Analysis of metabolites of bactrain camel milk in Alxa of China before and after fermentation with fermenting agent TR1 based on untargeted LC-MS/MS based metabolomics.
Camel milk produces many beneficial functional compounds and affects body health through metabolism. The differential metabolites of bactrain camel milk in Alxa before and after fermentation were identified by liquid chromatography-tandem mass spectrometry based metabolomics (LC-MS/MS). The differential metabolite pathway types were also identified in this paper. We obtained the following results that 148 and 82 differential metabolites were detected in positive and negative ion mode respectively, 85 differential metabolites were shown a significant upward trend and 63 with downward trend after fermentation in positive ion mode. Meanwhile, 32 differential metabolites characterized upward trend and 50 characterized downward trend in negative ion mode. The differential metabolites were mainly organic acids, amino acids, esters, vitamins and other substances contained in camel milk. Among them, most up-regulated substances had the functions of lowering blood pressure, lowering blood sugar, treatment of inflammation, antibiosis and other effects. Many harmful substances were significantly down-regulated after camel milk fermentation. However, there were also some metabolites whose prebiotic functions have been weakened by camel milk fermentation, which may provide reference values for healthcare function, exploitation and application of camel milk.


Smart Bandages: The Future of Wound Care.
Chronic non-healing wounds are major healthcare challenges that affect a noticeable number of people; they exert a severe financial burden and are the leading cause of limb amputation. Although chronic wounds are locked in a persisting inflamed state, they are dynamic and proper therapy requires identifying abnormalities, administering proper drugs and growth factors, and modulating the conditions of the environment. In this review article, we discuss technologies that have been developed to actively monitor the wound environment. We also highlight drug delivery tools that have been integrated with bandages to facilitate precise temporal and spatial control over drug release and review automated or semi-automated systems that can respond to the wound environment.


Intact neurotensin (NT) in human plasma: response to oral feeding.
Neurotensin-like immunoreactivity (NTLI) increases in human plasma postprandially. Intact neurotensin (NT) however, has been found to be a minor component of NTLI, the major components being the N-terminal fragments 1-11 and 1-8. Intact NT is the only known biologically-active form. A radioimmunoassay (RIA) has been developed which employs an antiserum unreactive to 1-11 or smaller N-terminal NT fragments. Using this RIA, intact NT response to a mixed meal has been assessed in 10 healthy humans. Intact NT levels were significantly elevated over basal 15 min after ingestion of the meal and remained so for the duration of the experiment (120 min). The suggestion that intact NT is a circulating hormone has been substantiated. Due to the rapidity of the rise in plasma NT after feeding it is proposed that the initial NT response is mediated by neural or hormonal means, rather than by direct luminal stimulation of the N cell-rich jejunoileum.


Results of a Phase I-II Study on Laser Therapy for Vaginal Side Effects after Radiotherapy for Cancer of Uterine Cervix or Endometrium.
Women who have previously received radiotherapy (RT) for gynecologic cancer often suffer from vaginal fibrosis and stenosis. The success of "non-ablative" laser therapy for postmenopausal vaginal atrophy has led to the idea of testing the laser in patients submitted to RT. In this prospective observational study, we selected patients who underwent pelvic RT followed by vaginal laser treatment. We scheduled three treatment sessions (at T0-T1-T2) and three controls (at T1-T2-T3) one month apart. The follow-up (at T4) was carried out six months after the last treatment. Vaginal Health Index (VHI) and vaginal length were evaluated. Sexual function was assessed through Female Sexual Function Index (FSFI). Overall, 43 patients with severe vaginal shortening, atrophy and stenosis was enrolled and treated with intravaginal non-ablative CO2 laser. We observed a progressive increase in vaginal length of 9% (p = 0.03) at T2 and 28% (p < 0.0001) at T3; effects were maintained at T4 (p < 0.0001). After the first application VHI showed a significant improvement of 57% at T3 (p < 0.0001). The results were maintained at T4 (p < 0.0001). No changes were found in FSFI. All procedures were well tolerated. In conclusion, laser therapy improved vaginal length and VHI in women undergoing pelvic RT; prospective studies are needed.


Diagnostic yield using whole-genome sequencing and in-silico panel of 281 genes associated with non-immune hydrops fetalis in clinical setting.
To investigate the diagnostic yield of clinical whole-genome sequencing (WGS) in prenatally diagnosed non-immune hydrops fetalis (NIHF). This was a retrospective study of 23 fetuses with prenatally diagnosed NIHF, negative for trisomies and copy-number variants, referred for analysis by WGS with an in-silico panel of 281 genes associated with hydrops fetalis. Due to identification of a high proportion of causative variants in the HRAS gene in the main cohort, Sanger sequencing of HRAS was performed in a replication cohort, consisting of 24 additional fetuses with NIHF that were negative for trisomies and copy-number variants and had not undergone WGS. Of the 23 fetuses in the main cohort, a molecular diagnosis was achieved in 12 (52.2%). Pathogenic or likely pathogenic variants were identified in seven genes: HRAS (n = 5), RIT1 (n = 2), FOXP3 (n = 1), GLB1 (n = 1), MAP2K1 (n = 1), PTPN11 (n = 1) and RASA1 (n = 1). The inheritance pattern of the 12 causative variants was autosomal dominant in 10 cases (HRAS, MAP2K1, PTPN11, RASA1, RIT1), autosomal recessive in one (GLB1) and X-linked recessive in one (FOXP3). Of the 24 fetuses in the replication cohort, a pathogenic variant in HRAS was identified in one, resulting in an overall frequency of causative HRAS variants of 12.8% (6/47) in our two cohorts. We demonstrate a diagnostic yield of 52% with clinical WGS in NIHF using an in-silico panel of 281 genes. However, the high diagnostic yield may be attributed to the small sample size and possible over-representation of severe phenotypes in the included fetuses. Bearing in mind that chromosomal abnormalities were excluded in our cohorts, a detection rate of up to 75% is possible in prenatally diagnosed NIHF when WGS analysis includes calling of chromosomal aberrations. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.


Phosphatidylinositol-3-kinase and protein kinase C are involved in the pro-cognitive and anti-anxiety effects of phytohormone abscisic acid in rats.
The phytohormone abscisic acid (ABA) exists in animal tissues particularly in the brain. However, the neurophysiological effects of ABA have not yet been fully determined. Signaling molecules such as PKC and PI3K have been implicated in anxiety-like behavior as well as learning and memory processes. Recently, it has been demonstrated that PKC and PI3K signaling pathways participate in some biological effects of ABA. This study was designed to evaluate the effects of central injection of ABA on spatial learning and memory and anxiety-like behavior and determine its possible signaling mechanisms. Spatial learning and memory and anxiety-like behaviors were determined using Morris water maze (MWM) and plus maze tests, respectively. ABA alone or in accompanied with selective inhibitors of PKC (chelerythrine) and PI3K (LY2940029) was injected bilaterally into the cerebral lateral ventricles. The results indicated that ABA (10μg/rat) significantly improved rats' performance in MWM which was blocked by PKC or PI3K inhibitors. In addition, ABA showed anti-anxiety effect in plus maze test, which was not observed in PKC or PI3K inhibitor-treated rats. Overall, the results indicated that ABA has positive effect on spatial learning and memory performance and elicits anti-anxiety effects which are performed, at least in part, through PI3K/PKC signaling pathway.


Staging of Anal Cancer: Role of MR Imaging.
Anal cancer is a relatively rare malignancy. Treatment consists of chemoradiation and most patients achieve a complete response. Local evaluation of the T and N stage is performed by MR imaging. Whole-body staging with 18F-fluorodesoxyglucose positron emission tomography computed tomography scans or computed tomography scans is used to detect metastases. T stage is based on tumor size or invasion of organs. N stage is based on nodal location. After chemoradiation, clinical evaluation and MR imaging is used to assess tumor and nodal response. Maximal response is achieved 6 months after chemoradiation. Beware of development of anal cancer in perianal fistulas.


[Priapism as a complication following diagnostic papaverine test].
In 5 out of 84 patients suffering from impotence a prolonged erection was observed after intracavernous papaverine injection. Treatment consisted of puncture of the cavernous body, blood evacuation and intracavernous adrenaline injection. In 4 patients erectile function could be preserved and in the fifth patient a penile prosthesis has been implanted.


The expression of m6A enzymes in the hippocampus of diabetic cognitive impairment mice and the possible improvement of YTHDF1.
Cognitive impairment is a severe diabetes-related complication and seriously challenges the demand for future health resources. However, the potential therapeutic targets and mechanisms are not fully understood. Herein, we investigated the expression of the m6A enzyme in the hippocampus of mice with diabetes-induced cognitive impairment and possible improvement with overexpression of YTHDF1. A type 1 diabetes (T1D) mouse model was established by streptozotocin (STZ) intraperitoneal injection. Diabetic mice showed significant cognitive dysfunction, which was detected by novel object recognition tests and novel place recognition tests. Western blot analysis showed that compared with the control group, the protein levels of YTHDC2 and ALKBH5 were significantly upregulated in the hippocampus in the STZ group, while the expression of YTHDF1, YTHDF3 and WTAP was significantly downregulated. Furthermore, overexpression of YTHDF1 by AAV-YTHDF1 injection in the hippocampus significantly improved STZ-induced diabetic cognitive dysfunction. These results indicate that the m6A enzyme may play a key role in the cognitive dysfunction induced by diabetes, and YTHDF1 may be a promising therapeutic target.


An in vivo investigative protocol for HDR prostate brachytherapy using urethral and rectal thermoluminescence dosimetry.
To develop an in vivo dosimetry based investigative action level relevant for a corrective protocol for HDR brachytherapy boost treatment. The dose delivered to points within the urethra and rectum was measured using TLD in vivo dosimetry in 56 patients. Comparisons between the urethral and rectal measurements and TPS calculations showed differences, which are related to the relative position of the implant and TLD trains, and allowed shifts of implant position relative to the prostate to be estimated. Analysis of rectal dose measurements is consistent with implant movement, which was previously only identified with the urethral data. Shift corrected doses were compared with results from the TPS. Comparison of peak doses to the urethra and rectum has been assessed against the proposed corrective protocol to limit overdosing these critical structures. An initial investigative level of 20% difference between measured and TPS peak dose was established, which corresponds to 1/3 of patients which was practical for the caseload. These patients were assessed resulting in corrective action being applied for one patient. Multiple triggering for selective investigative action is outlined. The use of a single in vivo measurement in the first fraction optimizes patient benefit at acceptable cost.


Major depression and clinical outcomes in patients with heart failure with preserved ejection fraction.
Limited data have been published concerning about depression in heart failure with preserved ejection fraction (HFpEF). Besides, among HFpEF patients with depression, the efficacy of antidepressants is poorly defined. Therefore, our current study was aimed to examine the relationship between major depression and clinical outcomes in HFpEF patients and further address the effects of antidepressants on prognosis in patients with major depression and HFpEF. A total of 1431 patients enrolled in the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist Trial (TOPCAT) were divided into 2 groups according to the baseline depression status. Major depression was diagnosed if the Patient Health Questionnaire-9 score (PHQ-9) ≥ 10. Univariable and multivariable Cox proportional hazards models tested the association of major depression with outcomes and the effects of antidepressants among HFpEF patients with major depression during a follow-up of 6 years. 26.7% (382/1431) of patients were diagnosed with major depression. After multivariable adjustment, major depression at baseline was not significantly associated with cardiovascular outcomes (fully adjusted hazard ratio (aHR) 0.95 [0.76-1.18] for primary outcomes; aHR: 0.86 [0.67-1.10] for HF hospitalization; aHR: 1.06 [0.91-1.23] for any hospitalization; aHR: 1.00 [0.70-1.43] for cardiovascular death; aHR: 1.24 [0.96-1.61] for all-cause death). Additionally, among HFpEF patients with major depression, the use of antidepressants was not associated with adverse events (P > .05 for all analyses). In HFpEF patients, major depression at baseline did not increase mortality or rehospitalization. Additionally, treatment with antidepressants might not improve prognosis among HFpEF patients with major depression. Future studies are warranted to explore the effects of antidepressants on HFpEF patients with depression.


Single-Cell RNA-Sequencing in Astrocyte Development, Heterogeneity, and Disease.
Astrocytes are the most plentiful cell type in the central nervous system (CNS) and perform complicated functions in health and disease. It is obvious that different astrocyte subpopulations, or activation states, are relevant with specific genomic programs and functions. In recent years, the emergence of new technologies such as single-cell RNA sequencing (scRNA-seq) has made substantial advance in the characterization of astrocyte heterogeneity, astrocyte developmental trajectory, and its role in CNS diseases which has had a significant impact on neuroscience. In this review, we present an overview of astrocyte development, heterogeneity, and its essential role in the physiological and pathological environments of the CNS. We focused on the critical role of single-cell sequencing in revealing astrocyte development, heterogeneity, and its role in different CNS diseases.


Serum chitotriosidase activity is increased in subjects with atherosclerosis disease.
This study was undertaken to analyze the relation between serum activity of chitotriosidase enzyme, a protein synthesized exclusively by activated macrophages, and atherosclerotic lesion extent in subjects with atherothrombotic stroke (ATS) and in subjects with ischemic heart disease (IHD). We assayed the serum chitotriosidase activity and a common chitotriosidase gene polymorphism that causes deficiency in chitotriosidase activity in 3 Spanish populations, ATS (n=153), IHD (n=124), and control (n=148) subjects. Statistical differences were found in serum chitotriosidase activity between ATS (88.1+/-4.6 nmol/mL. h, P<0.0001) and IHD subjects (79.0+/-6.3, P=0.002) versus control group (70.9+/-5.2). These observed differences were not attributable to a distinct allelic or genotype distribution. The extension of the atherosclerotic lesion in carotids of ATS subjects was measured by duplex sonography. Chitotriosidase activities were 66.9+/-9.6, 88.7+/-8.3, and 107.7+/-11.8 for subjects with carotid stenosis <or=30%, 31% to 60%, and >60%, respectively. Statistical differences were observed between subjects with major and intermediate stenosis grade compared with subjects with minor stenosis, P=0.005 and P=0.016, respectively. Serum chitotriosidase activity is significantly increased in individuals suffering from atherosclerosis disease and is related to the severity of the atherosclerotic lesion, suggesting a possible role as atherosclerotic extent marker.


Diabetes control in the Bedouin population in southern Israel.
The Bedouins in the Negev are a population in transition from traditional nomadic to a western sedentary lifestyle, characterized by changes in dietary habits and reduction in physical activity, with substantial changes in morbidity patterns. To describe the current state of diabetes prevalence and control among the Bedouin population in the Negev and to compare it to the non-Bedouin population. A cross-sectional study was performed utilizing the database of Clalit Health Services. In patients with a confirmed diagnosis of diabetes, the following variables were extracted from the laboratory records: hemoglobinA1c (HgA1C) level, urine microalbumin level and low density lipoprotein (LDL) level. Chi-square test was used to compare categorical parameters between the groups. Age-adjusted prevalence of diabetes was 5.1% in the Bedouin population as compared to 3.7% in the non-Bedouin population (p<0.001). Diabetes was more prevalent in urban as compared to rural settlements (5.5% vs. 3.9%, respectively, p<0.001). The proportion of Bedouins patients with controlled diabetes (HgA1C<7) was significantly lower in Bedouin patients (29.3%) as compare to Non-Bedouin patients (46.7%) (p<0.001). Age-adjusted prevalence of diabetes is increased in the Bedouin population as compared to the Non-Bedouin population in southern Israel. Despite similar performance status of laboratory tests and similar treatment regimens, the overall control of diabetes is poorer in the Bedouin population as compared to the Non-Bedouin population. These findings support previous observations that diabetes has become a major public health problem among Bedouins.


Phagonaute: A web-based interface for phage synteny browsing and protein function prediction.
Distant homology search tools are of great help to predict viral protein functions. However, due to the lack of profile databases dedicated to viruses, they can lack sensitivity. We constructed HMM profiles for more than 80,000 proteins from both phages and archaeal viruses, and performed all pairwise comparisons with HHsearch program. The whole resulting database can be explored through a user-friendly "Phagonaute" interface to help predict functions. Results are displayed together with their genetic context, to strengthen inferences based on remote homology. Beyond function prediction, this tool permits detections of co-occurrences, often indicative of proteins completing a task together, and observation of conserved patterns across large evolutionary distances. As a test, Herpes simplex virus I was added to Phagonaute, and 25% of its proteome matched to bacterial or archaeal viral protein counterparts. Phagonaute should therefore help virologists in their quest for protein functions and evolutionary relationships.


[Suggested interrelationships of RNA-polymerase sigma S subunit and nitrogen control system in Pseudomonas chlororaphis].
The effect of mutation in rpoS gene encoding sigma S subunit of RNA-polymerase on the capacity of Pseudomonas chlororaphis 449 to assimilate nitrogen was investigated. It has been shown that mutant cells with knocked-out rpoS gene had significantly lower capacity to utilize the nitrogen sources such as alanine, proline, histidine, arginine, urea, and ammonium and glutamine synthetase was downregulated in their cell free extracts. Both defects were abolished by glutamine supplementation to the medium. It is suggested that in Pseudomonas chlororaphis the association of the nitrogen control system and the system of gene expression is regulated by RNA-polymerase sigma S subunit, which can be responsible for cell adaptation at nitrogen supply limitation.


Using Morpholinos to Examine Gene Function During Fin Regeneration.
In the zebrafish regenerating fin, specific gene-targeting morpholinos have been widely utilized to assess gene function. Unlike in embryos, injection of standard morpholinos in the adult regenerating fin is not sufficient for cellular uptake. Rather, morpholinos are first injected extracellularly into the blastemal compartment, followed by electroporation for cellular uptake. Knockdown phenotypes are evaluated 1-4 days post electroporation. This chapter provides a description of the reagents, equipment, and procedure for successful injection and electroporation of morpholinos into the regenerating fin.


Are spouses' socio-economic classifications interchangeable? Examining the consequences of a commonly used practice in studies on social inequalities in health.
Indicators of socio-economic position are not always available for all subjects. To avoid losses of large parts of study populations, missing data are replaced by spouses' information. Despite this commonly practiced solution, systematic analyses of the consequences on substantive results of studies are rare. We examined the consequences of assigning the educational position of subjects to their partners. German statutory health insurance data from 2005 (N = 1,801,744) and 2011 (N = 1,987,707) were used. Diagnoses of type 2 diabetes were used as outcome. Effects were examined in terms of differences in diabetes prevalence and by the reproduction of social gradients in women and men as compared to their partners. Social gradients were reproduced for subjects and for their partners, but diabetes prevalences were higher in partners. From a pragmatic point of view the practice of replacing missing information by spouses' information turned out as viable. However, the usefulness of this solution has to be examined in every case anew, because it may not be suitable for every health-related outcome.


Effect of insulin on glucose oxidation and amino isobutyric acid transport and binding of insulin in chicken thymocytes.
In chicken thymocytes isolated from 15--40 day-old chickens, after a 2 h incubation at 37 degrees C, insulin stimulated amino isobutyric acid uptake (maximal response: 40--50% of increase at 1 microgram insulin/ml and half maximal response at 60 ng/ml) by specifically stimulating the influx without altering the efflux. Insulin also stimulated glucose oxidation (maximal response: 11% of increase at 1 microgram insulin/ml). Binding of 125I-labelled chicken insulin to thymocytes was rapid and higher at 15 degrees C than at 37 degrees C. At steady state, (90 min at 15 degrees C), chicken, porcine and goose insulins were equipotent in inhibiting the binding of 125I-labelled chicken insulin. Maximal binding capacity was estimated at 1250 pg insulin/10(8) cells, i.e., 1250 binding sites/cell with an apparent dissociation constant of 200 ng insulin/ml at 15 degrees C. Degradation of 125I-labelled chicken insulin in the incubation medium was negligible at 15 degrees C but very noticeable at 37 degrees C. Therefore, the low level of insulin binding at 15 degrees C reflects a true scarcity of insulin receptors in chicken thymocytes as compared to rat thymocytes.


The crystal structure of L-chiro-inositol.
The crystal structure of L-chiro-inositol is monoclinic, P21, with a = 6.867(3), b = 9.133(4), c = 6.217(3) A, beta = 106.59(4) degrees, Z = 2. The structure was solved by using MULTAN, and refined to R = 0.028 for 1065 intensities observed with Ni-filtered MoK alpha radiation. The molecule has the expected chair conformation, with puckering parameters Q = 0.561 A, theta = 4.4 degrees, phi = 51.2 degrees. The non-hydrogen molecular symmetry is close to C2, with deviations of less than 0.07 A from a weighted fit. The intramolecular hydrogen-bonding forms infinite chains which are cross-linked through the weaker component of a three-center bond. The C-C bond lengths range from 1.515 to 1.528 A, and the C-O bond lengths from 1.418 to 1.436 A. The C-C-C angles range from 109.7 to 113.1 degrees, and the C-C-O angles from 106.5 to 112.0 degrees.


Influence of serosal Cl on transport properties and cation activities in frog skin.
The effects of serosal substitution of isosmotic Na2SO4-Ringer solution for NaCl-Ringer solution were studied in the short-circuited frog skin (Rana pipiens, Northern variety). Despite prompt changes of transepithelial measurements, initial cellular effects were slight. After 30 to 45 min, however, the transcellular current had decreased and the cell electrical potential had depolarized, in association with decrease of the apical membrane fractional resistance and basolateral membrane conductance. Apical membrane slope conductance was unaffected. Similar effects were obtained with isolated epithelia. With the use of gluconate or NO3 in place of Cl, the effects on cellular current and conductance were minimal or insignificant, despite changes of the cell potential, fractional resistance, and basolateral conductance similar to those seen with sulfate. Following prolonged exposure to serosal SO4-Ringer, the extent of depolarization induced by raising the serosal K concentration decreased, indicating diminution of basolateral K conductance and the existence of other basolateral conductances. Equilibration in serosal gluconate-Ringer enhanced polarization on serosal restoration of Cl or removal of Na, again indicating a time-dependent change in the basolateral conductance pattern. Depolarization on removal of serosal Cl was not attributable to inhibition of the pump. Nor was it the result of decrease of the K equilibrium potential EK: exposure to serosal SO4-Ringer decreased cell K activity aKc from 104 +/- 6 to 58 +/- 4 mM (n = 5), but EK was reduced only slightly; exposure to serosal gluconate increased aKc and EK. Serosal sulfate lowered the cell Na activity aNac, but the electrochemical potential difference for Na across the apical surface was unaffected. The concurrent decrease of both aKc and aNac following serosal substitution of SO4 for Cl raises questions concerning mechanisms of osmoregulation.


Concomitant deletion of SLAM-family receptors, NKG2D and DNAM-1 reveals gene redundancy of NK cell activating receptors in NK cell development and education.
NK cells recognize "unwanted" cells using a variety of germline-encoded activating receptors, such as the seven members of signaling lymphocyte activating molecule (SLAM)-family receptors (SFRs), natural killer cell group 2D (NKG2D), and DNAX accessory molecule-1(DNAM-1). Whether these receptors redundantly or synergistically regulate NK cell development and effector function remains poorly understood. By generating mice lacking SFRs, NKG2D, and DNAM-1, separately or in combination, we found that SLAMF6, one of the SFR members, was associated with NK cell differentiation, but its absence had no severe effect on NK cell differentiation and function, likely due to SFR redundancy. Moreover, we revealed that SFRs might work with other NK cell activating receptors in regulating NK cell development and function. We found that SFR deficiency caused an increase in immature NK cell subsets (CD27+ CD11b- ), and this effect was further augmented by the additional deficiency of NKG2D but not DNAM-1. However, SFR-deficient NK cells exhibited elevated responsiveness against "missing-self" hematopoietic targets, whereas the deletion of either NKG2D or DNAM-1 could partially abrogate the elevated effect of SFR deficiency on NK cell activation. Therefore, our results reveal the complexity of activating receptors in regulating NK cell differentiation and activation, extending our insights into the gene redundancy and compensatory effect of NK cell activating receptors.


Anxiety management in Australian general practice: an analysis of encounters from 2006 - 2016.
Anxiety disorders are highly prevalent mental health conditions managed predominantly by general practitioners (GPs). This study aimed to examine the management of anxiety by Australian GPs since the introduction of the Better Access to Psychiatrists, Psychologists and General Practitioners initiative in 2006. We conducted secondary analysis of Bettering the Evaluation and Care of Health data on GP encounters for anxiety from 2006 to 2016 (N = 28,784). We calculated point estimates and used multivariate logistic regression to explore the effect of GP and patient characteristics on rates and types of management. The management rate of anxiety increased from 2.3% of GP encounters in 2006 to 3.2% in 2016. Over the 10-year period, increases were seen in referrals to psychologists (AOR = 1.09, 95%CI = 1.07-1.11, p < .0001) and selective serotonin / serotonin-noradrenalin reuptake inhibitors (AOR = 1.05, 95%CI = 1.03-1.06, p < .0001), and benzodiazepines decreased (AOR = 0.94, 95%CI = 0.92-0.95, p < .0001). Systematic differences in management were found for patient and GP characteristics, including high rates of benzodiazepines in certain groups. Anxiety is accounting for more of the GP workload, year on year. GP management of anxiety has become more closely aligned with practice guidelines since 2006. However, high rates of benzodiazepine prescribing in certain groups remains a concern. Further research is needed into GP treatment decision making for anxiety.


Catheter Ablation for the Management of Atrial Fibrillation: An Update of the Literature.
Catheter ablation has been shown to be more effective at maintaining sinus rhythm and improving quality of life when compared to antiarrhythmic drugs. Radiofrequency and cryoablation are two effective methods. However, catheter-only ablation strategies have not consistently produced high success rates in treating longstanding and persistent AF patients. The emerging treatment of choice for such cases is hybrid ablation, which involves a multidisciplinary and minimally invasive approach to achieve surgical ablation of the direct posterior left atrial wall in combination with endocardial catheter ablation. Studies have shown promising results for the hybrid approach when compared with catheter ablation alone, but it is not without risks. Large and randomised studies are necessary to further evaluate these strategies for managing AF.


1H NMR metabolic profiling of synovial fluid from patients with anterior cruciate ligament tears and hemarthrosis.
To compare the metabolic profiles of synovial fluid (SF) from patients with anterior cruciate ligament tears and hemarthrosis (HA) with that of normal controls, using 1H NMR spectroscopy (NMRS). Synovial fluid was collected from eleven patients undergoing arthroscopic debridement within 14 days following an anterior cruciate ligament (ACL) tear and hemarthrosis. Ten additional SF samples were obtained from the knees of osteoarthritis-free volunteers to serve as normal controls. The relative concentrations of twenty-eight endogenous SF metabolites (hydroxybutyrate, acetate, acetoacetate, acetone, alanine, arginine, choline, citrate, creatine, creatinine, formate, glucose, glutamate, glutamine, glycerol, glycine, histidine, isoleucine, lactate, leucine, lysine, phenylalanine, proline, pyruvate, threonine, tyrosine, valine, and the mobile components of glycoproteins and lipids) were evaluated using NMRS and quantified using CHENOMX metabolomics analysis software. Mean differences between groups were evaluated with t-tests controlling for multiple comparisons at an overall error rate of 0.10. Statistically significant increases in the levels of glucose, choline, the branched-chain amino acids leucine, isoleucine, and valine, and the mobile components of N-acetyl glycoproteins and lipids were observed in ACL/HA SF as compared with normal controls; lactate levels were reduced. Marked changes occur in the metabolic profiles of human knee fluid following ACL injury and hemarthrosis, suggestive of increased demand and accompanying inflammatory response; potentially increased lipid and glucose metabolism; and possible hyaluronan degradation within the joint following trauma.


Electrophysiological properties of hypoglossal motoneurons of guinea-pigs studied in vitro.
Intracellular recordings were made from the hypoglossal nuclear complex in brain slices from guinea-pigs. Retrograde transport of horseradish peroxidase from the tongue confirmed the identity of the visually identified hypoglossal nucleus. Eighteen neurons were stained by intracellular electrophoresis of Lucifer Yellow through the recording pipette. Two types of neurons were encountered, motoneurons with maximal discharge rates of 90 Hz and another type with maximal discharge rates of 250 Hz. Motoneurons were prevalent in the hypoglossal nucleus and the other type prevailed in the adjoining nucleus prepositus hypoglossi. In both nuclei the two types were mixed. Antidromic spikes elicited from hypoglossal root fibres had initial segment and somatodendritic components. Electrical stimulation of the reticular matter dorsolateral to the hypoglossal nucleus elicited excitatory postsynaptic potentials and strychnine sensitive inhibitory postsynaptic potentials. Motoneurons responded to depolarizing current pulses with a train of spikes. The initial spike interval was much shorter than the rest and fast adaptation occurred over three to four intervals. Slow adaptation was most prominent when the neuron was depolarized and discharged at a high rate. High threshold calcium spikes were evoked by depolarizing pulses when sodium spikes were blocked by tetrodotoxin and the potassium conductance reduced by tetraethylammonium bromide. Motoneurons discharged in a single range, inflections on the frequency-current plot being absent. Spikes and spike trains evoked by depolarizing pulses were followed by afterhyperpolarizations with fast and slow parts. The fast phase was eliminated by tetraethylammonium bromide, possibly because the delayed rectifier was involved. A calcium dependent potassium conductance was probably involved in the slow phase, because it was sensitive to inorganic calcium blockers. The amplitude of the afterhyperpolarization following trains of spikes depended on the frequency of the preceding spikes. At constant frequency, the amplitude depended, in addition, on the strength of stimuli arising from different hyperpolarized potentials. Afterdepolarizing potentials were absent. Lissajous plots of double ramp current stimulation showed anomalous rectification between resting potential and spike threshold. The rectification was sensitive to inorganic calcium blockers. Subthreshold responses showed initial sags and rebound responses in all healthy cells and these were eliminated by caesium. Barium, substituted for calcium, unleashed a depolarizing plateau potential sensitive to tetrodotoxin, indicating the presence of a persistent sodium conductance.(ABSTRACT TRUNCATED AT 400 WORDS)


Results of intraoral cortical bone screw fixation technique for mandibular fractures.
The intraoral cortical bone screw fixation technique carries many advantages over traditional methods of intermaxillary fixation. Simplicity of the technique, reduction of operative time, and reduction of risk of transmission of human immunodeficiency virus and hepatitis make this an important technique in the armamentarium of busy facial trauma surgeons. Since 1992, 45 mandibular fractures in 29 patients treated with the intraoral cortical bone screw technique for intermaxillary fixation were retrospectively analyzed. At our institution, this technique has become the workhorse method of repairing most mandibular fractures and is associated with minimal complications.


Determination of umami compounds in edible fungi and evaluation of salty enhancement effect of Antler fungus enzymatic hydrolysate.
The demand for low-salt foods is increasing due to their health benefits. Umami is known to enhance salty, and a large amount of umami components have been identified in edible fungi. 5'-nucleotides and umami amino acids from nine species of edible fungi were quantified. The equal umami concentration (EUC) in nine edible fungi was within the range of 37.7-1317.72 g MSG/100 g, and umami intensity as determined by electronic tongue and sensory evaluation was within the range of 11.22-13.53 and 2.85-5.55, respectively. Antler fungus had the highest umami intensity. Umami amino acids and nucleotides could increase salty intensity of NaCl at medium and high concentrations. The enzymatic hydrolysate of Antler fungus at higher concentrations could more effectively enhance salty taste of NaCl at lower concentration. This synergistic effect between umami and salty indicates that Antler fungus can potentially be used as an ingredient in low-salt foods.


Bacteriuria with intestinal loop urinary diversion in children.
Bacteriuria and intestinal loop urinary diversion with open (refluxing) ureterointestinal anastomoses did not prevent normal renal and body growth in 44 children, who were followed for 55.2 months. A comparison of the long-term use of sulfamethoxazole and nitrofurantoin with no treatment showed no statistically significant changes in the stoma, loop residual, renal function, serum electrolytes and treatment or prevention of bacteriuria.


Prevalence and risk factors of prehypertension/hypertension among freshman students from the Vietnam National University: a cross-sectional study.
Prehypertension (PHT) and hypertension (HTN) in young adults are essential risk factors for other cardiovascular diseases (CVD) in later years of life. However, there is a lack of knowledge about the burden and risk factors of PHT/HTN for Vietnamese youth. The aim of this study was to investigate the prevalence of PHT/HTN and risk factors among university students in Hanoi, Vietnam. This study was designed as a cross-sectional investigation with 840 students (394 males and 446 females) randomly sampled from freshmen of Vietnam National University, Hanoi (VNU). Socio-demographic, anthropometric, and lifestyle data were collected using questionnaire forms and physical measurements. HTN was defined as blood pressure (BP) ≥ 140/90 mmHg and/or current treatment with antihypertensive medications. PHT was defined as a systolic BP from 120 to 139 mmHg and/or a diastolic BP from 80 to 89 mmHg. Body mass index (BMI) was classified according to the WHO diagnostic criteria for Asian adults: normal weight (BMI 18.5-22.9 kg/m2), underweight (BMI < 18.5 kg/m2), overweight (BMI 23-24.9 kg/m2), and obese (BMI ≥ 25 kg/m2). Bivariable and multivariable log-binomial regression analyses were conducted to explore the association of PHT/HTN with different risk factors. The overall prevalence of prehypertension and hypertension was 33.5% [95% CI: 30.3-36.8%] (54.1% in men and 15.3% in women) and 1.4% [95% CI: 0.7-2.5%] (2.5% in men and 0.5% in women), respectively. Regarding CVD major risk factors, 119 (14.2%) were identified as overweight/obese, 461 (54.9%) were physical inactivity, 29.4% of men and 8.1% of women reported consuming alcohol. The multivariable analysis indicated the male sex (adjusted prevalence ratio [aPR] = 3.07; 95% CI: 2.32-4.06), alcohol consumption (aPR = 1.28; 95% CI: 1.03-1.59) and obesity (aPR = 1.35; 95% CI: 1.08-1.68) as the independent risk factors for PHT/HTN. The results revealed the high burden of prehypertension and hypertension among university freshmen in VNU. Male sex, alcohol consumption, and obesity were identified as important risk factors for PHT/HTN. Our study suggests an early screening program for PHT/HTN and campaigns to promote a healthy lifestyle for young adults in Vietnam.


Early rheumatoid arthritis treated with tocilizumab, methotrexate, or their combination (U-Act-Early): a multicentre, randomised, double-blind, double-dummy, strategy trial.
For patients with newly diagnosed rheumatoid arthritis, treatment aim is early, rapid, and sustained remission. We compared the efficacy and safety of strategies initiating the interleukin-6 receptor-blocking monoclonal antibody tocilizumab with or without methotrexate (a conventional synthetic disease-modifying antirheumatic drug [DMARD]), versus initiation of methotrexate monotherapy in line with international guidelines. We did a 2-year, multicentre, randomised, double-blind, double-dummy, strategy study at 21 rheumatology outpatient departments in the Netherlands. We included patients who had been diagnosed with rheumatoid arthritis within 1 year before inclusion, were DMARD-naive, aged 18 years or older, met current rheumatoid arthritis classification criteria, and had a disease activity score assessing 28 joints (DAS28) of at least 2·6. We randomly assigned patients (1:1:1) to start tocilizumab plus methotrexate (the tocilizumab plus methotrexate arm), or tocilizumab plus placebo-methotrexate (the tocilizumab arm), or methotrexate plus placebo-tocilizumab (the methotrexate arm). Tocilizumab was given at 8 mg/kg intravenously every 4 weeks with a maximum of 800 mg per dose. Methotrexate was started at 10 mg per week orally and increased stepwise every 4 weeks by 5 mg to a maximum of 30 mg per week, until remission or dose-limiting toxicity. We did the randomisation using an interactive web response system. Masking was achieved with placebos that were similar in appearance to the active drug; the study physicians, pharmacists, monitors, and patients remained masked during the study, and all assessments were done by masked assessors. Patients not achieving remission on their initial regimen switched from placebo to active treatments; patients in the tocilizumab plus methotrexate arm switched to standard of care therapy (typically methotrexate combined with a tumour necrosis factor inhibitor). When sustained remission was achieved, methotrexate (and placebo-methotrexate) was tapered and stopped, then tocilizumab (and placebo-tocilizumab) was also tapered and stopped. The primary endpoint was the proportion of patients achieving sustained remission (defined as DAS28 <2·6 with a swollen joint count ≤four, persisting for at least 24 weeks) on the initial regimen and during the entire study duration, compared between groups with a two-sided Cochran-Mantel-Haenszel test. Analysis was based on an intention-to-treat method. This trial was registered at ClinicalTrials.gov, number NCT01034137. Between Jan 13, 2010, and July 30, 2012, we recruited and assigned 317 eligible patients to treatment (106 to the tocilizumab plus methotrexate arm, 103 to the tocilizumab arm, and 108 to the methotrexate arm). The study was completed by a similar proportion of patients in the three groups (range 72-78%). The most frequent reasons for dropout were adverse events or intercurrent illness: 27 (34%) of dropouts, and insufficient response: 26 (33%) of dropouts. 91 (86%) of 106 patients in the tocilizumab plus methotrexate arm achieved sustained remission on the initial regimen, compared with 86 (84%) of 103 in the tocilizumab arm, and 48 (44%) of 108 in the methotrexate arm (relative risk [RR] 2·00, 95% CI 1·59-2·51 for tocilizumab plus methotrexate vs methotrexate, and 1·86, 1·48-2·32 for tocilizumab vs methotrexate, p<0·0001 for both comparisons). For the entire study, 91 (86%) of 106 patients in the tocilizumab plus methotrexate arm, 91 (88%) of 103 in the tocilizumab arm, and 83 (77%) of 108 in the methotrexate arm achieved sustained remission (RR 1·13, 95% CI 1·00-1·29, p=0·06 for tocilizumab plus methotrexate vs methotrexate, 1·14, 1·01-1·29, p=0·0356 for tocilizumab vs methotrexate, and p=0·59 for tocilizumab plus methotrexate vs tocilizumab). Nasopharyngitis was the most common adverse event in all three treatment groups, occurring in 38 (36%) of 106 patients in the tocilizumab plus methotrexate arm, 40 (39%) of 103 in the tocilizumab arm, and 37 (34%) of 108 in the methotrexate arm. The occurrence of serious adverse events did not differ between the treatment groups (17 [16%] of 106 patients in the tocilizumab plus methotrexate arm vs 19 [18%] of 103 in the tocilizumab arm and 13 [12%] of 108 in the methotrexate arm), and no deaths occurred during the study. For patients with newly diagnosed rheumatoid arthritis, strategies aimed at sustained remission by immediate initiation of tocilizumab with or without methotrexate are more effective, and with a similar safety profile, compared with initiation of methotrexate in line with current standards. Roche Nederland BV.


Naloxone has no effect on nitrous oxide anesthesia.
It has been reported that naloxone antagonizes general anesthesia in rats when the tail clamp is used as a painful stimulus to assess anesthesia. The authors' hypothesis is that this antagonism is to the analgesic component of anesthesia only, and that anesthesia assessed by a non-painful stimulus would not be antagonized by naloxone. Therefore, the anesthetic potency of nitrous oxide in mice was measured using loss of the righting reflex as a non-painful stimulus. Naloxone, 2 and 16 mg/kg, intraperitoneally, failed to antagonize nitrous oxide anesthesia measured 14--39 min after injection. Thus, 19 min after injection of naloxone, 2 mg/kg, the nitrous oxide ED50 was 1.25 +/- 0.0600 atm (n = 35), compared with 1.19 +/- 0.059 atm (n = 35) after injection of saline solution (control). Following naloxone, 16 mg/kg, the nitrous oxide ED50 was 1.18 +/- 0.059 atm (n =35), compared with 1.22 +/- 0.059 atm (n = 35) for saline solution. At neither dose of naloxone was the ED50 different from the control ED50, a finding that supports the author's hypothesis.


Identifying genetic variants for amyloid β in subcortical vascular cognitive impairment.
The genetic basis of amyloid β (Aβ) deposition in subcortical vascular cognitive impairment (SVCI) is still unknown. Here, we investigated genetic variants involved in Aβ deposition in patients with SVCI. We recruited a total of 110 patients with SVCI and 424 patients with Alzheimer's disease-related cognitive impairment (ADCI), who underwent Aβ positron emission tomography and genetic testing. Using candidate AD-associated single nucleotide polymorphisms (SNPs) that were previously identified, we investigated Aβ-associated SNPs that were shared or distinct between patients with SVCI and those with ADCI. Replication analyses were performed using the Alzheimer's Disease Neuroimaging Initiative (ADNI) and Religious Orders Study and Rush Memory and Aging Project cohorts (ROS/MAP). We identified a novel SNP, rs4732728, which showed distinct associations with Aβ positivity in patients with SVCI (P interaction = 1.49 × 10-5); rs4732728 was associated with increased Aβ positivity in SVCI but decreased Aβ positivity in ADCI. This pattern was also observed in ADNI and ROS/MAP cohorts. Prediction performance for Aβ positivity in patients with SVCI increased (area under the receiver operating characteristic curve = 0.780; 95% confidence interval = 0.757-0.803) when rs4732728 was included. Cis-expression quantitative trait loci analysis demonstrated that rs4732728 was associated with EPHX2 expression in the brain (normalized effect size = -0.182, P = 0.005). The novel genetic variants associated with EPHX2 showed a distinct effect on Aβ deposition between SVCI and ADCI. This finding may provide a potential pre-screening marker for Aβ positivity and a candidate therapeutic target for SVCI.


A comparison of the reproductive strategies of three species of Dysdercus from Africa (Hemiptera, Pyrrhocoridae).
Reproductive strategies have been investigated for three species of Dysdercus from Africa, D. intermedius, D. cardinalis and D. nigrofasciatus. Reproductive parameters were measured for each species on individuals cultured in the laboratory. D. cardinalis is associated more with herbaceous than with arboreal host plants and is intermediate in body size. It tended to have the least age at first reproduction, reproduced most frequently, and layed the smallest clutches on average, spreading relatively high amounts of parental investment in more clutches than the other two species. It also laid the greatest number of clutches and eggs in a lifetime. D. intermedius specializes on arboreal host plants, and is the largest of the three species. It had the greatest age at first reproduction, reproduced less frequently than D. cardinalis, and layed the largest clutches. Its parental investment over time declined earlier than that of D. cardinalis. D. intermedius layed the least number of clutches in a lifetime, but its lifetime gross reproduction was intermediate in magnitude. D. nigrofasciatus has the widest diet breadth, and is the smallest in body size. Its age at first reproduction was similar to that of D. cardinalis, but D. nigrofasciatus reproduced least frequently, laying relatively large clutches. It was similar to D. intermedius in its pattern of parental investment over time, and essentially layed the same number of clutches in a lifetime as the latter species, although its lifetime gross reproduction was the smallest.It is suggested that the reproductive strategies of the three species might have evolved as adaptations to selection events in the niches of the immature stages.


Modulation of the evoked release of noradrenaline in canine saphenous vein via presynaptic receptors for adenosine but not ATP.
The effects of adenosine, ATP and adenosine beta, gamma-methylene-5'-triphosphate (APPCP) were compared in the saphenous vein of the dog. Adenosine and ATP in concentrations which did not affect the response to exogenous noradrenaline, depressed that to nerve stimulation; this effect was antagonized by theophylline. APPCP increased tension in unstimulated veins and in those made to contract with noradrenaline and nerve stimulation. The results suggest that the inhibitory effect of ATP on adrenergic neurotransmission is due to its rapid breakdown to adenosine, which acts on prejunctional P1 purinoceptors.


Zwitterionic ionic liquid synergistically induces interfacial dipole formation and traps state passivation for high-performance perovskite solar cells.
Defects at the interface and grain boundaries of perovskite solar cells (PSCs) will result in severe non-radiative recombination and open-circuit voltage (Voc) loss. Herein, we reported a zwitterionic ionic liquid imidazolium tetrafluoroborate (IMBF4) to passivate the defects at tin dioxide (SnO2)/perovskite interface. The results showed that the electron-rich nitrogen atom contained IM+ could diffuse into the buried perovskite to exhibit a strong chemical passivation effect on the organic vacancy defect by interacting with uncoordinated Pb2+. The F- in BF4- has a strong coordination effect with Pb2+in perovskite and Sn2+ in SnO2 synchronously to fill the anion vacancy defect. Also, the BF4- anions could help to form an interface dipole layer to increase the charge transfer rate and reduce the work function. The IMBF4 modified device could achieve an efficiency enhancement from 20.18% to 23.05% by vacuum flash-assisted solution-processed, with the increased Voc from 1.09 V to 1.15 V. The unencapsulated IMBF4 modified device could maintain 93% of the initial efficiency after ageing for 2000 h under ambient conditions by the ISOS-D-1 stability-testing protocols. This work emphasizes the importance of multifunctional additives in passivating defects and improving interface contact for achieving efficient and stable perovskite solar cells.


Patient attendance at a UK dental hospital emergency clinic.
A questionnaire survey was performed within a dental emergency clinic at a London teaching hospital to determine patients' reasons for attendance and satisfaction with their care. Questionnaires were distributed to all patients registering for the dental emergency clinic over a four week period. A total of 1,058 questionnaires were returned, with an average satisfaction score of 9.3/10. The majority of patients (58%) reported symptomatic dental attendance. Common reasons for irregular attendance were lack of perceived 'need' for care and concerns about cost of care. Patients with irregular attendance were significantly more likely to report their past dental care had been affected by cost than regular attenders. Fifty-one percent of all respondents had tried to make an appointment with a dentist prior to attending the emergency clinic, and 21% of patients with a GDP reporting difficulty accessing urgent care at their practice. Forty-nine percent of patients attending the emergency clinic were referred to oral surgery clinics. Overall, this survey revealed high levels of satisfaction with care in this dental emergency clinic. Patients' reasons for attendance at the clinic can be considered in terms of 'push' and 'pull' factors, deterring them from primary dental care and drawing them into secondary/tertiary care environments.


[Meta-analysis: a new option in clinical research. Basic principles and a clinical example].
The authors present some basic concepts of meta-analysis, a process to evaluate and combine the results of conflicting studies. Authors illustrate the process by presenting a practical example in rheumatology.


Predictors of aging based on the analysis of heart rate variability.
The current significant progress in the use of heart rate variability in the solution of many diagnostic and therapeutic problems is determined by the availability of standardized methods of measurement and physiological interpretation of heart rate variability indices on the one hand and the high technological level of state-of-the-art electronic measuring equipment that is used for automatic registration and computer processing of cardio-signals. A retrospective analysis of anonymized cardio screening results of 22,433 adult residents of 565 settlements (cities and villages) across all 20 administrative districts of the Khmelnytskyi Region (Ukraine) was conducted to find a statistically significant connection between individual heart rate variability parameters and the age of people. Primary statistical analysis and visualization showed a correlation between the selected heart rate variability parameters and the age and sex of the examined persons. The study found values of the predicted age slightly over estimation versus the actual age for very young test subjects and below estimation for elderly subjects. The use of neural network computations and the modification of the algorithm through the construction of individual training samples for different age intervals, and the creation of individual ensembles of classification neural networks, therefore achieved a prediction of the age of examined persons based on the values of their time and frequency domain heart rate variability indices, with 87% accuracy for women and 85% accuracy for men in the 66-85 years age interval and at least 85% for age groups across the entire sample.


Expression and characterization of wild type, truncated, and mutant forms of the intracellular region of the receptor-like protein tyrosine phosphatase HPTP beta.
Human HPTP beta is unique among mammalian receptor-like protein tyrosine phosphatases in that it has only a single catalytic domain. The intracellular region of HPTP beta was expressed in bacteria, purified, and characterized. It exhibits high activity toward all substrates tested and is potently inhibited by zinc. Vanadate and polyanions also inhibited activity. The juxta-membrane segment of HPTP beta (residues 1622-1639) potentially functions as a negative regulatory sequence since its deletion can increase HPTP beta activity 5-fold. This segment contains up to two sites for protein kinase C phosphorylation, although in vitro phosphorylation by this kinase did not affect HPTP beta activity. The boundaries of the catalytic domain were delineated by truncation analyses. Successive deletion of N-terminal sequence prior to residue 1684 had little effect on substrate affinity and at most reduced activity about 6-fold. Further removal of residues 1684-1686 resulted in a marked 50-500-fold drop in activity, and loss of N-terminal sequence prior to residue 1690 abolished activity. Based on these analyses a highly conserved motif was identified in all mammalian tyrosine phosphatases (E/q) (F/y)XX(L/i), corresponding to positions 1684-1688 of HPTP beta. Mutation of residue 1684 or 1685 generally gave rise to proteins with marked temperature sensitivity. These mutant HPTP beta were active but had reduced activity compared to the wild type enzyme. In conjunction, these results suggest that this region represents the N-terminal border of the catalytic domain and is essential for correct phosphatase folding although not directly involved in catalysis. Parallel truncation studies have defined residues 1930-1939/40 as the C-terminal border of the catalytic domain.


Multiple kinases regulate mafA expression in the pancreatic beta cell line MIN6.
MafA is a basic leucine zipper transcription factor expressed within the beta cells of the pancreas and is required to maintain normal glucose homeostasis as it is involved in various aspects of beta cell biology. MafA protein levels are known to increase in response to high glucose through mechanisms that have yet to be fully characterized. We investigated whether discrete intracellular signaling events control mafA expression. We found that the general kinase inhibitor staurosporine induces mafA expression without altering the stability of the protein. Inhibition of the MAP-kinase JNK mimics the effects of staurosporine on the expression of mafA. Calmodulin kinase and calcium signaling are also important in stimulating mafA expression by high glucose. However, staurosporine, JNK, and calmodulin kinase have different effects on the induction of insulin expression. These data reveal that MafA levels are tightly controlled by the coordinated action of multiple kinase pathways.


Adverse psychological impact, glutamatergic dysfunction, and risk factors for Alzheimer's disease.
Alzheimer's disease (AD) is a neurodegenerative disorder characterized by cell loss and pathological changes in neuronal transmission. In particular, malfunction in glutamatergic activity may be associated with the impairment of memory seen in Alzheimer patients. Both hypoactivation and hyperactivation of glutamatergic systems seem to cause impeded cognitive processing in animals. Rats subjected to rearing in isolation display reduced levels of glutamate in temporal regions accompanied by impaired learning and memory. Similar cognitive deficits are also seen in animals exposed to behavioral stress. Stress appears to have deleterious effects on cognition caused by glutamate neurotoxicity leading to attenuated synaptic activity. It is suggested that stress may represent a potential risk factor for AD. The known risk factors for AD (age, heredity, head trauma, low education, depression) may all be related to glutamatergic dysfunction. Some difficulties with pharmacological approaches based on glutamatergic agonists are discussed. It is suggested that optimal glutamate-mediated neurotransmission throughout life may prevent the occurrence of mental decline associated with AD.


First-trimester screening for neural tube defects using alpha-fetoprotein.
To assess the potential value of maternal serum alpha-fetoprotein (AFP) at 11-13 weeks' gestation in early screening for fetal neural tube defects (NTDs). Maternal serum AFP at 11-13 weeks' gestation was measured in 32 cases of fetal NTDs, including 18 cases of acrania and 14 cases of spina bifida, and 1,500 unaffected controls. The measured serum AFP was converted into multiple of the expected median (MoM) after adjustment for gestational age and maternal characteristics and Mann-Whitney test was used to determine the significance of difference in the mean MoM of serum AFP in the NTD group to that in the controls. The mean AFP MoM in the NTD group (1.76, 95% CI 1.39-2.23) was significantly higher than in the controls (p < 0.0001). The mean AFP MoM was not significantly different between the cases of acrania and cases of spina bifida (1.78 vs. 1.75; p = 0.722). The detection rates of NTD in screening by serum AFP were 50.0% (95% CI 31.9-68.1) and 37.5% (95% CI 21.1-56.3) at fixed false-positive rates of 10 and 5%, respectively. Measurement of maternal serum AFP at 11-13 weeks' gestation may be useful in screening for fetal NTDs.


The Fox and the Rabbits-Environmental Variables and Population Genetics (1) Replication Problems in Association Studies and the Untapped Power of GWAS (2) Vitamin A Deficiency, Herpes Simplex Reactivation and Other Causes of Alzheimer's Disease.
Classical population genetics shows that varying permutations of genes and risk factors permit or disallow the effects of causative agents, depending on circumstance. For example, genes and environment determine whether a fox kills black or white rabbits on snow or black ash covered islands. Risk promoting effects are different on each island, but obscured by meta-analysis or GWAS data from both islands, unless partitioned by different contributory factors. In Alzheimer's disease, the foxes appear to be herpes, borrelia or chlamydial infection, hypercholesterolemia, hyperhomocysteinaemia, diabetes, cerebral hypoperfusion, oestrogen depletion, or vitamin A deficiency, all of which promote beta-amyloid deposition in animal models-without the aid of gene variants. All relate to risk factors and subsets of susceptibility genes, which condition their effects. All are less prevalent in convents, where nuns appear less susceptible to the ravages of ageing. Antagonism of the antimicrobial properties of beta-amyloid by Abeta autoantibodies in the ageing population, likely generated by antibodies raised to beta-amyloid/pathogen protein homologues, may play a role in this scenario. These agents are treatable by diet and drugs, vitamin supplementation, pathogen detection and elimination, and autoantibody removal, although again, the beneficial effects of individual treatments may be tempered by genes and environment.


Gas chromatography-mass spectrometry determination of ethylenethiourea hemoglobin adducts: a possible indicator of exposure to ethylene bis dithiocarbamate pesticides.
Ethylenebisdithiocarbamates (EBDC) are an important class of fungicides used to control crop diseases and prevent mold. Ethylenethiourea (ETU), reported to be their main degradation and metabolic product in animals and man, may have teratogenic and carcinogenic properties. The feasibility of monitoring exposure to ETU on the basis of the formation of adducts to hemoglobin (Hb) was investigated. Rats given a single oral dose of ETU (from 62.5 to 500 mg/kg body wt) formed stable covalent ETU-Hb adducts. Mild acid hydrolysis of the protein regenerated ETU, allowing its detection by isotope dilution gas chromatography-mass spectrometry (GC-MS). The amount of released ETU increased with the dose. The dose-response curve fitted a linear model only between 62.5 mg/kg and 250 mg/kg. Acid-releasable ETU was also positively identified in the hemoglobin of workers exposed to Mancozeb, an EBDC formulation. In the exposed group, 40% had ETU-Hb adducts levels ranging from 0.5 to 1.42 pmol ETU/mg Hb. Such adducts might be useful for measuring EBDC exposure in humans.


CD4+ T cell depletion in an untreated HIV type 1-infected human leukocyte antigen-B*5801-positive patient with an undetectable viral load.
We report a case of a patient infected with human immunodeficiency virus type 1 (HIV-1) for 20 years who has experienced CD4(+) T cell depletion in spite of maintaining undetectable viral loads. Our data suggest that immune activation can cause CD4(+) T cell depletion even when HIV-1 replication appears to be controlled by host factors.


Relationship Between Plasma Homocysteine and Bone Density, Lean Mass, Muscle Strength and Physical Function in 1480 Middle-Aged and Older Adults: Data from NHANES.
Hyperhomocysteinemia induces oxidative stress and chronic inflammation (both of which are catabolic to bone and muscle); thus, we examined the association between homocysteine and body composition and physical function in middle-aged and older adults. Data from the National Health and Nutrition Examination Survey was used to build regression models. Plasma homocysteine (fluorescence immunoassay) was used as the exposure and bone mineral density (BMD; dual-energy X-ray absorptiometry; DXA), lean mass (DXA), knee extensor strength (isokinetic dynamometer; newtons) and gait speed (m/s) were used as outcomes. Regression models were adjusted for confounders (age, sex, race/Hispanic origin, height, fat mass %, physical activity, smoking status, alcohol intakes, cardiovascular disease, diabetes, cancer and vitamin B12). All models accounted for complex survey design by using sampling weights provided by NHANES. 1480 adults (median age: 64 years [IQR: 56, 73]; 50.3% men) were included. In multivariable models, homocysteine was inversely associated with knee extensor strength (β = 0.98, 95% CI 0.96, 0.99, p = 0.012) and gait speed (β = 0.85, 95% CI 0.78, 0.94, p = 0.003) and borderline inversely associated with femur BMD (β = 0.84, 95% CI 0.69, 1.03, p = 0.086). In the sub-group analysis of older adults (≥ 65 years), homocysteine was inversely associated with gait speed and femur BMD (p < 0.05) and the slope for knee extensor strength and whole-body BMD were in the same direction. No significant associations were observed between homocysteine and total or appendicular lean mass in the full or sub-group analysis. We found inverse associations between plasma homocysteine and muscle strength/physical function, and borderline significant inverse associations for femur BMD.


Innovative angiography: a new approach to discover more hepatic vein collaterals in patients with cirrhotic portal hypertension.
The hemodynamics of patients with cirrhosis and portal hypertension are complex and variable. We aimed to investigate differences in venous pressures determined by innovative angiography and conventional angiography using balloon occlusion of the hepatic veins in patients with alcoholic cirrhosis and portal hypertension. A total of 134 patients with alcoholic cirrhosis who fulfilled the inclusion criteria from June 2017 to June 2020 were included. During transjugular intrahepatic portosystemic shunt, conventional and innovative angiography were performed, and venous pressures were measured. A paired t-test and Pearson's correlation coefficient were used for analysis. Conventional and innovative hepatic angiography detected lateral branches of the hepatic vein in 26 (19.4%) and 65 (48.5%) cases, respectively (P < 0.001). Innovative angiography detected a total of 65 patients with lateral shunts, of whom 37 (56.9%) had initial shunts. The average wedged hepatic venous pressure and portal venous pressure of the initial lateral branches were 21.27 ± 6.66 and 35.84 ± 7.86 mmHg, respectively, with correlation and determination coefficients of 0.342 (P < 0.05) and 0.117, respectively. The mean hepatic venous pressure gradient and portal pressure gradient were 9.59 ± 7.64 and 26.86 ± 6.78 mmHg, respectively, with correlation and determination coefficients of 0.292 (P = 0.079) and 0.085, respectively. Innovative angiography reveals collateral branches of the hepatic veins more effectively than conventional angiography. Hepatic vein collateral branches are the primary factors leading to underestimation of wedged hepatic venous pressures and hepatic venous pressure gradients, with the initial hepatic vein collateral branches resulting in the most severe underestimations.


Efficient Photodegradation of Eriochrome Black-T by a Trimetallic Magnetic Self-Synthesized Nanophotocatalyst Based on Zn/Au/Fe-Embedded Poly(vinyl alcohol).
This study presents a novel photocatalytic system for photocatalytic degradation of Eriochrome black-T (EBT) dye via green light-emitting diode (LED) light exposure. This photocatalyst is comprised of nanoscale components, i.e., poly(vinyl alcohol) (PVA), magnetic iron oxide nanoparticles (Fe3O4 NPs), gold NPs (Au NPs), and zinc oxide nanorods (ZnO NRs), rendering an active high surface area. The most highlighted property from the structural facet is the superparamagnetic behavior of Fe3O4 NPs, which provides a facile collection of magnetic photocatalyst NPs from the reaction flask and is successfully recycled eight times without considerable reduction in catalytic behavior. Briefly, the photocatalytic degradation at its highest efficiency reached 51.4% (10 ppm dye solution, 5.0 mL) and 64.75% (8 ppm dye solution, 5.0 mL) utilizing 10 mg of the designed photocatalyst (formulated as Fe3O4@PVA-Au/ZnO), a magnetic photocatalytic system under green LED light (7 W, 526 nm) exposure for 60 min. Besides, the photocatalytic degradation mechanism of the EBT dye by the as-prepared photocatalyst was proposed. Based on the obtained results, the presented photocatalytic method was recommended for scaling up and large-scale exploitation for the purification of the water resources.


Distribution of Langerhans cells and mast cells within the human oral mucosa: new application sites of allergens in sublingual immunotherapy?
Sublingual immunotherapy (SLIT) represents an alternative to subcutaneous immunotherapy. While antigen-presenting cells such as Langerhans cells (LCs) are thought to contribute to the effectiveness of SLIT, mast cells (MCs) most likely account for adverse reactions such as sublingual edema. As little is known about LCs and MCs within the oral cavity, we investigated their distribution in search for mucosal sites with highest LCs and lowest MCs density. Biopsies were taken simultaneously from human vestibulum, bucca, palatum, lingua, sublingua, gingiva, and skin. Immunohistochemistry and flow cytometry were used to detect MCs, LCs and high affinity receptor for IgE (FcepsilonRI) expression of LCs. Mixed lymphocyte reactions were performed to assess their stimulatory capacity. Highest density of MCs was detected within the gingiva, while the lowest density of MCs was found within the palatum and lingua. However, sublingual MCs were located within glands, which might explain swelling of sublingual caruncle in some SLIT patients. Highest density of LCs was detected within the vestibular region with lowest density in sublingual region. Highest expression of FcepsilonRI was detected on LCs within the vestibulum. Furthermore LCs from different regions displayed similar stimulatory capacity towards allogeneic T cells. In view of our data, different mucosal regions such as the vestibulum might represent alternative SLIT application sites with potent allergen uptake. Our data might serve as a basis for new application strategies for SLIT to enhance efficiency and reduce local adverse reactions.


Preoperative planning of breast implants using the breast implant planning device (BIPD).
Interstitial implantation of the tumor excision site is an important component of the treatment program of breast-conserving surgery and irradiation. The currently accepted method of designing and performing the implant in the operating room does not assure adequate coverage of the volume of tissue at risk, i.e., the tissue immediately adjacent to the walls of the original tumor excision cavity. This communication describes a technique of preoperative implant planning that consistently and reliably ensures adequate coverage of the volume of tissue at risk. An integral part of this technique is the use of a new device called the Breast Implant Planning Device. This device is a modification of previously described implant template devices.


NMDA receptor-mediated PIP5K activation to produce PI(4,5)P₂ is essential for AMPA receptor endocytosis during LTD.
NMDA receptor activation leads to clathrin-dependent endocytosis of postsynaptic AMPA receptors. Although this process controls long-term depression (LTD) induction in the hippocampus, how it is regulated by neuronal activities is not completely clear. Here, we show that Ca²⁺ influx through the NMDA receptor activates calcineurin and protein phosphatase 1 to dephosphorylate phosphatidylinositol 4-phosphate 5-kinaseγ661 (PIP5Kγ661), the major phosphatidylinositol 4,5-bisphosphate (PI(4,5)P₂)-producing enzyme in the brain. Bimolecular fluorescence complementation analysis revealed that the dephosphorylated PIP5Kγ661 became associated with the clathrin adaptor protein complex AP-2 at postsynapses in situ. NMDA-induced AMPA receptor endocytosis and low-frequency stimulation-induced LTD were completely blocked by inhibiting the association between dephosphorylated PIP5Kγ661 and AP-2 and by overexpression of a kinase-dead PIP5Kγ661 mutant in hippocampal neurons. Furthermore, knockdown of PIP5Kγ661 inhibited the NMDA-induced AMPA receptor endocytosis. Therefore, NMDA receptor activation controls AMPA receptor endocytosis during hippocampal LTD by regulating PIP5Kγ661 activity at postsynapses.


Interactions of Photobleaching and Inorganic Nutrients in Determining Bacterial Growth on Colored Dissolved Organic Carbon.
Abstract Bacteria are key organisms in the processing of dissolved organic carbon (DOC) in aquatic ecosystems. Their growth depends on both organic substrates and inorganic nutrients. The importance of allochthonous DOC, usually highly colored, as bacterial substrate can be modified by photobleaching. In this study, we examined how colored DOC (CDOC) photobleaching, and phosphorus (P) and nitrogen (N) availability, affect bacterial growth. Five experiments were conducted, manipulating nutrients (P and N) and sunlight exposure. In almost every case, nutrient additions had a significant, positive effect on bacterial abundance, production, and growth efficiency. Sunlight exposure (CDOC photobleaching) had a significant, positive effect on bacterial abundance and growth efficiency. We also found a significant, positive interaction between these two factors. Thus, bacterial use of CDOC was accelerated under sunlight exposure and enhanced P and N concentrations. In addition, the accumulation of cells in sunlight treatments was dependent on nutrient availability. More photobleached substrate was converted into bacterial cells in P- and N-enriched treatments. These results suggest nutrient availability may affect the biologically-mediated fate (new biomass vs respiration) of CDOC.


Adsorption of direct blue 106 dye using zinc oxide nanoparticles prepared via green synthesis technique.
Zinc oxide nanoparticles (ZnO-NPs) have in recent times shown effective adsorption capability for the confiscation of colour contaminants from aqueous environments (aquatic ecosystems or water bodies) due to the fact that ZnO contains more functional groups. Direct blue 106 (DB106) dye was selected for this present study as a model composite due to its wide range of uses in textiles (cotton and wools), woods, and paper industries, as well as their therapeutic applications, along with its potential for impairments. This study therefore focuses on the use of DB106 dye as a model composite due to its wide range of uses in textiles (cotton and wools), woods, and paper industries, as well as their therapeutic applications and their potential for impairments. Furthermore, the surface functionalization, shape, and composite pore size were revealed by TEM, FTIR, UV, and BET techniques. The current study uses green synthesis method to prepare ZnO-NPs as an adsorbent for the DB106 dye molecules adsorption under various conditions using the batch adsorption process. The adsorption of DB106 dye to the ZnO-NPs biosorbent was detected to be pH-dependent, with optimal adsorption of DB106 (anionic) dye particles observed at pH 7. DB106 dye adsorption to the synthesized ZnO-NPs adsorbent was distinct by means of the linearized Langmuir (LNR) and pseudo-second-order (SO) models, with an estimated maximum adsorption capacity (Qm) of 370.37 mg/g.


Bicycle incidents in children--abdominal trauma and handlebars.
To investigate the frequency and causes of bicycle related abdominal injuries in children and to examine the pattern of presentation. The study was a prospective study of bicycle related injury in children less than 15 years of age presenting to two paediatric hospitals (15 April-30 June 1992) and three general hospitals (1 August 1991-30 June 1992). In a series of 813 children, 41 sustained non-penetrating abdominal trauma due to a bicycle incident. In 21 cases, handlebar trauma was responsible. Ten of these children suffered life-threatening intra-abdominal injury. Handlebars with no plastic or foam covering of the metal ends were involved in all ten cases. In several of these cases, presentation to hospital was delayed and in others confirmation of the extent of injury took up to 48 hours. The length of hospital stay for those with significant intra-abdominal organ damage ranged from two to 156 days. Intra-abdominal trauma must be considered when dealing with children who are victims of bicycle trauma. Impact with handlebars may have occurred and some form of padded protection of handlebar ends is recommended unless their design can be suitably modified.


Glioblastoma multiforme: morphology and biology.
Glioblastoma multiforme, representing about 50% of all gliomas, encompasses a group of intrinsic tumours of the brain in later years (age peak around 50 years), the morphological hallmarks of which are an ensemble of variations in tumour cell and tissue structure featuring its biological malignancy. Glioblastoma, while sometimes appearing as a distinct "primary" tumour type, is usually accepted as an extreme manifestation of anaplasia and dedifferentiation of glia, mostly astrocytic. The astrocytic nature of most glioblastomas has been confirmed by ultrastructural studies and progressive differentiation of tumours maintained in organotypic tissue culture. Reproducible experimental models are particularly induced by oncogenic RNA (oncorna) viruses. The cell kinetic parameters are similar to those of other solid malignant tumours except for a comparatively low growth fraction of glioblastoma. The frequent occurrence of giant cells as well as of regressive changes with necrosis and vascular responses are indirect (secondary) indicators of malignancy which coincide with histochemical (enzymatic anisochronia) and biochemical data (lower level of glia specific S100 protein than in differentiated gliomas). Vascular proliferation, a characteristic feature of glioblastoma, may occasionally progress to sarcomatous transformation with development of gliosarcomas (mixed glial-mesenchymal tumours). While dissemination of glioblastoma through the cerebrospinal pathways is not uncommon, extraneural distant metastatic spread is rare, and usually observed after craniotomy. The results of modern neuro-oncology support the pathogenetic view that glioblastoma results from neoplastic transformation of glial elements with continuing dedifferentiation. This transformation can be experimentally induced by various factors including oncogenic DNA (oncorna) viruses by using a reverse transcriptase, while there is indirect evidence for an oncorna-virus information in human glioblastoma. The significance of immunological factors in the pathogenesis of brain tumours and in the course of neoplastic transformation of glia is not yet understood, but both morphological and immunological data are in favour of a cell mediated immunological reaction against tumour-specific antibodies. Since immunological factors and changes in cytokinetics are apparently active after the transformed tumour cells proliferate, all available therapeutic methods, including radiation, chemotherapy, and immunotherapy of glioblastoma only influence the final stages of neoplastic development with clinical manifestation of the tumour. In spite of modern combination and multimodality therapy schemes the prognosis of glioblastoma is still poor.


Age variation in the cancer risks from foetal irradiation.
A modified Mantel-Haenszel analysis of data from the Oxford Survey of Childhood Cancers has shown that cases associated with foetal irradiation (X-rayed cases) accounted for a higher proportion of deaths between 5 and 10 years than of earlier or later deaths. This finding is compatible with somewhat later origins for the cancers actually caused by the radiation exposures (radiogenic cases) than for other (idiopathic) cases which proved fatal before 10 years of age. Therefore the usual time for incurring congenital anomalies (or the first trimester of foetal life) could be the commonest time for initiating childhood cancers. The theoretical implications of this and other findings of the Oxford Survey are discussed within the framework of a theory which assumes that all mutant cells have cancer potentialities and that defects in the immune surveillance mechanism favour multiplication of these cells (or endogenous sources of self-replicating foreign proteins) as well as live pathogens (or exogenous sources of self-replicating foreign proteins).


A case of recurrent, bilateral ovarian mature teratoma in a young woman.
Ovarian mature cystic teratomas are common, benign, pelvic tumors that are easily detected by pelvic ultrasonography. However, patients with recurrent teratomas are rarely noted, and cases of bilateral teratomas are even less common. A young woman with a recurrent, right ovarian teratoma had previously undergone surgical removal 2 times. After the second surgery, she underwent regular out-patient follow-up, and no residual tumor was observed. However, 3 years after the second surgery, she developed recurrent, bilateral ovarian teratomas, in conjunction with elevated carbohydrate antigen-125 levels. Routine checking of the contralateral ovary during the surgical procedure along with frequent postoperative pelvic sonography for both ovaries in the patient at high recurrence rich is necessary. Additionally, the features of that kind tumor may mislead the surgeon into performing more extensive surgery that might compromise the fertility of young patients.


Correlation between visual examination of the cervix and digital examination.
To determine the correlation between visual assessment of the cervix and digital examination. Prospective study of patients presenting to Labor and Delivery. Exclusion criteria were preterm premature ruptured membranes (PPROM) and placenta previa. Visual and digital assessments of cervical dilation, effacement, position, and station of fetal presenting part were made. Correlation between visual and digital examinations was measured using Spearman rank correlation coefficient (COR). A p-value<0.05 was considered significant. The study involved a total of 107 patients at a mean gestational age of 32.3 weeks (range 17-41). Seven patients had ruptured membranes, and 46 were nulliparous. Visual assessment correlated with digital examination for all parameters measured with Spearman rank correlation coefficients between 0.618 and 0.686 (all significant at p<0.001). Correlations between visual and digital assessment of cervical dilation, effacement, station, and position were not as strong (0.291-0.699), but remained significant (p<0.02) in a subgroup of 50 preterm patients<34 weeks gestation. Visual assessment correlates with digital examination of the cervix. This correlation remained significant in a subset of preterm patients with intact membranes.


Clinical impact of reducing microalbuminuria in patients with type 2 diabetes mellitus.
Diabetic nephropathy in type 2 diabetes is a leading cause of end-stage renal disease worldwide. Its early clinical sign is microalbuminuria, which is not only a predictor for progression of nephropathy but also an independent risk factor for cardiovascular disease. A few decades ago, diabetic nephropathy was believed to be progressive and irreversible. Thus, the main therapeutic objective for type 2 diabetic patients with microalbuminuria was to prevent progression to overt proteinuria. However, there is now growing evidence regarding remission/regression of diabetic nephropathy. In recent clinical trials using the renin-angiotensin system blockade drugs, a reduction in microalbuminuria by the use of these drugs has been noted. We also reported that a reduction in microalbuminuria was more frequent than progression to overt proteinuria and that multifactorial control approach was important to the reduction of microalbuminuria. These results for type 2 diabetes are similar to those previously reported for type 1 diabetes. Furthermore, our recent study showed that the 8-year cumulative incidence rate of renal and cardiovascular events was significantly lower in patients with remission than in those without it. The annual decline rate of estimated glomerular filtration rate in patients with remission was also significantly slower. These studies provide clinical evidence implying that the reduction of microalbuminuria in type 2 diabetic patients occurs frequently and brings about renal and cardiovascular risk reduction. Reducing microalbuminuria is therefore considered to be an important therapeutic objective and may be a biomeasure of therapeutic success in type 2 diabetic patients.


Extraction of plant secondary metabolites.
This chapter presents an overview of the preparation of extracts from plants using organic solvents, with emphasis on common problems encountered and methods for their reduction or elimination. In addition to generally applicable extraction protocols, methods are suggested for selectively extracting specific classes of plant-derived compounds, and phytochemical procedures are presented for the detection of classes of compounds encountered commonly during extraction, including selected groups of secondary metabolites and interfering compounds. Successful extraction begins with careful selection and preparation of plant samples and thorough review of the appropriate literature for suitable protocols for a particular class of compounds or plant species. During the extraction of plant material, it is important to minimize interference from compounds that may co-extract with the target compounds, and to avoid contamination of the extract, as well as to prevent decomposition of important metabolites or artifact formation as a result of extraction conditions or solvent impurities.


Volatile organic compounds emissions from traditional and clean domestic heating appliances in Guanzhong Plain, China: Emission factors, source profiles, and effects on regional air quality.
Solid (biomass and coal) fuels burned for residential heating are major sources of atmospheric volatile organic compounds (VOCs). In this study, VOC samples were collected in-situ from chimneys in 10 typical heating scenarios in rural areas of the Guanzhong Plain. A modified SUMA canister approach was then employed, followed by gas chromatography/mass spectrometry analysis. Emission factors (EFs) (as received basis) of targeted non-methane VOCs (NMVOCs) varied from 90.3 ± 29.3 to 12300 ± 1510 mg kg-1 in descending order of fuel wood > maize straw > bitumite ≫ anthracite (p < 0.05). Both clean stove and coal briquetting technologies effectively reduced VOC EFs compared with traditional heating methods. The EFs of methane (CH4) had similar characteristics to those of NMVOCs. However, they yielded different correlations with CO because of their differing mechanisms of formation. Coefficient of divergence (CD) values showed that a semi-gasifier has a limited effect on changing VOC profiles compared with a traditional stove using the same fuels. However, different types of fuel produce CD values over 0.50, which should therefore be classified as different sub-categories in source apportionment models. Correlation analysis showed that volatile matter content (V%) and modified combustion efficiency (MCE) were the two primary factors influencing NMVOC and CH4 emissions. A stepwise linear regression analysis showed that V%, MCE, and element nitrogen content (N%) can be used to predict total VOC (TVOCs, including CH4 and NMVOCs) emissions with regression coefficients of 0.23, -72.8 and -6.53, respectively (R2 = 0.92, p < 0.001). Ozone formation potential (OFP) EFs from burning solid fuel ranged from 72 to 18680 mg kg-1, with an approximate 50% contribution from alkenes. VOCs from burning solid fuel were equivalent to 62 to 22200 mg kg-1 secondary organic aerosol formation potential (SOAP), most of which (>95%) were contributed by aromatics. A semi-gasifier and coal briquettes were effective in reducing TVOC emissions, even when used in conjunction with a traditional stove and fuels. It is estimated that over 15,000 ton year-1 emissions can be reduced in Guanzhong Plain by adopting a semi-gasifier and coal briquettes, resulting in a 57,000 and 65,000 ton year-1 reduction of OFP and SOAP emissions, respectively. These results demonstrate that the use of clean heating technologies in Guanzhong Plain has considerable potential in relation to emissions reduction and thus provides a feasible solution to mitigate VOCs and related secondary pollutants emitted by residential solid fuel burning.


Clinical significance of IgM and C3 deposition in children with primary immunoglobulin A nephropathy.
Mesangial IgM and C3 deposition is commonly observed in patients with primary immunoglobulin A nephropathy (IgAN), but its characteristics and prognosis have rarely been reported. The aim of this study was to investigate the relationship between combined mesangial IgM and C3 deposition and disease progression in children with IgAN. One hundred sixteen children diagnosed with IgAN between 2016 and 2020 were selected. Renal biopsies were scored by Oxford classification including the presence of mesangial hypercellularity, endocapillary hypercellularity, segmental glomerulosclerosis, tubular atrophy/interstitial fibrosis and crescents. The primary renal outcome was an event of either ≥ 50% reduction of eGFR from the baseline value or the onset of end-stage renal disease within the follow-up period. Cox regression analysis was performed to examine the effect of the combined mesangial IgM and C3 deposition on renal outcomes. Forty-seven (40.52%) patients presented combined mesangial IgM and C3 deposition. Compared with children without combined IgM and C3 deposition, children with combined IgM and C3 deposition presented higher mesangial hypercellularity, endocapillary hypercellularity and cresentic lesions in kidney biopsies, and higher prevalence of renal dysfunction (19.15% versus 2.90%; P = 0.007). Renal outcome was also significantly worse as revealed by Kaplan-Meier curves (P = 0.0034). Multivariable Cox analysis identified tubular atrophy/interstitial fibrosis lesions [hazard ratio (HR) 14.843, 95% CI, 3.497-62.997, P < 0.001] and intensity of IgM deposition (HR 2.838, 95% CI, 1.321-6.094, P = 0.007) as independent risk factors for poor renal function. Combined mesangial IgM and C3 deposition was associated with unfavorable histopathological features. Mesangial IgM deposition was an independent risk factor for poor renal outcomes in children with primary IgAN.


Transforming growth factor-beta and ovarian carcinoma cells: regulation of proliferation and surface antigen expression.
Transforming growth factor-beta (TGF-beta) is a multifunctional peptide regulating several processes in ovarian cells. The growth of ovarian carcinoma cell lines (OVCAR-3, HTB-77, 2780 and CRL-1572) was reduced by TGF-beta in a dose related manner. The antiproliferative activity was not improved by combination with other biological response modifiers. Treatment with TGF-beta augmented the expression of interferon-gamma induced class I and II antigens of the major histocompatibility complex. The presentation of another antigen namely the tumor marker CA-125 on the cell surface was markedly reduced by TGF-beta.


Role of Nurse Practitioners in Caring for Patients With Complex Health Needs.
The objective of this study was to estimate trends in the percentage of Medicare beneficiaries cared for by nurse practitioners from 2012 to 2017, to characterize beneficiaries cared for by nurse practitioners in 2017, and to examine how the percentage of beneficiaries cared for by nurse practitioners varies by practice characteristics. An observational study of 2012-2017 Medicare fee-for-service beneficiaries' ambulatory visits. We computed the percentage of beneficiaries with 1 or more ambulatory visits from nurse practitioners and the percentage of beneficiaries receiving the plurality of their ambulatory visits from a nurse practitioner versus a physician (ie, predominant provider). We compared beneficiary demographics, clinical characteristics, and utilization by the predominant provider. We then characterized the predominant provider by practice characteristics. In 2017, 28.9% of beneficiaries received any care from a nurse practitioner and 8.0% utilized nurse practitioners as their predominant provider-an increase from 4.4% in 2012. Among beneficiaries cared for by nurse practitioners in 2017, 25.9% had 3 or more chronic conditions compared with 20.8% of those cared for by physicians. Beneficiaries cared for in practices owned by health systems were more likely to have a nurse practitioner as their predominant provider compared with those attending practices that were independently owned (9.3% vs. 7.0%). Nurse practitioners are caring for Medicare beneficiaries with complex needs at rates that match or exceed their physician colleagues. The growing role of nurse practitioners, especially in health care systems, warrants attention as organizations embark on payment and delivery reform.


Species-area and species-distance relationships of terrestrial mammals in the Thousand Island Region.
The species-area and species-distance relationships of terrestrial mammals in the Thousand Island Region of the St. Lawrence River are totally consistent with the basic predictions of the equilibrium theory of island biogeography. The power model provides the best fit for the species-area relationship, and the z-value of 0.305 does not differ significantly from Preston's canonical value (0.26). Distance (D) is a normal determinant (Sαe -D 2) of mammalian richness, and 93% of the variability in richness is accounted for by island area and isolation. The high z-values and poor species-distance correlations reported in previous studies of mammalian island biogeography, rather than evidencing non-equilibrium, are predictions consistent with the equilibrium theory for distant archipelagoes or, equivalently, poor immigrators such as mammals.


[Effects of the volatile oil of Centipeda minima on acute pleural effusion in rats induced by an intrapleural injection of car].
To study the anti-inflammation effect of volatile oil of Centipeda minima and the mechanism of action. The animal model was induced by the Car injection into intrapleural of rats, to observe the effect of VOCM on acute inflammation. VOCM was able to inhibit the increase of NO, CRP and proinflammatory cytokines such as TNFalpha in the acute inflammation of the rat body. VOCM has a protective effect on acute pleural effusion in rats induced by an intrapleural injection of Car.


Outer surface protein E (OspE) mediates Borrelia burgdorferi sensu stricto strain-specific complement evasion in the eastern fence lizard, Sceloporus undulatus.
In North America, Lyme disease is primarily caused by the spirochetal bacterium Borrelia burgdorferi sensu stricto (Bb), which is transmitted between multiple vertebrate hosts and ixodid ticks, and is a model commonly used to study host-pathogen interactions. While Bb is consistently observed in its mammalian and avian reservoirs, the bacterium is rarely isolated from North American reptiles. Two closely related lizard species, the eastern fence lizard (Sceloporus undulatus) and the western fence lizard (Sceloporus occidentalis), are examples of reptiles parasitized by Ixodes ticks. Vertebrates are known to generate complement as an innate defense mechanism, which can be activated before Bb disseminate to distal tissues. Complement from western fence lizards has proven lethal against one Bb strain, implying the role of complement in making those lizards unable to serve as hosts to Bb. However, Bb DNA is occasionally identified in distal tissues of field-collected eastern fence lizards, suggesting some Bb strains may overcome complement-mediated clearance in these lizards. These findings raise questions regarding the role of complement and its impact on Bb interactions with North American lizards. In this study, we found Bb seropositivity in a small population of wild-caught eastern fence lizards and observed Bb strain-specific survivability in lizard sera. We also found that a Bb outer surface protein, OspE, from Bb strains viable in sera, promotes lizard serum survivability and binds to a complement inhibitor, factor H, from eastern fence lizards. Our data thus identify bacterial and host determinants of eastern fence lizard complement evasion, providing insights into the role of complement influencing Bb interactions with North American lizards.


Corrigendum: Diclofenac and other non-steroidal anti-inflammatory drugs (NSAIDs) are competitive antagonists of the human P2X3 receptor.
[This corrects the article DOI: 10.3389/fphar.2023.1120360.].