Diagnosis of bone and liver metastases in breast cancer comparing tumor markers and imaging techniques.
One hundred and forty-seven patients were examined by bone scintigraphy, ultrasonography and scintigraphic scan of the liver, at different times after surgical removal of a breast cancer, to rule out skeletal and hepatic metastases. At the same time as imaging procedures, serum levels of tumor markers (CEA, TPA and CA 15-3) were determined using radioimmunometric methods. One or more markers were elevated in all 13 patients with hepatic metastases; 9 out of 46 patients with bone metastases had all serum markers normal, with a sensitivity of 80%. Combined assay of the markers proved useful, TPA and CA 15-3 showing the best sensitivity in bone metastases, and all three markers in liver metastases.


Multiple concurrent collagenase clostridium histolyticum injections to Dupuytren's cords: an exploratory study.
Dupuytren's contracture (DC) is a progressive fibroproliferative disorder characterized by development of nodules and collagen cords within the palmar fascia of the hand. Collagenase clostridium histolyticum (CCH) is currently approved in adults with DC for the nonsurgical treatment of a single palpable cord during a 30-day treatment cycle. This open-label pilot study was designed to examine the safety, efficacy, and multiple-dose pharmacokinetics of injecting two cords (affected joints) with multiple doses of CCH concurrently into the same hand in subjects with DC and multiple contractures. Twelve subjects with DC were enrolled, each with ≥3 contractures caused by palpable cords. Efficacy assessments were taken 30 days after treatment and adverse events (AEs) were recorded throughout. In the first treatment period, all subjects were injected with a single dose of CCH (0.58 mg) into a single cord. The same subjects entered a second treatment period 30 days later, where two different cords (affected joints) were injected concurrently on the same hand. A finger extension procedure was performed 24 hours after each administration of CCH to disrupt the enzymatically weakened cord. For metacarpophalangeal (MP) joints, mean contracture reduction per joint treated was 29.0 ± 20.7 degrees following single injection vs 30.3 ± 10.9 degrees per treated joint following multiple injections. For proximal interphalangeal (PIP) joints, mean reduction in contracture was 30.7 ± 21.1 and 22.1 ± 4.9 degrees per treated joint, respectively, for the two periods. All patients (100%) were either "quite satisfied" or "very satisfied" following either treatment cycle. The most common treatment-related AEs were edema peripheral, contusion, and pain in the treated extremity; the differences in severity for local effects of the injections were minimal between treatment periods. No serious treatment-related AEs or systemic complications were reported. These results provide preliminary evidence that two cords (affected joints) can be treated concurrently with CCH with similar efficacy and safety as cords treated individually in a sequential fashion. Multiple concurrent injections would eliminate the 30-day wait between single treatments and allow for rapid and effective treatment of patients with multiple affected joints, a significant advantage for both patient and physician. Australian New Zealand Clinical Trials Registry #ACTRN12610001045000.


Dynamic radionuclide imaging as a means of evaluating vascular perfusion of the upper extremity: a preliminary report.
Vascular competence in the upper extremities of 44 patients was evaluated by three-phase bone scans consisting of rapid sequence dynamic radionuclide imaging (DRI), an immediate postinjection "blood pool" image, and a 3- to 4-hour delayed image. Findings were correlated with definitive anatomy determined by arteriography, operative findings, or both, in 50 extremities. DRI provided the correct diagnosis in all but four extremities (92%). Limited resolution precluded precise anatomic definition of aneurysms in three limbs and of digital artery occlusion, with adequate collateral circulation in the fourth limb. The greatest value of DRI was its provision of quantitative information about relative blood flow and preferential perfusion in every instance. We believe DRI to be a useful adjunct to preoperative and postoperative assessment of arterial perfusion.


Practice Variation in Perioperative Steroid Dosing for Brain Tumor Patients: An International Survey.
Steroids are commonly used to treat peritumoral edema and increased intracranial pressure in patients with brain tumors. Despite widespread use of steroids, relatively little evidence is available about their optimal perioperative dosing scheme. This study aimed to increase insight into practice variation of perioperative steroid dosing and tapering schedules used in the neurosurgical community. An electronic survey comprising 27 questions regarding steroid dosing, tapering schedules, and adverse events was administered to neurosurgeons between December 6, 2019, and June 1, 2020. The survey was distributed through the European Association of Neurosurgical Societies and social media platforms. Collected data were assessed for quantitative and qualitative analysis. The survey obtained 175 responses from 55 countries across 6 continents, including 30 from low- or middle-income countries; 152 (87%) respondents completed all questions. Of respondents, 130 (80%) indicated prescribing perioperative steroids. Reported doses ranged from 2 to 64 mg/day in schedules ranging from 1 to 4 times daily. The most prescribed steroid was dexamethasone in doses of 16 mg/day (n = 49; 31%), 12 mg/day (n = 31; 20%), and 8 mg/day (n = 18; 12%). No significant association was found between prescribed dose and physician and institutional characteristics. Steroids are commonly prescribed perioperatively in patients with brain tumors. However, there is great practice variation in dosing and schedules among neurosurgeons. Future investigation in a prospective and preferably randomized manner is needed to identify an optimal dosing scheme and implement international/national guidelines for steroid use.


The Link between depression in mothers and offspring: an extended twin analysis.
Family studies have shown that maternal depression is a risk factor for depression in children. It is unclear, however, to what extent the familial transmission of depression from mother to child involves genes and how much is due to environmental adversity. This study used an extended twin design to assess the importance of environmental factors in the association of depression in mothers and children while simultaneously accounting for genetic relatedness in a UK. community sample of twins aged 8 to 17 years and their mothers. A model that constrained the genetic and environmental parameters to be equal within the two generations and included genetic and environmental paths between mother and offspring (twins) was tested with data from 1468 families. Significant environmental paths were found when maternal ratings were used. When cross-informant data were used (maternal depression and child self-reports of depression), the environmental path was no longer significant. However, for cross-informant data where children were classified as having high depression scores or scores within the normal range, significant environmental effects were found. These findings are interpreted in light of the strengths and weaknesses of the extended twin and other designs.


Identification of Nocardia species using matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry.
The MALDI (matrix-assisted laser desorption/ionization) Biotyper system for bacterial identification has already been utilized in clinical microbiology laboratories as a successful clinical application of protoemics. However, in cases of Nocardia, mass spectra suitable for MALDI Biotyper identification are often not obtained if such specimens are processed like general bacteria. This problem is related to the insufficiencies in bacterial spectrum databases that preclude accurate specimen identification. Here, we developed a bacterial processing method to improve mass spectra from specimens of the genus Nocardia. In addition, with the new processing method, we constructed a novel in-house bacterial database that combines a commercial database and mass spectra of Nocardia strains from the Department of Clinical Laboratory at Chiba University Hospital (DCLC) and the Medical Mycology Research Center at Chiba University (MMRC). The newly developed method (Nocardia Extraction Method at DCLC [NECLC]) based on ethanol-formic acid extraction (EFAE) improved mass spectra obtained from Nocardia specimens. The Nocardia in-house database at Chiba University Hospital (NDCUH) was then successfully validated. In brief, prior to introduction of the NECLC and NDCUH, 10 of 64 (15.6%) clinical isolates were identified at the species level and 16 isolates (25.0%) could only be identified at the genus level. In contrast, after the introduction, 58 isolates (90.6%) were identified at the species level and 6 isolates (9.4%) were identified at the genus level. The results of this study suggest that MALDI-TOF (time-of-flight) Biotyper system can identify Nocardia accurately in a short time in combination with a simple processing method and an in-house database.


Depressive Symptoms and Frailty Among the Oldest Old: Evidence from a Multicenter Prospective Study.
There is a lack of studies disentangling whether changes in frailty are associated with subsequent changes in depressive symptoms or vice versa among the oldest old. Consequently, we aimed to disentangle this link. Three waves [follow-up (FU) wave 7 to FU wave 9; n = 423 individuals in the analytical sample] were used from the multicenter prospective cohort study "Needs, Health Service Use, Costs and Health-Related Quality of Life in a Large Sample of Oldest-Old Primary Care Patients (85+)" (AgeQualiDe). Primary care patients aged 85 years and older. The Canadian Study of Health and Aging (CSHA) Clinical Frailty Scale (CFS) was used to quantify frailty, and the Geriatric Depression Scale was used to measure depressive symptoms. It was adjusted for several covariates (sociodemographic and health-related factors) in regression analysis. Multiple linear regressions with first differences showed that initial increases in depressive symptoms (from FU wave 7 to FU wave 8) were associated with subsequent increases in frailty (from FU wave 8 to FU wave 9; β = 0.06, P < .05), whereas initial increases in frailty (from FU wave 7 to FU wave 8) were not associated with subsequent increases in depressive symptoms (from FU wave 8 to FU wave 9). The study findings suggest the relevance of increases in depressive symptoms for subsequent increases in frailty. Treatment of depressive symptoms may also be beneficial to postpone frailty.


Laser microdissection for microsatellite analysis in colon and breast cancer.
Microsatellite analysis is a frequently used method for detection of chromosomal deletions by loss of heterozygosity studies and for detection of microsatellite instability. For reliable microsatellite analyses, a tumor cell content of at least 80% is required. Therefore, laser microdissection is an important prerequisite for those studies, allowing the contamination-free isolation of morphologically defined pure tumor cell populations. The combination of exact microdissection and subsequent whole-genome amplification by improved primer extension preamplification polymerase chain reaction (I-PEP-PCR) facilitates the analysis of multiple microsatellite loci in small tumor samples. This is especially important for the investigation of malignant tumors with low tumor cellularity. This chapter describes in detail the use of whole genome amplification by I-PEP PCR and microsatellite analysis in laser microdissected specimens of colon and breast cancer.


Organisational downsizing, sickness absence, and mortality: 10-town prospective cohort study.
To examine whether downsizing, the reduction of personnel in organisations, is a predictor of increased sickness absence and mortality among employees. Prospective cohort study over 7.5 years of employees grouped into categories on the basis of reductions of personnel in their occupation and workplace: no downsizing (< 8% reduction), minor downsizing (8-18%), and major downsizing (> 18%). Four towns in Finland. 5909 male and 16 521 female municipal employees, aged 19-62 years, who kept their jobs. Annual sickness absence rate based on employers' records before and after downsizing by employment contract; all cause and cause specific mortality obtained from the national mortality register. Major downsizing was associated with an increase in sickness absence (P for trend < 0.001) in permanent employees but not in temporary employees. The extent of downsizing was also associated with cardiovascular deaths (P for trend < 0.01) but not with deaths from other causes. Cardiovascular mortality was 2.0 (95% confidence interval 1.0 to 3.9) times higher after major downsizing than after no downsizing. Splitting the follow up period into two halves showed a 5.1 (1.4 to 19.3) times increase in cardiovascular mortality for major downsizing during the first four years after downsizing. The corresponding hazard ratio was 1.4 (0.6 to 3.1) during the second half of follow up. Organisational downsizing may increase sickness absence and the risk of death from cardiovascular disease in employees who keep their jobs


Pre-diagnosis lifestyle, health history and psychosocial factors associated with stage at breast cancer diagnosis - Potential targets to shift stage earlier.
Early detection of breast cancer improves survival, so identifying factors associated with stage at diagnosis may help formulate cancer prevention messages tailored for higher risk women. The goal of this study was to evaluate associations between multiple potential risk factors, including novel ones, measured before a breast cancer diagnosis and stage at diagnosis in women from Alberta, Canada. Women enrolled in Alberta's Tomorrow Project completed health and lifestyle questionnaires on average 7 years before their breast cancer diagnosis. The association of previously identified and novel predictors with stage (I, II and III + IV) at diagnosis were simultaneously evaluated in partial proportional odds ordinal (PPO) regression models. The 492 women in this study were predominantly diagnosed in Stage 1 (51.4%), had college or university education (75.4%), were married or had a partner (74.6%), had been pregnant (90.2%), had taken birth control pills for any reason (86.8%), and had an average body mass index of 26.6. Most had at least one mammogram (83%) with five mammograms the average number. Nearly all reported previously having a breast health examination from a medical practitioner (92.5%). Statistically significant factors identified in the PPO model included protective ones (older age at diagnosis, high household income, parity, smoking, spending time in the sun during high ultraviolet times, having a mammogram and high daily protein intake) and ones that increased risk of later stage at diagnosis (a comorbidity, current stressful situations and high daily caloric intake). Shifting breast cancer stage at diagnosis downwards may potentially be achieved through cancer prevention programs that target higher risk groups such as women with co-morbidities, non-smokers and younger women who may be eligible for breast cancer screening.


Scoping review of acute stroke care management and rehabilitation in low and middle-income countries.
Stroke is a major public health concern, affecting millions of people worldwide. Care of the condition however, remain inconsistent in developing countries. The purpose of this scoping review was to document evidence of stroke care and service delivery in low and middle-income countries to better inform development of a context-fit stroke model of care. An interpretative scoping literature review based on Arksey and O'Malley's five-stage-process was executed. The following databases searched for literature published between 2010 and 2017; Cochrane Library, Credo Reference, Health Source: Nursing/Academic Edition, Science Direct, BioMed Central, Cumulative Index to Nursing and Allied Health Literature (CINNAHL), Academic Search Complete, and Google Scholar. Single combined search terms included acute stroke, stroke care, stroke rehabilitation, developing countries, low and middle-income countries. A total of 177 references were identified. Twenty of them, published between 2010 and 2017, were included in the review. Applying the Donebedian Model of quality of care, seven dimensions of stroke-care structure, six dimensions of stroke care processes, and six dimensions of stroke care outcomes were identified. Structure of stroke care included availability of a stroke unit, an accident and emergency department, a multidisciplinary team, stroke specialists, neuroimaging, medication, and health care policies. Stroke care processes that emerged were assessment and diagnosis, referrals, intravenous thrombolysis, rehabilitation, and primary and secondary prevention strategies. Stroke-care outcomes included quality of stroke-care practice, functional independence level, length of stay, mortality, living at home, and institutionalization. There is lack of uniformity in the way stroke care is advanced in low and middle-income countries. This is reflected in the unsatisfactory stroke care structure, processes, and outcomes. There is a need for stroke care settings to adopt quality improvement strategies. Health ministry and governments need to decisively face stroke burden by setting policies that advance improved care of patients with stroke. Stroke Units and Recombinant Tissue Plasminogen Activator (rtPA) administration could be considered as both a structural and process necessity towards improvement of outcomes of patients with stroke in the LMICs.


The effect of proteolytic enzymes and protease inhibitors on the interaction Trypanosoma cruzi-fibroblasts.
It has been shown previously that the capability to adhere to and infect fibroblastic cells by Trypanosoma cruzi is expressed only partially in trypomastigotes recently liberated from infected fibroblasts, but these parasites can increase several-fold their adhesion and infectivity by a time-dependent extracellular incubation. It is now shown that polyacrylamide gel electrophoresis patterns of 125I-labelled surface proteins of the parasites change during the activation process and that protease inhibitors of diverse specificity can block both these changes and the development of adhesion and infectivity. Treatment of fresh trypomastigotes with different proteases increases immediately adhesion and infection. The effect of trypsin has been studied in detail and it was found that this protease stimulates adhesion 4- to 6-fold, even in trypomastigotes obtained and assayed in the absence of serum. Trypomastigotes incubated for various periods and then exposed to trypsin increase their adhesion to values similar to those attained by prolonged incubation of trypomastigotes alone, but infection is stimulated in fresh trypomastigotes only. Trypomastigotes whose development of activation has been inhibited either by protease inhibitors, puromycin, and tunicamycin, and are thereafter trypsinized, show respectively, that: adhesion and infection are restored immediately to the same high values obtained when untreated controls are trypsinized, adhesion is restored, but not infection, and infection is not restored. These results suggest that the adhesion step of T. cruzi trypomastigotes to fibroblastic cells depends on a membrane protein(s) that is (are) already present in an inactive or hidden form in parasites recently liberated from infected fibroblasts. Upon extracellular maturation of these trypomastigotes this proteins(s) is activated or unmasked, probably through an endogenous proteolytic process, whose expression requires protein synthesis. The penetration step requires biosynthesis of a tunicamycin-sensitive glycoprotein(s) of the parasite and its full expression necessitates serum.


Reproducibility of pulse wave velocity and augmentation index measured by pulse wave analysis.
The aim of this study was to determine the reproducibility of pulse wave velocity (PWV) and augmentation index (AIx) measured using pulse wave analysis (PWA), prior to its use in large-scale clinical trials. Arterial pressure waveforms were recorded and analysed using an established technique (Sphygmocor). Subjects with and without a range of recognized cardiovascular risk factors were studied to provide a wide range of values. Measurements were made after a brief introduction to the technique in a clinical setting. Two observers recorded aortic and brachial PWV in 24 subjects, each on two occasions, in a random order. In a separate study, two different observers used PWA to determine AIx in 33 subjects, each on two occasions, in a random order. Data were analysed using Bland-Altman plots and presented as mean +/- SD. Brachial PWV was 8.65+/-1.58 m/s (range 6.16-10.95 m/s) and aortic PWV was 8.15+/-3.01 m/s (5.01-17.97 m/s). Within-observer variability was 0.14+/-0.82 m/s for brachial PWV and 0.07+/-1.17 m/s for aortic PWV. Corresponding between-observer values were -0.44+/-1.09 m/s and -0.30+/-1.25 m/s. AIx ranged from -15.0 to +45.0%, with a group mean of +19.6+/-12.0%. The within-observer difference was 0.49+/-5.37% and between-observer difference 0.23+/-3.80%. PWA is a simple and reproducible technique with which to measure PWV and AIx. Reproducibility accords with that reported by other workers using different methodologies. PWA may, therefore, be suitable for large-scale population and intervention studies investigating the clinical relevance of vascular stiffness.


Transradial versus transfemoral approach for percutaneous coronary intervention in cardiogenic shock: A radial-first centre experience and meta-analysis of published studies.
The transradial approach for percutaneous coronary intervention (PCI) is associated with a better outcome in myocardial infarction (MI), but patients with cardiogenic shock (CS) were excluded from most trials. To compare outcomes of PCI for MI-related CS via the transradial versus transfemoral approach. A prospective cohort of 101 consecutive patients admitted for PCI for MI-related CS were treated via the transradial (n=74) or transfemoral (n=27) approach. Cox proportional hazards models adjusted for prespecified variables and a propensity score for approach were used to compare mortality, death/MI/stroke and bleeding between the two groups. A complementary meta-analysis of six studies was also performed. Patients in the transradial group were younger (P=0.039), more often male (P=0.002) and had lower GRACE and CRUSADE scores (P=0.003 and 0.001, respectively) and rates of cardiac arrest before PCI (P=0.009) and mechanical ventilation (P=0.006). Rates of PCI success were similar. At a mean follow-up of 756 days, death occurred in 40 (54.1%) patients in the transradial group versus 22 (81.5%) in the transfemoral group (adjusted hazard ratio [HR]: 0.49, 95% confidence interval [CI] 0.28-0.84; P=0.012). The transradial approach was associated with reduced rates of death/MI/stroke (adjusted HR: 0.53, 95%CI: 0.31-0.91; P=0.02) and major bleeding (adjusted HR: 0.34, 95%CI: 0.13-0.87; P=0.02). The meta-analysis confirmed the benefit of transradial access in terms of mortality (relative risk [RR]: 0.63, 95%CI: 0.58-0.68) and major bleeding (RR: 0.43, 95%CI: 0.32-0.59). The transradial approach in the setting of PCI for ischaemic CS is associated with a dramatic reduction in mortality, ischaemic and bleeding events, and should be preferred to the transfemoral approach in radial expert centres.


Methotrexate loading in chitosan nanoparticles at a novel pH: Response surface modeling, optimization and characterization.
The aim of this study was to assess the feasibility of employing a novel but critical formulation pH (6.2) to encapsulate an anionic model drug (methotrexate, MTX) into chitosan(Cs)-tripolyphosphate nanoparticles(NPs). A response surface methodology using a three-level full factorial design was applied studying the effects of two independent variables namely; Cs concentration and MTX concentration. The responses investigated were the entrapment efficiency (EE%), mean hydrodynamic particle size (PS), polydispersity index (PDI) and zeta potential (ZP). In order to simultaneously optimize the series of models obtained, the desirability function approach was applied with a goal to produce high percent of MTX encapsulated into highly charged Cs-TPP NPs of homogenous optimum PS. MTX-loaded CsNPs were successfully prepared at the novel pH applied. The suggested significant models were found quadratic for EE, PS and ZP responses, while 2-factor interaction model for PDI. The optimization overlay graph showed that the maximum global desirability, D=0.856, was reached when the conditions were set at high Cs and MTX concentration. Thus, the use of such optimized conditions, at this novel pH, achieved a maximum drug EE% (73.38%) into NPs characterized by optimum PS (232.6nm), small PDI value (0.195) and highly surface charged (+18.4mV).


Identification of Genes Associated With Hirschsprung Disease, Based on Whole-Genome Sequence Analysis, and Potential Effects on Enteric Nervous System Development.
Hirschsprung disease, or congenital aganglionosis, is believed to be oligogenic-that is, caused by multiple genetic factors. We performed whole-genome sequence analyses of patients with Hirschsprung disease to identify genetic factors that contribute to disease development and analyzed the functional effects of these variants. We performed whole-genome sequence analyses of 443 patients with short-segment disease, recruited from hospitals in China and Vietnam, and 493 ethnically matched individuals without Hirschsprung disease (controls). We performed genome-wide association analyses and gene-based rare-variant burden tests to identify rare and common disease-associated variants and study their interactions. We obtained induced pluripotent stem cell (iPSC) lines from 4 patients with Hirschsprung disease and 2 control individuals, and we used these to generate enteric neural crest cells for transcriptomic analyses. We assessed the neuronal lineage differentiation capability of iPSC-derived enteric neural crest cells using an in vitro differentiation assay. We identified 4 susceptibility loci, including 1 in the phospholipase D1 gene (PLD1) (P = 7.4 × 10-7). The patients had a significant excess of rare protein-altering variants in genes previously associated with Hirschsprung disease and in the β-secretase 2 gene (BACE2) (P = 2.9 × 10-6). The epistatic effects of common and rare variants across these loci provided a sensitized background that increased risk for the disease. In studies of the iPSCs, we observed common and distinct pathways associated with variants in RET that affect risk. In functional assays, we found variants in BACE2 to protect enteric neurons from apoptosis. We propose that alterations in BACE1 signaling via amyloid β precursor protein and BACE2 contribute to pathogenesis of Hirschsprung disease. In whole-genome sequence analyses of patients with Hirschsprung disease, we identified rare and common variants associated with disease risk. Using iPSC cells, we discovered some functional effects of these variants.


Effects of iron glycine chelate on growth, tissue mineral concentrations, fecal mineral excretion, and liver antioxidant enzyme activities in broilers.
The study was conducted to determine the effects of iron glycine chelate (Fe-Gly) on growth, tissue mineral concentrations, fecal mineral excretion, and liver antioxidant enzyme activities in broilers. A total of 360 1-day-old commercial broilers (Ross × Ross) were randomly allotted to six dietary treatments with six replications of ten chicks per replicate. Broilers were fed a control diet with no Fe supplementation, while five other treatments consisted of 40, 80, 120, and 160 mg Fe/kg diets from Fe-Gly, and 160 mg Fe/kg from ferrous sulfate, respectively. After a 42-day feeding trial, the results showed that 120 and 160 mg Fe/kg as Fe-Gly improved the average daily gain (P < 0.05) and average daily feed intake (P < 0.05) of broilers (4-6 weeks). Addition with 120 and 160 mg Fe/kg from Fe-Gly and 160 mg Fe/kg from FeSO(4) increased Fe concentration in serum (P < 0.05), liver (P < 0.05), breast muscle (P < 0.05), tibia (P < 0.05), and feces (P < 0.01) at 21 and 42 days. There were linear responses to the addition of Fe-Gly from 0 to 160 mg/kg Fe on Fe concentration in serum (21 days, P = 0.005; 42 days, P = 0.001), liver (P = 0.001), breast muscle (P = 0.001), tibia (P = 0.001), and feces (21 days, P = 0.011; 42 days, P = 0.032). Liver Cu/Zn superoxide dismutase activities of chicks were increased by the addition of 80, 120, and 160 mg Fe/kg as Fe-Gly to diets at 42 days. There were no differences in liver catalase activities of chicks among the treatments (P > 0.05). This study indicates that addition with Fe-Gly could improve growth performance and iron tissue storage and improves the antioxidant status of broiler chickens.


Studies of the mechanisms of nuclear control over the synthesis of mitochondrial DNA in sea urchin eggs.
We have studied the contribution of nuclear genomic activity and of the cytoskeletal integrity in the negative control operated by the nucleus over the mitochondrial genome. We have found that the nuclear control is exerted even in the presence of nuclei that have undergone heavy irradiation such as to block at least DNA replication and in the absence of intact microtubules. Data are presented which suggest some implication of ion (Ca++) movements in this negative control.


Evaluation of the diagnostic role of transvaginal ultrasound measurements of endometrial thickness to detect endometrial malignancy in asymptomatic postmenopausal women.
To assess the diagnostic accuracy of endometrial thickness measurements of transvaginal ultrasound (TVUS) in asymptomatic postmenopausal women in the detection of endometrial malignancy. A retrospective cohort study in a university hospital was undertaken with 276 consecutive asymptomatic postmenopausal women undergoing dilatation and curettage (D&C) and hysteroscopy for an incidental finding of thickened endometrium (≥4 mm) between 2003 and 2012. Different endometrial thickness cutoff values were tested on the basis of a pathologic report with carcinoma conditions (endometrial hyperplasia with atypia and endometrial carcinoma). The mean age of patients was 59.8 ± 9.0 years. The mean duration of menopause was 11.2 ± 8.9 years. The final pathology diagnoses included 107 (38.8 %) patients with polyps, 42 (15.2 %) with atrophic endometrium, 39 (14.1 %) with estrogen exposure, and 19 (6.9 %) with normal endometrium. With regard to carcinoma conditions, nine patients (3.3 %) had endometrial hyperplasia with atypia and eight patients (2.9 %) had endometrial carcinoma. The area under the ROC curve was 0.52 (95 % CI 0.44-0.57), which indicated a poor accuracy of endometrial thickness of TVUS for carcinoma conditions. Routine use of endometrial thickness measurement with TVUS does not seem to be an effective diagnostic tool for endometrial cancer because it has a low diagnostic performance in asymptomatic postmenopausal women. Further prospective studies are required to assess the endometrial thickness measurement with TVUS as a screening method in these women.


Semicontinuous production of lactic acid from cheese whey using integrated membrane reactor.
Semicontinuous production of lactic acid from cheese whey using free cells of Bifidobacterium longum with and without nanofiltration was studied. For the semicontinuous fermentation without membrane separation, the lactic acid productivity of the second and third runs is much lower than the first run. The semicontinuous fermentation with nanoseparation was run semicontinuously for 72 h with lactic acid to be harvested every 24 h using a nanofiltration membrane unit. The cells and unutilized lactose were kept in the reactor and mixed with newly added cheese whey in the subsequent runs. Slight increase in the lactic acid productivity was observed in the second and third runs during the semicontinuous fermentation with nanofiltration. It can be concluded that nanoseparation could improve the lactic acid productivity of the semicontinuous fermentation process.


Hope and challenge: the importance of ultraviolet (UV) radiation for cutaneous vitamin D synthesis and skin cancer.
Abstract Solar ultraviolet (UV)-radiation is the most important environmental risk factor for the development of non-melanoma skin cancer (most importantly basal and squamous cell carcinomas), that represent the most common malignancies in Caucasian populations. To prevent these malignancies, public health campaigns were developed to improve the awareness of the general population of the role of UV-radiation. The requirements of vitamin D is mainly achieved by UV-B-induced cutaneous photosynthesis, and the vitamin D-mediated positive effects of UV-radiation were not always adequately considered in these campaigns; a strict "no sun policy" might lead to vitamin D-deficiency. This dilemma represents a serious problem in many populations, for an association of vitamin D-deficiency and multiple independent diseases has been convincingly demonstrated. It is crucial that guidelines for UV-exposure (e.g. in skin cancer prevention campaigns) consider these facts and give recommendations how to prevent vitamin D-deficiency. In this review, we analyze the present literature to help developing well-balanced guidelines on UV-protection that ensure an adequate vitamin D-status without increasing the risk to develop UV-induced skin cancer.


Implementation of Postoperative Standard Opioid Prescribing Schedules Reduces Opioid Prescriptions Without Change in Patient-reported Pain Outcomes.
To implement Standard Opioid Prescribing Schedules (SOPS) based on opioid use following urologic surgeries and to evaluate how evidence-based prescribing schedules affect opioid use and patient reported outcomes. Patients who underwent urologic surgeries within 6 procedure subtypes at UNC Health during the 2 study time periods ("pre-SOPS": 7/2017-1/2018, "post-SOPS": 7/2018-1/2019) were invited to complete a survey analyzing postoperative opioid usage, storage and disposal, and patient reported outcomes (including pain interference using a validated questionnaire). A pharmacy database provided medication prescribing data and patient demographics. During the pre-SOPS time period, baseline outcomes were measured. Following the pre-SOPS period, usage amounts were analyzed and Standard Opioid Prescribing Schedules were developed to guide prescriptions during the post-SOPS period. Descriptive summary statistics and appropriate t test or r2 were calculated. A total of 438 patients within 6 procedure types completed the survey (pre-SOPS: 282 patients, post-SOPS: 156 patients). Pre-SOPS, patients were prescribed significantly more 5-mg oxycodone tablets than used (20.9 vs 7.8, P <.001). Post-SOPS, compared to pre-SOPS amounts, patients were prescribed significantly fewer tablets (12.7 vs 20.9, P <.001) and used fewer tablets (5.3 vs 7.8, P = .003). No difference was observed in pain interference (average t-score (standard deviation): 54.33 (10.9) pre-SOPS vs 55.89 (9.1) post-SOPS, P = .125) or patient satisfaction (95% pre-SOPS vs 94% post-SOPS). Adherence to data-driven postoperative opioid prescribing schedules reduce opioid prescriptions and use without compromising pain interference or patient satisfaction. These results have important implications for urologists' ability to decrease opioid prescriptions and fight the opioid epidemic.


Applying Kern's Model to the Development and Evaluation of Medical Student Well-Being Programs.
The Liaison Committee on Medical Education (LCME) requires that well-being programs must be "effective." Yet most medical schools do not robustly assess their well-being programs. Most evaluate their programs using one question on the Association of American Medical College's annual Graduation Questionnaire (AAMC GQ) survey for fourth-year students on their satisfaction with well-being programs, which is inadequate and nonspecific and only assesses a specific time in training. In this perspective, we, as members of the AAMC Group on Student Affairs (GSA) - Committee on Student Affairs (COSA) Working Group on Medical Student Well-being, suggest adapting Kern's 6-step approach to curriculum development as an effective framework to guide the development and evaluation of well-being programs. We suggest strategies for applying Kern's steps to well-being programs, with attention to conducting needs assessments, identifying goals, implementation, and evaluation and feedback. While each institution will have unique goals emerging from their needs assessment, we put forth five common medical student well-being goals as examples. Applying a rigorous and structured approach to developing and evaluating undergraduate medical education well-being programs will involve defining a guiding philosophy and clear goals and implementing a strong assessment strategy. This Kern-based framework can help schools meaningfully assess the impact of their initiatives on student well-being.


Whole Exome Sequencing Identified two Novel Truncation Mutations in the CTNNB1 Gene Associated with Neurodevelopmental Disorder, Language Dysfunction, and Microcephaly in Chinese Children.
Recently, the loss-of-function, heterozygous, and de novo mutations of the CTNNB1 gene have been proven to be partially responsible for intellectual disability in some patients. Herein, we report two unrelated children with neurodevelopmental disorder, abnormal facial features, speech impairments, microcephaly, and dystonia. Based on whole exome sequencing (WES), two new heterozygous and pathogenic mutations in exon 10 (c.1586dupA:p.Q530Afs*42) and exon 4 (c.257dup:p.Y86*) were identified in the CTNNB1 gene for the first time. These findings not only enrich the genetic spectrum of the CTNNB1 gene but also provide evidence for its role in neuronal development.


Targeting autophagy in cardiac ischemia/reperfusion injury: A novel therapeutic strategy.
Acute myocardial infarction (AMI) is one of the leading causes of morbidity worldwide. Myocardial reperfusion is known as an effective therapeutic choice against AMI. However, reperfusion of blood flow induces ischemia/reperfusion (I/R) injury through different complex processes including ion accumulation, disruption of mitochondrial membrane potential, the formation of reactive oxygen species, and so forth. One of the processes that gets activated in response to I/R injury is autophagy. Indeed, autophagy acts as a "double-edged sword" in the pathology of myocardial I/R injury and there is a controversy about autophagy being beneficial or detrimental. On the basis of the autophagy effect and regulation on myocardial I/R injury, many studies targeted it as a therapeutic strategy. In this review, we discuss the role of autophagy in I/R injury and its targeting as a therapeutic strategy.


Induction of sister-chromatid exchanges in cultured human cells by an organophosphorous insecticide: malathion.
Because malathion is a widely used organophosphorous insecticide, the effects of non-toxic concentrations (2.5--40 micrograms/ml) on sister-chromatid exchange (SCE) frequencies were determined. Human fetal fibroblasts were exposed once or twice to malathion, with 20 h between exposures. A single exposure to a concentration of 40 micrograms/ml resulted in a highly significant increase in the number of SCEs. After a double exposure, a concentration of 20 micrograms/ml induced an even greater increase in SCE frequencies. Comparison of Sce frequencies after single and double exposures indicated a cumulative effect; the number of exchanges at concentrations of 5 micrograms/ml or higher was significantly greater after the double exposure. An analysis of SCEs by chromosome group showed that exchanges were distributed approximately according to chromosome length.


Mixed-matrix membranes with enhanced antifouling activity: probing the surface-tailoring potential of Tiron and chromotropic acid for nano-TiO2.
Mixed-matrix membranes (MMMs) were developed by impregnating organofunctionalized nanoadditives within fouling-susceptible polysulfone matrix following the non-solvent induced phase separation (NIPS) method. The facile functionalization of nanoparticles of anatase TiO2 (nano-TiO2) by using two different organoligands, viz. Tiron and chromotropic acid, was carried out to obtain organofunctionalized nanoadditives, FT-nano-TiO2 and FC-nano-TiO2, respectively. The structural features of nanoadditives were evaluated by X-ray diffraction, X-ray photoelectron spectroscopy, Raman and Fourier transform infrared spectroscopy, which established that Tiron leads to the blending of chelating and bridging bidentate geometries for FT-nano-TiO2, whereas chromotropic acid produces bridging bidentate as well as monodentate geometries for FC-nano-TiO2. The surface chemistry of the studied membranes, polysulfone (Psf): FT-nano-TiO2 UF and Psf: FC-nano-TiO2 UF, was profoundly influenced by the benign distributions of the nanoadditives enriched with distinctly charged sites ([Formula: see text]), as evidenced by superior morphology, improved topography, enhanced surface hydrophilicity and altered electrokinetic features. The membranes exhibited enhanced solvent throughputs, viz. 3500-4000 and 3400-4300 LMD at 1 bar of transmembrane pressure, without significant compromise in their rejection attributes. The flux recovery ratios and fouling resistive behaviours of MMMs towards bovine serum albumin indicated that the nanoadditives could impart stable and appreciable antifouling activity, potentially aiding in a sustainable ultrafiltration performance.


Heparanases and tumor metastasis.
The successful penetration of endothelial basement membranes is an important process in the formation of hematogenous tumor metastases. Heparan sulfate (HS) proteoglycan is a major constituent of endothelial basement membranes, and we have found that HS-degradative activities of metastatic B16 melanoma sublines correlate with their lung-colonizing potentials. The melanoma HS-degrading enzyme is a unique endo-beta-D-glucuronidase (heparanase) that cleaves HS at specific intrachain sites and is detectable in a variety of cultured human malignant melanomas. The treatment of B16 melanoma cells with heparanase inhibitors that have few other biological activities, such as N-acetylated N-desulfated heparin, results in significant reductions in the numbers of experimental lung metastases in syngeneic mice, indicating that heparanase plays an important role in melanoma metastasis. HS-degrading endoglycosidases are not tumor-specific and have been found in several normal tissues and cells. There are at least three types of endo-beta-D-glucuronidases based on their substrate specificities. Melanoma heparanase, an Mr approximately 96,000 enzyme with specificity for beta-D-glucuronosyl-N-acetylglucosaminyl linkages in HS, is different from platelet and mastocytoma endoglucuronidases. Elevated levels of heparanase have been detected in sera from metastatic tumor-bearing animals and malignant melanoma patients, and a correlation exists between serum heparanase activity and extent of metastases. The results suggest that heparanase is potentially a useful marker for tumor metastasis.


Microsurgical Clip Ligation of Ruptured, Previously Coiled A2-A3 Aneurysm Through Interhemispheric Approach in a Pediatric Patient.
Previously ruptured aneurysms treated with coil occlusion are at risk of recurrence and require thoughtful strategic planning for adequate aneurysm occlusion.1-3 Alternative strategies, such as coil extraction or trapping and bypass, are options when simple clipping is not feasible.2 A 15-year-old boy presented with a Hunt and Hess grade 4, Fisher grade 4 subarachnoid hemorrhage from a ruptured distal anterior cerebral artery aneurysm. The patient initially underwent coil embolization and craniotomy to evacuate an extensive corpus callosum hemorrhage. Follow-up angiography demonstrated early recurrence of the aneurysm. Subsequently, the patient underwent microsurgical clipping through an anterior interhemispheric approach, while carefully preserving a large venous complex to avoid potentially devastating venous infarction (Video 1).4-9 In this surgical video, we review the case presentation, surgical anatomy, operative technique, and postoperative course and outcome. We also describe various operative strategies with anatomical illustrations. The patient gave verbal consent for participating in the procedure and surgical video.


The effect of morphological variability of Dorello's canal on surgical procedures - a review.
Dorello's canal is an arched structure of bone-fibrous character located in the petroclival venous confluence atop the petrosal bone in the petroclival region. It is bordered by the petrosphenoidal ligament, the petrous part of the temporal bone and the lateral border of the upper part of clivus. Its content in the vast majority of variants comprises the abducens nerve, the inferior petrosal sinus, the venous drainage and the dorsal meningeal artery or its medial branch. With the development of microsurgical techniques, this area has gained huge clinical importance, mainly concerning the order in which the above-mentioned elements (especially the position of the abducens nerve) are arranged in relation to each other. These structures appear in different variant forms and necessitate an individual clinical approach. The main purpose of this review is to present condensed information about possible intercorrelations among them and to indicate, on the basis of the available literature and research, possible surgical approaches and the need to consider the variability when treatments in this region are planned.


Xerophilic aflatoxigenic black tea fungi and their inhibition by Elettaria cardamomum and Syzygium aromaticum extracts.
Black tea is consumed worldwide and is believed to play a role in cancer prevention. Xerophilic aflatoxigenic fungi are highly hazardous contaminants of tea since they are associated with tea quality impairment and human health risk. The present study reports isolation of such xerophilic and aflatoxigenic fungi associated with marketed tea. Twenty different tea samples collected from the local markets of Tamilnadu, India were investigated for fungal contamination. The results indicated contamination by 0.38% Aspergillus flavus. Other common contaminant fungi including Penicillium spp. (0.30%), Pacelomyces spp. (0.14%), and Mucor spp. (0.19%) were also isolated. Amongst the fungi isolated Aspergillus niger ML01 and A. flavus ML02 were found to be xerophilic aflatoxigenic mycoflora. Phylogenetic analysis based on 28S rRNA revealed their close ancestry. The chloroform and acetone extracts of spices Elettaria cardamomum and Syzygium aromaticum exhibited antifungal inhibitory activity on growth and toxin elaboration of both these xerophilic tea contaminants A. niger ML01 and A. flavus ML02. The results advocate the use of these spices plant or their extracts as novel antimicrobials which may add preservation and flavour in marketed tea.


Neuropeptide Y inhibits thyrotropin-releasing hormone-induced stimulation of melanotropin release from the intermediate lobe of the frog pituitary.
Previous studies have shown that the release of melanotropin from frog neurointermediate lobes is under the control of two neuropeptides: thyrotropin-releasing hormone (TRH) stimulates, while neuropeptide Y (NPY) inhibits alpha-melanocyte-stimulating hormone (alpha-MSH) secretion from intact neurointermediate lobes in vitro. The aim of the present study was to investigate possible interactions between the two regulatory peptides at the pituitary level. Whole neurointermediate lobes or acutely dispersed pars intermedia cells from Rana ridibunda were perifused in vitro for 2 to 7.5 hr and the concentrations of alpha-MSH released into the effluent perifusate were monitored by radioimmunoassay. Administration of TRH (10(-7) M) or NPY (10(-7) M) to dispersed cells induced, respectively, marked stimulation or inhibition of alpha-MSH release. The effects of the two neuropeptides were similar to those observed using intact neurointermediate lobes, suggesting that TRH and NPY act directly on melanotropic cells. Perifused whole neurointermediate lobes were exposed to NPY (10(-8) to 3 x 10(-7) M) for 120 min and a single dose of TRH (10(-8) M) was administered during the prolonged infusion of NPY. Using this procedure, we observed a dose-dependent inhibition of TRH-evoked alpha-MSH release. These data support the concept that TRH and NPY act through a common intracellular pathway to regulate alpha-MSH release.


Lipid Metabolism is Closely Associated with Normal Testicular Growth Based on Global Transcriptome Profiles in Normal and Underdeveloped Testis of Obese Zucker (fa/fa) Rats.
Zucker (fa/fa) obese rats often have non-identical and differently sized paired testes, leaving one testis underdeveloped. Our earlier study found that the underdeveloped testes, > 30% smaller than the normal ones, have a selective decrease in docosapentaenoic acid (22:5n-6), a dominant fatty acid in the testes. This study was conducted to examine global testicular transcriptome profile in underdeveloped testes relative to developed ones using Rat Gene 2.0 ST Array (Affymetrix, USA). Testes were obtained from 14-week-old, sexually mature male obese (fa/fa) Zucker rats. Out of the 1790 transcripts differentially expressed, 1108 and 682 were over-expressed in the underdeveloped and normal testis, respectively (fold change ≥ 2 and P < 0.05). The ingenuity pathway analysis indicated that transcripts that were under-expressed in the underdeveloped testis, relative to the normal testes, are involved in triacylglycerol biosynthesis, sphingomyelin metabolism and phosphatidylglycerol biosynthesis. Transcripts that were over-expressed in underdeveloped testes, relative to normal testis, are involved in the production of nitric oxide and reactive oxygen species, and nuclear factor (erythroid-derived 2)-like 2 mediated oxidative stress responses. These data indicate that genes involved in lipid metabolism and oxidative stress play a crucial role in testicular growth and the maintenance of testical health.


Taxonomy of several tobamoviruses from China as determined by molecular hybridization analysis with complementary DNA.
Molecular hybridization analysis (MHA) was used to show that several tobamoviruses isolated in China (namely Populus bushy top virus, Dihuang degeneration virus, common tobacco mosaic virus, tomato mosaic virus and a mutant of tomato mosaic) are closely related to the U1 strain of tobacco mosaic virus (TMV-U1). Youcai mosaic virus from rape is a distinct virus unrelated by MHA to the TMV-U1 group or to several other definitive representatives of the tobamoviruses.


Relationship-Based Care for Newborns With Down Syndrome and Endocardial Cushion Defect.
Down syndrome with endocardial cushion defect is a challenging diagnosis for parents as well as members of the health care team. Utilizing a framework of relationship-based care, nurses are in a position to positively affect parents' experience by providing education, advocacy, and support from initial diagnosis through discharge. The plan of care is multidisciplinary and focuses on critical developmental needs, such as bonding and feeding. Because Down syndrome is associated with multiple anomalies, anticipatory guidance is needed to assist parents with establishing a health maintenance plan for their child after discharge.


Decoding trajectories of imagined hand movement using electrocorticograms for brain-machine interface.
Objective. Reaching hand movement is an important motor skill actively examined in the brain-computer interface (BCI). Among the various components of movement analyzed is the hand's trajectory, which describes the hand's continuous positions in three-dimensional space. While a large body of studies have investigated the decoding of real movements and the reconstruction of real hand movement trajectories from neural signals, fewer studies have attempted to decode the trajectory of the imagined hand movement. To develop BCI systems for patients with hand motor dysfunctions, the systems essentially have to achieve movement-free control of external devices, which is only possible through successful decoding of purely imagined hand movement.Approach. To achieve this goal, this study used a machine learning technique (i.e. the variational Bayesian least square) to analyze the electrocorticogram (ECoG) of 18 epilepsy patients obtained from when they performed movement execution (ME) and kinesthetic movement imagination (KMI) of the reach-and-grasp hand action.Main results. The variational Bayesian decoding model was able to successfully predict the imagined trajectories of the hand movement significantly above the chance level. The Pearson's correlation coefficient between the imagined and predicted trajectories was 0.3393 and 0.4936 for the KMI (KMI trials only) and MEKMI paradigm (alternating trials of ME and KMI), respectively.Significance. This study demonstrated a high accuracy of prediction for the trajectories of imagined hand movement, and more importantly, a higher decoding accuracy of the imagined trajectories in the MEKMI paradigm compared to the KMI paradigm solely.


Sustained clinical improvement of Parkinson's disease in two patients with facially-transplanted adipose-derived stromal vascular fraction cells.
Cell-based therapy has been studied as an alternative for Parkinson's Disease (PD), with different routes of administration. The superficial fascia and facial muscles possess a rich blood supply, while venous and lymphatic access via the orbit and the cribriform plate provide a route to cerebral circulation. We here document positive clinical effects in two patients with PD treated with autologous adipose-derived stromal vascular fraction (SVF) cell preparation, implanted into the face and nasal cavity. Two patients with PD were transplanted with 60 million total nucleated cells in processed SVF into the facial muscles and nose. Serial evaluations were carried out up to 5 years (patient 1) and 1 year (patient 2), using the PDQ-39, the UPDRS, and serial videos. Video scoring was reviewed in a blinded fashion. Both patients reported qualitative improvement in motor and nonmotor symptoms following injection. Quantitatively, PDQ-39 scores decreased in all categories for both. On-medication UPDRS motor scores decreased in both (20 to 4 in patient 1, 18 to 3 in patient 2) despite taking the same or less medication (LEDD 350 to 350 in patient 1, LEDD 1175 to 400 in pt2). Both subjects had off-medication UPDRS scores similar to their pretreatment on-medication scores (20 to 14 in patient 1, 18 to 23 in patient 2). These preliminary findings describe local facial and nasal injections of SVF preparation followed by prolonged clinical benefit in two patients. Despite an unknown mechanism of action, this potential therapy warrants careful verification and investigation.


Detection of circulating antigen during acute infections with Toxoplasma gondii by enzyme-linked immunosorbent assay.
The serodiagnosis of toxoplasmosis is usually based on demonstration of antibodies by means of different serological methods. However, for confirmation of active toxoplasmosis, examination of paired sera is still needed. In this study a description is given of a sensitive enzyme method (enzyme-linked immunosorbent assay) with which it is possible to detect circulating antigens during the acute stage of mouse and human toxoplasmosis. Preliminary investigations of human sera suggested that circulating antigens are only found during a short period (active phase) of the toxoplasma infection and that they can be found in cases of fresh infections as well as during reinfections. The possible clinical relevance is discussed.


Altering the perceptions of WIC health professionals about childhood obesity using video with facilitated group discussion.
To determine if viewing a documentary video, followed by facilitated group discussion, could alter the perceptions of those providing public health nutrition services about the barriers and solutions to addressing the problem of obesity in low-income preschoolers. Before-after trial to determine how often study participants could identify any of the 17 barriers and seven solutions targeted in the video and during the facilitated group discussion. One hundred fifty-five attendees of the 2001 Kentucky Maternal and Child Health Conference participated in the study. Sixty percent were nurses, 24% were dietitians or nutritionists, and 64% had Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) counseling experience. Participants first viewed a 20-minute documentary video about three families enrolled in WIC. A 40-minute facilitated group discussion followed to highlight the 17 barriers (eg, WIC families are struggling with many demands in their lives that make nutrition a low priority and WIC health professionals "lecture" clients on what they "need to know") and seven solutions (eg, adjusting WIC counseling to assess parenting skills and to increase sensitivity to clients' life context and stresses). MAIN OUTCOME MEASURES/ANALYSES: Participants responded before and after the intervention to the same two open-ended questions, one about barriers and one about solutions. Participant responses were coded to count instances of identifying any of the 17 barriers and seven solutions. At baseline, 51% of participants were unable to record any of the barriers, and 91% could not identify any of the solutions. After the intervention, 37% could identify at least one more of the target barriers than they did at baseline, and 24% could identify at least one more of the target solutions. A documentary-style video, used with facilitated group discussion, can produce a short-term change in the perceptions of those providing public health nutrition services about addressing the problem of obesity in low-income preschool children.


Gender Differences do not Influence the Blood Coagulopathy in Patients Undergoing Total Knee Arthroplasty: A Retrospective Thromboelastography Analysis.
Deep vein thrombosis (DVT) is one of the severe complications after total knee arthroplasty (TKA). Gender has been considered to influence the incidence of the thrombosis formation in TKA patients. However, it remains controversial which gender would be more prone to form thrombosis. The aim of this study was to assess the effects of gender differences on coagulation status after TKA via the thromboelastography (TEG). A total of 57 male patients who underwent primary TKA from September 2015 to January 2021 were included in this study. According to the matching principle of age, body mass index (BMI), and anticoagulation treatment, 60 female patients were selected. The conventional coagulation tests, routine blood tests, and thromboelastography were conducted before the operation, 1 day and 7 days after the operation. In addition, Doppler ultrasound was also performed 1 day before the operation and at the 7 days after the operation. The parameters of conventional coagulation tests, routine blood tests, and thromboelastography were compared between the two groups. There were no significant differences in the blood transfusion rate, the incidence of DVT during the perioperative period, D-dimer (D-D), fibrin degradation products (FDP), hemoglobin (HB), hematocrit (HCT), prothrombin time (PT), activated partial thromboplastin time (APTT), and C-reactive protein (CRP) at any corresponding time point between the male group and the female group (P > .05). There were no significant differences in neutrophil-to-lymphocyte ratio (NLR) preoperatively; however, there were significant differences in NLR 1 day after the surgery and 7 days after the surgery between the two groups (P < .05). There were significant differences in reaction time (R) and α angle 1 day after the surgery between the two groups (P < .05), but there were no significant differences in other TEG indexes at any corresponding time point between the two groups (P > .05). Binary logistic regression analysis demonstrated that gender, age, BMI, tourniquet application time were not independent predictors (P > .05). Gender differences have no significant influence in TKA patients with regard to conventional coagulation tests and thromboelastography.


Swainsonine toxicosis suppresses appetite and retards growth in weanling rats.
Two groups of weanling rats were treated with swainsonine, the toxin responsible for 'pea-struck' and locoism in grazing animals, for 21 days. The initial dose rate was 46 mg kg-1 d-1 in one group, and 7.6 mg kg-1 d-1 in the other. Food and water intake, urinary volume and bodyweight gain were recorded for each rat and compared with those for pair-fed and ad libitum fed control individuals. At both dose rates, swainsonine caused marked retardation of growth consequent to profound suppression of appetite. In intoxicated rats, intake of water was also diminished.


Siglec1 suppresses antiviral innate immune response by inducing TBK1 degradation via the ubiquitin ligase TRIM27.
Type I interferon (IFN) production plays pivotal roles in host antiviral innate immune responses, but an excessive production of type I IFN leads to the development of immunopathological conditions. Investigations on the regulatory mechanisms underlying host type I IFN production are currently of great interest. Here, we found that the expression of lectin family member Siglec1 was upregulated by viral infection in macrophages, which was dependent on the IFN/JAK/STAT1 signaling pathway. Siglec1 was found to negatively regulate viral infection-triggered type I IFN production. Mechanistically, Siglec1 associates with DAP12 to recruit and activate the scaffolding function of SHP2; SHP2 then recruits E3 ubiquitin ligase TRIM27, which induces TBK1 degradation via K48-linked ubiquitination at Lys251 and Lys372. Therefore, viral infection-induced upregulation of Siglec1 feedback loop inhibits type I IFN production and suppresses antiviral innate immune responses. Our study outlines a novel mechanism of negative regulation of type I IFN production, which may help virus to escape immune elimination.


Intra-abdominal venous thrombosis after colectomy in pediatric patients with chronic ulcerative colitis: incidence, treatment, and outcomes.
Children with chronic ulcerative colitis (CUC) are at increased risk for venous thromboembolism, especially after colectomy procedures. We aim to review our patients with CUC who underwent a colectomy and suffered intra-abdominal thrombosis; moreover we wanted to define thrombotic incidence and outcomes In this is IRB approved retrospective study, we reviewed our patients who underwent colectomy for CUC from January 1999 to December 2011 for development of intra-abdominal thrombosis. Of 366 patients with CUC who underwent colectomy, 15 (4%) were diagnosed with a venous thromboembolism. All patients presented with acute abdominal pain. The locations of thrombus formation varied: 13 (87%) developed thrombi in the portal vein, 4 (27%) in the splenic vein, 2 (13%) in the superior mesenteric vein, 1 (7%) in the hepatic vein, and 1 (7%) in the hepatic artery. The mean number of post-operative days at diagnosis of thrombus was 38.7 days (range 3-180 days). Fourteen patients (93%) underwent anticoagulation for treatment. The mean number of days of anticoagulant therapy until documented resolution of thrombus on imaging was 96.3 days (range 14-364 days). All thrombi resolved with therapy. There was no mortality during follow-up. Four percent of our pediatric patients with chronic ulcerative colitis who underwent colectomy developed symptomatic intra-abdominal venous thromboembolism. 3 to 6 months of anticoagulant therapy is adequate treatment in almost all patients. Practitioners should have a high index of suspicion for intra-abdominal venous thrombus when these patients complain of abdominal pain postoperatively. Based on our experience, prophylactic anticoagulation should be strongly considered peri-operatively in this population.


[Fractional composition and methylation of liver cell nucleus histones during the early stages of radiation injury].
The radiation injury affects the quantitative ratio of histone fractions. The most pronounced changes in the percentage content towards a decrease are observed for the fractions F2a1 and F2a2 as well as for F2a 12 h and 24 h after irradiation, respectively. An increase by 41.8% is observed in the content of the fractions F2b+F3 12 h after irradiation. The methylation for all histones of the fractions increases considerably 2 h after irradiation, drops 12 h later in the fractions F2a1 and F3 and 24 h later in the fractions F3 and F1 as compared to the normal level.


Early-life exposure to the organophosphorus flame-retardant tris (1,3-dichloro-2-propyl) phosphate induces delayed neurotoxicity associated with DNA methylation in adult zebrafish.
Early-life exposure to toxicants could affect health outcomes in adulthood. We determined the effects of early-life exposure to the organophosphorus flame-retardant tris (1,3-dichloro-2-propyl) phosphate (TDCIPP) in adult zebrafish. Embryos were exposed to TDCIPP from early embryogenesis (2 h post-fertilization) to 10 days post-fertilization (dpf), and larvae were transferred to clean water until adulthood (150 dpf). TDCIPP showed accumulation in larvae, but returned to control levels after 7 days of depuration. In adult zebrafish exposed to TDCIPP in early life, vulnerability to anxiety-like behavior was observed in females but not males, suggesting gender-dependent neurotoxicity. Decreased dopamine (DA) concentration and down-regulation of dopaminergic signaling related genes were observed in the brains of adult females. Upregulation of DNA methylation transferases (dnmt1, dnmt3a, and dnmt3b) genes were observed in larvae and brains of adult females. Further, the promoter regions of the selected key genes (bdnf, drd4b, zc4h2 and th) showed increased DNA methylation status, accompanied by down-regulation of gene transcription in larvae and brains of adult females. Our results indicate that early-life exposure to TDCIPP could cause delayed neurotoxicity in adult zebrafish.


The endocrine basis of benign breast disorders.
There is sound clinical evidence that many benign breast conditions, especially pain, nodularity, and cysts, are likely to have their pathogenesis in hormonal events during reproductive life. Yet the classical theories of persisting hyperestrogenism and luteal progestogen deficiency have not stood up to detailed investigation. Recent work has demonstrated the importance of dynamic hormonal changes and of chronobiological rhythms--daily, menstrual, and seasonal. Recent developments and findings are reviewed to point to the directions in which the basic etiology of these conditions is likely to be discovered.


Conventional assessment of needle biopsy specimens is more useful than digital image analysis of proliferation and DNA ploidy in prediction of positive surgical margins at radical prostatectomy.
The preoperative prediction of the likelihood of positive surgical margins (+SMs) at radical retropubic prostatectomy (RRP) may be useful for counseling and determining the surgical approach. The aim of this study was to assess the additional value of digital image analysis (DIA) of ploidy and proliferation on needle biopsies, in addition to the known preoperative predictors of +SMs at RRP. We identified 454 patients treated by RRP at our institution from 1995 to 1998 for prostate cancer verified by transrectal ultrasound-guided biopsy, with a specimen adequate for DIA. Patients receiving preoperative hormonal therapy were excluded. The clinical features, transrectal ultrasound-guided biopsy findings, and DIA evaluation of MIB-I immunostaining and DNA ploidy were assessed in a multivariate logistic regression model to predict for +SMs at RRP. The mean +/- SD age at treatment was 64.5 +/- 6.5 years, the percentage of positive cores was 40.4% +/- 24.3%, the median prostate-specific antigen level was 6.3 ng/mL (range 0.6 to 112.0), median biopsy Gleason score was 6 (range 4 to 9), and median percentage of diploid nuclei was 67% (range 0% to 100%). Of the 454 patients, 185 (40.7%) had +SMs; this finding was time dependent (1995 to 1996, 45% and 1997 to 1998, 31%; P = 0.004). Univariately, preoperative prostate-specific antigen, biopsy Gleason score, extent of cancer on biopsy, MIB-1 expression, percentage of diploid or nondiploid nuclei, and year of surgery were predictive for +SMs. On multivariate analysis, the preoperative prostate-specific antigen level, biopsy Gleason score, percentage of positive cores, and year of surgery remained significant. The results of our study have shown that the likelihood of +SMs at RRP is best predicted on the basis of conventional prognostic factors. The DIA features of needle biopsies did not provide additional predictive power.


Determinants of demand: method selection and provider preference among US women seeking abortion services.
Medication abortion has the potential to increase abortion availability, primarily through new provider networks; however, without a better understanding of how and why women make decisions regarding both their abortion method and their provider, expansion efforts may be misguided and valuable resources may be wasted. We undertook an exploratory study to investigate method and provider preferences. Semistructured one-on-one interviews were conducted with 205 abortion clients at three family planning clinics. Study participants greatly preferred the clinic setting for their abortion; the majority of women in the study would not have gone to their regular physician if they had been given the option. In addition, method choice trumps provider choice for the majority of women who would have preferred their regular provider. Participants who chose the aspiration procedure were more likely to have previous knowledge about the medication method. Travel time was not a predictor of preferring one's regular physician over the clinic. Expanding provider networks via the private sector is unlikely to be a panacea. In addition to these efforts, more attention may need to be paid to addressing logistic barriers to access. Physicians offering abortion services need to let their patients know they offer such services prior to their patients' need for them. Questions remain regarding the information being circulated about medication abortion.


Trends in drug development: the 1985-86 new drug approvals.
New drug approvals in 1985 and 1986 were analyzed to determine whether any new trends have emerged in the US drug development process. Fifty-three new drugs (including three biologic products) were approved during this period; 46 met the Center for the Study of Drug Development's definition of a new chemical entity (NCE). More than 70% of the 46 approvals were granted in the fourth quarter, 50% in December alone. Four were FDA classified as 1A (important therapeutic gain), 24 as 1B (modest gain), and 16 as 1C (little or no gain); two biologics were not classified. Nine drugs were given orphan status. For the 37 non-orphan drugs, the duration of the "development phase" (IND filing to NDA submission) was 5.6 years; the "review phase" (NDA submission to approval) was 2.6 years; and the "total time" (IND filing to NDA approval) was 8.2 years. Review phase for the four 1A drugs was 2.4 years; for the 24 1B drugs, 2.6 years; for the 16 1C drugs, 2.8 years; and for the nine orphan drugs, 2.7 years. Of the 46 drugs, 33 (71.7%) were available in foreign markets prior to US approval with a mean of 5.5 years of prior marketing. Although the total of 46 NCE approvals in 1985 and 1986 represents a two-year high, there has been a dramatic shift towards fourth quarter approvals. Lengths of the development and FDA review phases are in keeping with those values for previous years.


Interference in melanoma CD248 function reduces vascular mimicry and metastasis.
Tumor vascular mimicry is an emerging issue that affects patient survival while having no treatment at the current moment. Despite several factors implicated in vascular mimicry, little is known about stromal factors that modulate tumor microenvironment and shape malignant transformation. CD248, a type-I transmembrane protein dominantly expressed in stromal cells, mediates the interaction between cells and extracellular matrix proteins. CD248 protein expression is associated with the metastatic melanoma phenotype and promotes tumor progression in the stromal cells. This study aimed to explore the cell-autonomous effects of CD248 in melanoma vascular mimicry to aid cancer therapy development. Loss-of-function approaches in B16F10 melanoma cells were used to study the cell-autonomous effects of CD248 on cell adhesion, migration, proliferation, and vascular mimicry. A solid-phase binding assay was performed to identify the interaction between CD248 and fibronectin. Horizontal and vertical cell migration assays were performed to analyze cell migration activity, and cell-patterned network formation on Matrigel was used to evaluate vascular mimicry activity. Recombinant CD248 (rCD248) proteins were generated, and whether rCD248 interfered with melanoma CD248 functions was evaluated in vitro. An experimental lung metastasis mouse model was used to investigate the effect of rCD248 treatment in vivo. CD248 protein expression in melanoma cells was increased by a fibroblast-conditioned medium. Knockdown of CD248 expression significantly decreased cell adhesion to fibronectin, cell migration, and vascular mimicry in melanoma cells. The lectin domain of CD248 was directly involved in the interaction between CD248 and fibronectin. Furthermore, rCD248 proteins containing its lectin domain inhibited cell adhesion to fibronectin and slowed down cell migration and vascular mimicry. Treatment with rCD248 protein could reduce pulmonary tumor burden, accompanied by a reduction in vascular mimicry in mice with melanoma lung metastasis. CD248 expression in melanoma cells promotes malignant transformation by increasing the activity of cell adhesion, migration, and vascular mimicry, whereas rCD248 protein functions as a molecular decoy interfering with tumor-promoting effects of CD248 in melanoma cells.


Comparison between Different Groups of Vegetarianism and Its Associations with Body Composition: A Literature Review from 2015 to 2021.
Vegetarian and vegan diets have become increasingly popular in the last years for many reasons, including their association with various health benefits when compared to omnivorous diets. The main objective of the study was to collect recent (2015-2021) scientific evidence for potential implications between a vegetarian/vegan diet and an individuals' body composition. A literature search was conducted in PubMed, with 22 studies selected for inclusion in our collective evaluation. Of the 22 studies included, there were 12 randomized controlled trials, 1 nonrandomized controlled trial, 1 comparative study, and 8 cross-sectional. The overall sample included in this study consists of 436,178 participants, 10,090 of whom were vegetarians, 5044 vegans, and 421,044 omnivores. Most studies, 17 out of 22, reported a significant positive relationship between a plant-based diet and body composition. There is scientifically sound evidence that vegan or vegetarian diets are associated with weight and body mass index reduction and, in some cases, fat mass distribution changes.


Structure-switching fluorescence aptasensor for sensitive detection of chloramphenicol.
The performance of chloramphenicol aptamer, including binding thermodynamics, structure switching, and binding domain, was investigated by isothermal titration calorimetry, circular dichroism, and molecular docking. Then, a new fluorescence aptasensor was developed with signal amplification mediated by exonuclease I-catalyzed reaction and hybridization chain reaction (HCR) for chloramphenicol detection. In this system, the aptamer-binding domain is blocked by the initiator of HCR, the aptamer undergoes structure switching in the presence of chloramphenicol, and DNA dissociation occurs. The released aptamer is subsequently recognized and cleaved by Exo I to set free chloramphenicol. With the Exo I-assisted chloramphenicol recycling, an increasing number of initiators were exposed from the digestion of the initiator-aptamer complex. Then, the chain-like assembly of FAM labeled H1 and H2 through HCR was triggered by the initiator, generating a long DNA polymer. Under optimum conditions, the aptasensor exhibited a log-linear range from 0.001 to 100 nM of chloramphenicol and a detection limit of 0.3 pM. Additionally, the designed biosensing platform was applied to determine chloramphenicol in milk and lake water with high accuracy. The current approach provides a new avenue to develop sensitive aptasensors with the assistance of binding mechanism between aptamer and target compounds. Graphical abstract.


The importance of continued exercise participation in quality of life and psychological well-being in previously inactive postmenopausal women: a pilot study.
Exercise and physical activity provide a wide range of health benefits for postmenopausal women, although the impact of maintained exercise participation on psychological well-being is unclear. An exploration of continued exercise participation in psychological well-being after a moderate-intensity exercise program in previously inactive postmenopausal women was therefore undertaken. : Twenty-three healthy sedentary postmenopausal women (age 56 +/- 4 years) were randomly assigned to two groups. All participants completed the Short Form-36, Hospital Anxiety and Depression Scale (HADS), and Health Anxiety Questionnaire (HAQ) and then began a 6-week walking program at 50% heart rate reserve defined by (.-)V(O(2)) treadmill testing. Post-intervention, all participants underwent (.-)V(O(2)) treadmill testing and questionnaires. Group 1 was then instructed to continue exercising, whereas group 2 was instructed to desist for an additional 6-week period. On completion of the 6-week follow-up, participants completed a final set of questionnaires. Participants performed 97% of the prescribed 15-hour (900 minute) exercise program (875.1 +/- 177.4 minutes) in an average of 26 +/- 5 sessions. Total HAQ (P = 0.001), health worry (P = 0.001), fear of illness (P = 0.037), reassurance seeking behavior (P = 0.037), SF-36 well-being (P = 0.037), total HADS (P = 0.019), and HADS depression (P = 0.015) improved significantly following the exercise program. At follow-up, group 1 had lower HADS anxiety (P = 0.013), total HADS (P = 0.02), total HAQ (P = 0.03), and HAQ interference with life (P = 0.03) and significantly higher SF-36 energy (P = 0.01) than group 2. Healthy postmenopausal women gain significant psychological benefit from moderate-intensity exercise. However, exercise participation must continue to maintain improvements in psychological well-being and quality of life.


Glial conditioned media inhibit the proliferation of cultured rat cerebellar astrocytes.
Conditioned medium (CM) obtained from rat cerebellar astrocytes cultured in a serum-containing medium was able to inhibit [3H]thymidine incorporation into proliferating astrocytes, when compared to fresh medium. This effect could be attributed to two fractions of the CM with different molecular weights. The low molecular weight fraction (Mr less than 1,000) inhibited the cellular transport of the labeled precursor, without significantly affecting cell proliferation. The high molecular weight fraction (Mr greater than 10,000) showed a strong inhibitory effect on astrocyte proliferation, which was documented using different assay techniques: i) [3H]thymidine incorporation performed in conditions preventing the effects of CM on transport; ii) [3H]thymidine autoradiography; iii) determination of the DNA content of the cultures. The inhibitory activity was present in media conditioned by non proliferating astrocytes treated with the antimitotic cytosine arabinoside, but not in media conditioned by neuron-enriched cultures nor in a chemically defined (N2) CM. The antiproliferative activity of astrocyte CM could be due either to a rapid depletion of mitogenic factors present in serum, or, to a secretion of growth inhibitory factor(s) by cultured astrocytes.


Hydrogeochemical characterisation and geospatial analysis of groundwater for drinking water quality in Ludhiana district of Punjab, India.
This study characterises the quality of groundwater for the Ludhiana district of Punjab, India by analysing water samples collected from 152 locations spread across 3767 km2. The samples were analysed for 18 parameters consisting of pH, EC, TDS, TA, TH, major anions and cations. The parameter values have been used to calculate the drinking water quality index of the study area which suggests that 2.6, 57.9, 32.9, 4 and 2.6% of the samples fall under the excellent, good, poor, very poor and unsuitable categories, respectively. The sequence of abundance for ions (in meq/l) as revealed from the laboratory tests is Na+ (37.1%) > Ca2+ (30.8%) > Mg2+ (29.1%) > K+ (2.8%) for cations and HCO3- (80%) > Cl¯ (8.9%) > CO32- (6.5%) > SO42- (3.9%) > NO3-, F-, PO43- (< 1%) for anions. The spatial variability of these parameters has been depicted through the use of interpolation maps. Evaluation of different ionic ratios indicates that carbonate weathering and silicate weathering are both significantly affecting the groundwater chemistry with a slight dominance of carbonate weathering. Also, the ion exchange process is taking place in the area as confirmed by CAI index values. In terms of saturation index, the groundwater is undersaturated with respect to halite, fluorite and sylvite, whereas it is supersaturated for calcite, dolomite and aragonite minerals. The principal components in PCA explained 75.4% of the total variance with 29.1 and 28.3% contributions from PC1 and PC2. Both of these components indicate towards the geogenic and anthropogenic influence on groundwater mineralization of the area. The analysis suggests that groundwater for the study area is suitable for drinking in most of the region expect in a few places. Such a study could be used to understand the current status of groundwater quality in the area, the results of which can be used to prevent further contamination and sustain the resource for the future.


Salivary gland surgery and nonviral respiratory-related hospitalizations in children with neurodevelopmental impairment.
Neurodevelopmentally impaired (NI) children with chronic sialorrhea are at elevated risk for aspiration and respiratory tract infections. Direct resection or ligation ("DROOL") of the submandibular glands (SMG) with parotid duct ligation are surgical interventions intended to decrease salivary output. The objective of this study is to determine the impact of DROOL surgery on the incidence of nonviral respiratory-related (NVR) post-procedure hospital encounters including emergency department visits and admissions. Retrospective case series of NVR related outcomes after DROOL surgery in children performed at a single institution, tertiary referral center. A total of 35 gastrostomy tube-dependent patients (60% male, average age 8.2 [SD 6.0] years) with NI underwent DROOL surgery (86% SMG excision). Pre- and post-surgical follow-up time was 3.6 and 3.2 years, respectively. Presurgical and postsurgical NVR hospital encounters occurred in 28 (80%) and 14 (40%) patients, respectively (p < 0.01). Mean (SD) postoperative NVR hospital encounters occurred less frequently when compared to presurgical period (0.4 [0.6] vs. 1.0 [1.2] per year, p < 0.01) with average change of -0.7 encounters per year (SD 1.4, 95% CI -1.0 to -0.2). Patients with encounters within a year preceding DROOL (OR 4.9, p = 0.04, 95% CI 1.1-22.8), or those with at least 3 preoperative encounters (OR 8.0, p = 0.01, 95% CI 1.6-40.3) were significantly associated with a postsurgical NVR event. Fewer patients used anti-sialorrhea medication postoperatively compared to preoperatively (60% vs. 17%, p < 0.01). No patient developed surgical site complications requiring operative interventions. DROOL surgery for chronic sialorrhea in patients with NI was associated with decreased hospitalization and ED visits for NVR respiratory events post-procedurally. Sialorrhea may be an actionable source of recurrent respiratory illnesses requiring hospitalizations.


Simultaneous action execution and observation optimise grasping actions.
Action observation and execution share overlapping neural resonating mechanisms. In the present study, we sought to examine the effect of the activation of this system during concurrent movement observation and execution in a prehension task, when no a priori information about the requirements of grasping action was available. Although it is known that simultaneous activation by observation and execution influences motor performance, the importance of the delays of these two events and the specific effect of movement observation itself (and not the prediction of the to-be-observed movement) on action performance are poorly known. Fine-grained kinematic analysis of both the transport and grasp components of the movement should provide knowledge about the influence of movement observation on the precision and the performance of the executed movement. The experiment involved two real participants who were asked to grasp a different side of a single object that was composed of a large and a small part. In the first experiment, we measured how the transport component and the grasp component were affected by movement observation. We tested whether this influence was greater if the observed movement occurred just before the onset of movement (200 ms) or well before the onset of movement (1 s). In a second experiment, to reproduce the previous experiment and to verify the specificity of the grasping movements, we also included a condition consisting of pointing towards the object. Both experiments showed two main results. A general facilitation of the transport component was found when observing a simultaneous action, independent of its congruency. Moreover, a specific facilitation of the grasp component was present during the observation of a congruent action when movement execution and observation were nearly synchronised. While the general facilitation may arise from a competition between the two participants as they reached for the object, the specific facilitation of the grasp component seems to be directly related to mirror neuron system activity induced by action observation itself. Moreover, the time course of the events appears to be an essential factor for this modulation, implying the transitory activation of the mirror neuron system.


Sparstolonin B suppresses lipopolysaccharide-induced inflammation in human umbilical vein endothelial cells.
Sparstolonin B (SsnB) is an isocoumarin compound isolated from the tubers of both Sparganium stoloniferum and Scirpus yagara. We previously demonstrated that SsnB blocked the Toll-like receptor (TLR) 2- and TLR4-triggered inflammatory signaling in macrophages by inhibiting the recruitment of MyD88 to the TIR domains of TLR2 and TLR4. The present study was designed to examine the effects of SsnB on vascular inflammatory responses in human umbilical vein endothelial cells (HUVECs) challenged by lipopolysaccharide (LPS, a TLR4 ligand). We found that SsnB dose-dependently attenuated the LPS-induced expression of interleukin (IL)-1β and monocyte chemoattractant protein 1 both at the transcription and translation levels in HUVEC. LPS-induced endothelial cell adhesion molecules, intercellular adhesion molecular-1 and vascular cell adhesion molecule-1 expressions were also reduced by treatment with SsnB. In addition, co-incubation with SsnB attenuated THP-1 monocyte adhesion to LPS-activated HUVECs. Furthermore, SsnB efficiently suppressed LPS-induced phosphorylation of extracellular -signal-regulated kinase (Erk1/2) and Akt in HUVECs. These findings show that SsnB can suppress endothelial cell inflammation, suggesting that SsnB might be suitable for development as a therapeutic agent for inflammatory cardiovascular disease.


Frailty and subsequent adverse outcomes in older patients with atrial fibrillation treated with oral anticoagulants: The Shizuoka study.
In older patients with atrial fibrillation (AF), frailty is frequently prevalent. However, the prognostic value of frailty for adverse events after initiation of oral anticoagulants (OACs) is unclear. We assessed whether frailty at the time of OAC initiation is associated with subsequent bleeding or embolic events. We extracted patients aged ≥65 years with nonvalvular AF in whom OACs were initiated from a universal administrative claims database incorporating primary and hospital care records in Shizuoka, Japan, between 2012 and 2018. Frailty was assessed using the electronic frailty index (eFI). The association of frailty with bleeding events and ischemic stroke/transient ischemic attack were evaluated using the Fine-Gray model and restricted cubic spline model. Among 12,585 patients with AF, 7.8% were categorized as fit, 31.5% as mildly frail, 34.8% as moderately frail, and 25.9% as severely frail. The risk of bleeding was associated with a higher eFI (adjusted subdistribution hazard ratio [95% CI] for fit or mild frailty: 1.15 [1.02-1.30]; moderate frailty: 1.42 [1.24-1.61]; and severe frailty: 1.86 [1.61-2.15]), whereas the association was weaker for ischemic stroke/transient ischemic attack. The spline models demonstrated that the relative hazard for bleeding increased steeply with increasing eFI. Patients with frailty in whom OAC therapy is initiated have higher risk of bleeding, highlighting the importance of discussing this increased risk with patients with AF who have frailty and assessing frailty at the time of OAC initiation.


Low molecular mass dermatan sulfate modulates endothelial cells proliferation and migration.
Low molecular mass dermatan sulfate, obtained by depolymerization, induced the entrance in S phase of mitosis, enhanced the activity of matrix metalloproteinase-2, and could modulate cell migration of endothelial cells, through mechanisms independent of TNF-α autocrine regulation. LMMDS located at the injured sites could influence early stages of angiogenesis.


Educational intervention for the prevention of occupational neck pain: protocol of randomized trial.
Neck pain is one of the most common work-related musculoskeletal disorders (WMSDs). It has important social and economic consequences such as reduced productivity due to absenteeism, leave, and early retirement and financial losses due to medical expenses for the workforce especially teachers. This study aims to evaluate whether a model-based social media intervention could change the high-risk behaviors that cause work-related neck pain among teachers. This is a randomized controlled trial that will be done in three steps. The first stage is a qualitative study to obtain the items and areas of the researcher-made questionnaire based on the health belief model (HBM), the second stage is the psychometric evaluation of the questionnaire, and the third stage is designing and implementation of model-based educational intervention in social media context. The study population is teachers who working in junior high school in the 19th district of education minister in Tehran, Iran, which are randomly divided into two groups of intervention and control. The intervention group receives training packages on social media, and the control group does not receive any training. The educational intervention tries to improve the knowledge, attitude, skills, and self-efficacy in adopting neck pain prevention behaviors among teachers. The study will also assess whether the intervention can promote preventive neck pain behavior among teachers. Work-related neck pain can have a negative impact on teachers' health. This study is an attempt to investigate the impact of developed interventions in promoting preventive behavior regarding work-related neck pain through social media context. Iranian registry of Clinical Trial (IRCT) IRCT20210301050542N1 . Registered on 16 March 2021 Ethics code: IR.MODARES.REC.1399.163.


Microfinance Interventions and HIV Treatment Outcomes: A Synthesizing Conceptual Framework and Systematic Review.
Microfinance interventions have the potential to improve HIV treatment outcomes, but the mechanisms through which they operate are not entirely clear. To construct a synthesizing conceptual framework for the impact of microfinance interventions on HIV treatment outcomes using evidence from our systematic review. We conducted a systematic review by searching electronic databases and journals from 1996 to 2018 to assess the effects of microfinance interventions on HIV treatment outcomes, including adherence, retention, viral suppression, and CD4 cell count. All studies in the review showed improved adherence, retention, and viral suppression, but varied in CD4 cell count following participation in microfinance interventions-overall supporting microfinance's positive role in improving HIV treatment outcomes. Our synthesizing conceptual framework identifies potential mechanisms through which microfinance impacts HIV treatment outcomes through hypothesized intermediate outcomes. Greater emphasis should be placed on assessing the effect mechanisms and intermediate behaviors to generate a sound theoretical basis for microfinance interventions.


Assessing physostigmine's contraindication in cyclic antidepressant ingestions.
Ingestion of cyclic antidepressant medications or prolongation of the electrocardiographic QRS interval are commonly considered as contraindications to the use of physostigmine as an antidote for antimuscarinic toxicity. This dictum seems to stem from a few well-publicized cases in which administration of physostigmine was temporally associated with the development of asystole. Before the report of these cases, physostigmine was more frequently used and had been considered a first-line antidote for both the neurologic and cardiac toxic effects of cyclic antidepressant overdose. This apparent inconsistency, and a resurgence of interest in physostigmine as an antidote, begs the question of the appropriateness of this drug's contraindication in all cyclic antidepressant ingestions. Review of the published clinical and experimental evidence provides little support for the clinical utility of using electrocardiographic criteria or the ingestion of cyclic antidepressants as contraindications to the use of physostigmine.


Protective Effect of Catheter Ablation of Atrial Fibrillation on the Renal Function in Patients With Hypertrophic Cardiomyopathy.
Atrial fibrillation (AF) is a common arrhythmia in patients with hypertrophic cardiomyopathy (HCM) and is associated with renal function deterioration. The protective effects of catheter ablation (CA) of AF on renal function in patients with HCM remain unsolved. From 2009 to 2020, a total of 169 consecutive patients with HCM and AF (age 70 ± 12, 87 males) were retrospectively evaluated. The estimated glomerular filtration rate (eGFR) was evaluated at the study enrollment or 1 month before the CA and reevaluated 3 and 12 months later. In the 169 patients, 63 underwent CA of AF (ablation group), and the remaining 106 did not (control group). After propensity score matching, 45 pairs were matched. The baseline eGFR was similar between the 2 groups (p = 0.83). During a mean follow-up period of 34 ± 27 months, sinus rhythm was maintained in 36 patients (80%) after 1.7 ± 0.8 ablation procedures. The eGFR significantly decreased from baseline to 3 months (p <0.01) and from baseline to 1 year (p <0.01) in the control group, whereas the eGFR in the ablation group was maintained both from baseline to 3 months (p = 0.94) and from baseline to 1 year (p = 1.00) after the CA. The change in the eGFR between baseline and 12 months was significantly smaller in the ablation group than in the control group (p <0.01). After logistic regression analysis, CA of AF was the independent predictor of an improvement of eGFR (odds ratio 2.81, 95% confidence interval 1.08 to 7.36, p = 0.04). In conclusion, CA of AF had a protective effect on renal function in patients with HCM.


Contributing factors of willingness and hesitancy regarding acceptance of COVID-19 vaccine in primary care settings: A qualitative study in an eastern state of India.
For any effective vaccination strategy, the willingness of the beneficiaries and its contributing factors are important. This study was conducted among the health-care workers (HCWs) and community members to find the perceptions regarding the COVID-19 vaccine and understand the influencers and the barriers of vaccine acceptance. A qualitative study was conducted from October 2020 to December 2020 in two primary care settings in an urban area. Eighteen in-depth interviews (IDIs) after taking consent were conducted with the help of IDI guide developed and validated beforehand by the experts. IDIs were done among the ten community members and eight HCWs selected conveniently. Data collection were continued till data saturation when no new information yielded from the interviews. Thematic analysis was performed. All the participants were hopeful about availability of the vaccine. The key influencers identified for promoting willingness to accept the vaccine among both the groups were opinion of the health-care providers, colleagues' and other people's acceptance of the vaccine, effectiveness of vaccine on other people, and perceived risk of the disease. Fear of adverse reactions was the most important barrier among all the respondents. The prevalent perception was that other preventive practices and vaccine together can only be the best solution to prevent COVID-19 illness. The HCWs perceived that acceptance of vaccine among the community members would be good overall but apprehended some initial difficulties. Mass campaign to promote COVID-19 vaccination and sensitization events are the need of the hour. Since opinion of health-care personnel emerged as an important influencer of vaccine acceptance, mass campaign and sensitization programs spearheaded by the health-care providers can bring about change by increasing the vaccine acceptance among the beneficiaries at large. Re-enforcement regarding practice of preventive measures should be made among the population irrespective of the vaccination status.