to verify the results obtained by the quantitative proton NMR (qHNMR) method. In the present study, 26 metabolites were identified in the 1HNMR spectra of QSYQ. In addition, a rapid and accruate qHNMR method was established for the simultaneous determination of protocatechualdehyde, rosmarinic acid, danshensu, calycosin-7-O-β-D-glucoside, and ononin in ten batches of QSYQ samples for the first time. Moreover, the proposed qHNMR method and HPLC method were compared using Bland-Altman and plots Passing-Bablok regression, indicating no significant differences and a strong correlation between the two analytical methods. This method is an important tool for the identification and quantification of major constituents in QSYQ. Compared with traditional HPLC, the established qHNMR method has the advantages of simple sample preparation, short analysis time, and non-destructive analysis.


Non-conventional starches isolated from agronomic-improved beans (Phaseolus vulgaris L.): a study of their structure and physicochemical properties.
Non-conventional starch sources are promising alternative food ingredients. Different bean varieties with agronomic improvements are constantly being developed and cultivated in the Northwestern Argentinean region (NOA) to increase yields and obtain high-quality seeds. However, the main attributes of their starches have not been studied. In this work, starches from four agronomic-improved bean cultivars were isolated and their structure and physicochemical properties were evaluated. High-purity starches were obtained, as shown by their low protein and ash content. Starch granules presented smooth surfaces with spherical to oval shapes, with a marked 'Maltese cross' and heterogeneous sizes. Their amylose content revealed a mean value of 318 g kg-1 and all presented resistant > slowly digestible > rapidly digestible starch fractions. Their Fourier transform infrared spectra were similar and X-ray diffraction analysis showed a CA -type pattern in all cases despite their different sources. Among thermal properties, Escarlata starch showed the lowest gelatinization peak temperature (69.5 °C) and Anahí starch the highest (71.3 °C). Starch pasting temperature varied from 74.6 to 76.9 °C, whereas peak viscosity and final viscosity showed a similar tendency, with Leales B30 < Anahí < Escarlata < Cegro 99/11-2 and Leales B30 < Anahí = Escarlata < Cegro 99/11-2, respectively. This study provides the basis for a better understanding of the characteristics of agronomic-improved NOA bean starches, enabling their use in product formulation as an alternative to starches from conventional sources. © 2023 Society of Chemical Industry.


miR-181c-5p suppresses neuronal pyroptosis via NLRP1 in Alzheimer's disease.
Alzheimer's disease (AD) is neurodegenerative disease common in the elderly, whose pathological mechanism is the deposition of amyloid-β (Aβ) plaques and neurofibrillary tangles in the brain. Pyroptosis is a programmed cell death mediated by Gasdermin protein. After the activation of inflammasomes, the cleaved caspase⁃ 1/4/5/11 activates GSDMD, which promotes the release of inflammatory substances and eventually causes cell swelling and death. Pyroptosis caused by inflammasomes plays a role in AD. However, the specific regulatory mechanism of pyroptosis in AD still needs more experimental studies. To further study the effects of NLRP1-induced pyroptosis on AD, miR-181c-5p, which could targeted bind to NLRP1, was knocked down or overexpression in HT22 cells to detect cell apoptosis with Tunel assay, the expression of inflammasome-related proteins with Western blot and the content of inflammatory factors with ELISA. miR-181c-5p was overexpressed in AD model mice to detect the learning and cognitive ability with morris water maze testing and the expression of inflammasoma-related proteins with Western blot. The results showed that miR-181c-5p mimic attenuated Aβ1-42-induced neuronal pyroptosis in HT22 cells, while up-regulation of NLRP1 aggravated neuronal pyroptosis in HT22 cells. In mice, miR-181c-5p agomir attenuated neuronal pyroptosis in both hippocampal and cortical tissues, and miR-181c-5p antagomir improved neuronal pyroptosis and cognitive impairment through NLRP1. Therefore, the study suggests that miR-181c-5p can alleviated AD process by targeted downregulation of NLRP1, which is expected to be a target site for AD treatment.


Unique adaptations in neonatal hepatic transcriptome, nutrient signaling, and one-carbon metabolism in response to feeding ethyl cellulose rumen-protected methionine during late-gestation in Holstein cows.
Methionine (Met) supply during late-pregnancy enhances fetal development in utero and leads to greater rates of growth during the neonatal period. Due to its central role in coordinating nutrient and one-carbon metabolism along with immune responses of the newborn, the liver could be a key target of the programming effects induced by dietary methyl donors such as Met. To address this hypothesis, liver biopsies from 4-day old calves (n = 6/group) born to Holstein cows fed a control or the control plus ethyl-cellulose rumen-protected Met for the last 28 days prepartum were used for DNA methylation, transcriptome, metabolome, proteome, and one-carbon metabolism enzyme activities. Although greater withers and hip height at birth in Met calves indicated better development in utero, there were no differences in plasma systemic physiological indicators. RNA-seq along with bioinformatics and transcription factor regulator analyses revealed broad alterations in 'Glucose metabolism', 'Lipid metabolism, 'Glutathione', and 'Immune System' metabolism due to enhanced maternal Met supply. Greater insulin sensitivity assessed via proteomics, and efficiency of transsulfuration pathway activity suggested beneficial effects on nutrient metabolism and metabolic-related stress. Maternal Met supply contributed to greater phosphatidylcholine synthesis in calf liver, with a role in very low density lipoprotein secretion as a mechanism to balance metabolic fates of fatty acids arising from the diet or adipose-depot lipolysis. Despite a lack of effect on hepatic amino acid (AA) transport, a reduction in metabolism of essential AA within the liver indicated an AA 'sparing effect' induced by maternal Met. Despite greater global DNA methylation, maternal Met supply resulted in distinct alterations of hepatic transcriptome, proteome, and metabolome profiles after birth. Data underscored an effect on maintenance of calf hepatic Met homeostasis, glutathione, phosphatidylcholine and taurine synthesis along with greater efficiency of nutrient metabolism and immune responses. Transcription regulators such as FOXO1, PPARG, E2F1, and CREB1 appeared central in the coordination of effects induced by maternal Met. Overall, maternal Met supply induced better immunometabolic status of the newborn liver, conferring the calf a physiologic advantage during a period of metabolic stress and suboptimal immunocompetence.


"My god…how did I miss it?": Women's experiences of their spouses' alcohol-related relapses.
Alcohol addiction is manifested by periods of abstinence and relapse in which the individual returns to previous problematic alcohol use. This may lead to unstable and stressful routines for the family and for women who live with a spouse diagnosed with an AUD. AUD may mentally and physically affect women living with a spouse diagnosed with AUD with respect to relapse. However, most studies have focused on the influence of AUD in general, and the way they cope with it; few have dealt with the experience of relapse as a distinctive stage. Women's experiences of their spouses' relapses are embedded within their broader life experience in the shadow of alcohol addiction. The pattern of transitions from closeness to distance in the ways women think, feel and actively respond to their spouses' relapses shows similarities with the ways in which individuals cope with repeated trauma. This helps relate these women's experiences of their spouses' repeated relapses to the potential complex trauma these women experience and leads to a better understanding of the internal emotional dynamics of these women's behavioural patterns. These women need a therapeutic solution that can help them cope with longstanding emotional burdens. Therapists should be sensitive to the complexity of their experience. When relevant, therapy should be based on therapeutic strategies from trauma practice, along with Alcohol Behavioural Couples Therapy that can reinforce the couple's mutual efforts to achieve sobriety or reduce AUD severity ABSTRACT: Introduction Alcohol use disorder (AUD) is manifested by periods of remission and relapse which can serve as a source of continuous stressors on the individuals and family. Women living with a spouse diagnosed with AUD can be mentally and physically affected by this behaviour. Most studies have focused on the general influence of AUD on these women and their attempts to cope with AUD; there are scant data on the influences of relapse as a distinctive stage. Aim To better understand how women whose spouses are diagnosed with AUD experience their relapses. Method A qualitative-naturalistic approach was implemented. Semi-structured, in-depth interviews were conducted with 12 women whose spouses were diagnosed with AUD. Results Content analysis revealed three main categories representing the transitions from: a) ignorance to realization, b) emotional opposition to acceptance and c) activity to inactivity. Each category reflects one cognitive, emotional or behavioural dimension of this experience. The overarching theme emerged as shifts from closeness to distance in the way these women think, feel and actively respond to their spouse's relapses and addiction. Discussion The shift from closeness to distance as manifested by the three transitions is argued to reflect the ways these women experience and cope with the chronic nature of AUD. It is suggested that this experience parallels the phenomenology of symptoms of complex trauma. Implications for practice Nurses should be alert to the potential accumulative stressors experienced by these women and implement intervention strategies developed in the trauma field in addition to Alcohol Behavioural Couples Therapy.


Impact of Stent Graft Design on External Iliac Artery Limb Occlusion Rates After Endovascular Aneurysm Repair: Post-hoc Analysis of a Japanese Multicentre Database.
It was hypothesised that a helical stent with expanded polytetrafluoroethylene (ePTFE) grafts could provide a preventive effect for external iliac artery (EIA) limb occlusion following endovascular aortic aneurysm repair (EVAR). Therefore, a post-hoc analysis of a Japanese multicentre database was conducted to assess the impact of the stent graft design on EIA limb occlusion rates. Patients who underwent EVAR with EIA limb deployment between 2008 and 2016 were evaluated. The stent graft limbs were divided into two groups: group A comprised stent graft limbs made of a helical stent with ePTFE grafts (Excluder; n = 255), and group B comprised stent graft limbs made of a Z stent with polyester grafts (Zenith, Flex and Endurant; n = 173). The main outcome was the incidence of limb occlusion and severe limb stenosis (EIA related limb complications). The risk factors for EIA related limb complications were analysed and the midterm results between groups A and B compared. Fine-Gray generalisation of the proportional hazards model was used after propensity score matching to calculate the hazard ratio (HR). One complication occurred in group A and 10 complications occurred in group B. The risk factors for EIA related limb complications for the entire group were a stent graft limb size ≤10 mm (HR 5.41; p = .01) and inclusion in group B (HR 14.9; p = .009). After propensity matching, group A (n = 159) was matched with group B (n = 159). The cumulative incidence function of EIA related limb complications at five years was 0.66% in group A and 7.8% in group B (HR 8.67; p = .039). Stent graft design can affect limb patency in EIA limb deployment. When EIA limb deployment is necessary for patients with a small EIA, such as Japanese patients, stent graft limbs made of a helical stent with ePTFE should be used to reduce the risk of limb occlusion.


Physiological plasticity to high temperature stress in chickpea: Adaptive responses and variable tolerance.
High temperature stress (HTS) is one of the most crucial factors that limits plant growth and development, and reduces crop yields worldwide. Cool-season crops, particularly the legumes, are severely affected by increasing ambient temperature associated with global climate change. We characterized the HTS-induced modulations of morpho-physicochemical traits and gene expression of several chickpea genotypes and the metabolic profile of the tolerant cultivar. Higher water use efficiency and photosynthetic capacity, minimal membrane lipid peroxidation in conjunction with increased abundance of osmolytes and secondary metabolites depicted thermotolerance of ICC 1205. The adaptive responses were accompanied by high transcript abundance of heat shock proteins and antioxidant enzymes. To integrate stress-responsive signalling and metabolic networks, the HTS-induced physicochemical analysis was further extended to metabolite profiling of the thermotolerant cultivar. The screening of the metabolome landscape led to the identification of 49 HTS-responsive metabolites that include polycarboxylic acid, sugar acids, sugar alcohols and amino acids which might confer thermotolerance in chickpea. The present study, to our knowledge, is the most comprehensive of its kind in dissecting cultivar-specific differential adaptive responses to HTS in chickpea, which might potentiate the identification of genetic traits extendible to improvement of thermotolerance of crops.


Synthesis, insecticidal activities and SAR of novel phthalamides targeting calcium channel.
In order to find novel and environmental friendly insecticides targeting the ryanodine receptor, three series of novel phthalamides containing heptafluoroisopropyl group, low fluorine atoms group and non-fluorine group were designed and synthesized. 35 novel structures of three series were obtained. Insecticidal activities of title compounds against oriental armyworm (Mythimna separata) and diamondback moth (Plutella xylostella) indicated that most of title compounds showed moderate to high activities at the tested concentration. The structure-activity relationship (SAR) was discussed in detail. During synthesizing title compounds B8, C7, D1, D9 and D12, their corresponding positional isomers (B8', C7', D1', D9' and D12') were afforded, and their structures were confirmed by 2D NMR. The calcium-imaging technique was also applied to investigate the effects of compounds B2, B10, C4 and C5 on the intracellular calcium ion concentration ([Ca(2+)]i), which indicated that they released stored calcium ions from endoplasmic reticulum, which denoted that some compounds are potential modulators of the insect ryanodine receptor (RyR).


The epidemiology of thyroid disease and implications for screening.
The burden of thyroid disease in the general population is enormous. As many as 50% of people in the community have microscopic nodules, 3.5% have occult papillary carcinoma, 15% have palpable goiters, 10% demonstrate an abnormal thyroid-stimulating hormone level, and 5% of women have overt hypothyroidism or hyperthyroidism. Despite this high prevalence of thyroid disease, screening for these disorders is not recommended by any major health agency. This article explores the epidemiologic issues surrounding this complex problem by analyzing prevalence, incidence, and mortality data from a worldwide variety of sources.


E-Cigarettes: Harmful or Harm-Reducing? Evaluation of a Novel Online CME Program for Health Care Providers.
Patients are asking health care providers about e-cigarettes, vaping, and other electronic nicotine delivery systems (ENDS). Provider advice on ENDS has varied greatly, suggesting a need for evidence-based continuing medical education (CME). A novel free online CME course was developed on ENDS risks and benefits, product types (e.g., vape pens, pods), and screening and counseling best practices for adults, adolescents, and different smoker profiles (e.g., daily, social). From January 2017 through June 2018, 1061 individuals accessed the course: 46% physicians, 7% physician assistants, 7% nurse practitioners, 15% nurses, 4% pharmacists, and 28% allied health/student/other; 41% were international. The course was built from observed online patient-provider interactions. Through video role-plays, expert interviews, and interactive activities, the course engaged learners in the evidence on ENDS. Completers earned 1.5 CME units. A total of 555 health care providers earned 832.5 CME units. Pre- to post-test scores significantly increased from 57 to 90%; 76% rated the course as above average (41%) or outstanding (35%); 99% indicated the course was free of commercial bias. Addressing the growing need for balanced provider education on ENDS, this interactive online CME engaged learners and increased knowledge on devices and evidence-based cessation approaches.


Correction: Highly modulated supported triazolium-based ionic liquids: direct control of the electronic environment on Cu nanoparticles.
[This corrects the article DOI: 10.1039/D0NA00055H.].


Delayed brain hemorrhage associated with prophylactic whole brain irradiation for pediatric malignant brain tumor: a case report.
Intraparenchymal hemorrhage in the left frontal lobe suddenly occurred in a 7-year-old girl who had undergone partial removal of an undifferentiated brain stem glioma and received craniospinal (30 Gy) and posterior fossa booster (20 Gy) irradiation at the age of 20 months. The brain hemorrhage was thought to be delayed irradiation effect. Follow-up neuro-imaging at age 9 years showed two more small occult chronic and subacute hemorrhages in the brain. The possibility of repeated hemorrhage as a delayed reaction to brain irradiation is emphasized.


Effects of chronic lithium treatment on protein kinase C and cyclic AMP-dependent protein phosphorylation.
Lithium inhibits the agonist-induced hydrolysis of phosphoinositides and the synthesis of cyclic AMP (cAMP) in rat brain preparations, each of which is linked to activation of specific protein kinases. Therefore, we examined the effects of chronic lithium treatment on protein kinase activities in rat hippocampus. Chronic lithium treatment did not alter the distribution or activity of protein kinase C in hippocampal soluble or particulate fractions. However, chronic lithium treatment increased protein kinase C-mediated phosphorylation of four endogenous proteins in the soluble fraction (16,17,20,22 kD) and reduced the phosphorylation of three proteins (18,19,87 kD) in the particulate fraction. Chronic lithium treatment did not alter cAMP-dependent phosphorylation of endogenous proteins in the soluble fraction but reduced phosphorylation of two proteins (54 and 71 kD) in the particulate fractions. These results demonstrate that besides inhibiting second messenger production in brain, chronic lithium treatment also causes specific alterations in the phosphorylation of endogenous proteins.


Simvastatin improves morphological and functional recovery of sciatic nerve injury in Wistar rats.
The purpose of this work is to investigate the effects of simvastatin on sciatic nerve regeneration in male Wistar Rats. Forty animals were allocated into four groups: (1) control (C); (2) control+simvastatin (CS); (3) lesioned animals+sterile PBS (LC) and (4) lesioned animals+simvastatin (LS). Lesioned animals were submitted to crushing lesion of right sciatic nerve. Simvastatin (20mg/kg/day, i.p.) was administered for five days. Footprints were obtained weekly for evaluation of functional locomotor recovery by means of the Sciatic Function Index (SFI). Blood samples were obtained weekly for quantifying circulating leukocytes. Animals were sacrificed after 21 days for histological analyses of sciatic nerve and spleen. LS Animals presented increased SFI scores, decreased areas of oedema and mononuclear cell infiltration during Wallerian degeneration and nerve regeneration (7,14 and 21 days; P<0.05). Spleen weight and white pulp areas was increased in LC animals after 21 days. Increased numbers of circulating neutrophils were observed in simvastatin treated animals (CS e LS) at seven, 14 and 21 days, compared to non-treated groups (C and LC). The study suggests that simvastatin accelerates the morphological and functional recovery process of the peripheral nervous system interfering with innate and acquired immunity.


Concordance of Helicobacter pylori infection among children in extended-family homes.
Helicobacter pylori is transmitted within households and high concordance is observed among siblings. To better understand the contributions of close interpersonal contact and family relatedness to transmission, we compared concordance of H. pylori infection among 241 sibling and non-sibling children aged 2-18 years in 68, predominantly low-income, Hispanic households with at least two nuclear families. Prevalence of H. pylori infection was 24%. Compared to children with no infected siblings or non-siblings and adjusting for age, odds of H. pylori infection were 1.2 (95% CI 0.52-2.9), 3.2 (95% CI 1.14-9.1), and 9.4 (95% CI 3.1-28.5) for children residing with at least one infected non-sibling, one infected sibling, and with at least one infected sibling and non-sibling, respectively. The study further implicates intersibling transmission as a pathway for H. pylori infection in childhood. In addition, living with a non-sibling in extended-family homes may contribute to infection risk but only in households with prevalent H. pylori infection within all family groups.


Neural and endocrine mechanisms underlying stress-induced suppression of pulsatile LH secretion.
Stress is well-known to inhibit a variety of reproductive processes, including the suppression of episodic Gonadotropin releasing hormone (GnRH) secretion, typically measured via downstream luteinizing hormone (LH) secretion. Since pulsatile secretion of GnRH and LH are necessary for proper reproductive function in both males and females, and stress is common for both human and animals, understanding the fundamental mechanisms by which stress impairs LH pulses is of critical importance. Activation of the hypothalamic-pituitary-adrenal axis, and its corresponding endocrine factors, is a key feature of the stress response, so dissecting the role of stress hormones, including corticotrophin releasing hormone (CRH) and corticosterone, in the inhibition of LH secretion has been one key research focus. However, some evidence suggests that these stress hormones alone are not sufficient for the full inhibition of LH caused by stress, implicating the additional involvement of other hormonal or neural signaling pathways in this process (including inputs from the brainstem, amygdala, parabrachial nucleus, and dorsomedial nucleus). Moreover, different stress types, such as metabolic stress (hypoglycemia), immune stress, and psychosocial stress, appear to suppress LH secretion via partially unique neural and endocrine pathways. The mechanisms underlying the suppression of LH pulses in these models offer interesting comparisons and contrasts, including the specific roles of amygdaloid nuclei and CRH receptor types. This review focuses on the most recent and emerging insights into endocrine and neural mechanisms responsible for the suppression of pulsatile LH secretion in mammals, and offers insights in important gaps in knowledge.


Long-Term Outcomes of Bacillary Layer Detachment in Neovascular Age-Related Macular Degeneration.
To evaluate the clinical characteristics, multimodal imaging features, and long-term treatment outcomes of eyes with neovascular age-related macular degeneration (nAMD) and bacillary layer detachment (BALAD) treated with intravitreal anti-VEGF therapy. Retrospective, longitudinal, case series. Treatment-naive patients with nAMD (n = 30) showing BALAD on OCT and undergoing anti-VEGF therapy. Clinical records and multimodal imaging results of up to 4 years after diagnosis were reviewed. Best-corrected visual acuity (BCVA) values were compared over time. The cumulative risk of and risk factors for subretinal fibrosis were assessed using Cox regression analyses, and adjusted hazard ratio (aHR) was computed. Thirty eyes of 30 patients were included. Macular neovascularization (MNV) subtypes were distributed as follows: type 1, 63%; type 2, 27%; mixed type 1 and 2, 3%; type 3, 3%; aneurysmal type 1, 3%. The BCVA significantly improved after anti-VEGF loading phase (Snellen equivalent, from 20 of 118 to 20 of 71, P = 0.03), but it returned to the baseline levels at 4 years (Snellen equivalent, 20 of 103, P = 0.6). The cumulative risk of subretinal fibrosis was 77% at 4 years. The risk factors associated with subretinal fibrosis included hemorrhagic BALAD (aHR, 2.02; 95% confidence interval [CI] 1.54-3.22; P < 0.01) and the presence of subretinal hyperreflective material (aHR, 1.83; 95% CI 1.35-3.14; P < 0.01). BALAD was found in association with all types of MNV in patients with nAMD. Long-term observation revealed poor functional outcomes related to the high risk of subretinal fibrosis.


Dyspeptic symptoms and water load test in patients with functional dyspepsia and reflux disease.
Hypersensitivity to gastric distension has been reported in functional dyspepsia (FD). The aim of this study was to assess the perception to gastric distension and its relationship to specific symptoms using the water load test (WLT) in FD and gastroesophageal reflux disease (GERD). A 5-min WLT was used to evaluate sensitivity of gastric distension in 47 FD and 61 GERD subjects, and 49 healthy controls (HC). A visual analogue scale (VAS) measuring symptom severity was obtained from all subjects and its relationship with the maximal ingested volume was determined. The maximal ingested volume was registered and the subjective symptoms were assessed at baseline and 30 min after the WLT. The maximal ingested volume by HC was 597 +/- 33 ml, which was statistically greater than that of FD (422 +/- 22 ml, p < 0.001) and GERD (504 +/- 23 ml, p < 0.02) subjects. The maximal ingested volume did not differ significantly between FD and GERD. The maximal ingested volume correlated well with nausea (r = -0.49, p < 0.01) and fullness (r = -0.33, p < 0.05) in FD. Male subjects ingested more water than females in the HC (p < 0.01) and GERD groups (p < 0.05), but not in FD (p = NS). Both FD and GERD subjects have altered perception to gastric fullness induced by the WLT compared to healthy controls. Good correlations have been observed between the WLT and dyspeptic symptoms such as early satiety and postprandial fullness, but not in GERD.


Apomixis: oh, what a tangled web we have!
Apomixis is a complex evolutionary trait with many possible origins. Here we discuss various clues and causes, ultimately proposing a model harmonizing the three working hypotheses on the topic. Asexual reproduction through seeds, i.e., apomixis, is the holy grail of plant biology. Its implementation in modern breeding could be a game-changer for agriculture. It has the potential to generate clonal crops and maintain valuable complex genotypes and their associated heterotic traits without inbreeding depression. The genetic basis and origins of apomixis are still unclear. There are three central hypothesis for the development of apomixis that could be: i) a deviation from the sexual developmental program caused by an asynchronous development, ii) environmentally triggered through epigenetic regulations (a polyphenism of sex), iii) relying on one or more genes/alleles. Because of the ever-increasing complexity of the topic, the path toward a detailed understanding of the mechanisms underlying apomixis remains unclear. Here, we discuss the most recent advances in the evolution perspective of this multifaceted trait. We incorporated our understanding of the effect of endogenous effectors, such as small RNAs, epigenetic regulation, hormonal pathways, protein turnover, and cell wall modification in response to an upside stress. This can be either endogenous (hybridization or polyploidization) or exogenous environmental stress, mainly due to oxidative stress and the corresponding ROS (Reacting Oxygen Species) effectors. Finally, we graphically represented this tangled web.


Rate of non-adherent cell loss from long-term cultures of murine bone marrow: effect of medium conditioned by the adherent cell population.
The rate of random spontaneous cell loss from the non-adherent cell population of long-term cultures of murine bone marrow was determined. The measured rate of non-adherent cell loss is affected by previous conditioning of the medium in which the non-adherent cells are suspended. Specifically, the measured rate of non-adherent cell loss is significantly slowed when the non-adherent cells are suspended in medium conditioned in long-term haematopoietic cultures instead of fresh medium. It appears that a subset of the adherent cell population is the source of the factor or factors within the medium which result in this slower measured rate of non-adherent cell loss. This effect may be due to the stimulation to division of haematopoietic progenitor cells, offsetting the lysis of other non-adherent cells.


Exposure to perchlorate, nitrate, and thiocyanate and the prevalence of abdominal aortic calcification.
Perchlorate, nitrate, and thiocyanate are reported to affect human health. However, it is unclear about the associations between exposure to these chemicals and abdominal aortic calcification (AAC). A total of 959 individuals were included in a large representative survey. Urinary levels of perchlorate, nitrate, and thiocyanate were measured by ion chromatography coupled with electrospray tandem mass spectrometry. AAC was diagnosed based on dual-energy X-ray absorptiometry (DXA). There were 276 (28.8%) cases of AAC among the participants. The level of urinary nitrate was significantly lower in AAC patients compared with non-AAC patients (36.4 mg/L [20.6, 59.5] vs. 42.4 [23.8, 68.3]; P = 0.013). In multivariable-adjusted logistic regression models, urinary nitrate was associated with the prevalence of AAC. Compared with the lowest quartile, the odds ratios (95% confidence intervals) across increasing quartiles were 1.06 (0.69-1.61; P = 0.799), 0.64 (0.41-1.00; P = 0.049) and 0.74 (0.47-1.15; P = 0.180). Restricted cubic splines suggested that urinary nitrate ranging between 43.7 and 115.4 mg/L was associated with a lower risk of AAC. Moderate exposure to nitrate was associated with a lower risk of AAC.


Outcomes in Patients With Mild Traumatic Brain Injury Without Acute Intracranial Traumatic Injury.
Traumatic brain injury (TBI) affects millions of people in the US each year. Most patients with TBI seen in emergency departments (EDs) have a Glasgow Coma Scale (GCS) score of 15 and a head computed tomography (CT) scan showing no acute intracranial traumatic injury (negative head CT scan), yet the short-term and long-term functional outcomes of this subset of patients remain unclear. To describe the 2-week and 6-month recovery outcomes in a cohort of patients with mild TBI with a GCS score of 15 and a negative head CT scan. This cohort study analyzed participants who were enrolled from January 1, 2014, to December 31, 2018, in the Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) study, a prospective, observational cohort study of patients with TBI that was conducted in EDs of 18 level I trauma centers in urban areas. Of the total 2697 participants in the TRACK-TBI study, 991 had a GCS score of 15 and negative head CT scan and were eligible for inclusion in this analysis. Data were analyzed from September 1, 2021, to May 30, 2022. The primary outcome was the Glasgow Outcome Scale-Extended (GOS-E) score, which was stratified according to functional recovery (GOS-E score, 8) vs incomplete recovery (GOS-E score, <8), at 2 weeks and 6 months after the injury. The secondary outcome was severity of mild TBI-related symptoms assessed by the Rivermead Post Concussion Symptoms Questionnaire (RPQ) total score. A total of 991 participants (mean [SD] age, 38.5 [15.8] years; 631 male individuals [64%]) were included. Of these participants, 751 (76%) were followed up at 2 weeks after the injury: 204 (27%) had a GOS-E score of 8 (functional recovery), and 547 (73%) had a GOS-E scores less than 8 (incomplete recovery). Of 659 participants (66%) followed up at 6 months after the injury, 287 (44%) had functional recovery and 372 (56%) had incomplete recovery. Most participants with incomplete recovery reported that they had not returned to baseline or preinjury life (88% [479 of 546]; 95% CI, 85%-90%). Mean RPQ score was 16 (95% CI, 14-18; P < .001) points lower at 2 weeks (7 vs 23) and 18 (95% CI, 16-20; P < .001) points lower at 6 months (4 vs 22) in participants with a GOS-E score of 8 compared with those with a GOS-E score less than 8. This study found that most participants with a GCS score of 15 and negative head CT scan reported incomplete recovery at 2 weeks and 6 months after their injury. The findings suggest that emergency department clinicians should recommend 2-week follow-up visits for these patients to identify those with incomplete recovery and to facilitate their rehabilitation.


Neospora caninum is not an important contributor to poor reproductive performance of primiparous ewes from southern Australia: evidence from a cross-sectional study.
Neospora caninum has been implicated as a sporadic cause of abortion and perinatal deaths in sheep flocks globally. However, its significance as a reproductive pathogen for sheep in Australia remains unknown. The aims of this study were to (i) determine the seroprevalence of N. caninum in Australian breeding ewes and (ii) examine if natural exposure to N. caninum is associated with poor reproductive performance of primiparous ewes in southern Australia. Thirty flocks of primiparous ewes (aged 1-2 years old at lambing) from 28 farms in three states (Western Australia, South Australia and Victoria) were monitored between mating and lamb marking. Blood samples were also collected from multiparous mature ewes (aged 3 years or older) at each farm. Seroprevalence for anti-N. caninum IgG using indirect ELISA was determined for a subset of primiparous ewes that were predominantly determined to be pregnant and subsequently failed to rear a lamb (n = 1279) and randomly selected mature multiparous ewes with unknown reproductive status (n = 558). Neopsora caninum apparent seroprevalence was 0.16% (95% confidence interval 0.03%, 0.5%) in primiparous ewes, with seropositivity identified in two ewes from farms located in South Australia and Victoria. There was no evidence of seropositivity in mature ewes with apparent seroprevalence 0% (0%, 0.45%). These findings suggest that N. caninum infection was not widespread in primiparous ewes or mature multiparous ewes on these farms, and exposure to N. caninum infection was unlikely to explain abortion and perinatal mortalities observed for primiparous ewes.


Comparison of the damping effect of different shoeing by the measurement of hoof acceleration.
The purpose of this study was to compare the damping effect of 16 types of shoeing by measuring hoof acceleration parameters on two trotting horses. At impact, maximal deceleration had extreme values such as 188 m/s2 (+/- 55) for the most damping combination (p < 0.01) and 746 m/s2 (+/- 14) for the steel shoe (mean = 551 m/s2 +/- 125). After the shock, the hoof was exposed to a mean vibrating acceleration at 418 Hz (+/- 84) which was progressively damped in 37.3 ms (+/- 10.5). According to these results, the damping ability of different farriery products significantly reduces (p < 0.05) shocks and vibrations at hoof impact in the athletic horse caused by runs on asphalt or similar surfaces. In practice, the use of the most efficient shoeing should help to reduce the incidence of the over-used joint diseases in the athletic horse caused by runs on hard surfaces.


Resolution of enantiomers of the antiarrhythmic drug encainide and its major metabolites by chiral derivatization and high-performance liquid chromatography.
Commercially available chiral columns were unable to provide adequate resolution of enantiomers of the antiarrhythmic drug encainide or its major metabolites. The homochiral derivatizing agent, (-)-menthyl chloroformate, was found to react at the tertiary piperidine nitrogen of racemic encainide providing two menthyl carbamate diastereomers. The individual diastereomers could be separated with baseline resolution on normal-phase high-performance liquid chromatography on a silica column. Structures of the derivatives were confirmed by electron impact mass spectrometry and 1H NMR spectroscopy. The method was adapted for the chiral analysis of the major metabolites of encainide. The limit of sensitivity for racemic encainide was 10 ng on column and it was possible to detect a mixture containing (+)- and (-)-encainide in a ratio of 1:99. Preliminary studies indicated that (-)-encainide was O-demethylated to a greater extent than the (+)-enantiomer by rat liver microsomes.


Evaluation of flexible endoscope steering using haptic guidance.
Steering the tip of a flexible endoscope relies on the physician's dexterity and experience. For complex flexible endoscopes, conventional controls may be inadequate. A steering method based on a multi-degree-of-freedom haptic device is presented. Haptic cues are generated based on the endoscopic images. The method is compared against steering using the same haptic device without haptic cues, and against conventional steering. Human-subject studies were conducted in which 12 students and 6 expert gastroenterologists participated. Experts are significantly faster when using the conventional method compared with using the haptic device, either with or without haptic cues. However, it is expected that the performance of the subjects with the haptic device will increase with experience. Using a haptic device may be a viable alternative to the conventional method for the control of complex flexible endoscopes. The results suggest that the use of haptic cues may reduce the patient discomfort.


Clinical features and management of carboplatin-related hypersensitivity reactions in pediatric low-grade glioma.
The effectiveness of carboplatin and vincristine chemotherapy in the treatment of low-grade glioma (LGG) is well established. However, carboplatin hypersensitivity reactions (CHR) are a major problem leading to premature cessation of therapy. We aimed to investigate the clinical features and the management strategies in CHR, retrospectively. Fifty LGG patients treated between October 1997 and January 2008 with carboplatin and vincristine were included in the study. Clinical features, management strategies, influence of demographic factors on CHR, and success rate in terms of continuation with carboplatin therapy were evaluated. CHR were observed in 20 (40%) patients and grade I reactions were the most common. The median number of carboplatin doses administered at the first episode of CHR was nine (range 1-41). Only younger age was found to be correlated with the presence of CHR. Nine patients had carboplatin desensitization protocol; eight patients were given various combinations of premedication while three had no modification. Treatment was terminated in five patients due to CHR. Overall success rate was 75%. This is the largest single-center study conducted to investigate the frequency and the management strategies in patients with CHR who were treated with the same chemotherapy protocol for LGG. Premedication and desensitization were the preferred modifications in case of CHR. Overall, the success rate for carboplatin continuation is high in comparison to previous studies. Carboplatin can be continued successfully in many cases with CHR if reactions are managed in a timely fashion.


Aberrant expression of JMJD3 in SLE promotes B-cell differentiation.
Systemic lupus erythematosus (SLE) is a typical autoimmune disease distinguished by multiple organ dysfunction, which is related to a variety of causative factors. B-cell overactivation is a key factor in SLE. However, the pathogenesis underlying anomalous B cells has not been well elucidated. B-cell fate is regulated in diverse epigenetic ways apart from traditional ways. As one of the mechanisms of epigenetics, histone modification mainly affects transcription and translation by changing the chemical groups on histones by histone modification enzymes. JMJD3, a histone demethylase, can promote T-cell proliferation in SLE patients, which exacerbates SLE. However, the mechanism of JMJD3 in B cells in SLE has not been studied. Here, we found that the mean fluorescence intensity (MFI) of JMJD3 in classical memory B cells (CMBs) was higher than that in naïve B cells (NBs) from human tonsil tissue; JMJD3 was overexpressed in B cells from the peripheral blood of SLE patients compared with healthy controls (HCs). In vitro, our experiment showed that JMJD3 could regulate B-cell differentiation by promoting naïve B-cell differentiation into CD27+ B cells, and Blimp-1 and Bcl-6 also decreased after inhibitor treatment. These findings provide a new direction for the pathogenesis of SLE and may supply a new idea for subsequent drug development.


Bis[μ-4-(1H-imidazol-3-ium-1-yl)benzoato-κO:O']bis-[(methanol)tris-(nitrato-κO,O')terbium(III)].
In the centrosymmetric dinuclear title complex, [Tb(2)(NO(3))(6)(C(10)H(8)N(2)O(2))(2)(CH(3)OH)(2)], the Tb atoms are bridged by the carboxyl-ate groups of the two 4-(1H-imidazol-3-ium-1-yl)benzoate (iba) ligands. The iba ligand adopts a zwitterionic form with a protonated imidazole group. The Tb atom adopts a distorted tricapped trigonal-prismatic coordination geometry and is coordinated by six O atoms of three chelating nitrate ions, one O atom of the methanol mol-ecule and two O atoms of two iba ligands. The intra-molecular Tb⋯Tb separation is 5.1419 (3) Å. O-H⋯O and N-H⋯O hydrogen bonds connect complex mol-ecules into a two-dimensional network.


ENDOGENOUS ENDOPHTHALMITIS IN THE SETTING OF COVID-19 INFECTION: A Case Series.
To describe endogenous endophthalmitis in the setting of COVID-19 pneumonia. Patients recovering from COVID-19 pneumonia who presented to our department with any or all of the following complaints: pain, watering, redness, and decreased vision were identified. All relevant data were collected for analysis. Three patients with endogenous endophthalmitis were identified. All patients had been treated for COVID-19 pneumonia and therefore had received remdesivir and systemic steroids; 2 of the 3 patients received tocilizumab. All patients received vitreous biopsy, vitrectomy, and intraocular antibiotic injection. Patient 1 demonstrated Klebsiella pneumoniae in blood culture, K. pneumoniae and Escherichia coli in urine culture, and K. pneumoniae in vitreous fluid, whereas Patients 2 and 3 demonstrated Stenotrophomonas maltophilia and methicillin-resistant Staphylococcus aureus in the blood and nasopharyngeal culture, respectively. Correspondingly, the same organism was cultured from vitreous in Patients 2 and 3. The visual acuity at the last follow-up in Patients 1 to 3 was 20/100, 20/80, and 20/40, respectively. The probable source of infection was identified in each as renal calculi, dental caries, and the pharynx, respectively. Real-time polymerase chain reaction demonstrated the presence of Severe Acute Respiratory Syndrome Coronavirus 2 in the vitreous fluid of Patient 1. We report good outcomes of early intervention for endogenous endophthalmitis in the setting of COVID-19 infection. We also document the presence of SARS-CoV-2 in vitreous.


Prostaglandin production by methylcholanthrene-transformed mouse BALB/3T3: inhibition by cytochalasin B.
Cytochalasin B inhibits the production of prostaglandins by serum-, thrombin-, and bradykinin-stimulated MC5-5 cells. The serum-stimulated release of arachidonic acid from cellular phospholipids also is inhibited. Cytochalasin B does not affect the cells' prostaglandin synthetase activity when exogenous arachidonic acid is present. Deacylation of phospholipids may be the step affected by cytochalasin B possibly as a result of disruption of microfilament organization. Colchicine and vinblastine, two drugs that can disrupt microtubule organization, do not inhibit prostaglandin production by cells.


The origin of DNA replication of bacteriophage f1 and its interaction with the phage gene II protein.
The origin of DNA replication of bacteriophage f1 consists of two functional domains: 1) a "core region", about 40 nucleotides long, that is absolutely required for viral (plus) strand replication and contains three distinct but partially overlapping signals, a) the recognition sequence for the viral gene II protein, which is necessary for both initiation and termination of viral strand synthesis, b) the termination signal, which extends for 8 more nucleotides on the 5' side of the gene II protein recognition sequence, c) the initiation signal that extends for about 10 more nucleotides on the 3' side of the gene II protein recognition sequence; 2) a "secondary region", 100 nucleotides long, required exclusively for plus strand initiation. Disruption of the "secondary region" does not completely abolish the functionality of the f1 origin but does drastically reduce it (1% residual biological activity). This region, however, can be made entirely dispensable by mutations elsewhere in the phage genome.


Social class barriers to traditional student leader roles.
This chapter acknowledges the historical origins and access points of positional leadership roles on campus. In addition to highlighting barriers for poor and working-class students, the chapter suggests broadening access to leadership learning from the lens of community cultural wealth.


In-vessel headspace liquid-phase microextraction.
A new mode of headspace liquid-phase microextraction termed in-vessel headspace liquid-phase microextraction (IV-HS-LPME) has been developed. A plastic vessel was used as a holder for an extraction phase. Problems with drop stability, limitations in the stirring speed, and too little volume of the acceptor phase have been completely eliminated. The proposed approach is fully compatible with ordinary instruments and microcuvettes used in spectrophotometry. The potential of the method was evaluated by determining the iodide concentration in various samples. Iodide in the donor phase was converted to volatile I2 by oxidation with 1 mmol L-1 K2Cr2O7. The reaction mixture was agitated on a magnetic stirrer for 30 min at a stirring speed of 1200 rpm. A 1% (w/v) aqueous solution of KI was used as the acceptor phase. The absorbance of the I3- ion formed in the acceptor phase was measured in a 50 μL microcuvette at 350 nm. For the case of extraction from 10 mL donor solution into 50 μL of acceptor phase, the calibration graph is linear in the range of 20-400 μg L-1 (as I-) with a detection limit of 6 μg L-1. The developed method has a high precision comparable to conventional spectrophotometric methods (0.6-1.5%). The extraction efficiency obtained in the optimal conditions was 10.5%. The distribution constants for equilibria between the donor solution and the headspace and between the headspace and the acceptor solution are 0.8 ± 0.1 and 16 ± 2, respectively. The developed method was successfully applied to determine the iodine content in natural waters, medicines and algae.


Phase II study of pemetrexed and cisplatin, with chest radiotherapy followed by docetaxel in patients with stage III non-small cell lung cancer.
Pemetrexed has emerged as one of the most active agents for the treatment of patients with advanced non-small cell lung cancer (NSCLC). We conducted a phase II study to assess the efficacy and feasibility of integrating pemetrexed in a concurrent therapy plan for patients with stage III NSCLC. Patients with stage III NSCLC with performance status 0 to 1, adequate organ function including pulmonary function, and V20 less than 40% were eligible. Patients were treated with cisplatin 75 mg/m² (first five patients 60 mg/m²) and pemetrexed 500 mg/m² every 21 days for three cycles with chest radiotherapy to 66 Gy. Patients then received three cycles of docetaxel 75 mg/m² every 21 days. Tumors were analyzed for Excision Repair Cross Complementation Group 1 and thymidylate synthase. Patient characteristics (N = 28) were median age, 60; males, 68%; stage IIIB, 64%; and squamous cell, 43%. Twenty-four patients (86%) completed all three cycles of cisplatin/pemetrexed. Of the 24 patients eligible for docetaxel, 21 (87%) received it. Grade 3/4 toxicities were neutropenia (39%), febrile neutropenia (14%), esophagitis (14%), and pneumonitis (4%). Median survival was 34 months, and 1-year survival was 66%. Survival was not significantly different in squamous and other histology patients. Tumor analysis in 16 patients showed that moderate/strong expression of thymidylate synthase was significantly associated with progression-free survival and overall survival. Integrating pemetrexed in a concurrent therapy regimen for patients with stage III NSCLC is feasible and was associated with a median survival of 34 months.


The impact of dance activities on the health of persons with Parkinson's disease in Sweden.
Purpose: Parkinson's disease (PD) is associated with motor and non-motor symptoms that negatively influence the person's quality of life. To reduce illness and increase quality of life, alternative treatments of PD such as dance might be experienced as beneficial. The aim of this study was to explore experiences of how a dance program in Sweden influences perceived physical, social, and emotional wellbeing in persons with PD.Method: A qualitative method with semi-structured interviews and content analysis was used, and 10 participants with variations in age, gender, and how long they had been diagnosed with the disease were interviewed.Results: The results showed that dancing was experienced as improving health, which implied feeling both calmed and excited, getting better sleep, and being able to move with more focus and freedom. The dance program was experienced as a social context through the importance of community, feelings of togetherness, and being able to compare oneself with others. Experiences of self-support included experiencing increased self-esteem and joy, but also a sense of being confirmed and having structure, which gave meaning to everyday life.Conclusions: To reduce illness and increase quality of life in persons with PD, it is important to investigate alternative treatment methods, and this study shows the importance of participating in a dance program in Sweden for the life situation and health of people with PD.


Magnetic source imaging in presurgical evaluation of paediatric focal drug-resistant epilepsy and its predictive value of surgical outcome in lesional cases: A single-centre experience from South India.
This study aims to evaluate the utility of magnetoencephalography in presurgical planning and in predicting post-surgical seizure outcome. This study included a cohort of 231 children (1-18 years) with focal drug-resistant epilepsy who underwent MEG as a part of their presurgical workup. Characteristics of MEG observations were described in all children. The concordance and agreement of Magnetic Source Imaging (MSI) of interictal discharges (IED) was estimated with either of the 3 subgroups - MRI lesion; presumed epileptogenic zone (EZ); or resection cavity. In operated children group, MEG dipole characteristics between good and poor outcome groups were assessed. A total of 153 cases (66.2%) showed frequent IEDs (60 spikes/60 min). Of the 173 cases where MSI showed clusters (74.9%), 151 had lesions and 22 were non-lesional. amongst patients with lesional epilepsy and MEG clusters, class I concordance (MEG localization either completely included or overlapped at least 60% with the MRI lesion) was seen in 60.92% with a Cohen's kappa of 0.608. In non-lesional epilepsy, class I concordance of MEG with presumed EZ was found in (81.81%) with an agreement of 0.317. Fifty-three children underwent surgery of whom 39 (73.58%) showed a good outcome (Engel I). In operated children, concordance between MEG focus and resection cavity was observed in 23 (58.97%) with good outcome and in 12 (86.72%) with poor outcome with no significant difference (p>0.05). However, MEG cluster regular organization and clusterectomy are associated with good seizure outcome postoperatively (p< 0.05). Presence of scatters were associated with poor outcome (p<0.05) in children with focal cortical dysplasia. MEG provides useful information that can serve as a biomarker for prognosticating the surgical outcome in paediatric epilepsy. Cluster removal and regular cluster organization shows predictive power in post-surgical prognostication in children and the presence of scatters predicts poor outcome in children with focal cortical dysplasia.


Chronic hepatic disease: usefulness of serial CT examinations.
Our purpose was to confirm whether the progression of chronic liver disease could be determined by serial CT examinations. We calculated the liver (right and left lobes) and spleen volumes of 34 patients with chronic liver disease, who were examined serially for >2 years using a helical CT scanner. Progression of collateral formations was also checked during follow-up. These CT findings were compared with the liver function tests by Child-Pugh score. The Child-Pugh score got worse in eight patients ("score-worse group") and did not change in the other patients ("score-static group"). The liver volume ratio between the first and last CT examinations was significantly smaller in the score-worse group than in the score-static group (p = 0.015). The right lobe volume ratio was also significantly smaller in the score-worse group (p = 0.009); however, the left lobe volume ratio and spleen volume ratio were not significantly different between the two groups (p = 0.656 and p = 0.365). In four patients of the score-static group, collateral formations progressed. Serial CT examinations are useful to evaluate patients with chronic liver disease. The left lobe does not become hypertrophied but tends to be preserved, in contrast to the right lobe, with the progression of the disease.


Role of mucosal immune response and histopathological study in European eel (Anguilla anguilla L.) intraperitoneal challenged by Vibrio anguillarum or Tenacibaculum soleae.
The external mucus layer that covers fish skin contains numerous immune substances scarcely studied that act as the first line of defence against a broad spectrum of pathogens. This study aimed to characterize and describe for the first time several humoral immune defence parameters in the skin mucus of the European eel (Anguilla anguilla) after intraperitoneal injection with Vibrio anguillarum or Tenacibaculum soleae. This study evaluated several immune-related enzymes and bactericidal activity against fish pathogenic bacteria in the skin mucus of European eels at 24, 48, and 72 h post-challenge. The results demonstrated that European eel skin mucus showed significant increments in peroxidase and lysozyme activity at 48 and 72 h after V. anguillarum challenge, compared to other experimental groups. In the case of antiprotease activity, an increase was observed at 24 h in the skin mucus of fish challenged with V. anguillarum compared to unchallenged fish, while this activity was undetected at 48 and 72 h. In contrast, protease activity had decreased at 48 and 72 h in the skin mucus of fish challenged with V. anguillarum compared to the unchallenged group. Regarding bactericidal activity, a high growth capacity of T. soleae was observed in the skin mucus of all experimental groups. Interestingly, the skin mucus from fish challenged with V. anguillarum exhibited increased bactericidal activity against this bacterium at 48 h, compared to unchallenged fish. Finally, severe histopathological alterations were observed in the gills and liver at the end of the trial (72 h), whereas the skin showed only an overspread presence of goblet cells in the challenged fish compared to unchallenged fish. The present results may give new insights into the mucosal immune system of this primitive species with potential applications in aquaculture.


Childhood-onset myasthenia gravis with thymoma.
Juvenile myasthenia gravis is an acquired, autoimmune disease occurring before age 16 years. Thymoma is exceedingly rare in children, especially in association with juvenile myasthenia gravis. We describe a 14-year-old boy with juvenile myasthenia gravis and thymoma. He presented with difficulties chewing and swallowing, nasal speech, and fluctuating weakness of the leg muscles. Neurologic examination revealed masticatory and bulbar muscle weakness with nasal speech, proximal muscle weakness, fatigability of the arms and legs, and distal muscle weakness of the legs. A diagnosis of juvenile myasthenia gravis was confirmed by a positive neostigmine test, a decremental response on repetitive nerve stimulation, and increased titers of serum anti-acetylcholine receptor antibodies. The patient received anticholinesterases, corticosteroids, azathioprine, and thymectomy. A pathohistologic analysis of the thymus gland indicated thymoma, Masaoka grade II. After 2 years of an unstable disease course, remission was achieved. Because only 10 cases of thymoma-associated myasthenia gravis are described in the pediatric population, this report offers an important contribution to a better understanding of this rare association.


Geographic Distribution of Cytomegalovirus Serology in Kidney and Pancreas Transplant Recipients in the United States.
Cytomegalovirus (CMV) negatively affects transplant outcomes. The current geographic distribution of CMV risk within the US has not been described. CMV serostatus of donors and recipients in each US state were collected from the Scientific Registry of Transplant Recipients between April 1, 2015, and March 31, 2019. The objective was to describe rates of CMV recipient seropositivity (R+) and high-risk serostatus (D+/R-) across the US in kidney transplant recipient (KTR) and pancreas transplant recipient (PTR) and explore geographic disparities. A total of 79 276 KTRs and 4023 PTRs were included. The average KTR R+ rate across states was 59.5% (range 39%-76%); PTR R+ rate was 49.5% but with a broader range (0%-100%). The average KTR D+/R- rate across the US was 19% (range 8.7%-25%); PTR D+/R- rate was notably higher (26.9%, range 0%-50%). KTR seropositivity varied geographically with more R+ recipients in the southern states, Alaska, and Hawaii. D+/R- KTRs also varied by region, with higher rates in the Rocky Mountain Region as well as the Midwest and the northern-most states of the Northeast. Trends found in KTR persisted in PTR. The distribution of CMV serostatus in the US varies by state and allograft type. These data may be useful in further discussion of national CMV donor-matching strategies.


Antioxidant and the ameliorating effect of Allium cepa (Onion) fortified feed against potassium bromate induced oxidative damage in Wistar rats.
Allium cepa Linn (Onion) Organosulfuric compounds and phytonutrients have medicinal benefits. The study estimated the antioxidant effect of Allium cepa in fortified feed against oxidative damage caused by potassium bromate. Commercial feed was fortified by substituting 10 %, 20 %, and 30 % of rat's daily ration with the respective portion of pulverized Allium cepa. Potassium bromate was administered orally to the rats in all the groups except rats in the normal control. The rats in the test groups were allowed access to the fortified feed ad libitum. The animals were sacrificed; consequently, the serum, liver, and kidney were obtained for biochemical assay and histological assessment. The percentage composition of some amino acids and some proximate were higher in the fortified feed. Furthermore, Malondialdehyde (MDA) level in the liver, kidney, and serum decreased significantly (P ≤ 0.05) in rats fed with fortified feed compared to administered only Potassium bromate. Similarly, the concentration of total protein increased significantly (P ≤ 0.05) in the liver, kidney, and serum of the animals fed with fortified feed. The hematology result was normal in rats fed with fortified feed. The liver and kidney cell architecture was normal in animals fed with fortified feed. Allium cepa may have conferred protection and amelioration to oxidative damage by potassium bromate in rats.


Gaussian synapses for probabilistic neural networks.
The recent decline in energy, size and complexity scaling of traditional von Neumann architecture has resurrected considerable interest in brain-inspired computing. Artificial neural networks (ANNs) based on emerging devices, such as memristors, achieve brain-like computing but lack energy-efficiency. Furthermore, slow learning, incremental adaptation, and false convergence are unresolved challenges for ANNs. In this article we, therefore, introduce Gaussian synapses based on heterostructures of atomically thin two-dimensional (2D) layered materials, namely molybdenum disulfide and black phosphorus field effect transistors (FETs), as a class of analog and probabilistic computational primitives for hardware implementation of statistical neural networks. We also demonstrate complete tunability of amplitude, mean and standard deviation of the Gaussian synapse via threshold engineering in dual gated molybdenum disulfide and black phosphorus FETs. Finally, we show simulation results for classification of brainwaves using Gaussian synapse based probabilistic neural networks.


Retention index of FDG-PET/CT SUVmax of the primary tumor in non-small cell lung cancer as a predictor of lymph node metastasis: a retrospective study.
Accurate staging of non-small cell lung cancer is key in treatment planning and prediction of prognosis. We investigated the correlation between the maximum standardized uptake value (SUVmax) retention index (RI) of the primary tumor and lymph node metastasis in non-small cell lung carcinoma. We also evaluated the tendencies according to the histological types. We retrospectively evaluated 218 non-small cell lung cancer (NSCLC) tumors from 217 patients who underwent preoperative fluorodeoxyglucose-positron emission tomography/computed tomography (PET/CT) followed by lung surgery and lymph node resection between July 2015 and August 2020. All primary tumors were calculated as the SUVmax at 50 min (SUVmaxearly [SUVmaxe]) and 120 min (SUVmaxdelayed [SUVmaxd]), and RI. The clinicopathological factors of interest were compared based on lymph node metastasis status and NSCLC histopathological subtype. The median SUVmaxe and SUVmaxd of the primary tumors were 3.3 and 4.2, respectively, and the median RI was 0.25. The RI was significantly higher in the pN(+) (n = 44) group (0.30) compared to the pN0 (n = 174) group (0.24) (p = 0.01). In patients with adenocarcinoma (n = 145), the RI was also significantly higher in the pN(+) (n = 29) group (0.29) compared to the pN0 (n = 116) group (0.16) (p < 0.01). A high RI of the primary tumor was an independent risk factor for lymph node metastasis, particularly in patients with adenocarcinoma (odds ratio: 12.30, p < 0.05). The RI of primary NSCLC tumors can help predict lymph node metastases, particularly in patients with adenocarcinoma.


High-throughput phenotyping accelerates the dissection of the dynamic genetic architecture of plant growth and yield improvement in rapeseed.
Rapeseed is the second most important oil crop species and is widely cultivated worldwide. However, overcoming the 'phenotyping bottleneck' has remained a significant challenge. A clear goal of high-throughput phenotyping is to bridge the gap between genomics and phenomics. In addition, it is important to explore the dynamic genetic architecture underlying rapeseed plant growth and its contribution to final yield. In this work, a high-throughput phenotyping facility was used to dynamically screen a rapeseed intervarietal substitution line population during two growing seasons. We developed an automatic image analysis pipeline to quantify 43 dynamic traits across multiple developmental stages, with 12 time points. The time-resolved i-traits could be extracted to reflect shoot growth and predict the final yield of rapeseed. Broad phenotypic variation and high heritability were observed for these i-traits across all developmental stages. A total of 337 and 599 QTLs were identified, with 33.5% and 36.1% consistent QTLs for each trait across all 12 time points in the two growing seasons, respectively. Moreover, the QTLs responsible for yield indicators colocalized with those of final yield, potentially providing a new mechanism of yield regulation. Our results indicate that high-throughput phenotyping can provide novel insights into the dynamic genetic architecture of rapeseed growth and final yield, which would be useful for future genetic improvements in rapeseed.


Bariatric surgery: severity, level of control, and time required for preoperative asthma control.
There is an increased prevalence of asthmatic, obese patients undergoing bariatric surgery. The objective of our study is to evaluate the severity, level of control, respiratory medication use, and time required for prebariatric surgery asthma control. This is a prospective study in which 88 obese asthmatics were evaluated by a pulmonologist in two steps, prebariatric surgery. In the first step, patients were evaluated for severity, level of control, and respiratory medication in use, categorized as bronchodilators and corticosteroids. In the second step, the time required for asthma control between steps and appropriate respiratory medication was determined. Thirty-eight obese patients (43.2%) had intermittent asthma, 22 had mildly persistent (25.0%), 24 moderately persistent (27.3%), and 4 severely persistent (4.5%). There were 43 patients with controlled asthma (48.9%), 31 partly controlled (35.2%), and 14 uncontrolled (15.9%). The study sample showed a significant increase in bronchodilators in the first step and corticosteroids in the second step (p ≤ 0.0001). Comparisons between steps showed significant differences with a reduction of bronchodilators and increase in corticosteroids in the second step (p ≤ 0.0001). The mean time (days) required for asthma control between steps was 28.98 ± 33.40 days, with significant differences between groups (p ≤ 0.001). In prebariatric surgery, there was a higher proportion of intermittent asthma and uncontrolled asthma, with asthma severity influencing the achievement of asthma control and the time required for surgical release.


The effect of Crocin on TFAM and PGC-1α expression and Catalase and Superoxide dismutase activities following cholestasis-induced neuroinflammation in the striatum of male Wistar rats.
Bile secretion is a physiological function that is disrupted following Bile Duct Ligation (BDL) and induces cholestasis. Cholestasis is a bile flow reduction that induces apoptosis, oxidative stress, and inflammation, and alters the expression of genes. Evidence shows the relationship between cholestasis and neuroinflammation. Cholestasis via attenuating mitochondrial biogenesis and anti-oxidant activity can induce neuroinflammation and apoptosis. Mitochondrial transcriptional factor A (TFAM) and Peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) are involved in mitochondrial biogenesis, and TFAM, PGC-1α, Catalase (CAT), and Superoxide dismutase (SOD) have a role in upregulating antioxidant pathways. On the other hand, many studies have shown the neuroprotective effects of Crocin, the water-soluble carotenoid of Saffron (Crocus sativus L.). In this study, we aimed to investigate the effect of Crocin on the level of TFAM, PGC-1α, CAT, and SOD following cholestasis-induced neuroinflammation in the rat's striatum. Cholestasis was induced by BDL surgery and administration of Crocin was intraperitoneal, at the dose of 30 mg/kg every day, 24 h after BDL surgery up to thirty days. The results showed that TFAM, PGC-1α, and SOD were decreased following cholestasis; while, CAT was increased. In addition, Crocin restored the effects of cholestasis on the level of TFAM, PGC-1α, and SOD. In conclusion, Crocin may have improvement effects on cholestasis-induced neuroinflammation in the rat's striatum.


Cryo-Electron Tomography and Automatic Segmentation of Cultured Hippocampal Neurons.
Cryo-electron tomography is fast becoming a preferred method for studying intracellular environments at the molecular scale. Increases in data collection throughput means that large numbers of tomograms can be generated at rates too fast for humans to easily explore quantitatively. Currently, there is a large effort to make data collection and segmentation tools more automated. Here, we describe a workflow for preparing cultured neurons on electron microscopy grids, batch tomographic data collection, reconstruction and automatic segmentation using freely and commercially available software.


Overexpression of erb B2 remains a major risk factor in non-metastatic breast cancers treated with high-dose alkylating agents and autologous stem cell transplantation.
The importance of dose intensity has been strongly emphasized in high-risk breast cancer. Overexpression of erb B2 is clearly correlated with an overall poor prognosis which could be limited in patients receiving intensive chemotherapy with alkylating agents and autologous stem cell transplants (SST). Thirty-five patients with high-risk non-metastatic breast cancer (>4 involved lymph nodes), treated with high-dose chemotherapy (HDC) followed by SST were analyzed. All were previously treated by four cycles of standard-dose anthracycline or anthracene dione. Nine had erb B2 overexpression. Minimum follow-up duration was 41 months (median 68 months). At 5 years, the actuarial relapse-free survival is 57.4% and actuarial overall survival 67.4%. Patients with overexpression of erb B2 had significantly lower disease-free survivals (P: 0.021) and overall survivals (P: 0.001). On multivariate analysis, erb B2 overexpression appeared to be the single independent poor prognosis factor for relapse (RR 3.25, range 1.12 to 9.45) and overall (RR 5.28, range 1.74 to 16.03) survival. These results suggest that poor prognosis of erb B2 overexpression is unchanged after HDC with alkylating agents but a possible benefit may exist in these patients with the additional monoclonal antibody, herceptin.


Usefulness of Magnetic Mallet in Oral Surgery and Implantology: A Systematic Review.
This systematic review aimed to answer the question: "Is the use of magnetic mallet effective in oral and implant surgery procedures in terms of tissue healing, surgery outcome, and complication rate compared to traditional instruments?" A literature search of PubMed, Scopus, and Web of Science databases (articles published until 1 October 2021) was conducted, in accordance with the PRISMA statement, using the keywords "magnetic mallet", "electric mallet", "oral surgery", "implantology", and "dental implant". Of 252 articles, 14 were included in the review (3 for teeth extraction, and 11 for implant dentistry). Out of a total of 619 dental extractions (256 patients) performed with the magnetic mallet (MM), no complications were reported. Implants inserted totaled 880 (525 patients): 640 in the MM groups (382), and 240 in control groups (133). The survival rate of implants was 98.9% in the MM groups, and 95.42% in the control groups. Seven patients experienced benign paroxysmal positional vertigo after implant surgery, all in control groups. Results are not sufficient to establish the effectiveness of MM in oral and implant surgery procedures. Randomized controlled trials with a large sample size are needed.


A machine learning-based approach for low-density lipoprotein cholesterol calculation using age, and lipid parameters.
Low-density lipoprotein cholesterol (LDL-C) is a critical biomarker for cardiovascular disease. However, no consensus exists on the best method for estimating LDL-C in Chinese laboratories. This study aimed to develop a machine learning (ML) method for LDL-C estimation. An extensive data set of 111,448 samples were randomized into five equal subsets. ML-based equations were developed using age, sex, and lipid parameters based on five-fold cross-validation. The trained ML equations were externally validated in three different data sets. The performance of the ML equations was compared with the Friedewald, Martin/Hopkins, and Sampson equations. The selected ML equations showed less bias with direct LDL-C than other LDL-C equations in the Chinese population, including those with triglycerides (TG) ≥ 400 mg / dL and LDL-C < 40 mg / dL. The performance of the ML equations was less susceptible to age. External validation showed the generalization of the ML equations. This study highlights the potential of integrating sex, age, and lipid parameters into the ML equations to obtain a more robust and reliable LDL-C calculation.


Pesticide safety behaviours among agricultural workers and farmers: A cross-sectional study.
The aim of this study is to investigate the pesticide safety behaviours and related factors among cabbage farmers in Kalaw Township, Myanmar. Unsafe chemical pesticide practices affect farmers' health and the environment. Understanding pesticide safety behaviours is necessary for healthcare providers to protect agriculture workers against unwanted adverse health effects. The cross-sectional study was conducted among 195 cabbage farmers from March to May 2019. Safety behaviours and factors applied in the PRECEDE-PROCEDE model as a framework were assessed using questionnaires. Bivariate and multivariate logistic regression was applied to identify any associations. Altogether, 72.1% of the farmers had a low level of safety behaviours. Goggles and masks were rarely used before and during pesticide applications. All of the farmers experienced adverse health effects after using pesticides. The attitudes toward pesticide poisoning; support from family, co-workers and healthcare providers; and the availability of personal protective equipment were significantly associated with safety behaviours. Our data provide novel empirical evidence for an opportunity to design effective nursing interventions to promote pesticide safety behaviours among Myanmar agricultural workers. Nurses should pay more attention to promoting comprehensive interventions to reduce both exposure and health effects among agricultural workers through the involvement of supported stakeholders.


Separation of craniopagus twins utilizing tissue expanders.
An example of craniopagus Siamese twins is presented. The methods used in their separation using skin expanders and scalp flaps to achieve primary closure of the wounds with hair-bearing scalp are outlined. A detailed discussion of the planning and the mathematical considerations of these skin expanders and scalp flaps is included.


Brain abscess and cystic fibrosis.
Brain abscess has only recently been considered a complication of cystic fibrosis. Three patients are reported here and a fourth cited from the literature. All of our patients were young adults with advanced pulmonary disease. The bacteria involved were mouth organisms and were found in the sputum culture in only one of the patients. Resistance was present to previously given antibiotics. As patients with cystic fibrosis survive into adulthood, the risk of developing a brain abscess appears to increase.


Activation of cytosolic phospholipase A2 in permeabilized human neutrophils.
Neutrophils (PMN) contain two types of phospholipase A2 (PLA2), a 14 kDa 'secretory' Type II PLA2 (sPLA2) and an 85 kDa 'cytosolic' PLA2 (cPLA2), that differ in a number of key characteristics: (1) cPLA2 prefers arachidonate (AA) as a substrate but hydrolyzes all phospholipids; sPLA2 is not AA specific but prefers ethanolamine containing phosphoacylglycerols. (2) cPLA2 is active at nM calcium (Ca2+) concentrations; sPLA2 requires microM Ca2+ levels. (3) cPLA2 activity is regulated by phosphorylation; sPLA2 lacks phosphorylation sites. (4) cPLA2 is insensitive to reduction; sPLA2 is inactivated by agents that reduce disulfide bonds. We utilized PMN permeabilized with Staphylococcus aureus alpha-toxin to determine whether one or both forms of PLA2 were activated in porated cells under conditions designed to differentiate between the two enzymes. PMN were labeled with [3H]AA to measure release from phosphatidylcholine and phosphatidylinositol; gas chromatography-mass spectrometry was utilized to determine total AA release (mainly from phosphatidylethanolamine) and to assess oleate and linoleate mass. A combination of 500 nM Ca2+, a guanine nucleotide, and stimulation with n-formyl-met-leu-phe (FMLP) were necessary to induce maximal AA release in permeabilized PMN measured by either method; AA was preferentially released. [3H]AA and AA mass release occurred in parallel over time. A hydrolyzable form of ATP was necessary for maximum AA release and staurosporin inhibited PLA2 activation. Dithiothreitol treatment had little affect on [3H]AA release and metabolism but inhibited AA mass release. Assay of cell supernatants after cofactor addition did not detect sPLA2 activity and the cytosolic buffer utilized did not support activity of recombinant sPLA2. These results strongly suggested that cPLA2 was the enzyme activated in the permeabilized cell model and this is the first report which unambiguously demonstrates AA release in response to activation of a specific type of PLA2 in PMN.


A prospective study of total gastrectomy for CDH1-positive hereditary diffuse gastric cancer.
Hereditary diffuse gastric cancer (HDGC) is an autosomal dominant cancer syndrome. Up to 30% of families with HDGC have mutations in the E-cadherin gene, CDH1. The role of prophylactic versus therapeutic gastrectomy for HDGC was studied prospectively. Eighteen consecutive patients with CDH1 mutations and positive family history were studied prospectively, including 13 without and 5 with symptoms. Proportions were compared by Fisher's exact test, and survival by the Breslow modification of the Wilcoxon rank-sum test. Each patient underwent total gastrectomy (TG), and 17 (94%) were found to have signet ring cell adenocarcinoma. Twelve of 13 asymptomatic patients had T1, N0 cancer, and only 2/12 (16%) had it diagnosed preoperatively despite state-of-the-art screening methods. Each asymptomatic patient did well postoperatively, and no patient has recurred. For five symptomatic patients, each (100%) was found to have signet ring cell adenocarcinoma (P = 0.002 versus asymptomatic) by preoperative endoscopy; three (60%) had lymph node involvement and two (40%) had distant metastases at time of operation. Two-year survival was 100% for asymptomatic and 40% for symptomatic patients (P < 0.01). The data show that asymptomatic patients with family history of HDGC and CDH1 mutation have high probability of having signet ring cell adenocarcinoma of the stomach that is not able to be diagnosed on endoscopy; when symptoms arise, the diagnosis can be made by endoscopy, but they have metastases and decreased survival. Surveillance endoscopy is of limited value, and prophylactic gastrectomy (PG) is recommended for patients with family history of HDGC and CDH1 mutations.


Gender differences in functional status and pain in a Medicare population undergoing elective total hip arthroplasty.
The major indication for total hip arthroplasty (THA) is pain and disability in the hip. Evidence from state and local studies suggests that women may be more disabled than men at the time of THA. Whether worse disability at the time to THA affects outcomes is unknown. To examine differences in functional status and pain in men and women at the time of THA and at 1 year in a nationally representative Medicare population. Cohort of patients undergoing THA. Data were collected at the time of THA, 4 to 6 months after surgery, and 1 year after surgery. All Medicare recipients older than age 65 in 12 selected states were eligible. One thousand six hundred forty patients who underwent THA were identified and 1120 (432 men and 688 women) were enrolled. Pain and functional status. At the time of THA, women were more likely than men to report severe pain with walking (67% vs. 58%; P <0.01), and needing assistance with walking (56% vs. 45%; P <0.01), housework (49% vs. 30%; P <0.01), and grocery shopping (51% vs. 31%; P <0.01). Men could also walk greater distances. These differences persisted after adjustment for comorbidities and age. One year following THA, women were more likely to report needing assistance with walking (30% vs. 21%; P <0.01), housework (29% vs. 23%; P <01), and grocery shopping (27% vs. 19%; P <0.01) and could walk shorter distances. These differences were partially accounted for by differences in comorbidities and baseline status. Compared with men, women in Medicare are more disabled at the time of THA and do not do as well at 1 year. Whether this difference arises from patients' preferences or bias in the health care system is unknown.


IGF-1-induced epithelial-mesenchymal transition in MCF-7 cells is mediated by MUC1.
Metastases are the major cause of death from cancer. IGF-1 signaling pathway has been shown to have strong implication in the epithelial-mesenchymal transition (EMT) process. However, the mechanisms of how IGF-1 promotes EMT have not been fully elucidated. Mucin 1 (MUC1), a transmembrane glycoprotein, engages in multiple cancer-related signaling pathways and functions as an oncoprotein that contributes to metastases. Here we provide evidence showing that IGF-1 upregulates MUC1 expression in MCF-7 cells in a PI3K/Akt signaling pathway-dependent manner. The overexpression of MUC1 is critical for IGF-1-induced EMT of MCF-7 cells because the knockdown of MUC1 prevented the EMT of MCF-7 cells as demonstrated by various EMT markers including the expression of E-cadherin, N-cadherin, vimentin, fibronectin and the nuclear translocalization of β-catenin. On the other hand, the knockdown of MUC1 had no impact on IGF-1-induced activation of PI3K/Akt or MAPK. In summary, our study demonstrated MUC1 as a critical downstream effector that mediates IGF-1-induced EMT of MCF-7 cells and suggested that MUC1 might be a potential therapeutic target for preventing tumor metastases.


[Automation of the determination of cardiac output by means of 4-electrode rheocardiography].
A method of cardiac output determination is described, based on automatic processing of the differential rheogram and arterial pressure traces, by a computer algorithm. All variable parameters of the rated formula are defined automatically. The method provides highly precise and rapid definition of the cardiac output.


Immunophenotyping of Circulating Endothelial Cells and Endothelial Microparticles.
Flow-cytometric detection of circulating endothelial cells and endothelial microparticles is an essential tool in studies of vascular diseases. Here we describe the principles and detailed methods for human blood sample processing, storage, labeling, and gating of circulating endothelial elements.


Understanding the mechanism of interaction of candidate soil stabilizing prototypes by using microscopy and spectroscopy techniques.
Globally, there is a high demand for bio-based soil stabilizers required for improving the strength properties of weak in situ soil. Microbes and microbial components such as Bacillus spp. have gained interest as soil stabilizers due to their production of spores, bio-enzymes, and bio-polymers. However, the current approach for any microlevel assessment of bio-additives and in situ soil improvement is limited. This paper provides data for microstructural evaluation of stabilized soil material for the postulation of the mode of action. In this study, the microbonding effect (i.e., bio-based cementation, bio-clogging, and soil particle bio-coating) is successfully observed within the various stabilizing prototypes, obtained from a novel Bacillus spp. using advanced methods, namely field emission gun-scanning electron microscopy and Fourier transform-infrared spectroscopy. The results show that treated soil versus untreated soil properties are altered by the bio-additive/s stabilizing effect. These indicator tests provide data for further bio-stabilizer product prototype development and processes (i.e., improved products in terms of strength and moisture susceptibility). The use of microscopy and spectroscopy was sufficient for the preliminary selection of suitable candidates for soil stabilization.


Efficacy of simvastatin plus metformin for polycystic ovary syndrome: A meta-analysis of randomized controlled trials.
The efficacy of simvastatin plus metformin to treat polycystic ovary syndrome (PCOS) remained controversial. Therefore, we conducted this meta-analysis to explore the influence of simvastatin plus metformin versus metformin monotherapy on the treatment of PCOS. We have searched PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases through June 2020 and included randomized controlled trials (RCTs) assessing simvastatin plus metformin versus metformin for PCOS. This meta-analysis was performed using the random-effect model. Five RCTs were included in the meta-analysis. Overall, compared with metformin monotherapy for PCOS, combined treatment with simvastatin plus metformin was associated with significantly reduced total testosterone (mean difference [MD] = -0.31; 95 % confidence interval [CI] = -0.50 to -0.13; P = 0.0009), leuteinizing hormone: follicle stimulating hormone (LH:FSH) ratio (MD = -0.92; 95 % CI = -1.62 to -0.23; P = 0.009) and low-density lipoprotein (LDL) cholesterol (MD = -34.90; 95 % CI = -39.33 to -30.47; P < 0.00001), but spontaneous menses per 6 months, volume of both ovaries, body mass index (BMI) and fasting glucose were found to be similar between two groups. Combined treatment with simvastatin plus metformin was better to treat PCOS than metformin alone as evidenced by significantly reduced total testosterone, LH:FSH ratio and LDL cholesterol.


Phenolic-rich extracts from acerola, cashew apple and mango by-products cause diverse inhibitory effects and cell damages on enterotoxigenic Escherichia coli.
This study aimed to evaluate the inhibitory effects of phenolic-rich extracts from acerola (Malpighia emarginata D.C., PEA), cashew apple (Anacardium occidentale L., PEC) and mango (Mangifera indica L., PEM) by-products on distinct enterotoxigenic Escherichia coli (ETEC) strains. The capability of PEA and PEC of impairing various physiological functions of ETEC strains was investigated with multiparametric flow cytometry. Procyanidin B2 , myricetin and p-coumaric acid were the major phenolic compounds in PEA, PEC and PEM, respectively. PEA and PEC had lower minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) (MIC: 31·25 mg ml-1 ; MBC: 62·5 mg ml-1 ) on ETEC strains than PEM (MIC and MIC: >1000 mg ml-1 ). PEA and PEC (15·6, 31·2, 62·5 mg ml-1 ) caused viable count reductions (P < 0·05) on ETEC strains after 24 h of exposure, notably the ≥3 log reductions caused by 62·5 mg ml-1 . The 24 h exposure of ETEC strains to PEA and PEC (31·2, 62·5 mg ml-1 ) led to high sizes of cell subpopulations with concomitant impairments in cell membrane polarization and permeability, as well as in enzymatic, respiratory and efflux activities. PEA and PEC are effective in inhibiting ETEC through a multi-target action mode with disturbance in different physiological functions.


Sunlight-induced Painful Skin (Sun Pain): A New Differential Diagnosis in Photodermatology.
Photodermatoses are characterized by the development of skin eruptions following exposure to ultraviolet radiation or visible light. We report here the clinical findings and results of laboratory investigations and phototesting of 6 patients who experience debilitating and excruciating pain after sun exposure ("sun pain") in the absence of any skin eruption. Phototesting with sub-erythemal doses of ultraviolet A radiation triggered localized pain in 4 patients. At follow-up, 3 female patients were found to have developed fibromyalgia, 2 male patients experienced a major depressive disorder, and another male patient had a conversion disorder. One patient also developed allodynia to tactile stimuli and one developed allodynia to thermal and tactile stimuli. Psychiatric conditions should be taken into consideration in patients presenting with excruciating and debilitating pain on exposure to ultraviolet radiation, but with absence of skin eruption. Further research is needed to evaluate whether it represents a type of allodynia triggered by exposure to ultraviolet radiation.


Multiple laser pulses in conjunction with an optical clearing agent to improve the curative effect of cutaneous vascular lesions.
Port-wine stains (PWSs) usually respond poorly to pulsed dye laser treatment because of the shallow penetration and light absorption of melanin in the epidermis. Multiple laser pulses (MLPs) Nd:YAG laser in conjunction with an optical clearing agent can help to reduce the total laser energy required for blood coagulation. The quantitative optical clearing effect (OCE) of glycerol was investigated by using a tissue-like phantom. Thereafter, an in vitro capillary tube experimental system and an in vivo hamster dorsal skin chamber experiment for the laser treatment of PWSs were established to visually obtain the quantitative relationship between the OCE and the blood coagulation properties under the irradiation of 1064 nm MLPs. Diffuse reflection coefficient decreases by 36.69% and transmission coefficient increases by 38.73% at 1064 nm, after applying 0.5 mL anhydrous glycerol for 10 min on the surface of the tissue-like phantom. The number of laser pulses required for blood coagulation decreases by 25% after the application of 0.5 mL anhydrous glycerol for 4 min, thrombosis appears after 10 min, and the 0.0854 clotting area completely blocks the capillary tubes in 6 pulses. For 10 min, the incident energy can be reduced by 35.09 and 29.82%. When the 0.3-mm vessel's buried depths are 1 and 0.5 mm, the pulse number can be reduced from 11 to 8 and from 6 to 4, respectively. Adding anhydrous glycerol directly on the hamster dorsal skin is an effective way to reduce the number of laser pulses from 4∼5 to 2∼3 for similar capillary tube diameter. Therefore, the MLPs of 1064 nm Nd:YAG demonstrates a substantial curative effect for large capillary tubes. In conjunction with glycerol, this approach may treat deeply buried cutaneous capillary tubes and prevent the unwanted thermal damage of normal dermal tissue.


Experimental discrimination of ion stopping models near the Bragg peak in highly ionized matter.
The energy deposition of ions in dense plasmas is a key process in inertial confinement fusion that determines the α-particle heating expected to trigger a burn wave in the hydrogen pellet and resulting in high thermonuclear gain. However, measurements of ion stopping in plasmas are scarce and mostly restricted to high ion velocities where theory agrees with the data. Here, we report experimental data at low projectile velocities near the Bragg peak, where the stopping force reaches its maximum. This parameter range features the largest theoretical uncertainties and conclusive data are missing until today. The precision of our measurements, combined with a reliable knowledge of the plasma parameters, allows to disprove several standard models for the stopping power for beam velocities typically encountered in inertial fusion. On the other hand, our data support theories that include a detailed treatment of strong ion-electron collisions.


Are You Your Own Best Judge? On the Self-Evaluation of Singing.
Singers are the first judges of their own performances. Although performers usually share a precise definition of pitch accuracy, do they correctly estimate their own ability to sing in tune? This study examines the accuracy of professional singers' self-evaluations and investigates the profiles of performers/judges. Eighteen highly trained soprano singers were invited to evaluate the pitch accuracy of peers' performances, selected from an existing corpus, and their own previously recorded performances in a pairwise comparison paradigm. The statistical model derived from the participants' evaluation of their peers allowed us to estimate the pitch accuracy of participants' own performances and served as a reference to quantify participants' evaluation and self-evaluation abilities. The results show that participants were surprisingly inaccurate when evaluating themselves. Specifically, most participants overestimated the accuracy of their own performances. Also, we observed a relationship between singing proficiency and self-evaluation ability, as well as the presence of different profiles. In addition to emphasizing that singers are not necessarily their own best judges, this study suggests potential role(s) for self-evaluation (in)accuracy in the development of exceptional skills.


Improving medical students' confidence in end-of-life consultations.
End-of-life discussions are associated with improved quality of care for patients. In the UK, the General Medical Council outlines a requirement for medical graduates to involve patients and their families in discussions on their care at the end-of-life. However medical students feel ill-equipped to conduct these discussions. In 2018, Sheffield Medical School introduced a small group role-play session on end-of-life discussions for all final year medical students. Scenarios were devised to improve confidence in the following learning domains: communicating prognosis with patients and family; ascertaining patient's goals, values and preferred place of death; discussing escalation of treatment, discussing do not attempt resuscitation orders, care in the dying phase of illness and pre-emptive prescribing. Evaluation was conducted over 16 weeks with a before and after questionnaire. Students rated their confidence in the above learning domains on a Likert-style scale and explained their ratings in free-text boxes. There was a 76% response rate to the questionnaire and analysis showed statistically significant improvements in confidence across all learning domains following the session. Qualitative analysis of free-text responses showed that prior to the sessions, students expressed low confidence due to lack of experience and fear of upsetting patients. After the session students felt they had gained skills but expressed persistent anxiety and a desire for further practice. Our innovation suggests that the opportunity to experience End-of-life discussions through role-play can significantly improve students' confidence in conducting these conversations. However, repeated sessions are likely necessary for students to feel prepared upon graduation.