Medication use during pregnancy among women with congenital physical disabilities.
Medication use during pregnancy is common, with up to 90% of pregnant women taking at least one medication. Women with congenital physical disabilities often report co-occurring conditions during pregnancy that may warrant pharmaceutical treatment, however, research is limited. We aim to describe medication use during pregnancy including: pain, psychotropic, and antibacterial medication, among women with and without congenital physical disabilities. We used data from the Slone Birth Defects Study (1976-2015), a case-control study that collected information on pre-pregnancy health conditions and exposures among participating mothers. Women with congenital physical disabilities (n = 132) included women with spina bifida, cerebral palsy, muscular dystrophy, limb deficiencies, and other skeletal/connective tissue conditions and were matched by interview year and study site to women without congenital physical disabilities (n = 528). Proportions and difference in proportions for each medication were compared between groups. Simple proportions were also calculated for duration and multiple medication use variables. Women with congenital physical disabilities more frequently reported use of pain (acetaminophen and opioids), psychotropic (antidepressants), and antibacterial medications during pregnancy. Women with congenital physical disabilities used pain and psychotropic medications for longer, frequent durations, and more frequently reported haven taken multiple medications during pregnancy. Women with congenital physical disabilities report higher medication use during pregnancy compared to women without physical disabilities. Patterns may be attributable to co-occurring conditions or increased risk of pregnancy complications in this population. Further research is needed to describe the patterns of medication use for clinical decisions regarding treatment of pregnant women with disabilities.


Analysis of the relationship among health awareness and health literacy, patient satisfaction levels with primary care in patients admitting to primary care health centers.
The aim of the study was to examine the relationships between health literacy, primary care satisfaction levels and health awareness of the patients who were admitted to primary care centers (Family Health Centers). This is a cross-sectional study conducted on individuals who were admitted to Family Health Centers (n = 1.055) in Eskisehir province. The study data were collected by using Turkish Health Literacy Scale, the European Patients Evaluate General/Family Practice Scale and Health Awareness Scale. As health literacy of participants increases, health awareness and satisfaction with primary care also increases (for each, p < .001). Health awareness increases health literacy by 0.55 points, health literacy increases satisfaction in primary care by 0.26 points. In the province of Eskisehir, the health literacy level of 7 out of 10 patients, who admitted to the primary care institution, is inadequate or problematic. As health awareness of participants increases, their level of health literacy also increases. As health literacy of participants increases, their satisfaction with family physicians also increases. As an integral part of preventive health services, studies should be performed to increase and improve the level of health literacy of patients who are admitted to primary care services.


You're the Flight Surgeon: lateral epicondylitis.
Wolf SJ. You're the flight surgeon: lateral epicondylitis. Aerosp Med Hum Perform. 2015; 86(12):1077-1080.


Faecal incontinence: A late side-effect of pelvic radiotherapy.
Despite advances in pelvic radiotherapy, damage to normal tissue can lead to chronic gastrointestinal problems. The frequency with which this affects quality of life is controversial. Faecal incontinence is not widely perceived to be a major issue after pelvic radiotherapy. The aim of this paper is to review the frequency and mechanisms for the development of faecal incontinence after pelvic radiotherapy, and to review treatment options for faecally incontinent patients. A search of original literature was carried out using MEDLINE and EMBASE databases from 1966 to 2005. The reliability of the published data is poor because patients frequently fail to admit to faecal incontinence, and because prospective studies are lacking that assess faecal incontinence as a specific end point using adequate, validated and reproducible methodology. The published rates of late new-onset faecal incontinence after pelvic radiation are between 3% and 53%. Patients treated for prostate rather than gynaecological, bladder, rectal or anal cancer may have a lower rate. Only 8-56% of affected patients state that faecal incontinence reduces their quality of life. Studies examining the physiological changes occurring after radiotherapy are generally not adequately controlled or powered, assessment of ano-rectal function is rarely comprehensive and loss of patients to follow-up frequently makes it difficult to extrapolate results to a wider population. Where there is agreement over the physiological changes that occur after radiotherapy, it is not clear at what threshold these changes cause symptoms. No prospective studies of any non-surgical treatment for faecal incontinence after radiotherapy have been published. Surgery other than colostomy probably carries a high risk of complications in this group of patients, but few data have been published. Now that improvements in outcome from combination treatments, including radiotherapy for pelvic cancer, are being achieved, it is time that serious attention is paid to determining how frequently significant gastrointestinal toxicity arises, and how best to optimise the quality of life of long-term survivors.


Contribution of P2Y(1) receptors to ADP signalling in mouse spinal cord cultures.
Mixed neuronal and glial cell spinal cord cultures from neonates express ADP sensitive P2Y(1,12&13) receptors. ADP (10microM) evoked increases in intracellular calcium that were essentially abolished by the P2Y(1) receptor antagonist MRS2179 (10microM), responses were also absent in preparations from P2Y(1) receptor deficient mice however UTP (100microM) evoked calcium rises were unaffected. ADP also evoked a robust increase in extracellular signal-regulated protein kinase (ERK) phosphorylation that was of similar magnitude in the cultures from wild type and P2Y(1) receptor deficient mice. These results suggest that ADP acts through P2Y(1) receptors to mediate an increase in intracellular calcium but not to stimulate ERK phosphorylation in the spinal cord.


A comparison of myelography and computer tomography in lumbar disc herniation.
We report a retrospective study of 219 patients with lumbar disc lesions in whom the operative findings were compared with the results of computer tomography (CT) and myelography. When used alone each method achieved virtually the same degree of accuracy (87.8% and 87.4%). Particular attention was paid to 70 "problem" cases in whom the initial CT diagnosis suggested herniations at different levels which were not in keeping with the clinical symptoms or signs. The operative findings showed that CT had produced 10.4% false positives and 4.4% false negatives. The corresponding results for myelography were 5.9% and 8.9%. Myelography is, therefore, a more exact method of diagnosis for segmental and lateral herniations. After initial computerised tomography, myelography is indicated when there is a discrepancy between CT and the clinical findings.


Severity of Writer's Cramp is Related to Faulty Motor Preparation.
We characterized, in 37 writer's cramp (WC) patients and 14 healthy volunteers (HV), the buildup of motor representations contralateral ("intended") and ispsilateral ("unintended") to the movement to be produced and the excitability changes in left primary motor cortex during the early reaction time (RT) of a pre-cued reaching movement to pick up a pen with either hand to write. We also tested the excitability of interhemispheric pathways from right dorsal premotor and motor cortices to left motor cortex. During early RT (1) the motor cortex excitability of unintended muscle representations did not decrease in patients as in HV and (2) the connection from the contralateral dorsal premotor cortex to the "intended" motor representation did not function in patients. In HV, the efficiency of intracortical GABA-ergic circuits at rest predicted the degree of excitability changes in the intended motor representation in the early RT. This was not true in patients who had lower efficiency of GABA-ergic circuits. Interestingly, the more severe was the writing impairment, the higher was the level of excitability in the intended and unintended motor representations. It demonstrates, for the first time, that abnormal motor preparation influences the severity of the writing impairment in WC patients.


Snapshot of the primary care waiting room: Informing practice redesign to align with the Patient's Medical Home model.
To describe the demographic characteristics, health, and health care experiences of adult patients in primary care waiting rooms in Quebec, and to determine which pillars of the Patient's Medical Home (PMH) are a priority to align primary care practices with the PMH model. Baseline survey of a prospective cohort study using self-administered on-site and mailed questionnaires. Twelve primary care clinics within the geographic boundaries of 4 local health care networks in metropolitan, urban, rural, and remote settings in Quebec. A total of 1029 adult patients aged between 25 and 75 who were selected during a 1-week period in the 12 primary care clinics; 789 returned questionnaires. Patients' health profiles, health behaviour patterns, reasons for the visit, and health care experiences. In this 2010 snapshot, 66.8% of patients waited longer than 2 weeks for their appointment, 71.0% of visits were for routine or follow-up care, and longer wait times and patient multimorbidity correlated with more reasons for the visit. After the visit, most patients reported being able to express their most important needs and that the doctor listened well; however, only 28.1% reported that the doctor had explored whether the recommendations would be realistic for them, and only 18.0% indicated that the doctor had explored the personal or family dimensions that affected their health. Among all patients, 56.9% reported having at least 3 chronic conditions (multimorbidity), and 30.3% reported having high or moderate levels of psychological distress. When describing their financial status, 30.7% of patients indicated it was "poor to squeezed or tight." Slightly more than half of patients did not have complementary private health insurance to cover costs of psychological services. In this study, the 4 priority pillars for practices to align with the PMH were timely access, team-based care, comprehensive care, and a patient-centred approach. Widespread implementation of advanced access is an urgent priority in light of persisting difficulties in timely access. Team-based and comprehensive care are needed to address the high prevalence of multimorbidity and psychological distress and to support health behaviour change. Finally, the patient-centred approach needs to underpin every care encounter.


In vivo probe-based confocal laser endomicroscopy in chronic interstitial lung diseases: Specific descriptors and correlation with chest CT.
Probe-based confocal laser endomicroscopy (pCLE) enables in vivo microimaging of the distal lung, during bronchoscopy. This study aims at identifying pCLE descriptors of chronic interstitial lung diseases (ILD), their correlations with chest HRCT and assessing inter-observer agreement. pCLE was performed in 21 healthy volunteers (HV) and 59 non-smoking ILD patients, including 19 patients with idiopathic pulmonary fibrosis (IPF) or asbestosis, 15 with connective tissue disease-associated ILD (CTD-ILD), 17 with sarcoidosis and 8 with hypersensitivity pneumonitis (HP). pCLE descriptors were identified in ILD on the basis of comparison with HV. Nine pCLE descriptors were more frequent in ILD compared to HV, with good inter-observer agreement, including fluorescent bronchiolar cells (sarcoidosis, CTD-ILD and HP), fluorescent alveolar cells (CTD-ILD and HP), small alveolar entrance rings (IPF or asbestosis and CTD-ILD), enlarged axial elastic fibres (IPF or asbestosis), septal fibres (IPF or asbestosis, CTD-ILD and HP), disorganized acinar network and rigid acinar network (IPF or asbestosis and CTD-ILD), dense elastic network (IPF or asbestosis) and alveolar fluorescent nodular structures (in sarcoidosis) (P < 0.01, Fisher's exact test, all comparisons). The distribution of nodules on computed tomography (CT) appeared to correlate with pCLE alveolar nodular structures, rigid acinar network and septal fibres, while reticulations were associated with septal fibres and disorganized or dense acinar network; ground-glass opacities on CT with small alveolar entrances, rigid elastic network and septal fibres; and honeycombing with septal fibres. In the four groups of ILD studied, 9 pCLE descriptors are described, which appear specific and reproducible, and correlate with chest HRCT patterns.


Patient Perceptions and Current Trends in Internet Use by Orthopedic Outpatients.
Many studies have highlighted concerns about the completeness and quality of information found online and how this may affect patients' education about their medical problems. One aspect of internet usage that has received less attention in the literature, however, is patient perception of the information that is gathered online, and how patients use it related to their musculoskeletal care. The objective of the study is to utilize a cross-sectional study design to describe internet usage and patient perceptions of orthopedic online information and to identify differences in usage patterns. One thousand two hundred ninety-six questionnaires were distributed to consecutive patients at orthopedic outpatient clinics which consisted of questions pertaining to patients' internet use. Basic demographic data were collected, and subgroup analyses were performed to examine the effect of three variables (age, gender, and clinic type) on various outcomes. 84.9% of patients reported access to the internet. Of patients with internet access, 64.7% reported using the internet for obtaining orthopedic information. 43.1% of the respondents who searched for orthopedic information rated it as "very useful," 56.3% found it "somewhat useful," and 0.6% found it "not at all useful". Younger patients were more likely to have used the internet for health and orthopedic information and to have found this information either very or somewhat useful. Males were more likely to have found the internet information very useful. Overall, only 33.7% of patients who researched their current orthopedic complaint accessed the institutional website for information. A large proportion of patients use the internet to research orthopedic information and most patients, especially younger males, find the information useful.


New technique of antireflux ureteroileal anastomosis and its clinical experiences.
Free ileoureteral reflux in patients with an ileal conduit has been indicated as the etiology of late renal complications. A new technique for ureteroileal anastomosis was devised in an attempt to prevent reflux without causing obstruction. This anastomosis has been done on 20 ureters from 11 patients with pelvic malignancies. Satisfactory results have been obtained in patients with normal as well as dilated ureters, with no serious operative complications, no episodes of pyelonephritis and no renal deterioration. The ureteroileal junction created with this technique has been demonstrated radiographically and histologically.


A nucleocytoplasmic-localized E3 ligase affects the NLR receptor stability.
Ubiquitination is a pivotal post-translational modification that regulates turnover of nucleotide-binding site and leucine-rich repeat receptors (NLRs). As a RING-type E3 ligase, BOI (Botrytis susceptible1 interactor) has been reported to interact with different proteins, and function in the nucleus. New studies have identified that BOI can interact and ubiquitinate L5 (AT1G12290), a CC-NBS-LRR protein in vitro, and mediate the proteasomal degradation of L5 in Nicotiana benthamiana and Arabidopsis thaliana. However, there still remains an unanswered question about where the degradation occurs at the subcellular level. In this study, the ubiquitination of L5 by BOI was determined in N. benthamiana. Meanwhile, we discovered that BOI exhibited nucleocytoplasmic localization and mediated the degradation of the plasma membrane localized L5 outside the nucleus. BOI and its homologs BRG1 and BRG3 function redundantly in negatively regulate the protein level of L5. Overall, this report reveals BOI and its homologs have multiple targets and function at different subcellular locations.


Association between blood pressure control status, visit-to-visit blood pressure variability, and cognitive function in elderly Chinese: A nationwide study.
Cognitive function is a concern among the elderly, which is related to the quality of life, life expectancy, and economic burdens. The relationship between blood pressure (BP) control status, visit-to-visit BP variability, and cognitive function remains controversial. We aimed to explore the association between BP control status at baseline, visit-to-visit BP variability, and cognitive function. This study included 3,511 elderlies in the China Health and Retirement Longitudinal Study, covering four waves for 7-year follow-up (baseline 2011, 2013, 2015, and 2018). BP was measured in Wave 2011, 2013, and 2015. Cognitive function was measured by Mini-Mental State Exam in Wave 2018. Participants were divided into two groups: mid-old group for reflecting midlife BP and cognition (45-59 years at baseline but aged 60 or over in Wave 2018), and old-old group for reflecting late-life BP and cognition (aged 60 or over at baseline). We use univariate analysis and general linear model to analyze. Late-life BP showed stronger associations with cognitive function than midlife BP. As to late-life BP control status, controlled hypertension group get higher cognitive score than uncontrolled hypertension group in language (adjusted β = -0.34, 95%CI -0.68 to 0.00), and untreated hypertension group in orientation (adjusted β = -0.41, 95%CI -0.72 to -0.11), language (adjusted β = -0.35, 95%CI -0.67 to -0.04), and total (adjusted β = -0.99, 95%CI -1.85 to -0.12). Regarding visit-to-visit BP variability, midlife visit-to-visit systolic blood pressure (SBP) variability was associated with language (adjusted β = -3.70, 95% CI -5.83 to -1.57), while late-life visit-to-visit SBP variability was associated with orientation (adjusted β = -2.99, 95% CI -4.84 to -1.14), recall (adjusted β = -1.69, 95% CI -2.89 to -0.48), language (adjusted β = -2.26, 95% CI -4.13 to -0.38), and total (adjusted β = -9.50, 95% CI -14.71 to -4.28); Midlife diastolic blood pressure (DBP) variability and pulse pressure (PP) variability showed a significant relationship with language (adjusted β = 3.25, 95% CI -1.31 to -5.19) and calculation (adjusted β = -0.26, 95% CI -0.47 to -0.04), respectively. No significant correlation was found between midlife BP control status, late-life visit-to-visit DBP variability, late-life visit-to-visit PP variability, and cognitive score. There was no significant correlation between BP and memory. BP control status and visit-to-visit BP variability were significantly related to cognitive function among the Chinese elderly. Receiving effective late-life antihypertensive treatment and keeping SBP stable might contribute to prevent the development of cognitive impairment and dementia, especially for orientation and language function.


Pharmacologic properties of a phosphate ester of dopamine.
The 3 or 4 phosphate ester of dopamine (PD) was hydrolyzed by homogenates of rat tissues to give inorganic phosphate (Pi) and dopamine. The rate of hydrolysis of PD by kidney homogenates was increased by exogenous MgCl2 but not CaCl2 or KCl. The activity of brain, heart or liver homogenates was insensitive to the added salts. Several lines of evidence indicate that alkaline phosphatase activity contributes to the high rate of PD hydrolysis by the kidney but not brain homogenate. The intravenous infusion of PD at 12 mumole/kg in one hr to anesthetized rats increased the dopamine content of the plasma, kidney and heart without altering brain or liver dopamine. The results suggest that PD may be more effective than dopamine for increasing dopamine levels of the kidney. In addition, the hydrolysis of PD by brain homogenates, which is independent of alkaline phosphatase activity, suggests that specific enzymes exist for the metabolism of PD.


Synthetic Evolution of Metabolic Productivity Using Biosensors.
Synthetic biology has progressed to the point where genes that encode whole metabolic pathways and even genomes can be manufactured and brought to life. This impressive ability to synthesise and assemble DNA is not yet matched by an ability to predictively engineer biology. These difficulties exist because biological systems are often overwhelmingly complex, having evolved to facilitate growth and survival rather than specific engineering objectives such as the optimisation of biochemical production. A promising and revolutionary solution to this problem is to harness the process of evolution to create microbial strains with desired properties. The tools of systems biology can then be applied to understand the principles of biological design, bringing synthetic biology closer to becoming a predictive engineering discipline.


Intravenous buspirone for the prevention of postoperative nausea and vomiting.
Buspirone, a partial 5HT(1A) agonist and D₂ and D₃ antagonist, has shown promising antiemetic efficacy when given parenterally in animal models, but its efficacy for the prevention of postoperative nausea and vomiting (PONV) is unknown. To study the efficacy and dose-responsiveness of intravenous buspirone for the prevention of PONV. A randomised, double-blind, placebo-controlled study was performed in adults at moderate to high PONV risk undergoing surgery with a general anaesthetic. Patients were randomised to receive an intravenous dose of buspirone (0.3, 1.0, 2.0, 3.0 mg) or placebo at the end of surgery. The primary endpoint was the cumulative 24-h PONV incidence (i.e. any nausea and/or vomiting). Vomiting included retching. Nausea was defined as a score of ≥ 4 on an 11-point verbal rating scale running from zero (no nausea) to ten (the worst nausea imaginable). A total of 257 patients received the study drug and fulfilled the criteria for inclusion in the primary efficacy and safety analyses. With placebo, the mean 24-h PONV incidence was 49.0 % (90 % confidence interval [CI] 37.5-60.5 %). With buspirone, that incidence ranged from a mean of 40.8 % (29.3-52.4 %) in the 1 mg arm to 58.0 % (46.5-69.5 %) in the 0.3 mg arm (P > 0.05 for all comparisons). There was no difference between placebo and buspirone at any dose for any other efficacy endpoint, nor in the number or severity of adverse events or any other safety measures. We were unable to show that intravenous single-dose buspirone, at the tested dose-range, was effective at preventing PONV in surgical adult patients. The present study emphasises the difficulty in extrapolating from animal models of emesis to clinical efficacy in PONV.


Inactivation of nuclear polyhedrosis virus (Baculovirus subgroup A) by monochromatic UV radiation.
Monochromatic radiation at wavelengths of 290, 300, 310, and 320 nm inactivated occluded nuclear polyhedrosis virus of the Douglas-fir tussock moth, Orgyia pseudotsugata (McDunnough). Data indicate that all of the wavelengths are capable of causing virus inactivation; much greater fluences are needed for virus inactivation as the wavelength increases.


A comparative analysis of different biofluids towards ovarian cancer diagnosis using Raman microspectroscopy.
Biofluids, such as blood plasma or serum, are currently being evaluated for cancer detection using vibrational spectroscopy. These fluids contain information of key biomolecules, such as proteins, lipids, carbohydrates and nucleic acids, that comprise spectrochemical patterns to differentiate samples. Raman is a water-free and practically non-destructive vibrational spectroscopy technique, capable of recording spectrochemical fingerprints of biofluids with minimum or no sample preparation. Herein, we compare the performance of these two common biofluids (blood plasma and serum) together with ascitic fluid, towards ovarian cancer detection using Raman microspectroscopy. Samples from thirty-eight patients were analysed (n = 18 ovarian cancer patients, n = 20 benign controls) through different spectral pre-processing and discriminant analysis techniques. Ascitic fluid provided the best class separation in both unsupervised and supervised discrimination approaches, where classification accuracies, sensitivities and specificities above 80% were obtained, in comparison to 60-73% with plasma or serum. Ascitic fluid appears to be rich in collagen information responsible for distinguishing ovarian cancer samples, where collagen-signalling bands at 1004 cm-1 (phenylalanine), 1334 cm-1 (CH3CH2 wagging vibration), 1448 cm-1 (CH2 deformation) and 1657 cm-1 (Amide I) exhibited high statistical significance for class differentiation (P < 0.001). The efficacy of vibrational spectroscopy, in particular Raman spectroscopy, combined with ascitic fluid analysis, suggests a potential diagnostic method for ovarian cancer. Raman microspectroscopy analysis of ascitic fluid allows for discrimination of patients with benign gynaecological conditions or ovarian cancer.


Reduced volume of the putamen in REM sleep behavior disorder patients.
The purpose of this study was to quantify volumes of specific subcortical gray matter nuclei implicated in Parkinson's disease (PD) as a preliminary step for identifying a non-invasive clinical biomarker for PD. We hypothesized that REM sleep behavior disorder (RBD) patients, at risk for developing PD, will demonstrate a pattern of neuronal degeneration reflected in reduced striatal volumes on T1-weighted MRI. We compared measures of RBD patients confirmed by polysomnography (PSG) with groups of age/gender-matched Control subjects and early PD (EPD) patients (Hoehn & Yahr < 2). Clinical measurements included the Unified Parkinson's disease Rating Scales (UPDRS), timed gait and finger tapping tasks, the Parkinson's Disease Questionnaire (PDQ-39), and a time-synchronized video recorded single-night PSG. Volumetric measurements were derived from high-resolution T1-weighted 3 T MRI images. The matched Control and EPD groups were statistically similar to the RBD group in age, gender, handedness, and total brain volumes. The RBD group had smaller bilateral putamen volumes (both raw and normalized by brain tissue volume), in addition to some clinical impairment on the UPDRS and PDQ-39. Reduced putamen volumes may be a structural marker for RBD and reflect a pattern of neurodegeneration that predicts the development of PD.


Metformin alters the expression profiles of microRNAs in human pancreatic cancer cells.
To investigate the effect of metformin on the expression profiles of microRNAs in human pancreatic cancer cells. MicroRNAs real-time PCR Array was applied to investigate differentially expressed miRNAs in Sw1990 cells treated with or without metformin. Stem-loop real time RT-PCR was used to confirm the results of the array assay in Sw1990 and Panc-1 cells. The effects of miR-26a on cell growth, apoptosis, invasion and migration abilities were respectively examined by CCK8 assay, Apoptosis assay, Matrigel invasion and migration assay. HMGA1 was proved to be a target of miR-26a by Luciferase reporter assay, Real-time PCR and Western-blotting. Nine miRNAs were significantly up-regulated in metformin treated cells. Metformin up-regulated the expression of miR-26a, miR-192 and let-7c in a dose-dependent manner. Forced expression of miR-26a significantly inhibited cell proliferation, invasion, migration and increased cell apoptosis, whereas knockdown of miR-26a obtained the opposite effect. Furthermore, we demonstrated that HMGA1, an oncogene, is a direct target of miR-26a. Nude mice xenograft models confirmed that metformin up-regulated the level of miR-26a and surpressed the expression of HMGA1 in vivo. These observations suggested that modulation of miRNA expression may be an important mechanism underlying the biological effects of metformin.


The long and winding road Obtaining funding for qualitative research proposals.
In this article, John Cutcliffe and Chris Stevenson drew on their experience of seeking funding for qualitative studies in order to offer researchers some helpful tips.


Extracellular correction of the androgen-receptor transformation defect in two families with complete androgen resistance.
We have characterized the cellular and extracellular phenotype of the mutant androgen receptor (AR) from two families who have complete androgen resistance despite a normal androgen-binding capacity (Bmax) in their genital skin fibroblasts (GSF). The cellular receptors fail to up-regulate their basal AR activity in response to prolonged incubation with 5 alpha-dihydrotestosterone (DHT), or with two synthetic androgens, methyltrienolone (MT) and mibolerone (MB), and form A-R complexes with increased equilibrium (Kd) and non-equilibrium (k) dissociation constants. In addition, they are thermolabile when recently dissociated, but not in their native state. A-R complexes made in normal or mutant cytosol at 4 degrees C elute from DEAE-Sephacel at approximately 0.25 M KCl (untransformed), with or without prior passage through Sephadex G-25; when made in cells at 37 degrees C, extracted with 0.4 M KCl in a buffer containing 10 mM Na2MoO4, and desalted by G-25, they elute at less than or equal to 0.1 M KCl. Normal KCl-extracted DHT- and MB-R complexes dissociate (37 degrees C) at the same slow, linear rate as their in-cell counterparts (transformed); the mutant ones dissociated more slowly than their rapidly-dissociating in-cell counterparts and, to a variable extent, nonlinearly-an early faster phase, a later slower (transformed). Thus, as judged by two conventional criteria of steroid-R complex transformation, the mutant A-R complexes can transform, possibly in two steps, under certain cell-free conditions. This behavior differentiates a class of structural AR mutations whose molecular definition awaits application of recombinant DNA techniques to the X-linked AR locus.


Mineralocorticoid receptor activation in myocardial infarction and failure: recent advances.
The classical view of aldosterone actions via the mineralocorticoid receptor (MR) limited to control of fluid balance and blood pressure homoeostasis has been progressively overcome by clinical and experimental evidence emphasizing the pleiotropic role of MR activation in the pathogenesis of cardiovascular disease. Clinical studies have shown the benefit of MR blockade in patients with left ventricular dysfunction and heart failure after myocardial infarction (MI), hypertension or diabetic nephropathy. Deleterious effects of MR activation include cardiac structural and electrical remodelling, cardiovascular fibrosis, inflammation and oxidative stress. Complexity of pathophysiological role of MR derives from the presence of circulating glucocorticoids at higher concentrations than aldosterone and the equal affinity of the MR for aldosterone, cortisol and corticosterone. Recent experimental studies using different animal models and genetic tools have deeply explored the cell-specific functional role of MR in cardiovascular pathology. This review addresses emerging preclinical studies as well as ongoing clinical trials regarding MR activation in MI and failure.


Reverse graft placement in the Florida sleeve procedure for aortic root aneurysm.
Since August 2009, 22 patients with aortic root aneurysm have been successfully operated on with our new aortic remodeling technique as follows: after placement of the Gelweave (Vascutek, Ltd., Inchinnan, UK) Valsalva vascular graft in the reverse manner to the Florida sleeve procedure, the aortic annulus was fixed with the collar of this prosthesis at the level of the basal ring and the aortic root was wrapped with the prosthesis. Furthermore, the aortic valve commissures were resuspended. The distal end of the graft and the transected aortic wall were sutured together with running sutures when they were anastomosed to the stump of the distal ascending aorta.


Poverty and health. Prospective evidence from the Alameda County Study.
To examine the reasons for the association between socioeconomic status and poor health, the authors examined the nine-year mortality experience of a random sample of residents aged 35 and over in Oakland, California. Residents of a federally designated poverty area experienced higher age-, race-, and sex-adjusted mortality over the follow-up period compared with residents of nonpoverty areas (relative risk = 1.71, 95 per cent confidence interval 1.20-2.44). This increased risk of death persisted when there was multivariate adjustment for baseline health status, race, income, employment status, access to medical care, health insurance coverage, smoking, alcohol consumption, physical activity, body mass index, sleep patterns, social isolation, marital status, depression, and personal uncertainty. These results support the hypothesis that properties of the sociophysical environment may be important contributors to the association between low socioeconomic status and excess mortality, and that this contribution is independent of individual behaviors.


Prediction of permeability-surface area product data by continuous-distribution pore models.
To investigate the ability of continuous-distribution pore models to accurately predict permeability-surface area product (PS) experimental data in skeletal muscle. Models having a water-only (WO) pathway and continuous distributions of microvascular transport-pathway sizes were fit to solute reflection-coefficient (sigma) experimental data (approximately 0.5-16 nm Stokes radii) obtained from skeletal muscle to determine optimal parameter values. Without further modification, these models were used to predict experimental PS values obtained from the literature for small solutes ranging in size from NaCl to inulin and for three proteins, alpha-lactalbumin, ovalbumin, and albumin (approximately 0.23-3.7 nm radii). The protein PSs were determined from fluorescent tracer-diffusion curves and a nonlinear model of tracer diffusion in the cat hindlimb preparation. The model's PS predictions were compared to those of a discrete-pore model previously developed and a fiber-matrix (FM) model. A log-normal (LN) continuous pore-size distribution plus WO-pathway model (three free parameters) fit the sigma data to within the 95% confidence intervals of each of eight solutes spanning a 32-fold size range and was nearly as close to the data as was the two discrete-pore plus WO-pathway model (four free parameters). Both models closely described the PS data for nine solutes spanning a 14-fold size range. The fit of a fiber-matrix plus WO-pathway model (three free parameters) to the sigma data was much poorer than for the other models. The LN and two-discrete-pore models accurately describe sigma and PS experimental data in cat and human skeletal muscle. Therefore, experimental data resulting from complex microvascular transport processes are well characterized by simple pore models.


[Thromboembolic complication following temporary discontinuance of anticoagulant therapy in a patient with mechanical heart valve].
Patients with mechanical heart valves are treated with oral anticoagulant therapy in order to minimize the risk of thromboembolism. During invasive procedures it is recommended to temporarily discontinue the oral anticoagulant therapy and substitute with injections of low-molecular-weight heparin. We describe a case where a patient discontinued the oral anticoagulant therapy and had no substitution with low-molecular-weight heparin. The patient had an embolism to the coronary arteries causing progressive heart failure, and the patient was subsequently heart transplanted.


Single-use versus reusable metallic laryngoscopes for non-emergent intubation: A retrospective review of 72,672 intubations.
Increased regulatory requirements for sterilization in recent years have prompted a widespread transition from reusable to single-use laryngoscopes. The purpose of this study was to determine if the transition from metallic reusable to metallic single-use laryngoscopes impacted the performance of direct laryngoscopy at an academic medical center. Single-site retrospective cohort study. General anesthetic cases requiring tracheal intubation. Adult patients undergoing non-emergent procedures. Data were collected two years before and two years after a transition from metallic reusable to metallic single-use laryngoscopes. The primary outcome was need for intubation rescue with an alternate device. Secondary outcomes were difficult laryngeal view (modified Cormack-Lehane grade ≥ 2b) and hypoxemia (SpO2 < 90% for >30 s) during direct laryngoscopy intubations. Subgroup analyses for rapid sequence induction, Macintosh blades, Miller blades, and patients with difficult airway risk factors (Obstructive Sleep Apnea, Mallampati ≥3, Body Mass Index >30 kg/m2) were performed. In total, 72,672 patients were included: 35,549 (48.9%) in the reusable laryngoscope cohort and 37,123 (51.1%) in the single-use laryngoscope cohort. Compared with reusable laryngoscopes, single-use laryngoscopes were associated with fewer rescue intubations with an alternate device (covariates-adjusted odds ratio [OR] 0.81 95% CI 0.66-0.99). Single-use laryngoscopes were also associated with lower odds of difficult laryngeal view (OR 0.86; 95% CI 0.80-0.93). Single use laryngoscopes were not associated with hypoxemia during the intubation attempt (OR 1.03; 95% CI 0.88-1.20). Similar results were observed for subgroup analyses including rapid sequence induction, Macintosh blades, Miller blades, and patients with difficult airway risk factors. Metallic single-use laryngoscopes were associated with less need for rescue intubation with alternate devices and lower incidence of poor laryngeal view compared to reusable metallic laryngoscopes.


201Tl, 99mTc-MIBI, 99mTc-tetrofosmin and 99mTc-furifosmin: relative retention and clearance kinetics in retrogradely perfused guinea pig hearts.
Myocellular kinetics of 201Tl, 99mTc-MIBI, 99mTc-tetrofosmin and 99mTc-furifosmin were investigated using retrogradely-perfused guinea-pig hearts. Relative retention decreased in the order 99mTc-MIBI ==> 99mTc-tetrofosmin ==> 99mTc-furifosmin. 201Tl and 99mTc-MIBI exhibited bi- (t1,t2), 99mTc-tetrofosmin and 99mTc-furifosmin triexponential (t1,t2,t3) time-activity-curves. Latest-phase elimination-half-life increased from 201Tl (t2) ==> 99mTc-MIBI (t2) ==> 99mTc-tetrofosmin (t3) ==> 99mTc-furifosmin (t3), showing a significant increase in deteriorating myocardium for all tracers but 99mTc-furifosmin. Delayed elimination in deteriorating myocardium explains at least partly the redistribution phenomenon of 201Tl, and suggests a similar phenomenon for 99mTc-MIBI and 99mTc-tetrofosmin.


Docking of the alkaloid geissospermine into acetylcholinesterase: a natural scaffold targeting the treatment of Alzheimer's disease.
Pharmacological studies from our group [Lima et al. Pharmacol Biochem Behav 92:508, (2009)] revealed that geissospermine (GSP), the major alkaloid of the bark extract of Brazilian Geissospermum vellosii, inhibits acetylcholinesterases (AChEs) in the brains of rats and electric eels (Electrophorus electricus). However, the binding mode (i.e., conformation and orientation) of this indole-indoline alkaloid into the AChE active site is unknown. Therefore, in order to propose a plausible binding mode between GSP and AChE, which might explain the observed experimental inhibitory activity, we performed comparative automatic molecular docking simulations using the AutoDock and Molegro Virtual Docker (MVD) programs. A sample of ten crystal structures of the Pacific electric ray (Torpedo californica) TcAChE, in complex with ten diverse active site ligands, was selected as a robust re-docking validation test, and also for GSP docking. The MVD results indicate a preferential binding mode between GSP and AChE, in which GSP functional groups may perform specific interactions with residues in the enzyme active site, according to the ligand-protein contacts detected by the LPC/CSU server. Four hydrogen bonds were detected between GSP and Tyr121, Ser122, Ser200, and His440, in which the last two residues belong to the catalytic triad (Ser200···His440···Glu327). Hydrophobic and π-π stacking interactions were also detected between GSP and Phe330 and Trp84, respectively; these are involved in substrate stabilization at the active site. This study provides the basis to propose structural changes to the GSP structure, such as molecular simplification and isosteric replacement, in order to aid the design of new potential AChE inhibitors that are relevant to the treatment of Alzheimer's disease.


Axillofemoral bypass relieves visceral malperfusion in type B aortic dissection.
A 58-year-old man with acute type B aortic dissection presented with right lower limb cyanosis, mesenteric ischemia, and acute renal failure. He was treated with extraanatomic right axillofemoral bypass surgery alone, recovered completely from renal, mesenteric, and lower extremity malperfusion shortly thereafter, and lived free of symptoms for the following year. Follow-up computed tomography angiograms documented adequate expansion of the true aortic lumen and good perfusion of visceral organs. Thus, managing such patients with coexisting visceral and extremity malperfusion may be accomplished with axillofemoral bypass exclusively, which can relieve ischemia of upstream abdominal organs and downstream lower extremities effectively and durably.


Arthroscopic posterior capsulolabral repair grants adequate outcomes in shoulders with posterior instability without glenoid cartilage lesions.
Posterior capsulolabral repair (posterior Bankart) is effective to restore shoulder stability and relieve pain, though a recent meta-analysis reported recurrent instability in 9.5% of patients, and that only 62.7% were able to resume sports. The purpose of this study was to assess the outcomes of arthroscopic posterior capsulolabral repair in a population of unselected patients, in terms of recurrence of instability, clinical scores, and return to sports. The authors retrospectively studied a consecutive series of 22 patients that underwent posterior capsulolabral repair between 2009 and 2019. Patients were assessed before posterior capsulolabral repair and at a minimum follow-up of 24 months, in terms of subjective shoulder value (SSV), Western Ontario Shoulder Instability Index (WOSI), as well as level of sport. Following surgery, all complications, reoperations or episodes of instability were noted. The cohort comprised 21 men (95%) and 1 woman (5%), aged 38.8 ± 12.5 years (range 17-61) at index surgery. Of the 20 patients that performed sports, only 2 (10%) stopped sports after surgery, while 18 resumed their main sport (90%). At a follow-up of 65.4 ± 34.8 months (range 25-146), the SSV was 85.1 ± 14.7, pain on VAS was 1.9 ± 2.1, and the Constant-Murley score was 71.6 ± 17.9. Five patients had subjective instability without dislocation (23%). Nine patients (41%) had no pain (0 points), 6 patients (27%) had mild pain (1-2 points), 4 patients (18%) had moderate pain (3 points), while 3 patients (14%) had severe pain (5-8 points). Arthroscopic posterior capsulolabral repair prevented recurrent dislocation in patients with posterior shoulder instability at a minimum follow-up of 2 years, despite persistent pain in 32%, and subjective instability in 23%. These complications were mainly observed in patients with work-related accidents and glenoid cartilage lesions. III, case series.


HCV reflex testing: A single-sample, low-contamination method that improves the diagnostic efficiency of HCV testing among patients in Alberta, Canada.
Hepatitis C virus (HCV) can be cured with antiviral treatments. Diagnosis normally requires two blood samples, one for serology screening and one for molecular confirmation. This multi-step process creates barriers in patient care and decreases testing for hard-to-reach populations. We used the cobas® 6800 to detect HCV RNA after antibody testing to investigate whether a single-sample reflex testing method is effective and efficient for diagnosing HCV-positive patients. HCV RNA-positive clinical samples (n = 152) were interchangeably loaded on the ARCHITECT i2000SR with negative samples (n = 152) in a checkerboard fashion, tested for HCV antibodies using fixed probes, and directly transferred to the cobas 6800 for molecular testing. Contamination rates, sensitivity, and specificity were determined by comparing Abbott m2000 and cobas 6800 viral loads. After implementing reflex testing, clinical data over a 6-month period were analyzed for diagnostic efficiency. Contamination was present in 5 of 152 pairs (3.29%) after reflex testing. Sensitivity and specificity were 99.3% (95% CI 95.1% to 99.9%) and 100% (95% CI 97.5% to 100%), respectively, using the cobas 6800 assay after serotesting. Approximately 97% of clinical patients received a conclusive test result with the reflex-testing algorithm. For HCV-positive patients, mean diagnostic turnaround times were significantly lower using reflex testing versus the two-sample method (4 versus 39 days; p < 0.0001). HCV reflex testing demonstrated low levels of contamination without compromising the integrity of the molecular assay. Implementation in clinical laboratories would increase the efficiency of diagnosis and decrease steps in the continuum of care for patients.


Medical castration using megestrol acetate and minidose estrogen.
Sixty-two men who presented with previously untreated metastatic carcinoma of the prostate (D0: 10 patients; D1: 29 patients; D2: 23 patients) received oral megestrol acetate (80 mg twice daily) and minidose estrogen (diethylstibestrol 0.1 mg or ethinyl estradiol 0.05 mg once daily) as a means of achieving total androgen ablation (testicular and adrenal). A high incidence of feminizing side effects (70-74%), a higher than expected rate of cardiovascular complications (18%), an unexpected need for cortisone replacement (13%), and failure of patients with Stage D2 disease to obtain results better than those of standard therapy during the first year of observation suggest this regimen offers no advantage over other more conventional therapy.


The Influence of Intersections on Fuel Consumption in Urban Arterial Road Traffic: A Single Vehicle Test in Harbin, China.
The calculating method for fuel consumption (FC) was put forward and calibrated and the characteristics of the fuel consumption on intersections were analyzed based on 18 groups of vehicular operating data which were acquired from the test experiment of a single vehicle along the urban arterial roads in Harbin, China. The results obtained show that 50.36% of the fuel consumption for the test vehicle was used at the area of intersections compared with 28.9% of the influencing distance and 68.5% of the running time; and 78.4% of them was burnt at the stages of acceleration and idling. Meanwhile, the type


Perforations associated with peripherally inserted central catheters in a neonatal population.
Peripherally inserted central catheters (PICCs) are increasingly used in neonates but perforations can result in devastating complications such as pericardial and pleural effusions. Identifying risk factors may guide surveillance and reduce morbidity and mortality. To determine the risk factors for PICC perforation in neonates. Retrospective case:control (1:2) study of neonates admitted between 2004-2014. Charts and imaging were reviewed for clinical and therapeutic risk factors. Among 3,454 PICCs, 15 cases of perforation (incidence 0.4%, 5 pericardial effusions, 10 pleural effusions) were matched to 30 controls, based on gestation and insertion date. Timing of perforations post-insertion was median 4 days for pericardial effusions and 21.5 days for pleural effusions. A risk factor for pericardial effusion was lower weight at PICC insertion compared with controls. There were no statistically significant differences between cases and controls in catheter material, insertion site, PICC size and lumen number. Among upper limb PICCs, pericardial effusions were associated with tip positions more proximal to the heart at insertion (P=0.005) and at perforation (P=0.008), compared with controls. Pleural effusions were associated with tip positions more distal from the heart at perforation (P=0.008). Within 48 h before perforation, high/medium risk infusions included total parenteral nutrition (100% cases vs. 56.7% controls, P=0.002) and vancomycin (60% cases vs. 23.3% controls, P=0.02). PICC-associated pericardial effusions and pleural effusions are rare but inherent risks and can occur at any time after insertion. Risk factors and etiologies are multifactorial, but PICC tip position may be a modifiable risk factor. To mitigate this risk, we have developed and disseminated guidelines for target PICC positions and routinely do radiographs to monitor PICCs for migration and malposition in our NICU. The increased knowledge of risk profiles from this study has helped focus surveillance efforts and facilitate early recognition and treatment.


Manipulations of cognitive strategies and intergroup relationships reduce the racial bias in empathic neural responses.
Social relationships affect empathy in humans such that empathic neural responses to perceived pain were stronger to racial in-group members than to racial out-group members. Why does the racial bias in empathy (RBE) occur and how can we reduce it? We hypothesized that perceiving an other-race person as a symbol of a racial group, rather than as an individual, decreases references to his/her personal situation and weakens empathy for that person. This hypothesis predicts that individuating other-race persons by increasing attention to each individual's feelings or enclosing other-race individuals within one's own social group can reduce the RBE by increasing empathic neural responses to other-race individuals. In Experiment 1, we recorded event related brain potentials from Chinese adults as they made race judgments on Asian and Caucasian faces with pain or neutral expressions. We identified the RBE by showing that, relative to neutral expressions, pain expressions increased neural responses at 128-188 ms after stimulus onset over the frontal/central brain regions, and this effect was evident for same-race faces but not for other-race faces. Experiments 2 and 3 found that paying attention to observed individual's feelings of pain and including other-race individuals in one's own team for competitions respectively eliminated the RBE by increasing neural responses to pain expressions in other-race faces. Our results indicate that the RBE is not inevitable and that manipulations of both cognitive strategies and intergroup relationships can decrease RBE-related brain activity.


[Cytogenetic diagnosis of first trimester spontaneous abortion].
About 15% of all pregnancies end in abortion. In approximately 60% of all losses are chromosomal abnormalities as a cause of pregnancy loss. To determine the importance of cytogenetic study in patients with spontaneous abortion. A series of cases of women diagnosed with spontaneous abortion less than 12 weeks and cytogenetic studies. Two groups, one group of women with normal cytogenetics and group 2 patients with abnormal cytogenetic result. 44 patients were excluded by cytogenetic study failed. We included 164 women, 55 and 65 for groups 1 and 2, respectively. In 44 cases the material was not suitable for performing karyotype. Of the 120 cases included, had abnormal karyotypes in 65 cases (54%), of which 34 cases (52.3%) were trisomy, 16 cases (24.6%) to polyploidy and 9 cases (13.8%) a monosomy. In addition, we found six cases (8.7%) with recurrent pregnancy loss. The maternal age limit increased incidence of chromosomal abnormalities occurred in the group of 31 and 35 years with 20 cases (30%). Of trisomies, the 16 were the mostfrequent with 11 cases (32.3%). The finding of 54% of chromosomal abnormalities in spontaneous abortion products demonstrates the importance of cytogenetic study, regardless of patient age and number of previous pregnancy losses.


Correction to: Posttraumatic Stress Disorder Disturbs Coronary Tone and Its Regulatory Mechanisms.
The original version of this article unfortunately contained a mistake in the co-author name.


More accurate measurement of vancomycin minimum inhibitory concentration indicates poor outcomes in meticillin-resistant Staphylococcus aureus bacteraemia.
Meticillin-resistant Staphylococcus aureus (MRSA) is an important pathogen associated with community-acquired and nosocomial infections. The aim of this study was to validate the vancomycin (VAN) minimum inhibitory concentration (MIC) and administration of VAN that may affect the prognosis of patients with MRSA bacteraemia. In total, 140 clinical MRSA strains from blood cultures were collected from January 2009 to December 2013 at a university hospital in Tokyo (Japan). Patient background, their clinical situation and the susceptibility of isolates to anti-MRSA agents in all cases were reviewed, and factors contributing to 30-day mortality were analysed. Susceptibility to anti-MRSA agents was measured by a microdilution susceptibility testing method. The VAN MIC was further evaluated at 0.25 μg/mL intervals from 0.5 μg/mL to 2.0 μg/mL. Multiple logistic regression analysis revealed a 4-fold increase in mortality of patients with a VAN MIC ≥1.5 μg/mL [odds ratio (OR)=3.952, 95% confidence interval (CI) 1.471-10.614; P=0.006]. A one-score increase in the Charlson co-morbidity index resulted in a 1.2-fold increase in the risk of death (OR=1.199, 95% CI 1.054-1.364; P=0.006). However, no significant difference was found in the ratio of the VAN 24-h area under the concentration-time curve to MIC between VAN MIC ≥1.5 μg/mL and <1.5 μg/mL. A significant increase in the MICs of teicoplanin and daptomycin was observed in strains with high VAN MICs. For patients with high VAN MICs, administration of these anti-MRSA antibiotics may have a poor outcome owing to cross-resistance.


Genetic variation in parotid basic proteins (Pb) in the Bozo (Mali, West Africa).
The frequency of variants in the Pb system was studied in 71 individuals from the Bozo tribe in the Bani-Niger area (Mali, West Africa), in 25 male students from different African countries, and in 110 Dutch students. The frequency of the Pb2 allele was 0.20 in the Bozo and 0.00 in the Dutch population. A comparison is made with the results of a study among American blacks and with a Japanese study. The Pb 2--2 phenotypes observed in this study favour the hypothesis that the Pb-2 c protein is derived from a larger precursor in a manner analogous to the generation of the Pb-1 b protein from Pb-1 protein e.


Childhood sarcoidosis in the middle Anatolia of Turkey.
This retrospective study aimed to describe the clinical and radiological features, diagnostic methods, laboratory findings, organ involvement, and treatment strategies of 22 patients who followed up with late-onset childhood sarcoidosis and compare them with the literature. This retrospective multicenter study reviewed the medical records of 22 children with sarcoidosis who applied to the Pediatric pulmonology department of Erciyes University Faculty of Medicine and Necmettin Erbakan Faculty of Medicine in 2012 and 2022. The mean age of the patients at the time of diagnosis was 13.1/year (interquartile range [IQR]1:6.3-[IQR]3:15.7). The most common first presenting symptom was cough 40.9% (n = 9), weight loss 31.8% (n = 7), and dyspnea 22.7% (n = 5). There were elevated levels of C-reactive protein (CRP; 59%), angiotensin-converting enzyme (ACE; 54.5%), erythrocyte sedimentation rate (ESR; 54.5%), and immunoglobulin G (IgG; 54.5%). Twenty patients (90%) received systemic steroid treatment. Eighteen (81.8%) of these patients responded positively to treatment. Two patients had a recurrence. The incidence of sarcoidosis in children in Turkey is currently unknown. However, a regional average of 2.2 cases per year has been documented for the first time. Contrary to previous studies, a significant prevalence of consanguineous marriage was observed in our study. While constitutional symptoms were most common in other studies, the cough was the most common symptom in our study. To our knowledge, this is one of the Turkish studies with the highest number of sarcoidosis in children and one of the few European studies on sarcoidosis in children.


Data on synthesis, ADME and pharmacological properties and early safety pharmacology evaluation of a series of novel NURR1/NOT agonist potentially useful for the treatment of Parkinson's disease.
This article describes the chemical synthesis, ADME and pharmacological properties and early safety pharmacology evaluation of a series of novel Nurr1/NOT agonist. It is meant as a support to an article recently published in Bioorganic and Medicinal chemistry Letters and entitled "Development of a novel NURR1/NOT agonist from hit to lead and candidate for the potential treatment of Parkinson's disease" [1] and presenting the discovery, scope and potential of these new ligands of these nuclear receptors.


Self-efficacy and diabetes: why is emotional 'education' important and how can it be achieved?
Adequate age-appropriate diabetes knowledge and skills are essential to the success of diabetes self- and parental care. Health professionals have a central role in providing diabetes education. A direct link between diabetes knowledge and diabetes regimen behaviour cannot be assumed. Health professionals have to help children and their parents to develop the emotional concept of 'self-efficacy for diabetes self-care', to ensure optimal diabetes control.


Biomechanical mechanism driving typical postural shifts of lower limbs during sleeping in an aircraft seat.
The purpose of this study was to determine the biomechanical mechanisms driving passengers' lower-limb postural shifts during seated sleep on a flight to prevent negative effects on passengers' physical health. Twenty subjects participated in an observational study and a subsequent experiment on fatigue development and tissue oxygenation changes during seated sleep in an economy-class aircraft seat. Three of the most frequently used postures, which involved four targeted muscles of the legs and the thigh-buttock region, were selected and examined in the experiment with the following measures: muscle electromyogram, tissue oxygenation, and body contact pressure distribution. The results showed that the fatigue of the tibialis anterior and gastrocnemius and the compression of the region under the medial tuberosities were relieved by alternations among the three positions-position 1 (placing the shanks forwards), position 2 (placing the shanks neutrally), and position 3 (placing the shanks backwards). This research reveals the mechanical properties of the biomechanical factors functioning in lower-limb postural shifts during seated sleep and provides design optimization strategies for economy-class aircraft seats to reduce the negative effects on passenger health.


Characteristics of distal radius fractures in east China-an observational cohort study of 1954 individual fractures.
To investigate the characteristics and seasonal patterns of distal radius fractures (DRFs) over the preceding five years, with the aim of establishing a clinical foundation for the prevention and management of such fractures within this region. Utilizing the Picture Archiving and Communication Systems (PACS), the clinical records of 1954 patients diagnosed with DRFs and admitted to the Affiliated Hospital of Jiangsu University between January 2017 and December 2021 were compiled. The analysis encompassed factors such as age, gender, visitation timing, fracture side, and presence of osteoporosis. Out of the total 1954 distal radius fractures, 731 were males (37.4%) and the male to female ratio was 0.59:1. The median age of patients with DRFs was 56 years, with the 25th percentile being 38 years and the 75th percentile being 67 years. The average age was 50 years (standard deviation 23.3) and 1033 cases (52.7%) occurred on the left side, 885 cases (45.1%) on the right side, and 36 cases (1.8%) were bilateral, with the left side being the most frequently affected. The age group of 61-70 years (23.9%, 467/1954) exhibited the highest proportion, and the most prominent age group for males was 11-20 years (23.8%, 174/731), whereas for females it was 61-70 years (30.83%, 377/1223). In the 50 years and older group, there were 276 males and 991 females (ratio 1:3.59), with osteoporosis in 536 cases, accounting for 42.03% of the group. In terms of seasonal distribution, the highest incidence occurred during the summer and autumn months (55.1%, 1076/1954) and there were gender differences in different seasons. In east China, DRFs were predominantly female and left-sided, with the highest proportion in the age group of 61-70 years and in summer and autumn. Furthermore, gender differences were observed between the warm and cold seasons.


Muscle pain in neuromuscular disorders and primary fibromyalgia.
Muscle fiber degeneration and regeneration, inflammation in the intramuscular connective tissue and hypoxia in resting muscle are not necessarily associated with pain. However, when sustained or dynamic muscle contractions are performed in an ischaemic muscle, severe pain develops. In the chronic muscle pain syndrome called fibromyalgia (or fibrositis) the most likely cause of the pain is a combination of muscle tension and muscle hypoxia. This conclusion is supported by the finding of a pathological distribution of tissue oxygen pressure in painful muscles and a subjective feeling of muscle tension and muscle stiffness in the majority of patients. A decrease of high energy phosphates is found in biopsies from painful muscle. The most characteristic morphological finding is the so-called ragged red fiber, a finding that can be seen in mitochondrial disorders. The morphological and chemical findings are possibly a consequence of a long standing hypoxia. The possibility that sympathetic nerve activity is important for the development of chronic muscle pain is discussed.


The source of IgM and IgG in the dog intestine.
The source of IgM and IgG2a,b in the dog intestine was investigated, using labelled dog immunoglobulins and chronic Thiry-Vella loops of dog small intestine. Clearancess of IgM and IgG2a,b from serum into intestinal secretions were similar, reflecting transfer of a greater mass of IgG2a,b than of IgM. Only 20% of the intestinal IgM derived from serum, irrespective of the marker used. About one third of the total intestinal IgG, of all sub-classes and accrued from all sources, was serum-derived IgG2a,b. This indicates that serum is a major contributor to dog intestinal IgG2a,b.


The range of the required anterolateral cortex osteotomy distance varied widely in biplanar open wedge high tibial osteotomy.
To evaluate the anterolateral cortex distance between the lateral edge of the flange and hinge point in surgical simulations of biplanar open wedge high tibial osteotomy (OWHTO) using computed tomography (CT) images. A total of 110 knees treated with OWHTO for medial knee osteoarthritis with varus malalignment were enrolled. Surgical simulations of biplanar OWHTO, including the transverse and ascending cuts, were performed in the standard manner using preoperative CT images. The distance between the lateral edge of the flange and the hinge point was measured. In addition, another plane of the ascending cut was defined through the hinge point. The angle between these two planes of the ascending cut was measured in the axial plane. The mean anterolateral cortex distance was 9.4 ± 4.6 mm (range, - 1.5 mm - 20.3 mm). In 3 knees, osteotomy of the anterolateral cortex was not needed. The mean value of the angle between the two ascending cut planes was 8.4 ± 3.6° (range, - 2.1° - 14.8°), which meant that osteotomy of anterolateral cortex was not needed when the ascending cut was performed at this angle. Moreover, these two values increased when the flange thickness was changed from one-third to one-fourth of the anteroposterior tibial diameter or the angle between the transverse and ascending cuts was changed from 110° to 120°. In biplanar OWHTO, anterolateral cortex osteotomy would be required. However, the range of the required anterolateral cortex osteotomy distance varied widely and the required anterolateral cortex osteotomy distance depended on the flange thickness and the angle between the transverse and ascending cuts. In addition, change of the ascending cut plane can change the necessity of anterolateral cortex osteotomy.


Suitability of kefir powder production using spray drying.
Spray drying was applied for the production of kefir powder. The survival of microorganisms after drying, storage and simulated gastrointestinal (GI) conditions was investigated. Kefir was obtained by fermentation of milk and whey permeate, and was dehydrated directly (traditional kefir) or using different carriers (skim milk, whey permeate and maltodextrin). Low survival (5.5 log and <2 log CFU/g for lactic acid bacteria and yeast respectively) of microorganisms was achieved when kefir was dehydrated without thermoprotectants (carriers). In contrast, survival of the microorganisms was significantly improved in the presence of different carriers. When skim milk (SM) was used as the carrier medium, lactic acid bacteria (LAB) survival was above 9 log CFU/g. In contrast, viability of yeast was dramatically reduced after spray drying in these conditions. When whey permeate was used as the carrier medium, LAB survival was 8 log CFU/g and yeast survival was above 4 log CFU/g. LAB in the kefir powder survived better the simulated GI conditions when spray drying was conducted in SM. LAB in kefir powder sample dehydrated in SM and SM plus maltodextrin remained stable for at least 60 days at 4 °C. Our results demonstrated that spray drying of kefir is a suitable approach to obtain a concentrated kefir-derived product.


Regulation of cerebral serotonin binding and metabolism in sleep-deprived rats.
Two different binding sites are found for serotonin binding to crude membrane fractions isolated from rat brain. After 12 h sleep deprivation (SD) the dissociation constant of the high affinity binding KD1 = 1.4 mM, remains unchanged whereas the dissociation constant, KD2, of the low affinity binding increased from 26 to 42 nM. The number of binding sites are only moderately affected. The dissociation constant of the low affinity binding, KD2, is decreased towards control values if SD is followed by 1 or 4 h sleep. As indicated by serotonin and 5-hydroxyindoleacetic acid analyses, a statistically significant increase in serotonin metabolism is found only, if SD is followed by 1 h recovery sleep.


Depth of resin penetration into enamel with 3 types of enamel conditioning methods: a confocal microscopic study.
The clinical efficiency of a bonding material relies on its bond strength and debonding characteristics; the depth of resin penetration into enamel affects both of these factors. The depth of resin penetration has been previously studied by researchers using laborious, indirect methods, including the scanning electron microscope and the optical microscope. We used a more direct method, confocal microscopy, to visualize the resin tags in enamel. Thirty maxillary first premolars were selected and divided into 3 groups. In group A, the buccal enamel surfaces were conditioned with 37% phosphoric acid; in group B, a self-etching primer was used; and group C was treated with air abrasion. Transbond XT adhesive (3M Unitek, Monrovia, Calif) was used to bond a modified bracket. Transbond XT primer (3M Unitek) mixed with rhodamine B fluorescent dye (Chennai Chemicals, Chennai, India) was applied in groups A and C. In group B, rhodamine was mixed with self-etching primer. After curing, the brackets were debonded, and the teeth were visualized under the fluorescent channel of the confocal microscope. Maximal resin penetration of 53.9 μm was observed in group A, followed by group B at 40.5 μm and group C at 39.9 μm. Confocal microscope evaluation showed that enamel conditioning with 37% phosphoric acid produced greater depths of resin penetration than did self-etching primer or air abrasion.


Purification and characterization of an extracellular laccase from solid-state culture of Pleurotus ostreatus HP-1.
A native isolate of Pleurotus ostreatus HP-1 (Genbank Accession No. EU420068) was found to have an excellent laccase producing ability. The extracellular laccase was purified to electrophoretic homogeneity from copper sulphate induced solid-state fermentation medium by ammonium sulphate precipitation and ion-exchange chromatography. The enzyme was determined to be monomeric protein with an apparent molecular mass of 68,420 kDa, and an isoelectric point (pI) of 3.5. The inductively coupled plasma spectroscopy showed a presence of iron, zinc and copper in the purified enzyme. The absorption spectrum in the range of 200-700 nm showed the maximum absorption at 610 nm characteristic of fungal laccase and corresponding to the presence of type I copper atom. The laccase was stable at different temperatures up to 70 °C and retained 61 % activity at 50 °C. The enzyme reaction was inhibited by cysteine; sodium azide and EDTA. The enzyme oxidized various known laccase substrates, its lowest Km value being for ortho-dianisidine and highest Kcat and Kcat/Km for ABTS. The purified laccase exhibited different pH optima for different substrates. The N-terminal sequence did not show any similarity with N-terminal sequence of other species of genera Pleurotus.


A note on genetic distance.
Various definitions of 'genetic distance' and 'frequency distance' are considered, together with the purposes for which they are used. There are at least seven simple definitions of 'genetic distance' which agree closely with each other and with a Mahalonobis-type D2 for qualitative characters, whereas other proposed definitions are mostly based on quite different approaches. The Mahalanobis-type definitions are also related to random drift.


Serum cholinesterase inhibitors in the commercial hexane impurities.
Commercial hexane was concentrated by distillation. The distillation residue (0.43 ml/l original solvent) contains material which inhibits human serum cholinesterase (ChE) "in vitro" with a slight effect on acetylcholinesterase. Phosphorus was detected equivalent to 0.33 mumol monophosphorus compound/litre original solvent. The inhibition was progressive with the enzyme-inhibitor preincubation time. A partial reactivation of the inhibited enzyme was obtained by treatment with hydroxylamine and 2-PAM. The results are coherent with a covalent inactivation by more than one inhibitor which acylate (probably phosphorylate) ChE, although it seems likely that a reversible but unstable inhibitor could also be present in the hexane residue. The results are discussed in the context of the known neurotoxic effects of n-hexane and some organophosphorus esters.


[Toxicity of matrine in Kunming mice].
To investigate the acute toxicity and assess the median lethal dose (LD50) of matrine in Kunming mice. Matrine at different doses were administered in Kunming mice via intraperitoneal injection, and the toxic reactions and LD50 of matrine was observed and determined. The acute toxicity test of matrine indicated that the tolerable dose of matrine was above 80 mg/kg in Kunming mice, and the LD50 was 157.13 mg/kg (95%CI, 88.08-280.31 mg/kg). Morphological observation revealed degenerative changes of the nerve cells in the brain tissue of the mice. The nervous system is the main target organ by the toxicity of matrine.


Effects of two different immunotherapies on triple negative breast cancer in animal model.
The ability of immune system to react specifically against tumors inspirited the study of triple negative breast cancer (TNBC) immunotherapies. Sixty spontaneous breast cancer TA2 mice were randomly divided into three groups: GM-CSF group, with therapy of granulocyte-macrophage colony-stimulating factor (GM-CSF) combined with breast cancer stem cells associated antigens and cytosine-phosphorothioate-guanine oligodeoxynucleotides (CpG-ODNs); DC-CIK group, with infusions of dendritic cells/cytokine-induced killer (DC/CIK) cells; and PBS group as controls. After therapy, the cellular immunity of mice in GM-CSF group and DC-CIK group was obviously increased, especially for GM-CSF group (P<0.05), tumor regression was obviously observed in GM-CSF group. The survival rate of mice in GM-CSF group was significantly higher compared to DC-CIK group and PBS group. These results indicated that tumor immunotherapy manifested strong killing activity against TNBC. The therapeutic effect of GM-CSF combined with antigens and CpG was better than DC-CIK cells.


Bacterial profiles and volatile flavor compounds in commercial Suancai with varying salt concentration from Northeastern China.
Suancai, a popular traditional fermented cabbage in northeast China, is commonly prepared by the spontaneous fermentation process at a certain salt concentration. The salt can affect the metabolites by affecting the microorganisms during Suancai fermentation. The bacterial community and volatile flavor compounds in commercial Suancai from different regions of Northeastern China at different salt concentrations were investigated using next-generation sequencing and GC-MS. Firmicutes and Cyanobacteria were the dominant phyla in the commercial Suancai, and Lactobacillus, Pediococcus, and Leuconostoc were the dominant genera. Among them, Lactobacillus and Pediococcus were considered as the biomarkers of the low and high salt Suncai, respectively. Eighty-five volatile flavor compounds were detected, and HS exhibited higher contents of volatile flavor compounds than LS. Based on the results of correlation analysis, Pediococcus were highly correlated with the alcohols and nitriles in Suancai. The contents of alcohols and nitriles significantly increased in the Suancai, fermented by Pediococcus pentosaceus. The co-inoculated fermentation of Lactobacillus plantarum and P. pentosaceus could increase the concentrations of alcohols, esters, aldehydes, hydrocarbons, and nitriles in Suancai. This study provides a perspective for understanding the ecology of Suancai fermentation and facilitating the fermentation with multispecies inoculation fermentation at an appropriate salt concentration.


Analysis of the role of behavioural factors in the development of tolerance to the benzodiazepine midazolam.
Two experiments were conducted on the acute and chronic effects of the short-acting benzodiazepine midazolam on fixed ratio schedule-maintained operant responding in rats. Acute administration of midazolam produced suppression of responding in large doses but elevation of responding in small doses. Following intermittent (every third day) chronic treatment tolerance developed rapidly to the rate-suppressant effects of large doses of midazolam but did not develop to the rate-elevating effects of small doses, even after chronic treatment with large doses of the drug. Thus, when tolerance was measured in terms of shifts in dose-effect curves, it was manifested as a non-parallel shift in the curve after chronic treatment. Since tolerance developed to the effects of large but not small doses, the observed tolerance could not be attributed to changes in disposition of the drug. The development of tolerance did not depend on whether the drug was given before or after behavioural testing. These findings contrast with data reported in behavioural studies with other sedative-hypnotics (ethanol, barbiturates). Animals tolerant to midazolam showed no cross-tolerance to ethanol, a drug for which there is reliable evidence indicating that behavioural factors play a role in acquisition of tolerance. Tolerance to midazolam cannot therefore be explained in terms of learned strategies acquired as a result of drug-induced loss of rewarding stimuli. This conclusion contrasts with recent suggestions (File, 1985; File and Pellow, 1985) that tolerance to benzodiazepines may be mediated by instrumental conditioning processes.


Zinc accumulation in the telencephalon of lizards.
The zinc concentration in the brains of two species of lizard was determined by atomic-absorption spectrophotometry. The zinc concentration was found to be highest in the telencephalon of Lacerta galloti (21.1 micrograms/g fresh weight) and Podarcis hispanica (16.77 +/- 0.8 micrograms/g) while the mesencephalon and brain stem exhibited lower zinc concentrations, i.e., 7.0 micrograms/g in Lacerta galloti and 6.08 +/- 0.4 micrograms/g in Podarcis hispanica. This high telencephalic concentration of zinc is paralleled by intense and well-defined Timm reactivity used for demonstrating the presence of zinc-containing boutons at the light-microscope level. Volumetric-densitometric studies of these Timm-reactive zones were performed using serial transverse sections of the same lizard brains.


(Oligo)thienyl-imidazo-benzocrown ether derivatives: synthesis, photophysical studies and evaluation of their chemosensory properties.
A series of novel (oligo)thienyl-imidazo-benzocrown ethers were synthesised through a simple method and evaluated as fluorimetric chemosensors for transition metal cations. Interaction with Ni(2+), Pd(2+), and Hg(2+) in ACN/DMSO solution (99:1) was studied by absorption and emission spectroscopy. Chemoselectivity studies in the presence of Na(+) were also carried out and a fluorescence enhancement upon chelation (CHEF) effect was observed following Hg(2+) complexation. Considering that most systems using fluorescence spectroscopy for detecting Hg(2+) are based on the complexation enhancement of the fluorescence quenching (CHEQ) effect, the present work represents one of the few examples for sensing of Hg(2+) based on a CHEF effect.


Single-stage reconstruction of skin-involving nasal paraffinoma with pericraniosubgaleal flap.
The removal of a paraffinoma over the nasal bridge may result in thinning and even loss of involved skin as well as a saddle nose deformity. For nasal reconstruction, a variety of techniques using a free graft of autogenous tissue such as fascia, dermofat, or cartilage have been used, either in immediate, single-stage or in delayed, multiphase treatment. However, such reconstructions can be challenging largely due to absorption of the grafted tissue and poor blood supply to the surrounding nasal tissue infiltrated with paraffin. This article reports the successful clinical outcomes of immediate, single-stage reconstructions by wrapping a pericraniosubgaleal flap over the nasal implant after removing a paraffinoma. Eleven patients with a paraffinoma showing a palpable lump, redness, or telangiectasia over the nasal skin were treated between November 1998 and March 2011. The mean follow-up period was 20.1 months. As much of the paraffinoma as possible was removed via a bidirectional approach (open rhinoplasty and frontal hairline incision), and the resulting deformity was reconstructed simultaneously using a pericraniosubgaleal flap and turning it over the sculpted nasal implant (ePTFE; GORE-TEX(®) in nine cases and silicone in two cases). Nine patients (81.8%) were treated successfully without complications and were satisfied with their results. However, the other two patients complained of incomplete removal of the paraffinoma requiring additional removal. Telangiectasia over the nose improved in four out of six patients after surgery. Nasal reconstruction using a pericraniosubgaleal flap is one of the most reliable surgical options for treating skin-involving nasal paraffinomas. The advantage of such a method is that a well-vascularized and durable flap, which is resistant to infection, is wrapped over the sculpted nasal implant in a single step. It also reinforces the thinned skin, which makes it easier to form various shapes, producing excellent cosmetic results. Finally, it can also serve as a tolerable graft bed in the case of overlying skin loss.


Smoking and its associations with sociodemographic and clinical characteristics and quality of life in patients with schizophrenia treated in primary care in China.
Maintenance treatment for clinically stable patients with schizophrenia is usually provided by Chinese primary care physicians, but no study has investigated smoking rates in this population. This study investigated the rate of smoking and its associations with sociodemographic and clinical characteristics and quality of life (QOL) in patients with schizophrenia treated in primary care in China. This was a cross-sectional, community-based survey. A total of 621 schizophrenia patients were recruited from 22 primary care services in Guangzhou, China, in 2013. Patients' sociodemographic and clinical characteristics, smoking status, and QOL were recorded. The frequency of current smoking was 23.8% in the whole sample; 41.5% for men and 2.5% for women. Multiple logistic regression analysis revealed that male gender, married status, alcohol use, older age at onset, fewer major medical conditions, lower education level and more hospitalizations were independently associated with current smoking. The frequency of smoking in Chinese schizophrenia patients treated by primary care physicians is lower than most figures reported from Western and Chinese psychiatric settings.


Pneumococcus beyond an Austrian syndrome - A case report.
Austrian syndrome is a rare entity characterized by Osler's triad: endocarditis, pneumonia and meningitis, caused by Streptococcus pneumoniae (Austrian, 1957 [1]). This aggressive syndrome is associated with high morbidity and mortality, often due to the involvement of the heart valves and their destruction (Nogué et al., 2019 [2], Araji et al., 2008 [3]). We present a case of Austrian syndrome in a splenectomised elderly patient with an unusual presentation: septic arthritis complicated by endocarditis, septic cerebral emboli, meningitis and pneumonia. Despite appropriate therapy, the prognosis remained poor and the patient died at day 7.


TOPK inhibits TNF-α-induced granulosa cell apoptosis via regulation of SIRT1/p53.
T-LAK cell originated protein kinase (TOPK) has been shown to regulate proliferation, invasion or migration of various cancer cells. However, the role of TOPK in follicle environments remains unknown. Here we reveal that TOPK inhibits TNF-α-induced human granulosa COV434 cell apoptosis. The expression of TOPK were increased in COV434 cells in response to TNF-α. TOPK inhibition also decreased TNF-α-induced SIRT1 expression but promoted TNF-α-induced p53 acetylation and expression of PUMA or NOXA. Accordingly, TOPK inhibition attenuated TNF-α-mediated SIRT1 transcriptional activity. In addition, SIRT1 inhibition augmented acetylation of p53 or expression of PUMA and NOXA in response to TNF-α, leading to COV434 cell apoptosis. We conclude that TOPK suppresses TNF-α-induced COV434 granulosa cell apoptosis via regulation of p53/SIRT1 axis, suggesting a potential role of TOPK in regulation of ovarian follicular development.


Peptidyl-prolyl isomerase 1 (Pin1) preserves the phosphorylation state of tissue factor and prolongs its release within microvesicles.
The exposure and release of TF is regulated by post-translational modifications of its cytoplasmic domain. Here, the potential of Pin1 to interact with the cytoplasmic domain of TF, and the outcome on TF function was examined. MDA-MB-231 and transfected-primary endothelial cells were incubated with either Pin1 deactivator Juglone, or its control Plumbagin, as well as transfected with Pin1-specific or control siRNA. TF release into microvesicles following activation, and also phosphorylation and ubiquitination states of cellular-TF were then assessed. Furthermore, the ability of Pin1 to bind wild-type and mutant forms of overexpressed TF-tGFP was investigated by co-immunoprecipitation. Additionally, the ability of recombinant or cellular Pin1 to bind to peptides of the C-terminus of TF, synthesised in different phosphorylation states was examined by binding assays and spectroscopically. Finally, the influence of recombinant Pin1 on the ubiquitination and dephosphorylation of the TF-peptides was examined. Pre-incubation of Pin1 with Juglone but not Plumbagin, reduced TF release as microvesicles and was also achievable following transfection with Pin1-siRNA. This was concurrent with early ubiquitination and dephosphorylation of cellular TF at Ser253. Pin1 co-immunoprecipitated with overexpressed wild-type TF-tGFP but not Ser258→Ala or Pro259→Ala substituted mutants. Pin1 did interact with Ser258-phosphorylated and double-phosphorylated TF-peptides, with the former having higher affinity. Finally, recombinant Pin1 was capable of interfering with the ubiquitination and dephosphorylation of TF-derived peptides. In conclusion, Pin1 is a fast-acting enzyme which may be utilised by cells to protect the phosphorylation state of TF in activated cells prolonging TF activity and release, and therefore ensuring adequate haemostasis.


The Clinical, Pathological, and Prognostic Value of High PD-1 Expression and the Presence of Epstein-Barr Virus Reactivation in Patients with Laryngeal Cancer.
Due to the development of molecular diagnostic techniques, the latest research in the diagnosis of cancer diseases, including laryngeal cancer, has been focused on the occurrence of specific types of molecular patterns, including markers expressed on cells of the immune system (e.g., PD-1, PD-L1, and CTLA-4), which may be directly or indirectly involved in the development of neoplastic diseases. Laryngeal cancer is one of the diseases that is diagnosed more often in men than in women, and many factors are involved in its development, including environmental and lifestyle factors, viral infections (e.g., HPV, HHV-1, and EBV), and disorders of the immune system. In this study, we determined the level of PD-1 receptor expression on T and B lymphocytes and their relationships based on the classification of the grade and TNM scale, in turn based on blood, tumor, and lymph node samples from patients diagnosed with laryngeal cancer. In addition, we determined the presence of EBV genetic material in the tested biological materials as well as the degree of cancer advancement and its correlation with the level of PD-1 receptor expression. The results suggested that the level of PD-1 expression on T and B lymphocytes was significantly higher in the tumor samples as compared to the lymph node samples, and their comparison with the immunophenotype results from the blood samples provided statistically significant data on changes in the incidence of individual subpopulations of T and B lymphocytes and the level of PD-1 receptor expression. The analysis of the individual parameters of the TNM scale also showed significant changes between the PD-1 expression and the tested biological material in individual subgroups of the scale. We also found that the expression of PD-1 on the CD4+ T cells from the lymph node samples caused an almost 1.5-fold increase in the risk of death. In the analyses of the presence of EBV, the highest concentration was recorded in the tumor samples, then for the lymph node samples, and followed by the blood samples. Furthermore, we showed that the presence of EBV genetic material was positively correlated with the level of PD-1 expression in the tested biological materials.


Germ line DDX41 mutations define a unique subtype of myeloid neoplasms.
Germ line DDX41 variants have been implicated in late-onset myeloid neoplasms (MNs). Despite an increasing number of publications, many important features of DDX41-mutated MNs remain to be elucidated. Here we performed a comprehensive characterization of DDX41-mutated MNs, enrolling a total of 346 patients with DDX41 pathogenic/likely-pathogenic (P/LP) germ line variants and/or somatic mutations from 9082 MN patients, together with 525 first-degree relatives of DDX41-mutated and wild-type (WT) patients. P/LP DDX41 germ line variants explained ∼80% of known germ line predisposition to MNs in adults. These risk variants were 10-fold more enriched in Japanese MN cases (n = 4461) compared with the general population of Japan (n = 20 238). This enrichment of DDX41 risk alleles was much more prominent in male than female (20.7 vs 5.0). P/LP DDX41 variants conferred a large risk of developing MNs, which was negligible until 40 years of age but rapidly increased to 49% by 90 years of age. Patients with myelodysplastic syndromes (MDS) along with a DDX41-mutation rapidly progressed to acute myeloid leukemia (AML), which was however, confined to those having truncating variants. Comutation patterns at diagnosis and at progression to AML were substantially different between DDX41-mutated and WT cases, in which none of the comutations affected clinical outcomes. Even TP53 mutations made no exceptions and their dismal effect, including multihit allelic status, on survival was almost completely mitigated by the presence of DDX41 mutations. Finally, outcomes were not affected by the conventional risk stratifications including the revised/molecular International Prognostic Scoring System. Our findings establish that MDS with DDX41-mutation defines a unique subtype of MNs that is distinct from other MNs.


Increased posterior shoulder capsule thickness in youth elite handball players: a sonographic investigation.
Range of motion adaptations in the shoulders of overhead throwing athletes have been reported, but knowledge about the development of soft-tissue adaptations is limited. The purpose of this study was to investigate differences in posterior shoulder capsule thickness and internal rotation between the throwing and non-throwing shoulder. On the basis of the sample size calculation, we assessed 63 youth elite handball players (33 boys and 30 girls, mean age: 13.6 ± 0.9 years) for glenohumeral internal and external rotational range of motion, humeral retrotorsion, and posterior capsule thickness (PCT) with a manual goniometer and a portable ultrasound device and calculated sports-specific differences between the throwing and non-throwing shoulder as well as correlations with PCT. Youth handball players showed side-to-side differences in internal rotation, external rotation, and humeral retrotorsion between the throwing and non-throwing shoulder. Posterior shoulder capsules were 1.21 times thicker (95% confidence interval: 1.1-1.3) in the throwing shoulder than in the non-throwing shoulder (1.3 ± 0.3 mm vs. 1.2 ± 0.2 mm, P < .0001). Loss of internal rotation did not correlate with PCT. In youth elite handball athletes, posterior shoulder tightness and subsequent sports-specific loss of internal rotation in the throwing shoulder are not related to PCT. Thus, in this age class, other (soft-tissue) factors must be responsible for this condition.


Imaging of distant metastases of prostate cancer.
The detection of distant metastases at the initial diagnosis of prostate cancer (PCa) establishes the treatment approach and has a prognostic value, nevertheless it is not well established. Since proposed staging approaches often contradict each other, we aimed to compare the current imaging techniques for staging of advanced PCa, including future applications of the most innovative methods. Conventional imaging techniques, including computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET) have been employed for metastatic staging (both N and M staging) of men with high-risk PCa, but surgical pelvic dissection remains the gold standard for N staging. However, functional MRI by using diffusion-weighted imaging, MR lymphography (MRL) with ultra-small paramagnetic iron oxide particles (USPIO), and hybrid PET/MRI imaging showed both high sensitivity and high specificity for nodal staging and depicting metastases. The standard of practice for M staging in PCa includes the radionuclide bone scan and targeted X-ray film, but their performance has generally been poor. Recently, MRI showed promising results with applications in both local and distant staging. Finally, with the development of new PET tracers, PET/CT and PET/MRI offer a combination of excellent pharmacokinetic characteristics, functional information, and precise anatomic localization and morphological correlation of tumor lesions.


Incorporation of Nanostructured Carbon Composite Materials into Counter Electrodes for Highly Efficient Dye-Sensitized Solar Cells.
Dye-sensitized solar cells (DSSCs) composed of nanostructured carbon composite materials-stacked counter electrodes (CEs) were fabricated in the present study. As the potential replacement of expensive platinum (Pt) thin film, various carbon composite materials, including zero-dimensional carbon nanoparticles (CNPs), one-dimensional multiwalled carbon nanotubes (MWCNTs), and two-dimensional graphene flakes (GFs) as a suitable charge transfer medium were deposited on the surface of CEs using a screen printing process. As the results, CNPs were found to result in deteriorating the charge transfer from CE to liquid electrolyte due to the formation of highly aggregated structures with very low specific surface area. However, MWCNTs and MWCNTs-added carbon composites (e.g., CNP/MWCNT, MWCNT/GF, CNP/MWCNT/GF) were found to enhance the charge transfer from CE to liquid electrolyte due to the formation of highly networked structures with high specific surface area. The resulting PCE of DSSCs composed of pure MWCNTs- and MWCNTs-added carbon composites-based CEs were very similar with that of DSSCs composed of Pt-based CEs. This suggests that the nanostructured carbon materials especially composed of MWCNTs and their composites are one of the promising candidates to replace the expensive Pt in the CEs of DSSCs.


Targeting the biased brain: non-invasive brain stimulation to ameliorate cognitive control.
Non-invasive brain stimulation has become important for the investigation of healthy and impaired neuronal functioning. Moreover, non-invasive brain stimulation has emerged as a new means of psychiatric treatment, although the mechanisms of action are still not understood and the optimal mode of application is still under development. Dysfunctional cognitive control is a central characteristic of various psychiatric disorders and is associated with dysregulations of prefrontal cortex activity and biased information processing. With non-invasive brain stimulation, enhancement and reduction of prefrontal cortex activity were shown to ameliorate and impair cognitive control, respectively. These findings suggest a neurocognitive mechanism of therapeutic effects and that non-invasive brain stimulation can be combined with training to target dysfunctional cognitive control and related clinical symptomatology. Nevertheless, the intra-individual and inter-individual diversity of neurocognitive processes, the multiplicity of possible stimulation parameters, and the complexity of interactions between those factors pose considerable challenges for interpretation of these findings and their clinical application.


1-(Methyl-α-d-gluco-pyran-osid-6-yl)-3-vinyl-imidazolium iodide di-methyl-formamide monosolvate.
The title solvated molecular salt, [MeGluVIm]I (MeGluVIm = 1-(methyl-α-d-gluco-pyran-osid-6-yl)-3-vinyl-imidazolium), or C12H19N2O5 +·I-·C3H7NO, was synthesized from methyl-α-d-6-iodo-gluco-pyran-oside and vinyl-imidazole in DMF. It crystallizes through precipitation from ethyl acetate solution directly after the reaction procedure. The crystal structure consists of an iodide anion and a [MeGluVIm] cation. Furthermore, the crystal structure contains one mol-ecule of DMF, which accepts two O-H⋯H hydrogen bonds from the OH groups of the gluco-pyran-oside.


Probabilistic human health risk assessment of arsenic under uncertainty in drinking water sources in Jiangsu Province, China.
Concentrations of arsenic (As) in 65 drinking water sources in Jiangsu Province of China were analyzed from January 2013 to December 2015. The drinking water sources are classified into five water systems of the Yangze River, the Taihu Lake, the Huai River, the Yishusi River, and other lakes or reservoirs, which are termed as WS-A, WS-B, WS-C, WS-D, and WS-E, respectively. Health risk assessments associated with As in terms of total carcinogenic risk and total hazard index were performed for children (0-5 years), teenagers (6-17 years), and adults (≥ 18 years), respectively. Probabilistic risk assessments were obtained by applying Monte Carlo approach with consideration of uncertainty. The results indicated that in drinking water sources of WS-A, WS-C, and WS-D, maximum concentrations of As were 28 μg/L, 40 μg/L, and 17 μg/L, respectively, which were higher than 10 μg/L recommended by the World Health Organization occurred. Based on the samples investigated in this study, the mean health risks are the highest in drinking water source WS-D and lowest in WS-E for both male and female children, teenagers, and adults. For drinking water source WS-A, the health risks of male children, male teenagers, and female adults are higher than female children and female teenagers, and male adults. However, for drinking water sources WS-B, WS-C, WS-D, and WS-E, the health risks of female children, male teenagers, and female adults are higher than male children, female teenagers, and male adults. The highest health risks occurred in female children consuming drinking water from WS-D. The sensitivity analysis indicated that the concentration of As is the primary factor for carcinogenic risk of all the five water systems. The results obtained can provide meaningful information for risk managers in Jiangsu Province.