A numeric-based machine learning design for detecting organized retail fraud in digital marketplaces.
Organized retail crime (ORC) is a significant issue for retailers, marketplace platforms, and consumers. Its prevalence and influence have increased fast in lockstep with the expansion of online commerce, digital devices, and communication platforms. Today, it is a costly affair, wreaking havoc on enterprises' overall revenues and continually jeopardizing community security. These negative consequences are set to rocket to unprecedented heights as more people and devices connect to the Internet. Detecting and responding to these terrible acts as early as possible is critical for protecting consumers and businesses while also keeping an eye on rising patterns and fraud. The issue of detecting fraud in general has been studied widely, especially in financial services, but studies focusing on organized retail crimes are extremely rare in literature. To contribute to the knowledge base in this area, we present a scalable machine learning strategy for detecting and isolating ORC listings on a prominent marketplace platform by merchants committing organized retail crimes or fraud. We employ a supervised learning approach to classify postings as fraudulent or real based on past data from buyer and seller behaviors and transactions on the platform. The proposed framework combines bespoke data preprocessing procedures, feature selection methods, and state-of-the-art class asymmetry resolution techniques to search for aligned classification algorithms capable of discriminating between fraudulent and legitimate listings in this context. Our best detection model obtains a recall score of 0.97 on the holdout set and 0.94 on the out-of-sample testing data set. We achieve these results based on a select set of 45 features out of 58.


Age-related changes in scalp biophysical parameters: A comparative analysis of the 20s and 50s age groups.
Age-related changes in scalp parameters affect hair quality and scalp condition. However, detailed data on biophysical parameters of the scalp across age groups remain scarce. We aimed to investigate the differences in scalp parameters between individuals in their 20s and 50s and analyze their sex-specific variations. Two hundred participants (160 women and 40 men) were equally divided into 20s and 50s age groups. Biophysical parameters of the scalp, including elasticity, pH, trans-epidermal water loss (TEWL), sebum production, desquamation, firmness, redness, and yellowness, were measured in the vertex, occipital, and temporal regions. Hair density and thickness were measured in the temporal region. The accumulation of advanced glycation end products (AGEs) in the skin was noninvasively measured in a subset of 60 women. Skin firmness and redness increased with age in women, whereas yellowness increased with age in both sexes. Sebum production and pH levels were significantly lower in the 50s age group than in the 20s age group, particularly in women. TEWL was lower in men in their 50s than in those in their 20s, particularly in the occipital region. A significant reduction in hair density was observed in the 50s age group in both sexes. AGE accumulation in the skin increased with age and was correlated with scalp skin yellowness. Age-related changes in scalp parameters have important implications for hair health and scalp condition. These findings emphasize the importance of considering age and sex when developing hair care strategies.


Clinical trials with the Equator-Plus camera.
The Equator-Plus camera can photograph a 148-degree view of the fundus, measured from the nodal point of the eye. We tested this instrument clinically more than 800 times on over 700 eyes. The large field, which is three to four times that of any conventional fundus camera, is achieved by using a special contact lens as the front element in the camera optics. Photographs taken with the Equator-Plus camera can resolve a lesion as small as one-eighth of a disk diameter, if the contrast is good. Protruding tumors, choroidal or retinal detachment, and extensive disease of the choroid and fundus show up well with this technique. We obtained good pictures in 87% of the clinical tests. We have not observed complications of any kind after photography with the Equator-Plus camera.


Determination of concentration and enantiomeric excess of amines and amino alcohols with a chiral nickel(II) complex.
A chiral N,N'-dioxide-Ni(II) complex was found to exhibit highly enantioselective fluorescent recognition of chiral amines and amino alcohols. It can be used to determine their concentration and ee value. Using a 96-well plate, high-throughput screening for enantiomer discrimination was accomplished.


Effects of Angiotensin Receptor Blockers (ARBs) on In-Hospital Outcomes of Patients With Hypertension and Confirmed or Clinically Suspected COVID-19.
There is an ongoing controversy about harms and benefits of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) in hypertensive patients with coronavirus disease 2019 (COVID-19). Given the unresolved debate, we investigated the association of ARBs with in-hospital outcomes of these patients. In this retrospective observational study, we studied patients with COVID-19 who referred to Sina Hospital in Tehran, Iran, from 20 February to 29 May 2020. Patients with either positive real-time reverse-transcriptase polymerase-chain-reaction test of swab specimens, or high clinical suspicion according to the World Health Organization's interim guidance were included. We followed-up patients for incurring death, severe COVID-19, and in-hospital complications. We evaluated 681 patients with COVID-19 of whom 37 patients were excluded due to incomplete medical records and 8 patients who used ACEIs which left 636 patients in the analysis. In this cohort, 108 (17.0%) patients expired and 407 (64.0%) patients incurred severe COVID-19. Of 254 (39.9%) patients with hypertension, 122 (48.0%) patients were receiving an ARB. After adjustment for possible confounders, we found no independent association between taking ARBs and in-hospital outcomes except for acute kidney injury (AKI), in patients with confirmed or clinically suspected COVID-19, either hypertensive or not-hypertensive. We found that discontinuation of ARBs during hospitalization was associated with a greater risk of mortality, invasive ventilation, and AKI (all P ˂ 0.002). We found that taking ARBs by patients with hypertension and confirmed or clinically suspected COVID-19 is not associated with poorer in-hospital outcomes after adjustment for possible confounders.


Social status and modern-type depression: A review.
Social hierarchy is one of the most influential social structures employed by social species. While dominants in such hierarchies can preferentially access rich resources, subordinates are forced into lower social statuses and lifestyles with inferior resources. Previous studies have indicated that the social rank regulates social behaviors and emotion in a variety of species, whereby individual organisms live within the framework of their ranks. However, in human societies, people, particularly young men, who cannot accept their own social status may show social withdrawal behaviors such as hikikomori to avoid confronting their circumstances. This article reviews the neural mechanisms underlying social status identified in animal studies with rodents and primates, and assesses how social rank affects animal's social behaviors and emotion which may be relevant to modern type depression. Several brain regions such as medial prefrontal cortex are implicated in the formation of animal's social status, which leads to the differences in vulnerability and resilience to social stress. On the basis of these findings, we propose that physical interventions such as voluntary exercise, diet, transcranial direct current stimulation, and psychotherapy, rather than psychotropic drugs, may be useful therapeutic approaches for modern type depression, which is a typical example of social status conflict and a phenotype of adjustment disorder to the traditional hierarchical social order.


High-dose radiotherapy with or without androgen deprivation therapy for intermediate-risk prostate cancer: cancer control and toxicity outcomes.
To evaluate the impact of short-course androgen deprivation therapy (ADT) on cancer control outcomes and toxicity in intermediate-risk prostate cancer treated with dose-escalated external beam radiotherapy (high-dose radiotherapy [HDRT]). Demographic, disease, and treatment characteristics of prostate cancer patients at 2 institution consortiums were charted. Of 296 men with intermediate-risk prostate cancer (defined as ≥T2b, prostate-specific antigen level >10 ng/mL, or Gleason score [GS] of 7, with none of the following: ≥T3, prostate-specific antigen level >20 ng/mL, GS ≥8, or positive nodes) treated with HDRT to a dose of 72 Gy or greater, 123 received short-course ADT and 173 did not. Univariate and multivariate analyses on biochemical failure-free survival (BFFS) (including subset analysis by disease factors) and on overall survival (OS) were performed, as were comparisons of gastrointestinal (GI) and genitourinary (GU) toxicity rates. For the whole group, the median dose was 75.6 Gy; the minimum follow-up was 2 years, and the median follow-up was 47.4 months. For ADT vs. no ADT, the 5-year BFFS rate was 86% vs. 79% (p = 0.138) and the 5-year OS rate was 87% vs. 80% (p = 0.159). On multivariate analysis, percent positive cores (PPC) (p = 0.002) and GS (p = 0.008) were significantly associated with BFFS, with ADT showing a trend (p = 0.055). The impact of ADT was highest in the subsets with PPC greater than 50% (p = 0.019), GS 4+3 (p = 0.078), and number of risk factors greater than 1 (p = 0.022). Only intensity-modulated radiotherapy use (p = 0.012) and GS (p = 0.023) reached significance for OS, and there were no significant differences in GU or GI toxicity. Although the use of ADT with HDRT did not influence BFFS, our study suggests a benefit in patients with PPC greater than 50%, GS 4+3, or multiple risk factors. No OS benefit was shown, and ADT was not associated with additional radiotherapy-related GI or GU toxicity.


Pulmonary emboli from a platelet-rich thrombus attached to a pacemaker electrode.
A patient with recurrent, fatal pulmonary emboli originating from thrombus attached to a permanently-implanted pacemaker electrode is described. While most thromboemboli are composed predominantly of fibrin and erythrocytes, histologic and immunologic studies showed this thrombus to be rich in platelets. A possible therapeutic approach to this rare situation is discussed.


Publisher Correction: A new regulatory mechanism for Raf kinase activation, retinoic acid-bound Crabp1.
An amendment to this paper has been published and can be accessed via a link at the top of the paper.


Decreased plasma levels of metastin in early pregnancy are associated with small for gestational age neonates.
To investigate whether pregnancies with small for gestational age (SGA) neonates, defined as customized birth weight below the 10th centile, are associated with altered levels of metastin in maternal plasma in the first trimester. Maternal blood was obtained between 8 and 14 weeks of pregnancy. Levels of metastin were measured in pregnancies with (n = 31) or without SGA-neonates (n = 31), matched for gestational age at venipuncture. Measurement of beta-hCG was included to study the influence of gestational age and placental volume on plasma levels of the measured markers. Metastin was significantly lower in SGA-pregnancies compared to an equal number of matched uneventful pregnancies (metastin: 1376 +/- 1317 pmol/L vs 2035 +/- 1260 pmol/L, p = 0.035; mean +/- standard deviation). beta-hCG levels were not different. Metastin is significantly lower in maternal plasma in the first trimester, in pregnancies with SGA-neonates. It might therefore be used in combination with other markers for risk estimation of growth impairment in the first trimester.


Myelomatous pleural effusion - Thoracoscopic evaluation of a rare entity.
Multiple myeloma is a malignant neoplasm of plasma cell origin that mainly affects bone marrow and skeletal system, producing large amount of light chain immunoglobulins. Pleural involvement in multiple myeloma is a rare complication which carries very poor prognosis. We report a case of multiple myeloma who presented with recurrent pleural effusion that was evaluated by means of thoracoscopy.


Coexistence in a guild of filter feeding caddis larvae: do different instars act as different species?
Guild structure and coexistence of filter feeding caddis larvae was studied in three lake-outlet streams in northern Finland. Natural stones were used as sampling units, and for each stone measurements of six microhabitat variables were taken. Species and species instar relationships in the multivariate microhabitat space were analyzed by a method based on Principal Components Analysis. Seven species of filtering caddis larvae were found at the study sites, but detailed analysis was restricted to the four most abundant ones (Polycentropus flavomaculatus, Hydropsyche angustipennis, H. pellucidula, H. saxonica). P. flavomaculatus was the microhabitat generalist of the guild, whereas all the hydropsychids were narrowly specialized in at least one larval instar. In all species, different instars utilized the microhabitat somewhat differentially. Moss content and Froude number were significantly different between instar microhabitats in all comparisons. Ontogenetic niche changes not only separated species instars from each other, but also profoundly changed the biotic as well as abiotic environment of the species at different phases of larval development. This may have important effects on the dynamics of interacting species and, consequently, on the guild structure. While some of the more classical models of coexistence may also be relevant for understanding coexistence in this guild of sessile stream insects, ontogenetic niche changes clearly need to be taken into consideration in future studies of guild structure and species interactions of filter feeding caddisfly larvae.


Chemical components and emulsification properties of mucilage from Dioscorea opposita Thunb.
The properties of mucilage obtained from Dioscorea opposita, generated during industrial manufacturing were investigated in this study. Characteristics such as monosaccharide content, amino acid content, molecular weight, and structural features were measured, whereas morphology was observed using a scanning/transmission electron microscope. Additionally, emulsification properties at different concentrations (0.2%, 0.4%, 0.6%, 0.8%, and 1.0%) and under acidic and basic pH (5.0 and 9.0) conditions were studied. The results showed that emulsions prepared from mucilage and medium-chain triglycerides presented more effective emulsifying functions and higher stability, especially at low concentrations. Both, acidic and basic conditions improved the overall emulsification properties, which suggested that the isoelectric point of amino acids may be involved in the emulsification properties. The results of this study show that mucilage from Dioscorea opposita can be considered as a sustainable resource of a natural emulsifier obtained from industrial waste.


VEGF165 expression in the tumor microenvironment influences the differentiation of bone marrow-derived pericytes that contribute to the Ewing's sarcoma vasculature.
We previously demonstrated that bone marrow (BM) cells migrate to Ewing's tumors and differentiate into endothelial cells within the tumor vasculature. Recent evidence suggests that the roles of BM cells in tumors are more diverse. We investigated whether non-endothelial cell types critical for tumor vessel development are also derived from migrated BM cells. We utilized BM transplantation with GFP(+) transgenic mice as BM donors and nude mice as recipients to track the fate of migrated BM cells. After engraftment, we injected recipient mice either subcutaneously or intramuscularly with Ewing's sarcoma cells. We labeled functional tumor vessels using intravascular perfusion staining with tomato lectin. We assessed BM cell recruitment/differentiation within the tumor microenvironment using immunohistochemistry. Ewing's tumors contained BM-derived cells that had differentiated into endothelial cells lining perfused tumor vessels. A substantial fraction of recruited BM cells also resided in the vessel vicinity and expressed desmin and PDGFR-beta, indicating smooth muscle cell differentiation. In order to further characterize the role of stem/progenitor cells in Ewing's sarcoma, we sorted Tie2(-) BM cells from Tie2-GFP transgenic mice and then injected them intravenously into Ewing's tumor-bearing mice. Tie2(-) BM progenitors migrated to Ewing's tumors and differentiated into Tie2(+) cells occupying a perivascular residence and expressing alpha-smooth muscle actin, desmin and PDGFR-beta, as well as VEGFR-2. We did not observe differentiation of Tie2(-) cells into Tie2(+) perivascular cells in VEGF(165)-inhibited TC/siVEGF(7-1) tumors. The differentiation of Tie2(-) BM cells into Tie2(+) cells in parental but not VEGF(165)-inhibited tumors indicates that the tumor microenvironment may influence the differentiation pathway.


Chemogenetics revealed: DREADD occupancy and activation via converted clozapine.
The chemogenetic technology DREADD (designer receptors exclusively activated by designer drugs) is widely used for remote manipulation of neuronal activity in freely moving animals. DREADD technology posits the use of "designer receptors," which are exclusively activated by the "designer drug" clozapine N-oxide (CNO). Nevertheless, the in vivo mechanism of action of CNO at DREADDs has never been confirmed. CNO does not enter the brain after systemic drug injections and shows low affinity for DREADDs. Clozapine, to which CNO rapidly converts in vivo, shows high DREADD affinity and potency. Upon systemic CNO injections, converted clozapine readily enters the brain and occupies central nervous system-expressed DREADDs, whereas systemic subthreshold clozapine injections induce preferential DREADD-mediated behaviors.


Concise Review: Fluorescent Reporters in Human Pluripotent Stem Cells: Contributions to Cardiac Differentiation and Their Applications in Cardiac Disease and Toxicity.
In the last decade, since the first report of induced pluripotent stem cells, the stem cell field has made remarkable progress in the differentiation to specialized cell-types of various tissues and organs, including the heart. Cardiac lineage- and tissue-specific human pluripotent stem cell (hPSC) reporter lines have been valuable for the identification, selection, and expansion of cardiac progenitor cells and their derivatives, and for our current understanding of the underlying molecular mechanisms. In order to further advance the use of hPSCs in the fields of regenerative medicine, disease modeling, and preclinical drug development in cardiovascular research, it is crucial to identify functionally distinct cardiac subtypes and to study their biological signaling events and functional aspects in healthy and diseased conditions. In this review, we discuss the various strategies that have been followed to generate and study fluorescent reporter lines in hPSCs and provide insights how these reporter lines contribute to a better understanding and improvement of cell-based therapies and preclinical drug and toxicity screenings in the cardiac field.


Evaluation of selected parameters of immune response to rubella virus, hepatitis B virus and varicella-zoster virus infections in children born to mothers after kidney or liver transplantation.
The immune status of children exposed prenatally to immunosuppressants is not fully understood. A single-center study evaluated possible differences in antibody levels between children prenatally exposed to immunosuppressants born to mothers after hepatic or kidney transplantation (study group) compared to children without prenatal exposure to immunosuppressants (control group). Children from the study and control group were age-matched at the time of the examination and gestational age-matched, so as to obtain similar stages of the vaccination schedule and to enable reliable comparison of the results. The selection of children was made in a 1:1 ratio. The study population, a total of 138 children, was divided according to the age of the children at the time of the study into three age groups: newborns, infants (from 29 days to 1 year) and children aged >1 year. Immunoenzymatic tests were used to analyze the titers of the chickenpox virus (VZV-IgG), rubella (RuV-IgG) and hepatitis B virus (HBV, HBsAb). The studied differences were compared depending on the age group and the immunosuppressive regimen used by the pregnant mother. In neonates born to mothers after liver transplantation, significant differences were found in HBsAb levels (>250 mIU/ml) compared to newborns without prenatal exposure to immunosuppressants taken by pregnant mothers (11/16, 69% vs. 4/14, 29%, respectively; p = .028). A similar difference in the level of HbsAb was no longer noted at later stages of children's lives. In infants, these values were 80% (4/5) vs. 33% (2/6), and in children over 1 year of age 15% (7/48) vs. 12% (6/49), respectively. No other significant differences were noted when compared the distribution of measured parameters of VZV and RuV in both analyzed groups (children of mothers after kidney or liver transplantation chronically treated with immunosuppression and children without prenatal exposure to immunosuppression). Prenatal exposure to immunosuppressive therapy does not appear to affect VZV, RuV and HBV antibody levels in children of mothers who have had a kidney or liver transplant. Initially elevated HBSAb levels in newborns of mothers after liver transplantation are not observed in later stages of life.


Characterization of the novel HLA-DPB1*04:01:42 allele by sequencing-based typing.
HLA-DPB1*04:01:42 differs from HLA-DPB1*04:01:01:05 by one nucleotide substitution in codon 178 in exon 3.


Corrections to the human mitochondrial ribosomal RNA sequences.
Two new errors and one consensus change were identified in the human mitochondrial Cambridge consensus sequence. The errors are an A to G substitution at nucleotide 750 in the 12S rRNA gene and a single nucleotide deletion at nt 3107 in the 16S rRNA gene. The consensus change is nt 2706 A-->G in the 16S rRNA gene.


The Relation of Calcium Volume Score and Stenosis of Carotid Artery.
The aim of this study was to investigate the value of extracranial carotid artery calcium score in predicting severity of carotid arterial stenosis. 200 patients who had indication of contrast neck multi detector computed tomography were included. Calcium volume score of each calcified plaque (density more than 130 HU) was determined by multiplying area of calcified plaque in slice increment and presented as cubic centimeter (cc). Calcium score of each side (right or left) and each patient were determined. Severity of carotid stenosis in axial images was estimated and categorized. Statistical analysis was performed. 87 cases were female with mean age of 58.90 ± 10.67 and 113 cases were male with mean age of 59.61 ± 11.89 years old. The mean of volume score for all evaluated 800 vessels was .079 ± .046 cc. There was no significant difference between calcium score of right and left side (P value = .16). The mean "patient score" was .080 ± .049 cc (range: 0-.15 cc).Nine patients had volume score of 0 and all of them had no evidence of luminal stenosis. Significant increase in severity of stenosis was seen with increase in "patient score".(P value < .001, r = .875).According to receiver operating characteristic analysis, "patient score" of .09 cc with sensitivity of 97% and "patient score" of .12 cc with sensitivity of 95% can predict 50% and 70% stenosis, respectively. Promising role of calcium score for predicting severity of carotid stenosis could be considered.


Anatomic reconstruction of the lateral ligaments using allograft tendon and suspensory fixation for chronic lateral ankle instability with poor remnant quality: results and complications.
Treatment of chronic lateral ankle instability (CLAI) with poor remnant quality is challenging. The aim of the present study was to evaluate clinical results and complications of anatomic reconstruction of the lateral ligaments using allograft tendon and suspensory fixation in the treatment of such patients. One hundred and eight patients with CLAI, who were treated surgically using anatomic reconstruction with allograft tendon and suspensory fixation between April 2016 and January 2018 at our hospital, were retrospectively analysed. None of the patients had sufficient ligament remnants for the modified Broström procedure during the intraoperative evaluation. Eighteen patients were excluded. Seventeen patients were lost to follow-up and 73 patients completed the study. The mean duration of instability symptoms was 39.1 months (range, 6-480 months). The mean follow-up time was 57.5 months (range, 48-69 months). Clinical results were evaluated using the Karlsson scoring scale, American Orthopaedic Foot and Ankle Society-Ankle and Hindfoot (AOFAS-AH) score, visual analogue scale (VAS), patients' subjective satisfaction, and incidence of complications. Mechanical stability was evaluated using the varus talar tilt angle (TTA) and anterior talar displacement (ATD). The AOFAS-AH scores significantly improved from 67.7 ± 8.5 points to 89.8 ± 9.5 (p < 0.001). The Karlsson scoring scales evolved from 58.8 ± 16.5 to 88.4 ± 11.2 (p < 0.001). VAS scores significantly decreased from 2.9 ± 1.3 to 1.1 ± 1.0 (p < 0.001). On stress radiographs, TTA decreased from 15.1 ± 2.5 degrees to 5.8 ± 2.1 degrees (p < 0.001), whereas ATD reduced from 13.4 ± 2.9 mm to 5.7 ± 1.5 mm (p < 0.001). Patients' subjective satisfaction indicated 46 excellent, 20 good, 5 fair, and 2 bad results. Postoperatively, 15 cases (20.5%) did not achieve complete relief of discomfort or swelling, 9 cases (12.3%) experienced joint stiffness or decreased range of motion, and 6 cases (8.2%) had soft tissue irritation. Residual instability and reoperation are rare. Allograft rejection or wound infection was not observed. For the CLAI patients with poor remnant quality, anatomic reconstruction of the lateral ligaments using allograft tendon and suspensory fixation is an effective procedure, while the top three complications in incidence were residual discomfort, joint stiffness, and soft tissue irritation. Level IV, retrospective case series.


Autoregulatory Management in Traumatic Brain Injury: The Role of Absolute Pressure Reactivity Index Values and Optimal Cerebral Perfusion Pressure Curve Shape.
The aim of this study was to investigate if the absolute pressure reactivity index (PRx) value influenced the association between cerebral perfusion pressure (CPP) and outcome and if the optimal CPP (CPPopt) curve shape influenced the association between deviation from CPPopt and outcome in traumatic brain injury (TBI). We included 383 TBI patients treated at the neurointensive care in Uppsala between 2008 and 2018 with at least 24 h of CPP data. To determine the influence of absolute PRx values on the association between absolute CPP and outcome, the percentage of monitoring time for combinations of CPP and PRx were correlated with outcome (Extended Glasgow Outcome Scale [GOS-E]) in a heatmap. To determine the association between CPP and the relatively best PRx (CPPopt), the percentage of monitoring time of ΔCPPopt (actual CPP-CPPopt) ±5 mm Hg was analyzed in relation to GOS-E. To determine the association between CPP and the relatively best PRx within a certain absolute PRx range (curve shape), both the percentage of ΔCPPopt within the absolute limits of reactivity (PRx <0.00, < 0.15, etc.) and within certain confidence intervals of PRx-deterioration (+0.025, +0.05 etc.) from CPPopt were analyzed in relation to GOS-E. The heatmap of PRx and absolute CPP versus outcome indicated that the CPP range (55-75 mm Hg) associated with favorable outcome was wider when PRx was below 0, whereas the upper CPP-threshold decreased as PRx increased. CPPopt could be calculated during 53% of the monitoring time. Higher percentage of monitoring time with ΔCPPopt ±5 mm Hg, ΔCPPopt within the reactivity-thresholds (PRx <0.30), and ΔCPPopt within the PRx-confidence interval +0.025 were all independently associated with favorable outcome in separate logistic regressions. These regressions had similar area under receiver operating curve and were not superior to a similar regression when the CPPopt-target was replaced by the percentage of monitoring time within the traditional fixed CPP-targets 60 to 70 mm Hg. Individualized CPPopt-targets exhibited a comparable outcome association as traditional CPP targets and different definitions of the best CPPopt range based on the PRx value had a limited effect on the association between deviation from CPPopt and outcome. Since CPPopt could only be calculated during half of the time, an alternative approach would be to assess the absolute PRx to anticipate a safe CPP range.


Views on Augmented Reality, Virtual Reality, and 3D Printing in Modern Medicine and Education: A Qualitative Exploration of Expert Opinion.
Although an increased usage and development of 3D technologies is observed in healthcare over the last decades, full integration of these technologies remains challenging. The goal of this project is to qualitatively explore challenges, pearls, and pitfalls of AR/VR/3D printing applications usage in the medical field of a university medical center. Two rounds of face-to-face interviews were conducted using a semi-structured protocol. First an explorative round was held, interviewing medical specialists (8), PhD students (7), 3D technology specialists (5), and university teachers (3). In the second round, twenty employees in high executive functions of relevant departments were interviewed on seven statements that resulted from the first interviewing round. Data analysis was performed using direct content analyses. The first interviewing round resulted in challenges and opportunities in 3D technology usage that were grouped in 5 themes: aims of using AR/VR/3D printing (1), data acquisition (2), data management plans (3), software packages and segmentation tools (4), and output data and reaching end-user (5). The second interviewing round resulted in an overview of ideas and insights on centralization of knowledge, improving implementation of 3D technology in daily healthcare, reimbursement of 3D technologies, recommendations for further studies, and requirement of using certified software. An overview of challenges and opportunities of 3D technologies in healthcare was provided. Well-designed studies on clinical effectiveness, implementation and cost-effectiveness are warranted for further implementation into the clinical setting.


[The experimental validation of a method for the intraoperative assessment of the degree of severity of pancreonecrosis].
In the experiment on 35 dogs, it was established that the normal pancreas had constant bioimpedance parameters: ohmic resistance, polarization coefficient and capacitance. In development of pancreonecrosis, the capacitance increases, and the ohmic resistance and polarization coefficient decrease.


Nutritional Considerations for the Neonate With Congenital Heart Disease.
The importance of nutrition in managing critically ill infants with congenital heart disease (CHD) is foundational to optimizing short- and long-term health outcomes. Growth failure and malnutrition are common in infants with CHD. The etiology of growth failure in this population is often multifactorial and may be related to altered metabolic demands, compromised blood flow to the intestine leading to nutrient malabsorption, cellular hypoxia, inadequate energy intake, and poor oral-motor skills. A dearth of high-quality studies and gaps in previously published guidelines have led to wide variability in nutrition practices that are locally driven. This review provides recommendations from the nutrition subgroup of the Neonatal Cardiac Care Collaborative for best evidence-based practices in the provision of nutritional support in infants with CHD. The review of evidence and recommendations focused on 6 predefined areas of clinical care for a target population of infants <6 months with CHD admitted to the ICU or inpatient ward. These areas include energy needs, nutrient requirements, enteral nutrition, feeding practice, parenteral nutrition, and outcomes. Future progress will be directed at quality improvement efforts to optimize perioperative nutrition management with an increasing emphasis on individualized care based on nutritional status, cardiorespiratory physiology, state of illness, and other vulnerabilities.


A stroke -- or something else?
The patient -- who'd had a CVA the year before -- was experiencing numbness and weakness in her right leg and foot, and had an increasingly unsteady gait. Initial lab work provided no clues.


Free and decomplexed human immunodeficiency virus p24 antigenaemia in black patients with AIDS and AIDS-related disorders.
To determine the clinical signification of free and decomplexed p24 antigenaemia in HIV1-infected black individuals. Sixty African patients with pre-AIDS (n = 12) and AIDS (n = 48), hospitalized in the Centre National Hospitalier Universitaire de Bangui, Central African Republic, were prospectively included. 15 HIV1-seronegative healthy African subjects served as controls. Serum p24 antigenaemia was detected using a polyclonal and a monoclonal sandwich enzyme immunoassay (EIA). All sera were tested again after acid pretreatment (45 mn incubation of serum with a 0.5 N solution of HCl at +37 degrees C). The polyclonal EIA and the monoclonal EIA detected respectively four (7%) to six (10%) free p24 antigen positive samples from the HIV1-infected individuals, with a similar frequency in pre-AIDS and AIDS patients. None of the controls were found p24 antigen positive. After acid pretreatment, the rate of detectable p24 antigenaemia increased significantly, leading with the monoclonal EIA to a 47% positivity rate (p < 0.001), and the patients with AIDS became more frequently p24 antigen positive (54%), than the patients with pre-AIDS (17%) (p = 0.02). Detectable p24 antigenaemia in HIV1-infected African subjects could be obtained in nearly half of cases by increasing the sensitivity of the assay using monoclonal EIA and acid hydrolysis of circulating immune complexes. Decomplexed p24 antigenaemia in HIV1-infected Black African patients could have predictive signification similar to free p24 antigenaemia in Caucasians.


Female urinary incontinence--consultation behaviour and patient experiences: an epidemiological survey in a Norwegian community.
The objective was to study explanatory factors for help-seeking among incontinent women, and what was the outcome of the treatment. A questionnaire was mailed to all 2366 women aged 20 or over in the rural community of Rissa, Norway. Women confirming incontinence gave information about duration, precipitating factors, frequency, amount of leakage, and impact. Questions about doctor consultation or planned consultation, treatment and results were included. Women with incontinence which had resolved without treatment were also recorded. A total of 77% answered the questionnaire. Twenty per cent of women with incontinence (n = 535) had consulted a doctor, 18% had planned to consult. Increasing age and duration, and urge/mixed type of incontinence were determinative factors for doctor consultation, while increasing severity and impact were determinative for planned consultation. Drugs, exercises, pads, and electrostimulation were all important treatment options: 21% were cured, 40% much better after treatment. Of all the women, 8% reported that they had been incontinent in the past, and only 18% of these had consulted a doctor.


Antiviral activity of PHA767491 against human herpes simplex virus in vitro and in vivo.
Herpes simplex virus (HSV) is a common human pathogen that causes a variety of diseases, including oral-labial, genital lesions and life-threatening encephalitis. The antiviral nucleoside analogues such as acyclovir are currently used in anti-HSV therapies; however, clinical overuse of these drugs has led to the emergence of drug-resistant viral strains. Hence, there is an urgent need to develop new anti-HSV agents. To identify novel anti-HSV-1 compounds, we screened the LOPAC small scale library of 1280 bioactive compounds to identify inhibitors of HSV-1-induced necroptosis. Further experiments including western blot analysis, Q-PCR analysis and immunohistochemistry were performed to explore the antiviral mechanism of the compounds. Here, we identified PHA767491 as a new inhibitor of HSV. PHA767491 potently blocked the proliferation of HSV in cells, as well as HSV induced cell death. Further, we found that PHA767491 strongly inhibited HSV infection post viral entry. Moreover, PHA767491 reduced the expression of viral genes required for DNA synthesis including UL30/42 DNA polymerase and UL5/8/52 helicase-primase complex. The essential immediate early (IE) genes such as ICP4 and ICP27 are critical for the expression of the early and late genes. Of note, PHA767491 inhibited the expression of all IE genes of both HSV-1 and HSV-2. Importantly, PHA767491 reduced viral titers in the tissues from the mice infected with HSV-1. Consistently, immunohistochemistry analysis showed that PHA767491 dramatically attenuated expression of viral protein gB in the livers. Taken together, PHA767491 has potent anti-HSV activity by inhibiting viral replication both in vitro and in mouse model. Thus, PHA767491 could be a promising agent for the development of new anti-HSV therapy.


Thyroid hormones in milk and blood of lactating donkeys as affected by stage of lactation and dietary supplementation with trace elements.
The traditional utilization of donkeys (Equus asinus) as dairy animals has recently attracted substantial scientific interest with regard to human nutrition. Donkey milk is well tolerated by infants with cows' milk allergy, useful in the treatment of human immune-related diseases, in the prevention of atherosclerosis, and in-vitro studies showed an anti-proliferative effect. Active 3-3'-5-triiodothyronine (T3) in colostrum and milk could play different physiological roles, systemic and paracrine, for both the mother and the suckling offspring. The aim was to evaluate whether thyroid hormones (TH) concentrations in milk and blood of lactating donkeys change with the advancing lactation and whether they can be affected by dietary supplementation with several trace elements, some of them directly involved with TH synthesis (I), metabolism (Se) and action (Zn). Sixteen lactating jennies were divided into two groups (CTL and TE). Mixed feed for TE was added with Zn, Fe, Cu, Mn, I, Se and Co. Every 2 weeks milk and blood samples were collected at 11·00. Total concentrations of T3 in milk (T3M) and T3 and T4 in plasma (T3P and T4P) were assayed using ELISA kits, validated for the donkey species. T3M was not correlated with TH concentrations in blood, did not change with the stage of lactation, and was significantly higher in TE (4·09 ± 0·07 ng/ml, mean ± SE) than in CTL group (3·89 ± 0·08 ng/ml). T4P (81·8 ± 5·2 ng/ml) and T3P (15·2 ± 1 ng/ml) significantly changed with time, but were not significantly affected by dietary treatment. T3P/T4P ratio was significantly lower in TE group. This study indicates that in donkey milk the concentration of T3, a human-like bioactive compound, can be affected by trace elements intake.


Epigenetic synergy between decitabine and platinum derivatives.
Aberrant epigenetic silencing of tumor suppressor genes has been recognized as a driving force in cancer. Epigenetic drugs such as the DNA methylation inhibitor decitabine reactivate genes and are effective in myeloid leukemia, but resistance often develops and efficacy in solid tumors is limited. To improve their clinical efficacy, we searched among approved anti-cancer drugs for an epigenetic synergistic combination with decitabine. We used the YB5 cell line, a clonal derivative of the SW48 colon cancer cell line that contains a single copy of a hypermethylated cytomegalovirus (CMV) promoter driving green fluorescent protein (GFP) to screen for drug-induced gene reactivation and synergy with decitabine. None of the 16 anti-cancer drugs tested had effects on their own. However, in combination with decitabine, platinum compounds showed striking synergy in activating GFP. This was dose dependent, observed both in concurrent and sequential combinations, and also seen with other alkylating agents. Clinically achievable concentrations of carboplatin at (25 μM) and decitabine reactivated GFP in 28 % of the YB5 cells as compared to 15 % with decitabine alone. Epigenetic synergy was also seen at endogenously hypermethylated tumor suppressor genes such as MLH1 and PDLIM4. Genome-wide studies showed that reactivation of hypermethylated genes by the combination was significantly better than that induced by decitabine alone or carboplatin alone. Platinum compounds did not enhance decitabine-induced hypomethylation. Rather, we found significantly inhibited HP1α expression by carboplatin and the combination. This was accompanied by increased histone H3 lysine 4 (H3K4) trimethylation and histone H3 lysine 9 (H3K9) acetylation at reactivated genes (P < 0.0001) and reduced occupancy by methyl-binding proteins including MeCP2 and methyl-CpG-binding domain protein 2 (MBD2) (P < 0.0001). Our results suggest that the combination of decitabine with platinum analogs shows epigenetic synergy that might be exploited in the treatment of different cancers.


Insights into product design students' perception of, and engagement with, creativity in design education.
Creativity is acknowledged as an essential component of the design process and considered a key design graduate attribute. Despite this assertion, several studies have highlighted that the teaching of creativity in design education is often implicit rather than explicit. Moreover, there is a paucity of research on product design students' experience of creativity in design education, leaving a gap in knowledge relevant to how creativity may be better fostered in design education. In this study, reflexive thematic analysis was used to analyse the data from online focus groups conducted with product design students. The three themes constructed provide insights into how students perceive and engage with creativity. Theme 1, the influence of social factors on creativity, uncovers the diametric effect students' social eco-system can have on their creativity. These include an aversion to being associated with it due to weight of expectation and negative perceptions around creativity, as well as the 'invisible support system' created by peers. Theme 2, sanctuary seeking tendencies of novice design students, reveals behaviours that oppose essential creative attributes: a freedom from risk and ambiguity and desire for certainty and achievability. Theme 3, tension between passion for and pursuit of creativity, outlines the conflict between participants' ideologies and actions when pursuing creativity highlighting a reluctance to utilise structured creativity tools while gravitating towards unstructured methods such as 'relaxed attention'. Together, the three themes form a picture of product design students' complex relationship with creativity and importance of self-efficacy. The findings of this study make an important contribution to our understanding of design students' perception of, and engagement with, creativity in design education. As such these findings are relevant for both design education and future creativity tool development.


Therapeutic effect of traditional Chinese medicine on coagulation disorder and accompanying intractable jaundice in hepatitis B virus-related liver cirrhosis patients.
To observe the therapeutic effects of new traditional Chinese medicine (TCM) therapy on coagulation disorder and accompanying intractable jaundice in HBV-related liver cirrhosis patients. Using stratified random sampling according to fibrinogen (Fib) levels, 145 liver cirrhosis patients due to hepatitis B complicated by coagulation disorder were treated. Of them, 70 in research group were treated with TCM by "nourishing yin, cooling blood and invigorating blood circulation" and Western medicine, 75 in control group were treated with conventional Western medicine. The indexes of liver function, coagulation function and bleeding events were observed and compared. The prothrombin time (PT) was shorter and the fibrinogen (Fib) level was higher in the research group than in the control group (Fib = 1.6-2.0 g/L, 1.1-1.5 g/L, and < or = 1.0 g/L). The total bilirubin (TBIL) level was significantly lower in the research group than in the control group, except for the subgroup of FIB < or = 1.0 g/L. TCM therapy can improve coagulation fuction and decrease TBIL.


Two types of inflammatory vascular disease in Sjögren's syndrome. Differential association with seroreactivity to rheumatoid factor and antibodies to Ro (SS-A) and with hypocomplementemia.
Two types of inflammatory vascular disease (IVD) occur in Sjögren's syndrome: neutrophilic IVD (NIVD) and mononuclear IVD (MIVD). In 45 patients with Sjögren's syndrome, we examined the 2 types of IVD with respect to serologic associations. NIVD, unlike MIVD, was significantly associated with seroreactivity reflected by hyperglobulinemia (P = 0.01), rheumatoid factor (P = 0.002), antinuclear antibodies (P = 0.02), and antibodies to Ro (SS-A) (P = 0.00006), and with hypocomplementemia (P = 0.03). The differential association of the 2 types of IVD with serologic reactivity and hypocomplementemia suggests that there may be basic differences in the immunopathogenesis of these 2 forms of IVD in Sjögren's syndrome.


Invasive Pneumococcal Disease Following the Introduction of 13-Valent Conjugate Vaccine in Children in New York City From 2007 to 2012.
Invasive pneumococcal disease (IPD) is a leading cause of pneumonia, meningitis, and bacteremia in children. In March 2010, a 13-valent pneumococcal conjugate vaccine (PCV13) was introduced to the routine childhood immunization schedule. The PCV13 contains 6 serotypes not included in the previously recommended 7-valent pneumococcal conjugate vaccine, including serotype 19A, the predominant cause of IPD prior to the introduction of PCV13. To describe changes in the epidemiology and incidence of IPD in children younger than 5 years in New York City (NYC) after the introduction of PCV13 and assess PCV13 coverage in NYC. Retrospective analysis of population-based IPD surveillance data of the general population residing in NYC between January 1, 2007, and December 31, 2012. Invasive pneumococcal disease cases were identified by laboratory reporting of positive pneumococcal cultures from a normally sterile body site in NYC residents younger than 5 years. Isolates were serotyped. Participants included 468 cases younger than 5 years with IPD reported through routine surveillance to the NYC Department of Health and Mental Hygiene. Absolute differences and percentage changes in IPD incidence before and after the introduction of PCV13 by serotype grouping, age, and race/ethnicity. The number of PCV13 doses administered to children younger than 5 years was calculated using the NYC immunization information system. There were 468 IPD cases from 2007 to 2012. The incidence of IPD decreased by 69.6% (95% CI, -79.3% to -55.5%) from 21.0 cases per 100 000 (2007-2009 mean) pre-PCV13 to 6.4 cases per 100 000 (2011-2012 mean) post-PCV13. Estimates of disease caused by serotypes included in the PCV13 decreased by 82.5% (95% CI, -90.0% to -69.3%), including a 79.7% reduction in serotype 19A (95% CI, -89.0% to -62.4%). Reductions in IPD incidence were seen in all age groups, with the largest reduction in children younger than 12 months (80.4%; P = .005). Incidence decreased significantly in all racial/ethnic groups. The percentage of children younger than 5 years in NYC with 1 or more doses of PCV13 increased from 47.8% in 2010 to 89.8% in 2012. The incidence of IPD in NYC children younger than 5 years and, particularly, the incidence of IPD caused by serotype 19A decreased dramatically following the introduction of PCV13, with reductions among all age and racial/ethnic groups. This represents a significant achievement for public health immunization programs and underscores the importance of achieving high immunization coverage.


Physical properties and in vivo bioavailability in human volunteers of isradipine using controlled release matrix tablet containing self-emulsifying solid dispersion.
Poorly water-soluble drug with a short half-life such as isradipine (IDP) offer challenges in the controlled release formulation because of low dissolution rate and poor bioavailability. Self-emulsifying solid dispersions (SESD) of IDP consisted of surfactant and fatty acid in poloxamer 407 (POX 407) as a carrier and were manufactured by the melting method. Then, controlled release HPMC matrix tablet containing SESD were prepared via direct compression. The dissolution behaviors and in vivo bioavailability of controlled release matrix tablet in healthy human volunteers were investigated. The physical properties of solid dispersion were also examined using differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD) and scanning electron microscopy (SEM). It was shown that structure of IDP was amorphous in the solid dispersion. The dissolution rate of IDP from SESD was markedly enhanced because of increased solubility and wetting effect. Controlled release HPMC matrix tablets containing SESD released drug in a controlled manner and were stable during storage over 3 months at 40 °C/75% RH. Furthermore, the tablet containing 5mg IDP SESD showed significantly increased oral bioavailability and extended plasma concentration compared with the marketed 5 mg Dynacirc(®) capsule. A combined method of solid dispersion and controlled release technology could provide versatile dosage formulations containing IDP with poor water solubility and short half-life.


A novel tripodal colorimetric and fluorescence "turn on" chemosensor for AcO(-) and F(-) anions in CH3CN.
A novel chemosensor, 3',3‴,3‴″-(((nitrilotris(ethane-2,1-diyl))tris(azanylylidene))tris(methanylylidene))tris(4-hydroxy-4'-biphenylcarbonitrile) (L) was synthesized and characterized by the combination of (1)H,(13)C, APT, COSY NMR, FT-IR, and elemental analysis. The behavior of the receptor (L) toward different anions was investigated using UV-visible and fluorescence spectroscopy. The receptor (L) indicated an efficient colorimetric "naked-eye" and "turn on" fluorescent response for fluoride and acetate in CH3CN, respectively.


Benefit of an electronic head-mounted low vision aid.
To evaluate the efficacy of electronic head-mounted low vision aid (e-LVA) SightPlus (GiveVision, UK, givevision.net) and to determine which people with low vision would see themselves likely using an e-LVA like this. Sixty participants with low vision aged 18 to 93 used SightPlus during an in-clinic study session based on a mixed methods design. Visual acuity (ETDRS), contrast sensitivity (Pelli-Robson) and reading performance (MNREAD) were measured binocularly at baseline (no device), with the device in 'normal' mode (zoom only), and with preferred enhanced mode (zoom and one of four digital image enhancements). At the end of the session, a short questionnaire recorded willingness to use an e-LVA like SightPlus, potential use cases, positive/negative comments and adverse effects. Binocular distance visual acuity improved significantly by 0.63 logMAR on average (p < 0.0001) to 0.20 logMAR. Contrast sensitivity improved significantly by 0.22 log units (p < 0.0001) to 1.21 log units with zoom only and by 0.40 log units to 1.37 log units with zoom and preferred image enhancement. Reading performance improved significantly for near visual acuity and critical print size (p < 0.015), although reading speed significantly decreased (p < 0.0001). Nearly half (47%) of the participants indicated they would use an e-LVA like SightPlus, especially for television, reading and entertainment (e.g. theatre). Multivariate logistic regression showed that proportion of lifetime affected by sight loss, baseline contrast sensitivity and use of electronic LVAs explained 41% of the variation in willingness to use. SightPlus improves visual function in people with low vision and would be used in its current form by one half of the people who tried it. Adverse effects were infrequent and resolved when the device was removed. Future work should focus on comparing e-LVAs through repeatable real-world tasks and impact on quality of life.


Do written diagnosis-treatment recommendations on microbiological test reports improve the management of Staphylococcus aureus bacteremia? A single-center, retrospective, observational study.
The objective of this study was to assess the impact of microbiological test reports that provide specific written recommendations on the appropriate management of Staphylococcus aureus bacteremia (SAB). We performed a retrospective analysis of laboratory and clinical data of all SAB patients treated at one German University hospital, 2012-2015. Among 467 included patients, methicillin-resistant S. aureus (MRSA) accounted for 15.2% of all SAB cases. All-cause in-hospital mortality was 25.2%, and was significantly elevated in individuals aged >55 years, in MRSA bacteremia and if the source of infection remained unidentified. Focus identification was achieved in 71.1%, with the most prevalent foci being catheter-associated bloodstream infection (23.1%), soft tissue infection (15.4%), osteomyelitis (5.1%) and endocarditis (4.9%). Standardized written recommendations on microbiological test reports led to a significant increase of transesophageal echocardiography, additional imaging studies for focus identification and more frequent follow-up blood cultures, but no significant effect on mortality was observed.


Fatty acids in colostrum from mothers of children at high risk of atopy in relation to clinical and laboratory signs of allergy in the first year of life.
It remains controversial whether fatty acid (FA) composition of breast milk relates to development of atopy in the infant. This study evaluates FA in colostrum from mothers of children at high risk of atopy in association with atopy at the age of 1 year. The FA of colostrum were analyzed for 218 children (60 with low birth weight between 1500 and 2500 g, 84 with a history of maternal atopy, and 74 with an elevated cord blood immunoglobulin (Ig)E of >0.9 IU/ml). Total lipids were extracted, methylated and separated by gas-liquid chromatography. Laboratory screening for allergic sensitization and clinical examination took place within the Leipzig Allergy Risk Children's Study (LARS). Low birth weight was correlated with low percentage levels of 20:2n-6, 22:2n-6, and 22:3n-3 (r = 0.14, P < 0.05; r = 0.14, P < 0.05 and r = 0.20, P < 0.01, respectively) and low gestational age at birth was correlated with low 22:3n-3 (r = 0.15, P < 0.05). There was no association between FA and atopic eczema at the age of 1 year. However, high linoleic acid (LA, 18:2n-6) was linked to high specific IgE against cow's milk protein (P < 0.05), and low docosapentaenoic acid (DPA, 22:5n-3) was associated with elevated total serum IgE (P < 0.05) at the age of 1 year, respectively. The polyunsaturated fatty acid composition of colostrum in a high risk newborn population shows associations with atopic sensitization at the age of 1 year and may be predictive for later atopic disease.


A symplectic pseudospectral method for nonlinear optimal control problems with inequality constraints.
A symplectic pseudospectral method based on the dual variational principle and the quasilinearization method is proposed and is successfully applied to solve nonlinear optimal control problems with inequality constraints in this paper. Nonlinear optimal control problem is firstly converted into a series of constraint linear-quadratic optimal control problems with the help of quasilinearization techniques. Then a symplectic pseudospectral method based on dual variational principle for solving the converted constrained linear-quadratic optimal control problems is developed. In the proposed method, inequality constraints which can be functions of pure state, pure control and mixed state-control are transformed into equality constraints with the help of parameteric variables. After that, state variables, costate variables and parametric variables are interpolated locally at Legendre-Gauss-Lobatto points. Finally, based on the parametric variational principle and complementary conditions, the converted problem is transformed into a standard linear complementary problem which can be solved easily. Numerical examples show that the proposed method is of high accuracy and efficiency.


METTL3 promotes colorectal cancer metastasis by stabilizing PLAU mRNA in an m6A-dependent manner.
Colorectal cancer (CRC) is one of the most common tumors and ranks second in tumor mortality. N6-methyladenosine (m6A) modification is the most prevalent RNA modification in eukaryotes. As the critical m6A methyltransferase, the role of METTL3 in the metastasis regulation of CRC might be controversial and need to be further explored. In this study, we confirmed that METTL3 could promoted CRC metastasis in vitro and in vivo. METTL3 was upregulated in CRC tissues and led to poor survival in CRC metastasis. We found METTL3 upregulated PLAU mRNA in an m6A-dependent manner, and then participated in MAPK/ERK pathway to promote angiogenesis and metastasis in CRC. Our study provided new therapeutic targets in CRC metastasis treatment.


Silver staining of high molecular weight proteins on large-pore polyacrylamide gels.
A large-pore gel for electrophoresis in the presence of sodium dodecyl sulfate, composed of 2.55% polyacrylamide crosslinked with 2.75% methylenebisacrylamide, is described. This gel has a resolving power for very high molecular weight proteins and can be stained with silver. The gel is suitable for fractionation of factor VIII/von Willebrand factor directly from plasma samples. Visualization by silver staining revealed a series of covalently bound multimers with molecular weights of up to 8 X 10(6). The procedure described should be useful also for studies on other very high molecular weight proteins and nucleic acids.


Impact of citrus fruit intake on the mental health of patients with chronic heart failure.
The full impact of the intake of citrus fruits on the risk of depression in individuals with chronic heart failure (HF) is unknown. Here, we examined the associations between the estimated habitual intakes of citrus fruits and depressive symptoms in patients with chronic HF. We enrolled 150 stable outpatients with chronic HF who had a history of worsening HF. To assess the patients' daily dietary patterns, we used a brief self-administered diet-history questionnaire to calculate the daily consumption of foods and nutrients. To assess the patients' mental state, we used a nine-item Patient Health Questionnaire (PHQ-9). Twelve patients (8%) were identified as having moderate-to-severe depression (PHQ-9 score ≥10). The patients with PHQ-9 ≥10 had lower daily intakes of citrus fruits compared to those with no or mild depressive symptoms (PHQ-9 <10). The daily intakes of various antioxidants, including vitamin C, β-carotene, and β-cryptoxanthin, all of which are abundant in citrus fruits, were reduced in the patients with PHQ-9 ≥10, accompanied by higher serum levels of 8-isoprostane (an oxidative stress marker). A multivariate logistic regression analysis using forward selection showed that a lowered daily intake of citrus fruits was an independent predictor of the comorbidity of moderate-to-severe depression in patients with chronic HF, after adjustment for age, gender, and the hemoglobin value. A lower daily consumption of citrus fruits was associated with higher prevalence of depression in patients with chronic HF. Our findings support the hypothesis that a daily consumption of citrus fruits has a beneficial effect on the prevention and treatment of depression in chronic HF patients.


Plasmon-Enhanced Photoelectrochemical Current and Hydrogen Production of (MoS2-TiO2)/Au Hybrids.
Three component hybrid (MoS2-TiO2)/Au substrate is fabricated by loading plasmonic Au nanorods on the MoS2 nanosheets coated TiO2 nanorod arrays. It is used for photoelectrochemical (PEC) cell and photocatalyst for hydrogen generation. Owing to the charge transfer between the MoS2-TiO2 hetero-structure, the PEC current density and hydrogen generation of TiO2 nanoarrays are enhanced 2.8 and 2.6 times. The broadband photochemical properties are further enhanced after Au nanorods loading. The plasmon resonance of Au nanorods provides more effective light-harvesting, induces hot-electron injection, and accelerates photo-excited charges separation. The results have suggested a route to construct nanohybrid by combining one-dimensional arrays and two-dimensional nanosheets, meanwhile have successfully utilized plasmonic nanorods as a sensitizer to improve the photochemical properties of the semiconductor nanocomposite.


CircIL4R facilitates the tumorigenesis and inhibits ferroptosis in hepatocellular carcinoma by regulating the miR-541-3p/GPX4 axis.
Ferroptosis is a specific iron-dependent cell death form that can induce the production of lipid peroxide, but the roles of circular RNAs (circRNAs) in ferroptosis are completely unaware. Circ-interleukin-4 receptor (circIL4R) was reported to express highly in hepatocellular carcinoma (HCC). This study focused on the function of circIL4R dysregulation in tumor progression and ferroptosis of HCC, as well as its molecular mechanism. The quantitative real-time polymerase chain reaction was implemented for measuring RNA expression. Cell proliferation and survival were evaluated using 3-(4,5-dimethylthiazol-2-y1)-2,5-diphenyl tetrazolium bromide. Apoptotic cells were detected via flow cytometry. The quantification of protein expression was executed through western blotting analysis. The target binding was assessed via the dual-luciferase reporter, RNA immunoprecipitation, and RNA pull-down assays. The experiment in vivo was performed using a xenograft model. CircIL4R was abnormally overexpressed in HCC tissues and cells. CircIL4R knockdown impeded oncogenesis and expedited ferroptosis of HCC cells. CircIL4R could directly sponge microRNA-541-3p (miR-541-3p) and miR-541-3p inhibition mitigated the effects of circIL4R knockdown on HCC cells. CircIL4R acted as a miR-541-3p sponge to regulate its target glutathione peroxidase 4 (GPX4). GPX4 upregulation relieved the miR-541-3p-induced tumor inhibition and ferroptosis aggravation. CircIL4R played an oncogenic role in HCC via the miR-541-3p/GPX4 axis in vivo. Our data suggested that circIL4R served for a tumor promoter and ferroptosis inhibitor in HCC by the miR-541-3p/GPX4 network.


The effect of exercise on plasma high density lipoproteins.
The influence of vigorous activity in man on plasma lipids and lipoproteins is reviewed, with particular emphasis on high density lipoproteins. Both cross sectional and longitudinal (or training) studies have been reported, many of them of less than ideal design. Nonetheless, a consistent pattern emerges in which increased exercise levels lead to lower plasma concentrations of triglycerides and very low density lipoproteins, and of low density lipoproteins. High density lipoprotein levels increase. Sometimes, but not uniformly, plasma total cholesterol level falls as the result of these changes. The increase in plasma high density lipoprotein appears to be the result largely of an increase in the less dense HDL2 subfraction. Plasma apolipoprotein A-I levels (but not apo-A-II levels) seem to increase concomitantly. The precise biochemical mechanism responsible for these changes has not been elucidated; but the recent finding of increased lipoprotein lipase activity in adipose tissue and muscle of endurance runners suggests that increased lipolytic rate of triglyceride-rich lipoproteins may be an initial step in a sequence of events leading to higher plasma levels of HDL-2.


A case of post-anoxic encephalopathy with initial massive myoclonic status followed by alternating Jacksonian seizures.
To contrast stimulus-sensitive generalized myoclonus with ensuing multifocal localized myoclonus in a patient with post-anoxic coma, we stressed the clinical as well as electroencephalographical differences between his initial generalized and subsequent focal myoclonus. While generalized myoclonus was presumably of extracortical origin and responsive to valproic acid, alternating Jacksonian seizures were definitely cortical and suppressed with phenytoin. These two different types of myoclonus should not be confused in post-anoxic coma.


Methyltransferase-Glo: a universal, bioluminescent and homogenous assay for monitoring all classes of methyltransferases.
To develop a homogenous, nonradioactive, antibody-free and universal assay for diverse families of methyltransferases and monitor the activity of these enzymes in a high-throughput format. The assay conditions are optimized for monitoring the enzymatic activity of a broad range of methyltransferases regardless of the chemical structure or nature of the enzyme substrate in a low- and high-throughput-formatted protocols. The assay detects S-adenosyl-L-homocysteine, the universal reaction products of all methyltransferases. We demonstrate the utility of using this protocol to determine the activity of DNA, protein methyltransferases and also to determine kinetic parameters of several inhibitors using purified enzymes. The assay is sensitive (20-30 nM of S-adenosyl-L-homocysteine) and robust. The methyltransferase Glo is nonradioactive, antibody-free and homogenous, universal assay to determine enzyme activity of diverse families of methyltransferases. The assay is formatted to meet the requirements of high-throughput screening in drug discovery programs searching for modulators of methyltransferases.


Phylogeny of hoplocercine lizards (Squamata: Iguania) with estimates of relative divergence times.
Hoplocercine lizards form a clade of 11 currently recognized species traditionally placed in three genera (Enyalioides, Hoplocercus, and Morunasaurus) that occur in the lowlands on both sides of the Andes between Panama and the Brazilian Cerrado. We analyze 11 mitochondrial and two nuclear loci using probabilistic methods and different partitioning strategies to (1) infer the phylogenetic relationships among species of Hoplocercinae, (2) examine amounts of inter- and intraspecific sequence divergence, (3) address monophyly of four species, (4) test previous phylogenetic hypotheses, and (5) estimate divergence times. Our preferred hypothesis places H. spinosus as the sister taxon to all other species of hoplocercines, with M. annularis nested within Enyalioides. Species with multiple samples are monophyletic except for Enyalioides oshaughnessyi, which is paraphyletic relative to an undescribed species of Enyalioides. All previously published phylogenetic hypotheses for hoplocercines are rejected. Monophyly of Enyalioides cannot be rejected and, consequently, the position of Morunasaurus remains unclear. The most recent common ancestor of Hoplocercinae probably occurred east of the Andes; western taxa included in our analyses originated from at least two separate colonizations whether pre- or post-dating vicariance resulting from uplift of the Andes.


Effect of immersive virtual mirror visual feedback on Mu suppression and coherence in motor and parietal cortex in stroke.
We investigated the activation pattern of the motor cortex (M1) and parietal cortex during immersive virtual reality (VR)-based mirror visual feedback (MVF) of the upper limb in 14 patients with chronic stroke and severe upper limb hemiparesis and in 21 healthy controls. Participants performed wrist extension with unaffected wrists (dominant side in controls). In the MVF condition, movement of the affected hand was synchronized with that of the unaffected hand. In the no-MVF condition, only the movement of unaffected hand was shown. Mu suppression in bilateral M1 and parietal cortex and mu coherence were analyzed. In patients with stroke, MVF induced significant mu suppression in both the ipsilesional M1 and parietal lobes (p = 0.006 and p = 0.009, respectively), while mu suppression was observed in the bilateral M1 (p = 0.003 for ipsilesional and p = 0.041 for contralesional M1, respectively) and contralesional parietal lobes in the controls (p = 0.036). The ipsilesional mu coherence between the M1 and parietal cortex in patients with stroke was stronger than controls, regardless of MVF condition (p < 0.001), while mu coherence between interhemispheric M1 cortices was significantly weaker in patients with stroke (p = 0.032). Our findings provide evidence of the neural mechanism of MVF using immersive VR in patients with stroke.


Melatonin for rapid eye movement sleep behavior disorder in Parkinson's disease: A randomised controlled trial.
Melatonin may reduce REM-sleep behavior disorder (RBD) symptoms in Parkinson's disease (PD), though robust clinical trials are lacking. To assess the efficacy of prolonged-release (PR) melatonin for RBD in PD. Randomized, double-blind, placebo-controlled, parallel-group trial with an 8-week intervention and 4-week observation pre- and postintervention (ACTRN12613000648729). Thirty PD patients with rapid eye movement sleep behavior disorder were randomized to 4 mg of prolonged-release melatonin (Circadin) or matched placebo, ingested orally once-daily before bedtime. Primary outcome was the aggregate of rapid eye movement sleep behavior disorder incidents averaged over weeks 5 to 8 of treatment captured by a weekly diary. Data were included in a mixed-model analysis of variance (n = 15 per group). No differences between groups at the primary endpoint (3.4 events/week melatonin vs. 3.6 placebo; difference, 0.2; 95% confidence interval = -3.2 to 3.6; P = 0.92). Adverse events included mild headaches, fatigue, and morning sleepiness (n = 4 melatonin; n = 5 placebo). Prolonged-release melatonin 4 mg did not reduce rapid eye movement sleep behavior disorder in PD. © 2019 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.


A correlated random parameters tobit model to analyze the safety effects and temporal instability of factors affecting crash rates.
Numerous studies have previously used a variety of count-data models to investigate factors that affect the number of crashes over a certain period of time on roadway segments. Unlike past studies which deal with crash frequency, this study views the crash rates directly as a continuous variable left-censored at zero and explores the application of an alternate approach based on tobit regression. To thoroughly investigate the factors affecting freeway crash rates and the potentially temporal instability in the effects of crash factors involving traffic volume, freeway geometries and pavement conditions, a classic uncorrelated random parameters tobit (URPT) model and a correlated random parameters tobit (CRPT) model were estimated, along with a conventional fixed parameters tobit (FPT) model. The analysis revealed a large number of safety factors, including several appealing and interesting factors rarely studied in the past, such as the safety effects of climbing lanes and distance along composite descending grade. The results also showed that the CRPT model was not only able to reflect the heterogeneous effects of various factors, but also able to estimate the underlying interactions among unobserved characteristics, and therefore provide better statistical fit and offer more insights into factors contributing to freeway crashes than its model counterparts. Additionally, the results showed significant temporal instability in CRPT models across the studied time periods indicating that crash factors (including unobserved characteristics and the underlying interactions among them) and their effects on crash rates varied over time, and more attentions should be paid when interpreting crash data-analysis findings and making safety policies. The modeling technique in this study demonstrates the potential of CRPT model as an effective approach to gain new insights into safety factors, particularly when the heterogeneous effects of factors on safety are interactive. Additionally, findings from this study are also expected to assist in developing more effective countermeasures by better understanding the safety effects of factors associated with freeway design characteristics and pavement conditions.


Meta-research: justifying career disruption in funding applications, a survey of Australian researchers.
When researchers' careers are disrupted by life events - such as illness or childbirth - they often need to take extended time off. This creates a gap in their research output that can reduce their chances of winning funding. In Australia, applicants can disclose their career disruptions and peer reviewers are instructed to make appropriate adjustments. However, it is not clear if and how applicants use career disruption sections or how reviewers adjust and if they do it consistently. To examine career disruption, we used surveys of the Australian health and medical research community. We used both a random sample of Australian authors on PubMed and a non-random convenience sample. Respondents expressed concerns that sharing information on career disruption would harm their chances of being funded, with 13% saying they have medical or social circumstances but would not include it in their application, with concerns about appearing 'weak'. Women were more reluctant to include disruption. There was inconsistency in how disruption was adjusted for, with less time given for those with depression compared with caring responsibilities, and less time given for those who did not provide medical details of their disruption. The current system is likely not adequately adjusting for career disruption and this may help explain the ongoing funding gap for senior women in Australia. National Health and Medical Research Council Senior Research Fellowship (Barnett).


Bioprosthesis replacement with mechanical valve implantation on the bioprosthetic ring. Surgical and 2D echo considerations.
Removal of a failing bioprosthesis can be a delicate operation and extensive damage can be caused. Eighteen patients with failing bioprostheses underwent excision of the leaflets, then the "new" mechanical valve was sewn onto the "old" bioprosthetic ring. At follow-up, clinical and 2D color-flow echo-Doppler evaluations showed good hemodynamic performance of the mechanical valves.


Active suspension control with consensus strategy for dynamic posture tracking of wheel-legged robotic systems on uneven surfaces.
This work presents a dynamic posture tracking control strategy for wheel-legged systems on uneven surfaces. Based on the kinematic model of a wheel-legged robotic system, the expected positions for the end-effectors of wheel-legs are calculated according to posture references and sensor feedback. The position control problem for a general wheel-leg is investigated for the active mechanism to imitate a passive suspension and respond to the external contact forces. The position tracking accuracy of the wheel-leg is sacrificed to enhance the compliance performance under rough terrain. Because of the unique contact state with the uneven ground for each wheel-leg, the position responses are different. As a result, the forces from the wheel-legs to the fuselage are inconsistent, which leads to the risk of posture oscillations. Equipping the wheel-legs with an undirected communication network, a consensus scheme for the robotic system is developed with proven global asymptotic stability to improve the posture tracking property. A novel robotic system is established with Stewart-structured wheel-legs, which are connected by a user datagram protocol network. Comparative experimental results are carried out on the physical prototype to validate the effectiveness of the proposed approach.


Levonorgestrel-releasing intrauterine system or hysterectomy in the treatment of essential menorrhagia: predictors of outcome.
Levonorgestrel-releasing intrauterine system (LNG-IUS) has been advocated as an effective alternative to hysterectomy in the treatment of menorrhagia. The outcome predictors have been poorly known. In this study the amount of menstrual blood loss (MBL) turned out to be the single most important outcome predictor of these treatments. However, the treatment with LNG-IUS seemed to be an appropriate alternative to hysterectomy for all women who perceived their MBL heavy.


Antihypertensive effect of propranolol in conscious spontaneously hypertensive rats: central hemodynamics, plasma volume, and renal function during beta-blockade with propranolol.
In order to obtain a better insight into the hemodynamic changes during beta-blockade, we measured central hemodynamics, plasma volume, and renal function during both acute and long-term beta-blockade in conscious spontaneously hypertensive rats (SHR). Acutely, both 1 and 5 mg/kg propranolol immediately decreased heart rate (HR) and cardiac output (CO). However, total peripheral resistance (TPR) rose sharply, thus preventing mean arterial pressure (MAP) from falling during the first hours after injection. After 4 h TPR had returned to control values and, because CO was still reduced, MAP was lowered. This decrease of MAP persisted for more than 20 h. During 5-day infusion of propranolol (5 mg/kg/day) CO fell on the 1st day and remained lowered during the 5-day period. MAP was lowered from the second day onward. Despite the reduced CO and MAP, plasma volume (PV) did not increase during the 5-day infusion. Acute injection of 5 mg/kg/day did, however, result in a decreased PV at 1 h postinjection. In this time span central venous pressure remained unchanged. Quantitation of water and sodium excretion revealed an immediate diuresis and natriuresis after acute administration of propranolol. This occurred despite a reduced glomerular filtration rate and effective renal plasma flow, as quantitated by indicator clearance methods. We conclude that propranolol reduced tubular sodium reabsorption, possibly through blockade of tubular beta-receptors. This effect may be essential for the long-term antihypertensive efficacy of beta-blockers because it prevents sodium and water retention in a state of reduced MAP and CO.


Antibiotic Resistance Genes in Freshwater Biofilms May Reflect Influences from High-Intensity Agriculture.
Antibiotic resistance is a major public health concern with growing evidence of environmental gene reservoirs, especially in freshwater. However, the presence of antibiotic resistance genes in freshwater, in addition to the wide spectrum of land use contaminants like nitrogen and phosphate, that waterways are subjected to is inconclusive. Using molecular analyses, freshwater benthic rock biofilms were screened for genes conferring resistance to antibiotics used in both humans and farmed animals (aacA-aphD to aminoglycosides; mecA to ß-lactams; ermA and ermB to macrolides; tetA, tetB, tetK, and tetM to tetracyclines; vanA and vanB to glycopeptides). We detected widespread low levels of antibiotic resistance genes from 20 waterways across southern New Zealand throughout the year (1.3 % overall detection rate; 480 samples from three rocks per site, 20 sites, eight occasions; July 2010-May 2011). Three of the ten genes, ermB, tetK, and tetM, were detected in 62 of the 4800 individual screens; representatives confirmed using Sanger sequencing. No distinction could be made between human and agricultural land use contamination sources based on gene presence distribution alone. However, land use pressures are suggested by moderate correlations between antibiotic resistance genes and high-intensity farming in winter. The detection of antibiotic resistance genes at several sites not subject to known agricultural pressures suggests human sources of resistance, like waterway contamination resulting from unsatisfactory toilet facilities at recreational sites.


Association of alveolar rhabdomyosarcoma with the Beckwith-Wiedemann syndrome.
Rhabdomyosarcoma (RMS) is a soft tissue tumor of childhood frequently diagnosed between the first and fifth year of life. Children with the Beckwith-Wiedemann syndrome (BWS), a congenital overgrowth syndrome characterized by exomphalos, macroglossia, and macrosomia, have an increased risk of developing childhood tumors including Wilms tumor, hepatoblastoma, neuroblastoma, and RMS. Although an association between RMS and the BWS is well accepted, only four cases have been reported to date, and of these, three were reported as embryonal RMS. Based on these data, an association between BWS and embryonal RMS has been proposed. We report three additional cases of BWS with RMS and review the clinical data for each patient as well as the pathology of their tumors. All three cases of BWS had histology consistent with alveolar RMS and were diagnosed at 6 weeks and 5 and 13 years of age. In two of these BWS cases, constitutional defects of 11p15 imprinting were demonstrated. Furthermore, cytogenetic analysis of the tumors did not detect the t(2;13) or t(1;13) translocations that generate the PAX3- or PAX7-FKHR fusion proteins common to alveolar RMS. These observations suggest that the development of alveolar RMS tumors in BWS may occur without the chromosomal rearrangement producing the PAX-FKHR fusion protein. In summary, we present three new cases of RMS demonstrating a new association between BWS and an uncommon subtype of alveolar RMS. The absence of the translocations commonly associated with alveolar rhabdomyosarcoma suggests a common 11p15 pathway for alveolar RMS and BWS.


Influence of anesthesia on spontaneous activity and receptive field size of single units in rat Sm1 neocortex.
Spontaneous and cutaneously driven unit activity was recorded in the hindfoot region of rat Sm1 neocortex under controlled intravenous infusion, at three selected rates, of the steroid anesthetic agent Althesin. Increasing depth of anesthesia decreased average spontaneous firing rates of 67 single units from 2.5 to 11 Hz during light anesthesia to 0 to 2.5 Hz in deep anesthesia. Thresholds to cutaneous stimulation for 58 units were innocuous (from 15 to 190 micron) using a 5-ms ramp displacement of the skin in the center receptive field. Responses from 13 sites on the hindfoot were classified according to response probability for each of the 58 units in reply to stimuli at 1.5 times center receptive field threshold. Small receptive fields were seen only under conditions of deep anesthesia, considerable expansion of both center and excitatory surrounds occurring with lighter anesthesia. Mean values for total receptive field size (center plus surround excitatory receptive field) were 10.8, 7.8, and 3.4 sites, respectively, for light, moderate, and deep anesthesia. The size of the receptive field was also influenced by stimulus repetition rate; moderate increases of this and anesthetic depth could eliminate substantial receptive fields. Surround inhibition of evoked activity was more effective in deeper anesthesia with little effect in light anesthesia. We suggest that receptive field expansion in light anesthesia arises from a relative increase in excitability of afferent pathways and an accompanying increase in the preponderance of surround excitation vis à vis surround inhibition.


Intraventricular haemorrhage from a renal cell carcinoma pituitary metastasis.
Symptomatic pituitary metastasis and intraventricular haemorrhage from a cerebral metastasis are exceptional events in the natural history of a renal cell carcinoma. We report the first case of a metastatic renal cell carcinoma to the pituitary gland presenting with intraventricular haemorrhage. The origin of intraventricular haemorrhage and its association with renal cell carcinoma pituitary metastasis are discussed.


Significance of hepatic xanthine oxidase and uric acid in aged and dietary restricted rats.
Xanthine oxidase (XOD), one of the major intracellular sources of superoxide production, is well characterized as a causative factor in ischemia/reperfusion related damage. In the present study, we investigated age-effect on the status of XOD, an enzyme interconvertible with xanthine dehydrogenase (XDH) under oxidative stress. We also examined the modulation of the enzyme using the anti-oxidative action of dietary restriction (DR). We obtained evidence showing XOD activity to be significantly increased by DR, peaking at 24 months, although no progressive, age-related changes were noticed. On the other hand, while XDH activity decreased in ad libitum fed rats with age, DR maintained higher activity levels at 18 and 24 months of age. During aging, the conversion of XDH to XOD was slightly increased, as indicated by the XOD/XDH ratio. One novel finding of the present study is DR's ability to elevate the uric acid level, which likely augments the anti-oxidative defense system, thereby buffering against oxidatively stressed conditions during aging. Based on what is known about the antioxidative abilities of DR and uric acid, we propose that the high uric acid levels we observed in DR rats may well serve as part of a defense strategy to protect redox balance.


Therapy of ocular toxoplasmosis.
We performed a prospective multicentre study to evaluate the efficacy of therapeutic strategies currently used for ocular toxoplasmosis in a large number of patients (n = 106). Treatment was given for at least four weeks and consisted of three triple drug combinations: group 1, pyrimethamine, sulphadiazine and corticosteroids (n = 29); group 2. clindamycin, sulphadiazine and corticosteroids (n = 37); and group 3. cotrimoxazole (trimethoprim and sulphamethoxazole) and corticosteroids (n = 8). Patients with peripheral retinal lesions remained without systemic therapy (group 4, n = 32). Patients from group 1 received leucovorin 5 mg twice a week. No difference in the duration of inflammatory activity was observed between the treated and untreated patients or between the separate groups of patients. The most important factor predicting the duration of inflammatory activity was the size of the retinal focus itself, independently of the therapy given (P less than 0.05). We showed a reduction in size of the retinal inflammatory focus in 52% of the pyrimethamine patients as compared to 25% of untreated cases. However the most frequent side effects were also associated with pyrimethamine medication and included hematologic complications as thrombocytopenia and leucopenia despite leucovorin medication.


Intestinal gas in ulcerative colitis.
Intestinal gas was measured planimetrically on plain abdominal films from 25 healthy subjects and 47 patients with active ulcerative colitis (mild, moderate, severe and toxic megacolon). Compared with controls, significant colonic distention was found in toxic megacolon. Gas in the small bowel was significantly increased in toxic megacolon and in severe colitis but was within the normal range in the mild and moderate forms. Two groups of patients with severe colitis were identified, showing either normal or increased gas content in the small bowel. Two of seven patients in the latter group developed toxic megacolon in spite of intensive medical treatment. Intestinal gas values showed a linear correlation with arterial blood pH, ESR and body temperature. No correlation was found between intestinal gas and other features of severity. It is suggested that an abnormal collection of gas in the small bowel loops associated with metabolic alkalosis corresponds to an early stage of a toxic complication ("impending megacolon").


Rural-urban differences in food insecurity and associated cognitive impairment among older adults: findings from a nationally representative survey.
Due to rapid urbanization, Covid-19 pandemic and increasing food prices, a higher rate of food insecurity has been observed in recent years in India. Thus, we aim to study the prevalence of food insecurity among older Indian adults and the association of food insecurity as a modifiable risk factor with late-life cognitive impairment. Data for this study were obtained from the recent release of the Longitudinal Ageing Study in India (2017-18). The total sample size for the study was 31,464 older adults aged 60 years and above. Cognitive functioning was measured through five broad domains (memory, orientation, arithmetic function, executive function, and object naming) adapted from the cognitive module of the US Health and Retirement Study (HRS). Descriptive statistics along with cross-tabulation were presented in the study. Additionally, multivariable logistic regression analysis was used to fulfil the objectives of the study. It was found that 7.7% of older adults in rural areas reduced their size of meals due to unavailability (urban, 3.2%), 41.2% of them did not eat enough food of their choice (urban, 38.3%), 6.9% were hungry but did not eat food (urban, 2.6%), 5.0% did not eat for whole day (urban, 2.2%), and 6.9% lost weight due to lack of food in their household (urban, 2.9%). It was found that older adults who did not have enough food of their choice had significantly higher odds [AOR: 1.24; CI: 1.14, 1.35] of suffering from cognitive impairment in reference to their counterparts. Similarly, the older adults who were hungry but did not eat were 30% [AOR: 1.30; CI: 1.02, 1.73] more likely to suffer from cognitive impairment in reference to their counterparts. Interaction model revealed that older adults who had food insecurity in rural areas had higher odds of cognitive impairment than older adults who had food insecurity in urban areas. The findings of the study highlight that the food security status in older adults may bring about greater challenges due to their limited economic resources. Interventions focusing on food security may have unintended positive impacts on late-life mental wellbeing as the older age is associated with higher cognitive deficits.


Electrospun Nanofibrous Biocomposite of Royal Jelly/Chitosan/Polyvinyl Alcohol (RJ/CS/PVA) Gel as a Biological Dressing for P. aeruginosa-Infected Burn Wound.
Burn wounds are vulnerable to various infections due to damage to the tissue and changes in immune responses. Pseudomonas aeruginosa is a critical bacterium that can cause burn wound infections, which can be life-threatening and delay wound healing. Therefore, it is essential to develop an efficient strategy to prevent the spread of infection in burn wounds. The present study aims to investigate the effectiveness of electrospun nanofibers of royal jelly on a chitosan/polyvinyl alcohol polymer scaffold in repairing burn wounds infected with Pseudomonas aeruginosa. To achieve this, the researchers analyzed the morphology and physicochemical properties of the synthesized nanofibers using SEM, FTIR, BET, and TGA analyses. They also examined the antibacterial properties of the nanofibers using agar diffusion and spread plate techniques. In addition, hemolysis tests were carried out to assess biocompatibility. Finally, the ability of the nanofibers to repair burn wounds infected with Pseudomonas aeruginosa was evaluated using a laboratory mouse model. The study results showed that the synthesized nanofibers had desirable morphology and physicochemical properties and significant antibacterial effects in both in vitro and in vivo conditions. Also, loading RJ into the polymer scaffold significantly reduced erythrocyte lysis. The wound healing and contraction rates were significantly higher than the control groups, and tissue repair, re-epithelialization, and collagen synthesis occurred faster, preventing the spread of infection to deeper tissue areas. Based on these findings, the synthesized system has the potential to serve as a suitable substitute for some invasive treatments and chemical drugs to improve chronic wounds and manage infection control in burn injuries.


Cell-to-Cell Crosstalk: A New Insight into Pulmonary Hypertension.
Pulmonary hypertension (PH) is a disease with high pulmonary arterial pressure, pulmonary vasoconstriction, pulmonary vascular remodeling, and microthrombosis in complex plexiform lesions, but it has been unclear of the exact mechanism of PH. A new understanding of the pathogenesis of PH is occurred and focused on the role of crosstalk between the cells on pulmonary vessels and pulmonary alveoli. It was found that the crosstalks among the endothelial cells, smooth muscle cells, fibroblasts, pericytes, alveolar epithelial cells, and macrophages play important roles in cell proliferation, migration, inflammation, and so on. Therefore, the heterogeneity of multiple pulmonary blood vessels and alveolar cells and tracking the transmitters of cell communication could be conducive to the further insights into the pathogenesis of PH to discover the potential therapeutic targets for PH.


Overexpression of T-bet gene regulates murine autoimmune arthritis.
To clarify the role of T-bet in the pathogenesis of collagen-induced arthritis (CIA). T-bet-transgenic (Tg) mice under the control of the CD2 promoter were generated. CIA was induced in T-bet-Tg mice and wild-type C57BL/6 (B6) mice. Levels of type II collagen (CII)-reactive T-bet and retinoic acid receptor-related orphan nuclear receptor γt (RORγt) messenger RNA expression were analyzed by real-time polymerase chain reaction. Criss-cross experiments using CD4+ T cells from B6 and T-bet-Tg mice, as well as CD11c+ splenic dendritic cells (DCs) from B6 and T-bet-Tg mice with CII were performed, and interleukin-17 (IL-17) and interferon-γ (IFNγ) in the supernatants were measured by enzyme-linked immunosorbent assay. CD4+ T cells from B6, T-bet-Tg, or T-bet-Tg/IFNγ-/- mice were cultured for Th17 cell differentiation, then the proportions of cells producing IFNγ and IL-17 were analyzed by fluorescence-activated cell sorting. Unlike the B6 mice, the T-bet-Tg mice did not develop CIA. T-bet-Tg mice showed overexpression of Tbx21 and down-regulation of Rorc in CII-reactive T cells. Criss-cross experiments with CD4+ T cells and splenic DCs showed a significant reduction in IL-17 production by CII-reactive CD4+ T cells in T-bet-Tg mice, even upon coculture with DCs from B6 mice, indicating dysfunction of IL-17-producing CD4+ T cells. Inhibition of Th17 cell differentiation under an in vitro condition favoring Th17 cell differentiation was observed in both T-bet-Tg mice and T-bet-Tg/IFNγ-/- mice. Overexpression of T-bet in T cells suppressed the development of autoimmune arthritis. The regulatory mechanism of arthritis might involve dysfunction of CII-reactive Th17 cell differentiation by overexpression of T-bet via IFNγ-independent pathways.


Interleukin-10 promoter variability is associated with the susceptibility, severity, and clinical outcomes of aplasitc anemia in Han-Chinese population.
Acquired aplastic anemia (AA), a heterogeneous bone marrow (BM) failure disease, is mainly mediated by the immune destruction of hematopoietic stem cells (HSCs). Given the predominant role of immunosuppressive therapy (IST) in AA, it is sensible to theorize that variants of cytokine genes might affect the outcome of IST. In this study, we analyzed three single nucleotide polymorphisms (SNPs) of interleukin (IL)-10 gene in promoter region to clarify their relationship with susceptibility, clinical efficacy and prognosis of AA. We observed that CT genotype of IL-10 rs1800896 was associated with a decreased risk of AA (adjusted OR = 0.541 [95% CI 0.295-0.993], p = .047). Besides, the disease severity differed considerably by IL-10 gene promoter genotypes and alleles. Furthermore, IL-10 SNPs influenced efficacy of IST, with unfavorable response exhibited by rs1800871 and rs1800872 in dominant models (GG + AG vs. AA, adjusted OR = 0.409 [95% CI 0.178-0.943, p = .036] for rs1800871 and GG + GT vs. TT, adjusted OR = 0.396 [95% CI 0.173-0.909, p = .028] for rs1800872, respectively). The polymorphisms of IL-10 promoter region were informatively genetic risk factors which might be conducive to the insights into the mechanisms of AA and the design of individual regimens.


RNA polymerase modulators and DNA repair activities resolve conflicts between DNA replication and transcription.
Organisms rely on close interplay between DNA replication, recombination, and repair to secure transmission of the genome. In rapidly dividing cells, there is also great pressure for transcription, which may induce conflict with replication. We investigated the potential for conflict in bacterial cells, where there is no temporal separation of these processes. Eliminating the stringent response regulators ppGpp and DksA or the GreA and Mfd proteins, which revive or dislodge stalled transcription complexes, and especially combinations of these factors, is shown to severely reduce viability when DNA repair is also compromised. Both ppGpp and certain RNA polymerase (RNAP) mutations reduce accumulation of backed-up arrays of stalled transcription complexes. We propose these arrays are formidable obstacles to replication that are normally kept in check in wild-type cells by ppGpp, DksA, GreA, and Mfd. When arrays do obstruct replication, the consequences are resolved by one of the many pathways available to rescue stalled forks.