Experiences of Size Inclusive Physical Activity Settings Among Women With Larger Bodies.
Purpose: Size inclusive physical activity settings may help mitigate the impact of physical activity-related weight stigma. In this interpretive description study, we aimed to understand how women with larger bodies experienced size inclusive physical activity settings. The study was informed by a settings-based approach to health promotion. Method: We interviewed nine women with larger bodies who participated in size inclusive physical activity and used an inductive approach to analyze the data. Findings: At the individual level, size inclusion was experienced as an enhancement of well-being, self-worth, and belonging. This was closely tied to the interpersonal level, whereby weight-neutral practices used by fitness instructors and lack of judgment from other exercisers contributed to experiences of size inclusion. At the organizational level, the organization's culture, marketing, programs, and physical spaces could enhance or limit inclusion and participation. However, weight stigma was prevalent in women's experiences outside the physical activity setting. Conclusion: We provide recommendations to improve size inclusion in physical activity settings.


Hormonal function of a granulosa cell tumor.
Granulosa and theca cell tumors are rather common gonadal stromal tumors. A postmenopausal patient with a granulosa cell tumor, who complained chiefly of breast tenderness and enlarging, abdomen, is presented. Preoperative and postoperative studies including serum estrone, estradiol, prolactin, FSH, and LH,as well as urinary estrogens, 17-ketosteroids, and 17-hydroxysteroids are reported. A plan of treatment and followup is suggested. It is recommended that survival data on patients with such slow-growing tumors be adjusted to reflect the true incidence of death from the specific tumor in question.


Comparative assessment on rodent impacts and cultural perceptions of ecologically based rodent management in 3 Afro-Malagasy farming regions.
Rodents generate negative consequences for smallholder farmers in Africa that directly impact household and livestock damage, food security, and public health. Ecologically Based Rodent Management (EBRM) seeks sustainable solutions for the mitigation of rodent damage through assessments of rodent population dynamics, agro-ecosystems, and socio-cultural contexts. We adopt a comparative approach across 3 rural Afro-Malagasy smallholder farming regions in South Africa, Tanzania, and Madagascar to assess the household impacts of rodent pests and current perceptions and preferences associated with several rodent control measures. We conducted focus group questionnaires and interviews in different study site locations. Rodents assert multiple impacts on Afro-Malagasy farmers demonstrating recurrent and emerging agricultural and household costs, and public health impacts. We identify a significant knowledge gap in educating communities about the application of different EBRM approaches in favor of acute poisons that are perceived to be more effective. Cultural issues and taboos also have a significant impact on the social acceptance of rodent hunting as well as biological control using indigenous predators. We advocate for an enhanced investigation of the socio-cultural beliefs associated with different rodent practices to understand the factors underlying social acceptance. A collaborative approach that integrates the perspectives of target communities to inform the design of EBRM initiatives according to the specific agro-ecosystem and socio-cultural context is necessary to ensure programmatic success.


Dendrite-to-soma input/output function of continuous time-varying signals in hippocampal CA1 pyramidal neurons.
We examined how hippocamal CA1 neurons process complex time-varying inputs that dendrites are likely to receive in vivo. We propose a functional model of the dendrite-to-soma input/output relationship that combines temporal integration and static-gain control mechanisms. Using simultaneous dual whole cell recordings, we injected 50 s of subthreshold and suprathreshold zero-mean white-noise current into the primary dendritic trunk along the proximal 2/3 of stratum radiatum and measured the membrane potential at the soma. Applying a nonlinear system-identification analysis, we found that a cascade of a linear filter followed by an adapting static-gain term fully accounted for the nonspiking input/output relationship between the dendrite and soma. The estimated filters contained a prominent band-pass region in the 1- to 10-Hz frequency range that remained constant as a function of stimulus variance. The gain of the dendrite-to-soma input/output relationship, in contrast, varied as a function of stimulus variance. When the contribution of the voltage-dependent current I(h) was eliminated, the estimated filters lost their band-pass properties and the gain regulation was substantially altered. Our findings suggest that the dendrite-to-soma input/output relationship for proximal apical inputs to CA1 pyramidal neurons is well described as a band-pass filter in the theta frequency range followed by a gain-control nonlinearity that dynamically adapts to the statistics of the input signal.


Relationship between volume of submandibular salivary stones in vivo determined with Cone-Beam Computer Tomography and in vitro with micro-Computer Tomography.
Successful removal of salivary stones depends on exact pretreatment information of the location, the size and shape of the stones. This study aimed to compare the volume of submandibular sialoliths determined by preoperative Cone-Beam Computer Tomography (CBCT) scans with the volume of the removed stones on micro-Computer Tomography (micro-CT) scans. In this study, using twenty-one submandibular sialoliths, the pretreatment volumes in-vivo measured on CBCT were compared to the volumes of removed stones determined by micro-CT scans. The volume measured on micro-CT scans served as the gold standard. Pre-operative CBCT's and in-vitro micro-CT's were converted into standard tessellation language models (STL-models) using an image segmentation software package. The CBCT and micro-CT images of the stones were subsequently metrologically assessed and compared to each other using reverse engineering software. Volumes of submandibular sialoliths determined by CBCT's correlated significantly with volumes measured on micro-CT's (Spearman's coefficient r = 0.916). The interquartile range (IQR) for the volume measured with micro-CT was 117.23. The median is 26.41. For the volume measured with CBCT the IQR was 141.3 and the median 36.61. The average volume on micro-CT is smaller than on CBCT. When using CBCT-scans for the detection of submandibular sialoliths one should realize that in-vivo those stones are actually a fraction smaller than assessed on the preoperative scan. This is important when cut-off values of sizes of stones are used in the pretreatment planning of stone removal.


Possible role of apoptosis in the pathogenesis and clinical evolution of radicular cyst: an immunohistochemical study.
To investigate whether the apoptotic cascade is activated through the extrinsic pathway in epithelial lining and connective tissue of radicular cysts. Fifteen radicular cysts were fixed in formalin, embedded in paraffin wax and processed for immunohistochemistry to evaluate the expression of polyclonal antibodies against Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL), DR5 and caspase-3. Immunocomplexes were treated with the secondary antibodies and finally detected using the avidin-biotin-peroxidase complex. Immunoreactivity was visualized by development with 3,3'-diaminobenzidine. Data were analysed using the Mann-Whitney U-test; P < 0.05 was considered significant. The three antibodies were detected in connective tissue fibroblasts of all radicular cysts; TRAIL and DR5 immunoexpression was significantly greater (P < 0.05) compared with that of caspase-3. The three antibodies were also expressed in almost all epithelial layers and in endothelial cells of newly formed vessels. The involvement of apoptosis in the pathogenesis of radicular cysts, demonstrated by the immunoexpression patterns of TRAIL, DR5 and caspase-3 in lining epithelium and connective tissue, may explain their bland clinical aggressiveness and slow, benign evolution.


Detection of antibodies against adenovirus protein IX, fiber, and hexon in human sera by immunoblot assay.
The 51 serotypes of human adenoviruses (HAdVs) of the genus Mastadenovirus are classified into the six species HAdV-A to HAdV-F. For the detection of genus- and species-specific antibodies in human sera an immunoblot assay was developed. The recombinant long fiber of HAdV-41[F] (Ad41Fi) and the native hexon of HAdV-5[C] were used as genus-specific antigens. The recombinant capsid protein IX (pIX) of HAdV-2 (Ad2pIX[C]) and HAdV-41 (Ad41pIX[F]), the C-terminal pIX part of HAdV-3 (Ad3pIXC[B]), and the fiber knob of HAdV-8 (Ad8FiKn[D]) were evaluated as representative species-specific antigens. Hence, the pIX amino acid sequences of numerous serotypes of all HAdV species were compared, and the cross-reactivities of pIX antigens with rabbit hyperimmune sera among HAdV-A to -F were analyzed. In an epidemiological study, 667 human patient sera, not selected for viral infection, were screened for adenovirus seroprevalence. The genus-specific antibody prevalences directed against the Ad41Fi and HAdV-5 hexon were 82.8 and 98.8%, respectively. The species-specific antibody prevalence of 44.7% against Ad2pIX[C], 36.6% against Ad41pIX[F], 26.4% against Ad8FiKn[D], and 18% against Ad3pIXC[B] showed an age-dependent distribution and correlated well with the frequency of isolated serotypes of the respective species in earlier studies (except HAdV-D). In conclusion, the immunoblot assay using pIX, fiber, and hexon antigens represents a valuable and new serological tool for refined adenovirus diagnosis as shown in an epidemiological study.


Trends in Reoperation After Initial Lumpectomy for Breast Cancer: Addressing Overtreatment in Surgical Management.
Surgery after initial lumpectomy to obtain more widely clear margins is common and may lead to mastectomy. To describe surgeons' approach to surgical margins for invasive breast cancer, and changes in postlumpectomy surgery rates, and final surgical treatment following a 2014 consensus statement endorsing a margin of "no ink on tumor." This was a population-based cohort survey study of 7303 eligible women ages 20 to 79 years with stage I and II breast cancer diagnosed in 2013 to 2015 and identified from the Georgia and Los Angeles County, California, Surveillance, Epidemiology, and End Results registries. A total of 5080 (70%) returned a survey. Those with bilateral disease, missing stage or treatment data, and with ductal carcinoma in situ were excluded, leaving 3729 patients in the analytic sample; 98% of these identified their attending surgeon. Between April 2015 and May 2016, 488 surgeons were surveyed regarding lumpectomy margins; 342 (70%) responded completely. Pathology reports of all patients having a second surgery and a 30% sample of those with 1 surgery were reviewed. Time trends were analyzed with multinomial regression models. Rates of final surgical procedure (lumpectomy, unilateral mastectomy, bilateral mastectomy) and rates of additional surgery after initial lumpectomy over time, and surgeon attitudes toward an adequate lumpectomy margin. The 67% rate of initial lumpectomy in the 3729 patient analytic sample was unchanged during the study. The rate of final lumpectomy increased by 13% from 2013 to 2015, accompanied by a decrease in unilateral and bilateral mastectomy (P = .002). Surgery after initial lumpectomy declined by 16% (P < .001). Pathology review documented no significant association between date of treatment and positive margins. Of 342 responding surgeons, 69% endorsed a margin of no ink on tumor to avoid reexcision in estrogen receptor-positive progesterone receptor-positive cancer and 63% for estrogen receptor-negative progesterone- receptor-negative cancer. Surgeons treating more than 50 breast cancers annually were significantly more likely to report this margin as adequate (85%; n = 105) compared with those treating 20 cases or fewer (55%; n = 131) (P < .001). Additional surgery after initial lumpectomy decreased markedly from 2013 to 2015 concomitant with dissemination of clinical guidelines endorsing a minimal negative margin. These findings suggest that surgeon-led initiatives to address potential overtreatment can reduce the burden of surgical management in patients with cancer.


Clinical efficacy of myometrial and endometrial microwave ablation in the treatment of patients with adenomyosis who had anemia.
This study evaluated the clinical efficacy of myometrial and endometrial microwave ablation (MEWA) for treating adenomyosis in patients with anemia. This retrospective study enrolled 64 patients with adenomyosis who had anemia treated with either MEWA (MEWA group) or myometrial microwave ablation (MMWA group) between May 2019 and May 2021. The uterine volumes, uterine-volume reduction rates, hemoglobin (Hb) levels, cancer antigen 125 (CA125) levels, dysmenorrhea visual analog scale (VAS) scores, uterine fibroblast symptoms and health-related quality of life (UFS-QOL) scores, menstrual flow scores (MFS) before and 3, 6, and 12 months post-treatment, and adverse events and complications in both groups were collected to assess clinical efficacy. No statistically significant preoperative differences were observed in any measured factors. Postoperatively, there was a significant reduction in uterine volume and CA125 level, an increase in Hb level, and improvement in the UFS-QOL, dysmenorrhea VAS score, and MFS. No differences were observed in postoperative uterine volume, CA125 level, overall response rate, and adverse event rate during the follow-up period until 12 months postoperatively. However, the MEWA group showed a better uterine-volume reduction rate 6 months postoperatively and improvement in Hb level, USF-QOL score, dysmenorrhea VAS score, and MFS postoperatively. MEWA and MMWA demonstrated high clinical efficacy in treating adenomyosis and anemia. However, MEWA is a more effective therapy that successfully improves anemia, resulting in improved quality of life.


Microbial culture collections as pillars for promoting fungal diversity, conservation and exploitation.
Fungi are a diverse group of organisms with an overall global number of 1.5M up to 3.3M species on Earth. Besides their ecological roles as decomposers, fungi are important in several aspects of applied research. Here, we review how culture collections may promote the knowledge on diversity, conservation and biotechnological exploitation of fungi. The impact of fungi diversity on biotechnological studies is discussed. We point out the major roles of microbial repositories, including fungal preservation, prospecting, identification, authentication and supply. A survey on the World Data Center for Microorganisms (WDCM) powered by the World Federation for Culture Collections and on the Genetic Heritage Management Council (CGEN) database revealed that 46 Brazilian culture collections registered in these databases are dedicate to preserving fungi. Most of these culture collections are located in the Southeast of Brazil. This scenario also demonstrates that Brazil has many collections focused on fungal strains, but the lack of up-to-date information in WDCM as well as of a solid national platform for culture collections registration do not allow accurate assessment of fungal preservation.


Chromosomal deletion 4p15.32----p14 in a Treacher Collins syndrome patient: exclusion of the disease locus from and mapping of anonymous DNA sequences to this region.
Treacher Collins syndrome is an autosomal dominant condition of bilateral craniofacial abnormalities of structures derived from the first and second branchial arches. A patient with severe manifestations of Treacher Collins syndrome and a de novo chromosomal deletion in region 4p15.32----p14 was identified. Anonymous DNA sequences of loci D4S18, D4S19, D4S20, D4S22, and D4S23 were mapped to the deleted region. DNA probes previously mapped to loci on chromosome 4p (D4S10, D4S15, D4S16, D4S26, D4S35, D4S95, D4S144, RAF1P1, QDPR, and HOX7) were not deleted in this patient. Linkage analysis between the D4S18, D4S23, and QDPR loci and Treacher Collins syndrome in eight families excluded the Treacher Collins syndrome locus from the region of the deletion.


Treatment of chronic myelogenous leukemia with allogeneic bone marrow transplantation after preparation with busulfan and cyclophosphamide (BuCy2): an update.
Allogeneic bone marrow transplantation (BMT) has been shown to result in long-term disease-free survival in patients with leukemia. However, the utility of this treatment approach is limited by treatment-related morbidity and mortality. We present an update of a study in which a BMT preparative regimen consisting of a 4-day course of busulfan and a 2-day course of cyclophosphamide (BuCy2) was used in patients with chronic myelogenous leukemia. Patient survival depended on disease stage, with a 58% survival rate for patients in first chronic phase, 41% for those in accelerated phase, and 25% for those in the blast transformation stage. There was a significant difference in patient survival between those who received transplants within 1 year of diagnosis and those who received transplants more than 1 year after diagnosis (70% v 40%). This difference appeared to be due to the extent of previous exposure to busulfan. The overall mortality rate in this study was 46%. We conclude that the BuCy2 preparative regimen is similar in effectiveness to regimens that include total body irradiation and results in comparable levels of transplant-related mortality. Our results strongly indicate that patients with chronic myelogenous leukemia who receive BMT within the first year after diagnosis have a significantly better clinical outcome than those who receive BMT later in the course of the disease.


Malaria, primigravidae, and antibodies: knowledge gained and future perspectives.
Pregnant women have an increased risk of malaria infection, independent of previously acquired immunity. Women in their first pregnancy and children under the age of five are the primary victims of malaria worldwide. Pregnant women develop antibodies against placenta-adhesive parasites in a parity-dependent manner. Various efforts to understand the targets, quality, and quantity of this antibody response could aid the design of an effective vaccine against placental malaria. This review focuses on the research that has led to the current understanding of the antibody response that primigravidae (PG) acquire to Plasmodium falciparum malaria and draws from this knowledge to suggest serology and PG as sentinels for malaria transmission.


Molecular characterization of antibodies bearing Id-460. I. The structure of two highly homologous VH genes used to produce idiotype positive immunoglobulins.
The heavy chain immunoglobulin genes encoding a variety of antibodies specific for DNP or Pasteurella pneumotropica and bearing the dominant idiotype of MOPC 460, Id-460, were cloned and sequenced. The VH genes encoding the M460 and D35 (DNP binding) antibodies were found to be homologous but not identical to the VH gene encoding the LB8 (P. pneumotropica binding) monoclonal antibody. Two of at least eight genes in the VH460 cross-hybridizing gene family can encode Id-460 positive antibodies. The VH460 gene family overlaps with the gene family described by VH36-60 and more completely describes this germ-line VH gene family. We have previously demonstrated a genetic requirement for VK1 expression in order to observe the expression of Id-460 in anti-DNP antibody responses. Southern blot analysis of these monoclonal antibody-producing cells demonstrates, as with the cross-hybridizing VH, that two cross-hybridizing VK1 genes (VK1A and VK1C) can be used to encode Id-460-positive immunoglobulins. We demonstrate that immunoglobulin idiotype determinant expression can be the result of the expression of nonidentical but highly homologous genes in the VH460 cross-hybridizing VH gene family and also in the VK1 cross-hybridizing VL family.


Identification of unusual butanetriol dialkyl glycerol tetraether and pentanetriol dialkyl glycerol tetraether lipids in marine sediments.
Glycerol serves as the principal backbone moiety bound to various acyl/alkyl chains for membrane lipids of Eukarya, Bacteria, and Archaea. In this study, we report a suite of unusual tetraether lipids in which one of the two conventional glycerol backbones is substituted by butanetriol or pentanetriol. Identification of these lipids was achieved via diagnostic fragments and their expected acetylation products using liquid chromatography/mass spectrometry (LC/MS), and their diagnostic ether cleavage products using gas chromatography/mass spectrometry (GC/MS). We observed structural variations in the polyol backbones and alkyl chains and term these core lipid derivatives: isoprenoidal butanetriol dialkyl glycerol tetraethers (iso-BDGTs), isoprenoidal pentanetriol dialkyl glycerol tetraethers (iso-PDGTs), and hybrid isoprenoidal/branched BDGTs and PDGTs (ib-BDGTs, ib-PDGTs). Of these, iso-BDGTs were the most abundant with a methylation at either the sn-1 or sn-3 position of glycerol and were also found as part of intact polar lipids, adjoined to mono- or diglycosidic headgroups. Iso-BDGTs and iso-PDGTs are likely produced by Archaea, as indicated by the presence of the characteristic biphytanyl moieties. Butanetriol- and pentanetriol-based tetraether lipids occur in modern estuarine and deeply buried subseafloor sediments, suggesting the presence of alternative backbones in archaeal lipids.


Pushed Out and Drawn In: Exclusionary Discipline, Mental Health, and Protective Factors Among Youth in Public Schools.
Exclusionary discipline (ED) has long been an educational equity concern, but its relationship with student health and protective factors is less understood. Using population-based public school student data (N = 82,216), we examined associations between past-month ED and positive depression and anxiety screening instrument results. We also assessed whether each of 9 potential protective factors moderated the ED-mental health relationship by testing interaction effects. Over 1 in 10 youth experienced past-month ED, with variation by sex, gender identity, special education status, poverty, region, race/ethnicity, and adverse childhood experiences. Net of sociodemographic factors, youth who experienced ED had higher likelihood for current depression (adjusted odds ratio [AOR]: 1.64, 95% confidence interval [CI]: 1.55, 1.73) and anxiety (AOR: 1.49, 95% CI: 1.41, 1.58) symptoms. Significant associations were robust across 5 racial/ethnic groups, except for anxiety among American Indian/Alaska Native youth. Individual, interpersonal, and school-level protective factors appeared to mitigate depression and anxiety regardless of disciplinary experience. Our findings document ED disproportionality and possible ramifications for emotional well-being. In concert with structural efforts to reduce reliance on ED, strategies that bolster protective factors may support youth already impacted by ED and/or mental health problems.


The impact of COVID-19 pandemic on IBD endoscopic procedures in a high-volume IBD Center.
Background and study aims The COVID-19 pandemic is having a major clinical and also organizational impact on national health care systems, particularly in high-volume hospitals that are utilized for several essential clinical needs. We aimed to analyze the short-term impact of the SARS-CoV-2 pandemic on management of endoscopic procedures in patients with inflammatory bowel disease (IBD). Patients and methods This was an observational prospective study exploring major clinical and organizational changes in endoscopic management at the IBD Center - CEMAD of the Fondazione Policlinico Gemelli IRCCS, Rome, Italy since the beginning of SARS-CoV-2 pandemic. Results Our IBD Unit, with up to 1,500 IBD patients receiving biotechnological or experimental therapy, represents a high-volume Italian and European IBD center. Since the beginning of the outbreak, our hospital has been extremely impacted by care related to COVID-19 cases, with a consequent need to dramatically reorganize management of endoscopic procedures for IBD. Conclusions Outbreak restrictions have significantly impacted the volume of endoscopic activities for IBD. Specific strategies have been designed to guarantee a high level of safety for both patients with IBD and healthcare personnel dedicated to their treatment.


Characterization of interferons produced by peripheral blood mononuclear cells from healthy subjects in response to Corynebacterium parvum or poly I: poly C.
The biological significance of acid labile interferon alpha is presently unknown. We examined the putative production of acid labile interferon in vitro from human peripheral blood mononuclear cells induced with Corynebacterium parvum or poly I: poly C. Both agents induced up to 1200 IU/ml interferon, and the interferon was 80 to 90% acid labile. The interferons were typed by antibody neutralization of their antiviral activity. Contrary to previous reports, C. parvum induced predominantly interferon gamma, which is normally acid labile, whereas poly I: poly C induced an acid labile interferon alpha activity with characteristics similar to those of acid labile interferon alpha reported in serum in certain human diseases.


Infant feeding and allergy: 12-month prospective study of 500 babies born into allergic families.
This investigation studied 487 babies for symptoms of allergic disease during their first year of life. Because of their positive family histories all the babies are at high risk of becoming allergic. The babies were randomly divided such that cows' milk was deliberately withheld from one group; infants in this group were fed with a soya substitute where required. No benefit resulted from withholding cows' milk, indeed symptoms were more usually associated with this group. Breast feeding, even for a short period, was clearly associated with a lower incidence of wheeze, prolonged colds, diarrhoea, and vomiting. It seemed that the duration of breast feeding was less important than whether or not the child had been breast-fed at all. Wheezing was both more common among boys than girls (P less than .05) and if the mother was a smoker. Other environmental features related to wheezing were social class, month of birth, lack of breast feeding, exposure to dampness, mould and coal fires, but not to domestic pets nor to the numbers of mites found in bedding and carpets. Mite exposure was, however, associated with prolonged colds. Eczema was the only allergic symptom not positively associated with any environmental factor; moreover, it was neither associated with a lack of breast feeding nor with inclusion of cows' milk in the diet. Eczema was associated with the incidence of positive skin prick tests and IgE antibodies to egg white. IgE and IgG4 antibodies were estimated at birth (mothers' and cord bloods) and 3 and 12 months later.(ABSTRACT TRUNCATED AT 250 WORDS)


Retrograde study of hypocretin-1 (orexin-A) projections to subdivisions of the dorsal raphe nucleus in the rat.
A retrograde tracer, WGA-apo-HRP-gold (WG), was injected into each subdivision of the dorsal raphe (DR) nucleus, and subsequent orexin-A immunostaining was performed for the tuberal region of the hypothalamus in order to investigate orexin projections to the DR. Similar to previous studies, the majority of orexin-single-labeled neurons were observed at the dorsal half of the lateral hypothalamus (LH), the circle around the fornix, i.e., perifornical nucleus (PeF), and the area dorsal to the fornix. The present study reports that hypothalamic neurons exhibited differential projections to each subdivision of the DR. Following WG injections into rostral DR, WG-single-labeled cells were observed at the dorsal half of the LH as well as dorsomedial hypothalamic nucleus. The major input to the intermediate DR originates from the ventromedial portion of the LH, PeF, and the area dorsal to the PeF, whereas one to lateral wing DR derived from PeF as well as the ventrolateral portion of the LH. Following WG injections into caudal DR, WG-single-labeled cells were located at ventromedial LH and the ventrolateral portion of the posterior hypothalamus. Following WG injections into each DR subdivision, WG/orexin-double-labeled neurons were observed at LH, PeF, and the area dorsal to the PeF. Only a few double-labeled cells were observed in dorsomedial and posterior hypothalamic nuclei. Our observations suggest that various hypothalamic neurons differentially project to each subdivision of the DR, a portion of which is orexin-immunoreactive. These orexin-immunoreactive DR-projecting hypothalamic neurons might have wake-related influences over a variety of brain functions subject to DR efferent regulation, including affective behavior, autonomic control, nociception, cognition, and sensorimotor integration.


[Effect of thrombus aspiration during primary percutaneous coronary intervention in patients with ST-segment elevation myocardial infarction].
Objective: To investigate the effect of thrombus aspiration during primary percutaneous coronary intervention (PPCI) in patients with ST-segment elevation myocardial infarction (STEMI). Methods: This retrospective study included 321 STEMI patients who underwent PPCI at Beijing Chaoyang hospital from January 2013 to March 2014. Patients were divided into the PPCI group (189 cases) and the PPCI plus thrombus aspiration group (132 cases). Baseline and perioperative clinical data, procedural characteristics were collected, and primary endpoint events including all-cause death, re-myocardial infarction, and coronary revascularization and secondary endpoint events including cardiac death, recurrent angina, target lesion revascularization, and stent thrombosis were recorded during the follow-up. Results: There were no significant difference between PPCI group and PPCI plus aspiration group in age ((59.8±12.5) years old vs. (58.3±14.4) years old, P=0.060) and male ratio (82.5% (156/189) vs. 82.6% (109/132), P=0.993). The number of disease vessels (1.59±0.81 vs. 1.47±0.70, P=0.039) and the prevalence of left anterior descending as infarction related artery (52.3% (69/132) vs. 38.6% (73/189), P=0.022) were significantly higher in the PPCI plus aspiration group than that in the PPCI group.The symptom onset time (3.0 (2.0,4.8) hours vs. 4.0 (2.0,7.0) hours, P=0.027) and myocardial ischemia time (3.9 (2.7,6.2) hours vs. 4.7 (2.9,7.9) hours, P=0.022) were significantly in the PPCI plus aspiration group than in the PPCI group. The percent of thrombolysis in myocardial infarction (TIMI) thrombosis score≥ grade 4 (92.4% (122/132) vs. 75.1% (142/189), P<0.001)and postoperative TIMI flow grade 3 (70.5% (93/132) vs. 60.8% (115/189), P=0.003) was significantly higher in the PPCI plus aspiration group than in the PPCI group. The PPCI group patients were followed up for (31.6±7.5) months, and PPCI plus aspiration group patients were followed up for (32.2±6.7) months (P=0.466). During the follow-up period, there was no significant difference in the incidence of primary endpoint events between the PPCI plus aspiration group and the PPCI group (17.1% (22/129) vs. 16.9% (31/184), P=0.962). Recurrent angina was more frequent in the PPCI plus aspiration group than in the PPCI group (25.6% (33/129) vs. 16.3% (30/184), P=0.044). There was no significant difference in cardiac death (3.1% (4/129) vs. 3.3% (6/184), P=1.000), target lesion revascularization (3.9% (5/129) vs. 3.3% (6/184), P=0.765), and stent thrombosis (3.1% (4/129) vs. 2.7% (5/184), P=1.000) between the PPCI plus aspiration group and the PPCI group. Multivariate Cox regression analysis showed that the number of diseased vessels (RR=1.901, 95%CI 1.217-2.970, P=0.005) and postoperative TIMI flow grade (RR=0.455, 95%CI 0.221-0.934, P=0.032) were the risk factors for coronary revascularization after PPCI. The number of diseased vessels was a risk factor for major endpoint events after PPCI (RR=1.421, 95%CI 1.017-1.986, P=0.040). Conclusion: The incidence of clinical events is similar in patients with STEMI treated with PPCI alone or PPCI plus aspiration.


Coasting (withholding gonadotrophins) for preventing ovarian hyperstimulation syndrome.
Ovarian hyperstimulation syndrome (OHSS) is an iatrogenic and potentially life threatening condition resulting from excessive ovarian stimulation. Reported incidence of moderate to severe OHSS ranges from 0.6% to 5% of in vitro fertilization (IVF) cycles. The factors contributing to OHSS have not been completely explained. The release of vasoactive substances secreted by the ovaries under human chorionic gonadotrophin (hCG) stimulation may play a key role in triggering this syndrome. This condition is characterised by a massive shift of fluid from the intravascular compartment to the third space, resulting in profound intravascular depletion and haemoconcentration. To assess the effect of withholding gonadotrophins (coasting) on the prevention of ovarian hyperstimulation syndrome in assisted reproduction cycles. For the update of this review, we searched the Cochrane Gynaecology and Fertility Group Trials Register, CENTRAL, MEDLINE (PubMed), CINHAL, PsycINFO, Embase, Google, and clinicaltrials.gov to 6 July 2016. We included only randomized controlled trials (RCTs) in which coasting was used to prevent OHSS. Two review authors independently selected trials and extracted data. They resolved disagreements by discussion. They contacted study authors to request additional information or missing data. The intervention comparisons were coasting versus no coasting, coasting versus early unilateral follicular aspiration (EUFA), coasting versus gonadotrophin releasing hormone antagonist (antagonist), coasting versus follicle stimulating hormone administration at the time of hCG trigger (FSH co-trigger), and coasting versus cabergoline. We performed statistical analysis in accordance with Cochrane guidelines. Our primary outcomes were moderate or severe OHSS and live birth. We included eight RCTs (702 women at high risk of developing OHSS). The quality of evidence was low or very low. The main limitations were failure to report live birth, risk of bias due to lack of information about study methods, and imprecision due to low event rates and lack of data. Four of the studies were published only as abstracts, and provided limited data. Coasting versus no coastingRates of OHSS were lower in the coasting group (OR 0.11, 95% CI 0.05 to 0.24; I² = 0%, two RCTs; 207 women; low-quality evidence), suggesting that if 45% of women developed moderate or severe OHSS without coasting, between 4% and 17% of women would develop it with coasting. There were too few data to determine whether there was a difference between the groups in rates of live birth (OR 0.48, 95% CI 0.14 to 1.62; one RCT; 68 women; very low-quality evidence), clinical pregnancy (OR 0.82, 95% CI 0.46 to 1.44; I² = 0%; two RCTs; 207 women; low-quality evidence), multiple pregnancy (OR 0.31, 95% CI 0.12 to 0.81; one RCT; 139 women; low-quality evidence), or miscarriage (OR 0.85, 95% CI 0.25 to 2.86; I² = 0%; two RCTs; 207 women; very low-quality evidence). Coasting versus EUFAThere were too few data to determine whether there was a difference between the groups in rates of OHSS (OR 0.98, 95% CI 0.34 to 2.85; I² = 0%; 2 RCTs; 83 women; very low-quality evidence), or clinical pregnancy (OR 0.67, 95% CI 0.25 to 1.79; I² = 0%; 2 RCTs; 83 women; very low-quality evidence); no studies reported live birth, multiple pregnancy, or miscarriage. Coasting versus antagonistOne RCT (190 women) reported this comparison, and no events of OHSS occurred in either arm. There were too few data to determine whether there was a difference between the groups in clinical pregnancy rates (OR 0.74, 95% CI 0.42 to 1.31; one RCT; 190 women; low-quality evidence), or multiple pregnancy rates (OR 1.00, 95% CI 0.43 to 2.32; one RCT; 98 women; very low-quality evidence); the study did not report live birth or miscarriage. Coasting versus FSH co-triggerRates of OHSS were higher in the coasting group (OR 43.74, 95% CI 2.54 to 754.58; one RCT; 102 women; very low-quality evidence), with 15 events in the coasting arm and none in the FSH co-trigger arm. There were too few data to determine whether there was a difference between the groups in clinical pregnancy rates (OR 0.92, 95% CI 0.43 to 2.10; one RCT; 102 women; low-quality evidence). This study did not report data suitable for analysis on live birth, multiple pregnancy, or miscarriage, but stated that there was no significant difference between the groups. Coasting versus cabergolineThere were too few data to determine whether there was a difference between the groups in rates of OHSS (OR 1.98, 95% CI 0.09 to 5.68; P = 0.20; I² = 72%; two RCTs; 120 women; very low-quality evidence), with 11 events in the coasting arm and six in the cabergoline arm. The evidence suggested that coasting was associated with lower rates of clinical pregnancy (OR 0.38, 95% CI 0.16 to 0.88; P = 0.02; I² =0%; two RCTs; 120 women; very low-quality evidence), but there were only 33 events altogether. These studies did not report data suitable for analysis on live birth, multiple pregnancy, or miscarriage. There was low-quality evidence to suggest that coasting reduced rates of moderate or severe OHSS more than no coasting. There was no evidence to suggest that coasting was more beneficial than other interventions, except that there was very low-quality evidence from a single small study to suggest that using FSH co-trigger at the time of HCG administration may be better at reducing the risk of OHSS than coasting. There were too few data to determine clearly whether there was a difference between the groups for any other outcomes.


[Detection of clinically significant prostate cancer in lesions of PI-RADS score 3 in different histological zones of the prostate and MRI/TRUS fusion prostate biopsy].
To investigate the detection rate of clinically significant PCa (CSPCa) in lesions of prostate imaging-reporting and data system (version 2) (PI-RADS v2) score 3 in different histological zones of the prostate, the value range of clinical parameters, and the possibility of improving the detection rate by MRI/TRUS fusion prostate biopsy. This retrospective study included 297 patients with prostatic lesions of PI-RADS v2 score 3 undergoing transperineal prostate biopsy in Nanjing Drum Tower Hospital from January to December 2019. We analyzed their clinical data, the detection rate of CSPCa in the four histological zones of the prostate and the value range of the clinical parameters. The detection rates of CSPCa in the peripheral zone, transitional zone, central zone and anterior fibromuscular stroma were 23.8%, 11.2%, 40.0% and 50.0%, respectively. In comparison with conventional biopsy, additional MRI/TRUS image fusion biopsy improved the detection rate of CSPCa in the four zones, though with no statistically significant difference. The patients with CSPCa, compared with those in the non-CSPCa group, showed a lower value of free PSA/total PSA (fPSA/tPSA) (0.12 ± 0.05 vs 0.18 ± 0.07) but a higher tPSA level ([13.06 ± 10.07] vs [8.61 ± 5.86] μg/L) and PSA density (PSAD) ([0.35 ± 0.34] vs [0.16 ± 0.11] μg/L2). In prostate lesions of PI-RADS v2 score 3, the detection rate of CSPCa was higher in the peripheral zone, even higher in the central zone and anterior fibromuscular stroma, than in the transitional zone. Prostatic biopsy is strongly recommended for patients with fPSA/tPSA < 0.12 or PSAD > 0.35 μg/L2, and additional MRI/TRUS image fusion biopsy is preferable for the lesions in the transitional or central zone.


Healthcare Resource Utilization and Costs Associated with Autosomal Dominant Polycystic Kidney Disease.
Background: Autosomal dominant polycystic kidney disease (ADPKD), a hereditary nephropathy, eventually leads to end-stage renal disease (ESRD), typically by mid-life. Objectives: The objective of this study was to assess real-world healthcare resource utilization and cost among commercially insured (COM) and Medicare Advantage (MAPD) ADPKD patients in addition to the cost profile by chronic kidney disease (CKD) stage. Methods: Patients diagnosed with ADPKD (two or more claims) with ≥30 days of continuous medical and pharmacy benefits and no evidence of autosomal recessive polycystic kidney disease were selected (Optum Research Database and Impact National Benchmarking Database: 1/1/06-8/31/12). Plan and patient paid healthcare costs and resource utilization per patient per month (PPPM) were described in total and by insurance type. CKD stage was established based on serum creatinine laboratory values or dialysis-related codes. Adjusted, CKD stage-specific costs were predicted for 4 years using regression models. Results: Of the 36,253,096 patients in the databases (1/1/06-8/31/12), 5,051 had evidence of ADPKD. Following exclusion criteria, 4,356 COM and 468 MAPD ADPKD patients remained. Total healthcare resource utilization and costs were high, and costs increased substantially from CKD stage 1-5. PPPM healthcare costs were 37% for ADPKD management and 52% for dialysis services. Predicted 4-year healthcare costs by CKD stage were $40,164 (stage 1), $33,397 (stage 2), $42,686 (stage 3), $148,402 (stage 4), and $207,548 (stage 5). Conclusions: Healthcare resource utilization and costs associated with ADPKD were substantial, irrespective of payer type, and primarily driven by CKD stage. Of the total healthcare costs, 88% were ADPKD- and dialysis-related. Most impactful was the spike in predicted cost when patients progressed from CKD stage 3 to stage 4 (by 348%) after multivariate adjustment. These stage 4-associated costs are primarily due to ultimate progression into stage 5 and ESRD within the 4-year time frame.


[Ballooning mitral valve in tricho-rhino-phalangeal syndrome (author's transl)].
The ballooning mitral valve defect has been repeatedly found in hereditary disorders of connective tissue such as the Marfan syndrome, osteogenesis imperfecta and the Ullrich-Turner syndrome. The present report concerns a nine year old girl with tricho-rhino-phalangeal dysplasia type I and this peculiar anomaly of the mitral valve. Since a literature review disclosed two more cases with tricho-rhinophalangeal dysplasia I and mitral insufficiency, the association may be more than fortuitous. Apparently the mesenchymal changes in tricho-rhino-phalangeal dysplasia I are not limited to the skeletal system.


Biochar Soil Amendment Effects on Arsenic Availability to Mountain Brome ().
Biochar is a renewable energy byproduct that shows promise for remediating contaminated mine sites. A common contaminant at mine sites is arsenic (As). In this study, the effects of biochar amendments to a mine-contaminated soil on As concentrations in mountain brome ( Nees ex Steud.) were investigated. In the biochar-amended soil, mountain brome had greater root biomass and decreased root and shoot As concentrations. X-ray absorption near-edge structure spectroscopy results showed that arsenate [As(V)] is the predominant species in both the nonamended and biochar-amended soils. Soil extraction tests that measure phosphate and arsenate availability to plants failed to accurately predict plant tissue As concentrations, suggesting the arsenate bioavailability behavior in the soils is distinct from phosphate. Results from this study indicate that biochar will be a beneficial amendment to As-contaminated mine sites for remediation.


Development of a core outcome set for clinical trials in squamous cell carcinoma: study protocol for a systematic review of the literature and identification of a core outcome set using a Delphi survey.
Squamous cell carcinoma (SCC) is a common skin cancer that poses a risk of metastasis. Clinical investigations into SCC treatment are common, but the outcomes reported are highly variable, omitted, or clinically irrelevant. The outcome heterogeneity and reporting bias of these studies leave clinicians unable to accurately compare studies. Core outcome sets (COSs) are an agreed minimum set of outcomes recommended to be measured and reported in all clinical trials of a given condition or disease. Although COSs are under development for several dermatologic conditions, work has yet to be done to identify core outcomes specific for SCC. Outcome extraction for COS generation will occur via four methods: (1) systematic literature review; (2) patient interviews; (3) other published sources; and (4) input from stakeholders in medicine, pharmacy, and other relevant industries. The list of outcomes will be revaluated by the Measuring PRiority Outcome Variables via Excellence in Dermatologic surgery (IMPROVED) Steering Committee. Delphi processes will be performed separately by expert clinicians and patients to condense the list of outcomes generated. A consensus meeting with relevant stakeholders will be conducted after the Delphi exercise to further select outcomes, taking into account participant scores. At the end of the meeting, members will vote and decide on a final recommended set of core outcomes. The Core Outcome Measures in Effectiveness Trials (COMET) organization and the Cochrane Skin Group - Core Outcome Set Initiative (CSG-COUSIN) will serve as advisers throughout the COS generation process. Comparison of clinical trials via systematic reviews and meta-analyses is facilitated when investigators study outcomes that are relevant and similar. The aim of this project is to develop a COS to guide use for future clinical trials.


Pancreatic β-Cell Rest Replenishes Insulin Secretory Capacity and Attenuates Diabetes in an Extreme Model of Obese Type 2 Diabetes.
The onset of common obesity-linked type 2 diabetes (T2D) is marked by exhaustive failure of pancreatic β-cell functional mass to compensate for insulin resistance and increased metabolic demand, leading to uncontrolled hyperglycemia. Here, the β-cell-deficient obese hyperglycemic/hyperinsulinemic KS db/db mouse model was used to assess consequential effects on β-cell functional recovery by lowering glucose homeostasis and/or improving insulin sensitivity after treatment with thiazolidinedione therapy or glucagon-like peptide 1 receptor agonism alone or in combination with sodium/glucose cotransporter 2 inhibition (SGLT-2i). SGLT-2i combination therapies improved glucose homeostasis, independent of changes in body weight, resulting in a synergistic increase in pancreatic insulin content marked by significant recovery of the β-cell mature insulin secretory population but with limited changes in β-cell mass and no indication of β-cell dedifferentiation. Restoration of β-cell insulin secretory capacity also restored biphasic insulin secretion. These data emphasize that by therapeutically alleviating the demand for insulin in vivo, irrespective of weight loss, endogenous β-cells recover significant function that can contribute to attenuating diabetes. Thus, this study provides evidence that alleviation of metabolic demand on the β-cell, rather than targeting the β-cell itself, could be effective in delaying the progression of T2D.


Reliable and repeatable characterization of optical streak cameras.
Optical streak cameras are used as primary diagnostics for a wide range of physics and laser experiments at facilities such as the National Ignition Facility. To meet the strict accuracy requirements needed for these experiments, the systematic nonlinearities of the streak cameras (attributed to nonlinearities in the optical and electrical components that make up the streak camera system) must be characterized. In some cases the characterization information is used as a guide to help determine how experiment data should be taken. In other cases, the characterization data are applied to the raw data images to correct for the nonlinearities. In order to characterize an optical streak camera, a specific set of data is collected, where the response to defined inputs are recorded. A set of analysis software routines has been developed to extract information such as spatial resolution, dynamic range, and temporal resolution from this data set. The routines are highly automated, requiring very little user input and thus provide very reliable and repeatable results that are not subject to interpretation. An emphasis on quality control has been placed on these routines due to the high importance of the camera characterization information.


Glucosamine Modulates T Cell Differentiation through Down-regulating N-Linked Glycosylation of CD25.
Glucosamine has immunomodulatory effects on autoimmune diseases. However, the mechanism(s) through which glucosamine modulates different T cell subsets and diseases remain unclear. We demonstrate that glucosamine impedes Th1, Th2, and iTreg but promotes Th17 differentiation through down-regulating N-linked glycosylation of CD25 and subsequently inhibiting its downstream Stat5 signaling in a dose-dependent manner. The effect of glucosamine on T helper cell differentiation was similar to that induced by anti-IL-2 treatment, further supporting an IL-2 signaling-dependent modulation. Interestingly, excess glucose rescued this glucosamine-mediated regulation, suggesting a functional competition between glucose and glucosamine. High-dose glucosamine significantly decreased Glut1 N-glycosylation in Th1-polarized cells. This finding suggests that both down-regulated IL-2 signaling and Glut1-dependent glycolytic metabolism contribute to the inhibition of Th1 differentiation by glucosamine. Finally, glucosamine treatment inhibited Th1 cells in vivo, prolonged the survival of islet grafts in diabetic recipients, and exacerbated the severity of EAE. Taken together, our results indicate that glucosamine interferes with N-glycosylation of CD25, and thereby attenuates IL-2 downstream signaling. These effects suggest that glucosamine may be an important modulator of T cell differentiation and immune homeostasis.


[Computation of mixed venous oxygen saturation in intracardial shunts and its dependence on age, anesthesia and premedication].
In patients with an intracardiac shunt, the oxygen saturation of the mixed venous blood cannot be measured, but it must be estimated from the oxygen saturation in the superior and in the inferior vena cava. We have evaluated the results of patients who had definitively no shunt and who had been catheterized for other reasons. Based on statistical principles we developed formulas to calculate the oxygen saturation of the mixed venous blood. We examined three group of patients: a) Children up to 11 years catheterized during general anaesthesia (58 patients) b) Children up to 11 years catheterized after premedication but without general anaesthesia (53 patients) c) Adults catheterized without general anaesthsia (59 patients) We found that the formulas from the patients who had been catheterized during general anaesthesia were quite different from those without anaesthesia. In the patients without an anaesthesia the superior vena cava was coupled with a much higher factor than the inferior vena cava; in patients with anaesthesia, the contribution of the inferior vena cava was stronger. The age of the patients had no significant influence on our formulas.


Family History of Type 2 Diabetes: Does Having a Diabetic Parent Increase the Risk?
It is well established that there is an important genetic predisposition for type 2 diabetes mellitus (T2DM). To summarise available epidemiological data regarding T2DM transmission in various populations. Narrative review. The estimated risk for the diagnosis of T2DM increases approximately by 2-4 times, when father, mother or both have this condition. Conversely, many T2DM patients have family members with DM. Studies have suggested that the likelihood of T2DM in the next generation is higher in the event of a diabetic mother than father. Both genetic factors, such as mitochondrial DNA mutations, and environmental components, such as intra-uterine environment, have been implicated in the higher maternal transmission of T2DM. Despite the above findings, some studies in populations with high frequency of T2DM have not corroborated the predominantly maternal transmission. Such works have shown either an excess paternal or an equal transmission of T2DM. It appears that potential biases in reporting family history data, especially between the various racial groups, have contributed to the controversy over the existence of excess maternal transmission of DM.


[Palindromic sequence-mediated de novo chromosome translocation in sperm samples derived from normal and oligospermic males].
To systematically explore the occurrence of a novel type of chromosome translocation in human sperm samples. Specific translocation junction fragments were quantified using nested and/or multi-nested PCR in sperm DNA derived from 28 oligospermic patients and 32 normal controls. t(11;22) was detected in 49 samples. At least 4 samples were found to have t(1;22) (p21.2;q11.2), t(17;22) (q11;q11) or t(X;22) (q27;q11). The mutation rate seemed to be associated not with age or semen volume, but with sperm concentration (r = -0.389, P < 0.05) and motility (r = -0.397, P < 0.05). Correlation was not found between homology of palindromic sequences and mutation rate. Palindromic sequence mediated chromosome translocation is common in human sperm, and associated with sperm concentration and motility. Measurement of such mutations may provide a molecular-level reference for assessing sperm quality.


Kinetics of interleukin 2 mRNA and protein produced in the human T-cell line Jurkat and effect of cyclosporin A.
The kinetics of interleukin 2 mRNA accumulation in the leukemic T-cell line Jurkat, which can be induced with phytohemagglutinin and phorbol 12-myristate 13-acetate to produce large amounts of interleukin 2, was analyzed by a modified DNA-excess solution hybridization assay using a 5'-32P-labeled oligodeoxyribonucleotide 30 bases long as probe. Cyclosporin A was used as a valuable tool to gain more insight into the quantitative aspects of interleukin 2 production, on the basis of the assumption that transcription of the interleukin 2 gene is completely inhibited shortly after administration of cyclosporin A. The half-life of interleukin 2 mRNA was estimated to be approximately 2 h. With the aid of simple mathematical models, we have been able to relate the concentration of interleukin 2 protein in the supernatant to the interleukin 2 mRNA kinetics. This novel quantitative kinetic analysis revealed that, independent of the absence or presence of cyclosporin A, interleukin 2 protein is synthesized at a rate of approximately 1.3 molecules per molecule of interleukin 2 mRNA per second and secreted within 2 h after it is synthesized and that its half-life in the supernatant is approximately 10 h.


The level of household satisfaction with community-based health insurance and associated factors in Southern Ethiopia.
Community-based health insurance (CBHI) is a program intended to prevent financial hardship brought on by the cost of medical care. All of Ethiopia's regions are implementing it; however, it has not yet been researched how the program is being received by the local population. This study's objective is to determine how satisfied Southern Ethiopian households are with community-based health insurance programs and connected variables. A community-based cross-sectional study was conducted from April to May 2021. Information was gathered from 528 households (HHs) selected at random in the Gurage Zone of Southern Ethiopia using a questionnaire. Bivariate and multivariate logistic regression, as well as descriptive statistics, were applied. p values less than 0.05 was used as a cutoff point for identifying the self-determining factors. The adjusted odds ratio (AOR) for HHs with the poorest wealth status was 2.40 (95% confidence interval:1.14-4.90); for HHs with a good knowledge of the CBHI, it was 1.81 (95% CI: 1.87-3.40); and for households with illness in the past 3 months, it was 5.22 (95% CI: 2.91-9.34). Recurrent visits to the facility (AOR:5.04, 95% CI:1.18-23.44), a Model household in rural health extension program (AOR:3.21, 95% CI:1.76-5.85), being enrolled in the scheme for three years or less (AOR:0.55, 95% CI: 0.30-0.95), and having faith in the leadership of the governing board (AOR:10.53, 95% CI:4.690-23.54) and the availability of the prescribed medication (AOR:14.64, 95% CI:5.37-39.84) were the significant influencing factors. This study revealed several variables that affected HHs' satisfaction with CBHI. We strongly advise all responsible parties to focus on increasing HH knowledge of the CBHI scheme, supporting HHs to serve as role models for rural health extension packages, and completing the CBHI pledged package to improve HHs' satisfaction with the CBHI scheme, which may then play a role in the sustainability of CBHI.


Inflammation and C-reactive protein in atrial fibrillation: cause or effect?
Atrial fibrillation is associated with substantial morbidity and mortality rates. The incompletely understood pathogenesis of this cardiac dysrhythmia makes it difficult to improve approaches to primary and secondary prevention. Evidence has accumulated in regard to a relationship between inflammation and atrial fibrillation. Investigators have correlated the dysrhythmia with myocarditis, pericardiotomy, and C-reactive protein levels, suggesting that inflammation causes atrial fibrillation or participates in its onset and continuation. Conversely, other investigators suggest that atrial fibrillation induces an inflammatory response. In this review, we summarize and critically discuss the nature and clinical role of inflammation and C-reactive protein in atrial fibrillation.


Chyluria: the state of the art.
Chyluria is the passage of chyle in the urine. The cause seems to be the rupture of retroperitoneal lymphatics into the pyelocaliceal system, giving urine a milky appearance. This communication is caused by the obstruction of lymphatic drainage proximal to intestinal lacteals, resulting in dilatation of distal lymphatics and the eventual rupture of lymphatic vessels into the urinary collecting system.This condition, if left untreated, leads to significant morbidity because of hematochyluria, recurrent renal colic, nutritional problems due to protein losses and immunosuppression resulting from lymphocyturia.In this review, we summarize the state of the art of this condition and the newest treatments available.


Thrombin modulates vectorial secretion of extracellular matrix proteins in cultured endothelial cells.
We have identified a novel cellular action of thrombin on cultured rat adrenal medullary endothelial cells (RAMEC). Five-minute incubation of RAMEC with physiological concentrations of thrombin (<1 U/ml) caused within 3 h an increase in the basolateral deposition of the extracellular matrix (ECM) proteins fibronectin, laminin, and collagens IV and I, concomitant with a corresponding decrease in the apical release of these proteins into the medium. This shift in vectorial secretion of ECM proteins, quantitated with enzyme-linked immunoassays, was time dependent. Maximal stimulation of ECM protein deposition was observed after incubation of cells with thrombin for 5-15 min. Prolonged exposure (>1 h) to thrombin resulted in loss of proteins from the ECM. Thrombin-stimulated ECM protein deposition exhibited a bell-shaped dose dependence, peaking for all proteins at 0.25 U/ml of thrombin, and was independent of de novo mRNA or protein synthesis. Maximal amounts of deposited proteins increased between 2.5-fold (fibronectin) and 4-fold (collagen I) over baseline values. Similar results were obtained with thrombin receptor agonist peptide (TRAP), proteolytically active gamma-thrombin, and, to a lesser extent, other serine proteases such as trypsin and plasmin. A scrambled TRAP, proteolytically inactive PPACK-thrombin, DIP-thrombin, and type IV collagenase were ineffective. Together, these results suggest that the thrombin effects are mediated by proteolytic activation of the thrombin receptor. Possible involvement of the phospholipase C-signaling pathway in thrombin-mediated ECM protein deposition was also investigated. Inhibition or downregulation of protein kinase C (PKC) and chelation of intracellular or extracellular Ca2+ did not suppress, but rather enhanced, basal and thrombin-stimulated ECM protein deposition. Quantitative differences in augmentation of basolateral deposition by these treatments suggest differential regulatory pathways for individual ECM proteins. Our data indicate that, in cultured RAMEC, short-term activation of the thrombin receptor causes an increase in amounts of deposited ECM protein by a cellular signaling pathway that is independent of PKC activation and/or elevation of intracellular Ca2+.


A simple method for point-of-need extraction, concentration and rapid multi-mycotoxin immunodetection in feeds using aqueous two-phase systems.
The rapid detection of mycotoxins in feed samples is becoming an increasingly relevant challenge for the food production sector, in order to effectively enforce current regulations and assure food and feed safety. To achieve rapid mycotoxin detection, several biosensing strategies have been published, many reaching assay times of the order of a few minutes. However, the vast majority of these rely on sample preparation based on volatile organic solvents, often comprising complex multi-step procedures and devoid of clean-up and/or concentration effects. Here, a novel sample preparation methodology based on a green, non-toxic and inexpensive polyethylene glycol-sodium citrate aqueous two-phase system is reported, providing single-step extraction and concentration of three target mycotoxins within 20min: aflatoxin B1 (AFB1), ochratoxin A (OTA) and deoxynivalenol (DON). With point-of-need applications in mind, the extraction procedure was optimized and validated using a rapid multi-toxin microfluidic competitive immunoassay. The assay was successfully tested with spiked complex solid matrices including corn, soy, chickpea and sunflower-based feeds and limits of detection of 4.6ngg-1±15.8%, 24.1ngg-1±8.1% and 129.7ngg-1±53.1% (±CV) were obtained in corn for AFB1, OTA and DON, respectively. These sensitivities are fit-for-purpose at the required regulatory and recommended limits for animal feed, providing an effective and safe semi-quantitative mycotoxin analysis that can be performed in the field.


Suicidality among university students in the Eastern Mediterranean region: A systematic review.
The prevalence of suicide attempts and suicidal ideation among university students is a global concern. Cultural values, social determinants, religion, and especially growing stress all play an important role in this. This systematic review aimed to identify potential protective and risk factors thought to be associated with suicidal ideation among students in the Eastern Mediterranean region and highlight the importance of developing an effective health care response. MEDLINE, CINAHL, Embase, PsycINFO, WHO Global Health Library, IMEMR, Web of Science Core Collections and Farsi and Arabic databases were searched for papers in English, Farsi, and Arabic. A combination of validated filters, free text keywords, and Mesh and Non-Mesh terms were used to retrieve relevant literature. A total of 2774 papers were found after the search, 257 selected for full-text review, and 72 papers included in the final review. Family and peer support play a potential protective role in the development of suicidal ideation among university students, while adverse life events, bullying, depression, anxiety, and other mental health conditions were identified as risk factors. Suicidality was likely under-reported due to stigma around social and cultural factors. Factors involving religion and culture may act as both protective and risk factors and require more in-depth investigation. The student population in the Eastern Mediterranean region face many challenges. The common theme of suicidality emerged as an indicator of an imbalance of resources and stress, which needs to be addressed proactively, given a most likely underreporting of suicidal ideation and attempts due to stigma.


[Hesnard, educator].
The vast majority of analysts maintain considerable distance between themselves and their patients. Above all, they do not allow themselves to be educators, with the exception of didacticians who voluntarily assume this role. But they are deluding themselves in believing that they can escape the educational role, when their entire effort has the objective of making their patients masters of their drives. Neither Freud nor A. Hesnard committed such an error. Both of them assumed their role as educators.


Hysteresis in the random-field Ising model and bootstrap percolation.
We study hysteresis in the random-field Ising model with an asymmetric distribution of quenched fields, in the limit of low disorder in two and three dimensions. We relate the spin flip process to bootstrap percolation, and show that the characteristic length for self-averaging L small star, filled increases as exp[exp(J/Delta)] in 2D, and as exp(exp[exp(J/Delta)]) in 3D, for disorder strength Delta much less than the exchange coupling J. For system size 1<<L<L small star, filled, the coercive field h(coer) varies as 2J-DeltalnlnL for the square lattice, and as 2J-DeltalnlnlnL on the cubic lattice. Its limiting value is 0 for L-->infinity for both square and cubic lattices. For lattices with coordination number 3, the limiting magnetization shows no jump, and h(coer) tends to J.


Photoionization studies of sulfur radicals and products of their reactions.
A discharge flow-photoionization mass spectrometric system coupled to a synchrotron is employed to study intermediates and products of sulfur radical reactions related to atmospheric chemistry. Sulfur radicals are generated from reactions of oxygen or chlorine atoms with sulfur compounds in a flow tube. The gaseous reaction products are sampled into the ionization region via a three-stage differential pumping scheme. Photoionization spectra and ionization energies are measured by dispersing synchrotron radiation to ionize the samples. Using this technique, photoionization spectra and ionization energies of HSO, CH(3)SO, C(2)H(5)SO, HSCl, and some secondary reaction products, SSCl, HSSCl, HSSSH, CH(3)SOH and CH(3)SS(O)CH(3), were measured for the first time.


Best intentions or best practice? A case study of the nutritional needs and outcomes of a person with dementia living in a residential aged care home.
To evaluate the nutritional status and needs of a person with dementia living in an aged care home, including identification of barriers to, and effective strategies for, the provision of person-centred care. Nutrition and hydration care are integral to quality of life for adults with dementia, but there is little research on whether staff knowledge around effective care strategies for residents is translated into optimal care. Focused ethnographic single-case design. The perspectives of the resident, her prime family member, and six care staff were triangulated through interviews, observation, document audit, and medical file review to investigate the resident's nutrition and hydration status and needs (October 2014-April 2015). During 3 years in care, this resident had lost weight steadily. Staff appeared attentive but did not maintain a systematic record of body mass index. At meals, staff encouraged eating but used ineffective strategies. Food was not served in ways that facilitated active participation. Eating and drinking were structured as tasks to be completed rather than activities to be enjoyed. This instrumental case study identified a task-oriented, rather than person-centred, approach to nutrition and hydration care, adversely affecting the resident's nutritional health and capability to participate actively.


Mucin levels in glands of the colonic mucosa of rats with diversion colitis subjected to enemas containing sucralfate and n-acetylcysteine alone or in combination.
To evaluate the tissue content of neutral and acidic mucins, sulfomucins and sialomucins in colonic glands devoid of intestinal transit after enemas containing sucralfate and n-acetylcysteine alone or in combination. Sixty-four rats underwent intestinal transit bypass. A colonic segment was collected to compose the white group (without intervention). After derivation, the animals were divided into two groups according to whether enemas were performed daily for two or four weeks. Each group was subdivided into four subgroups according to the substance used: control group: saline 0.9%; sucralfate group (SCF): SCF 2 g/kg/day; n-acetylcysteine group (NAC): NAC 100 mg/kg/day; and SCF+NAC group: SCF 2 g/kg/day + NAC 100 mg/kg/day.Neutral and acidic mucins were stained by periodic acid-Schiff and alcian-blue techniques, respectively. The distinction between sulfomucins and sialomucin was made by the high alcian-blue iron diamine technique. The content of mucins in the colonic glands was measured by computerized morphometry. The inflammatory score was assessed using a validated scale. The results between the groups were compared by the Mann-Whitney's test, while the variation according to time by the Kruskal-Wallis' test (Dunn's post-test). A significance level of 5% was adopted. There was reduction in the inflammatory score regardless of the application of isolated or associated substances. Intervention with SCF+NAC increased the content of all mucin subtypes regardless of intervention time. The application of SCF+NAC reduced the inflammatory process of the colonic mucosa and increased the content of different types of mucins in the colonic glands of segments excluded from fecal transit.


Predictors and a remedy for noncompliance with amblyopia therapy in children measured with the occlusion dose monitor.
Noncompliance is one of the limiting factors in the success of occlusion therapy for amblyopia. Electronic monitoring was used to investigate predictors of noncompliance, and, in a prospective randomized clinical trial, determined the effectiveness of an educational program. Compliance was measured electronically during 1 week every 3 months in 310 newly diagnosed amblyopic children. The family's demographic parameters and the child's clinical parameters were assessed for their influence on the level of compliance. In addition to standard orthoptic care, children were randomized to receive an educational cartoon story, reward stickers, and an information sheet for the parents (intervention group), or a picture to color (reference group). These and the electronic device were distributed during home visits by researchers. The primary outcome measure was the percentage of compliance (actual/prescribed occlusion time) in the two groups. The secondary outcome measure was the influence of demographic and clinical factors on compliance. Compliance was associated with parental fluency in the national language, country of origin, level of education, and initial visual acuity of the child. During the first 1-week measurement period children in the intervention group had better compliance than the reference group had (78% +/- 32% vs. 57% +/- 40%; P < 0.0001), and fewer children were not occluded at all (3 vs. 23 in the reference group; P < 0.0001). This difference remained throughout the study period. Poor parental fluency in the national language, a low level of education, and poor acuity at the start of treatment were predictors of low compliance. An educational program primarily aimed at the child improved compliance and reduced the number of children who did not comply with occlusion at all.


P120 catenin is associated with desmogleins when desmosomes are assembled in high-Ca2+ medium but not when disassembled in low-Ca2+ medium in DJM-1 cells.
We recently showed that p120 catenin (p120ctn), which is an armadillo family protein member that binds to E-cadherin (E-cad), is also localized to desmosomes by directly or indirectly binding to desmogleins (Dsg). We examined whether p120ctn is associated with Dsg1 and Dsg3, as compared with E-cad and plakoglobin (PG), in keratinocytes grown in high or low Ca2+, using a human squamous cell carcinoma cell line, DJM-1 cells. The cell lysate of DJM-1 cells grown in high- or low-Ca2+ media was immunoprecipitated with anti-Dsg1/2 and Dsg3 antibodies, and we examined whether p120ctn is associated with Dsg1 and Dsg3. Then, we observed the co-localization between Dsg3 and p120ctn in cells grown in high- or low-Ca2+ medium on double-staining immunofluorescence microscopy using anti-p120ctn and anti-Dsg3 antibodies. Immunoprecipitates with anti-Dsg1/2 and Dsg3 antibodies in cells grown in high-Ca2+ medium contained p120ctn. In contrast, in low-Ca2+ medium, p120ctn was co-immunoprecipitated with neither Dsg1 nor Dsg3, but was co-immunoprecipitated with E-cad in cells grown in both high- and low-Ca2+ media. Dsg3 was associated with PG in cells grown in both low- and high-Ca2+ media. On immunofluorescence microscopy, p120ctn and Dsg3 were independently observed in cells grown in low-Ca2+ medium; p120ctn, but not Dsg3, was observed in a linear pattern at the cell-cell boundary. However, they were co-localized at cell-cell contacts in cells grown in high-Ca2+ medium. Thus, these proteins are not co-localized in low Ca2+ medium. These results suggest that p120ctn plays an important role in Ca2+-induced desmosome formation.


Clinical heterogeneity in retinitis pigmentosa caused by variants in RP1 and RLBP1 in five extended consanguineous pedigrees.
The aim of this study is to identify disease-causing variants in five consanguineous Jordanian families with a history of autosomal recessive retinitis pigmentosa (RP), and to investigate the clinical variability across the affected individuals. Exome sequencing (ES) and ophthalmic examinations were performed to classify the underlying RP-causative variants and their pathogenic consequences. The candidate variants in the affected and unaffected family members underwent segregation analyses with Sanger sequencing. We described four variants in the RP1 and RLBP1 genes as disease-causing across the five families, including novel (c.398delC; p.Pro133GlnfsTer126) and recurrent (c.79delA; p.Thr27ProfsTer26) variants in RLBP1 and two previously reported variants in RP1 ((c.1126C>T; p.Arg376Ter) and (c.607G>A; p.Gly203Arg)). The consequent clinical manifestations were thoroughly investigated using a battery of ophthalmic tests, including electroretinography (ERG), optical coherence tomography (OCT), visual acuity (VA), and fundus examination. The phenotypes indicated clinical heterogeneity, typical RP for variants in RP1, and retinitis punctata albescens (RPA) for variants in RLBP1. This study extends the pathogenic variant spectrum for the RP1 and RLBP1 genes. The study also revealed the consequent clinical progression, severity, and presentation of RP. Furthermore, we confirm that ES is an efficient molecular diagnostic approach for RP.


An assessment of environmental contamination arising from the use of some automated equipment in microbiology.
The generation of aerosols and the contamination of surfaces arising from some equipment used to automate tasks in the microbiology laboratory have been assessed using a microbiological test method. When used for the designed purposes none of the equipment is likely to present any significant aerosol hazard. Some of the equipment gave rise to surface contamination, and it is recommended that decontamination of work surfaces should be carried out at frequent intervals.


Incorporating equity in economic evaluations: a multi-attribute equity state approach.
In publicly funded health care systems, decision makers must continually balance often conflicting priorities of efficiency and equity. Health economists have developed a set of highly sophisticated analytical methods for assessing efficiency, but less attention has been paid to formally incorporating equity considerations into analyses. As a result, where equity is considered is often informal, ad hoc and/or simplistic. This paper is a proposal for a mechanism for formally incorporating equity within the decision process. It begins with an overview of the current literature on equity weighting. It then considers the case of a single equity domain and illustrates how this is currently applied in practice by the UK's National Institute for Health and Care Excellence. It then proposes a more comprehensive method for considering the multi-attribute equity state, where a population exhibits more than one trait considered worthy of differential weighting. Finally, the paper proposes a mechanism by which this could be applied in practice, and concludes with a discussion of the challenges for applying multi-attribute equity weighting.


Meta-Analysis: Placebo Response and Its Determinants in Functional Dyspepsia.
Placebo response rates are relatively higher in clinical trials of disorders of brain-gut interaction. However, placebo response in functional dyspepsia (FD) has not been well described. Minimizing placebo response is important in drug development. We therefore conducted a meta-analysis to determine placebo response in trials for FD and to identify factors affecting placebo response rates. PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials were searched to identify double-blinded randomized controlled trials (RCTs) comparing medication with placebo in patients with FD. Both symptom improvement and complete relief were considered as separate primary endpoints in the analysis. Proportions of placebo patients experiencing any symptom improvement or complete relief were calculated. Dropouts after randomization for any reason were assumed to represent treatment failure for data extraction and analysis. Placebo response was pooled by a random-effects model, and effects of trial characteristics on the magnitude of placebo response were evaluated. In 58 eligible placebo-controlled RCTs of FD from 52 selected citations, 6,732 of 17,890 participants in all trials received placebo. Pooled placebo response rates for symptom improvement and complete relief were 44.3% and 15.6%, respectively. The placebo response rate was lower when improvements were assessed for ≥8 weeks. Trials assessing complete symptom relief showed lower placebo response rates even in trials for <8 weeks. Our systematic review and meta-analysis showed that pooled placebo response rates in double-blinded RCTs of FD depended on efficacy criteria. Trials assessing complete symptom relief showed stable low placebo response rates in short-term trials.


Activation of Epithelial Signal Transducer and Activator of Transcription 1 by Interleukin 28 Controls Mucosal Healing in Mice With Colitis and Is Increased in Mucosa of Patients With Inflammatory Bowel Disease.
We investigated the roles of interleukin 28A (also called IL28A or interferon λ2) in intestinal epithelial cell (IEC) activation, studying its effects in mouse models of inflammatory bowel diseases (IBD) and intestinal mucosal healing. Colitis was induced in C57BL/6JCrl mice (controls), mice with IEC-specific disruption of Stat1 (Stat1IEC-KO), mice with disruption of the interferon λ receptor 1 gene (Il28ra-/-), and mice with disruption of the interferon regulatory factor 3 gene (Irf3-/-), with or without disruption of Irf7 (Irf7-/-). We used high-resolution mini-endoscopy and in vivo imaging methods to assess colitis progression. We used 3-dimensional small intestine and colon organoids, along with RNA-Seq and gene ontology methods, to characterize the effects of IL28 on primary IECs. We studied the effects of IL28 on the human intestinal cancer cell line Caco-2 in a wound-healing assay, and in mice colon wounds. Colonic biopsies and resected tissue from patients with IBD (n = 62) and patients without colon inflammation (controls, n = 23) were analyzed by quantitative polymerase chain rection to measure expression of IL28A, IL28RA, and other related cytokines; biopsy samples were also analyzed by immunofluorescence to identify sources of IL28 production. IECs were isolated from patient tissues and incubated with IL28; signal transducer and activator of transcription 1 (STAT1) phosphorylation was measured by immunoblots and confocal imaging. Lamina propria cells in colon tissues of patients with IBD, and mice with colitis, had increased expression of IL28 compared with controls; levels of IL28R were increased in the colonic epithelium of patients with IBD and mice with colitis. Administration of IL28 induced phosphorylation of STAT1 in primary human and mouse IECs, increasing with dose. Il28ra-/-, Irf3-/-, Irf3-/-Irf7-/-, as well as Stat1IEC-KO mice, developed more severe colitis after administration of dextran sulfate sodium than control mice, with reduced epithelial restitution. Il28ra-/- and Stat1IEC-KO mice also developed more severe colitis in response to oxazolone than control mice. We found IL28 to induce phosphorylation (activation) of STAT1 in epithelial cells, leading to their proliferation in organoid culture. Administration of IL28 to mice with induced colonic wounds promoted mucosal healing. IL28 controls proliferation of IECs in mice with colitis and accelerates mucosal healing by activating STAT1. IL28 might be developed as a therapeutic agent for patients with IBD.


Kikuchi-Fujimoto disease in Nepal: a study of 6 cases.
Kikuchi-Fujimoto disease is a benign disorder, predominantly affecting young women with a predilection for cervical lymphadenopathy. Although the disease has been recognized worldwide, to our knowledge no cases have been reported previously from Nepal. To determine the prevalence of Kikuchi-Fujimoto disease in Nepal and to analyze clinicopathologic features. We reviewed 6 cases of Kikuchi-Fujimoto disease recorded at 3 different hospitals in Nepal during a period from June 1998 to June 2002. Clinical data and histopathology are presented. This study included 5 females and 1 boy, aged 13 to 32 years. These patients presented with prolonged fever and lymphadenopathy. The 5 female patients had cervical lymphadenopathy, and the boy had axillary lymphadenopathy. Complete blood counts revealed raised erythrocyte sedimentation rates in all patients and anemia in 2 patients. The size of excised lymph nodes (in greatest dimension) ranged from 1.5 to 5 cm. Typical histologic features were seen, namely, architectural effacement due to presence of pale nodular lymphohistiocytic foci with karyorrhectic debris, coagulation necrosis, eosinophilic debris, and absence of granulocytic infiltration. In a follow-up of the cases, disease recurrence was not found. Our study emphasizes that Kikuchi-Fujimoto disease should be considered as one of the differential diagnoses in patients with prolonged fever and cervical lymphadenopathy and that it should be differentiated from tuberculous lymphadenitis in regions where tuberculosis is prevalent.


Small intestinal response to 'elemental' and 'complete' liquid feeds in the rat: effect of dietary bulk.
The effect of oral isocaloric feeding on small intestinal structure and function was studied in the rat. The liquid 'elemental' enteral feed Vivonex HN, the liquid 'complete' feed Ensure and the same liquid complete feed with 9% bulk Enrich were compared with solid chow containing 21% bulk (normal rat chow), all given for four weeks. Weight gain was significantly less in the group fed Vivonex HN than that of any other groups. The bulkless Vivonex HN and Ensure increased proximal jejunal mass compared to Enrich with 9% bulk or to normal rat chow. Jejunal mucosal DNA and protein levels also tended to be higher in Ensure and Vivonex HN fed animals, as was jejunal sugar absorption. In the terminal ileum, however, total weight was decreased by both elemental and complete feeds with and without bulk, but particularly by the elemental diet. Bulkless feeds therefore increase jejunal and reduce terminal ileal mass. The striking atrophy of the terminal ileum produced by the elemental diet may be important for its efficacy in treating inflammatory bowel disease.


Connexin43 enhances the expression of osteoarthritis-associated genes in synovial fibroblasts in culture.
Recent work has shown that the gap junction protein connexin43 (Cx43) is upregulated in cells of the joint during osteoarthritis (OA). Here we examined if the OA-associated increase in Cx43 expression impacts the function of synovial fibroblasts by contributing to the production of catabolic and inflammatory factors that exacerbate joint destruction in arthritic disease. Using rabbit and human synovial fibroblast cell lines, we examined the effects of Cx43 overexpression and Cx43 siRNA-mediated knockdown on the gene expression of OA-associated matrix metalloproteinases (MMP1 and MMP13), aggrecanases (ADAMTS4 and ADAMTS5), and inflammatory factors (IL1, IL6 and PTGS2) by quantitative real time RT-PCR. We examined collagenase activity in conditioned media of cultured synovial cells following Cx43 overexpression. Lastly, we assessed the interplay between Cx43 and the NFκB cascade by western blotting and gene expression studies. Increasing Cx43 expression enhanced the gene expression of MMP1, MMP13, ADAMTS4, ADAMTS5, IL1, IL6 and PTGS2 and increased the secretion of collagenases into conditioned media of cultured synovial fibroblasts. Conversely, knockdown of Cx43 decreased expression of many of these catabolic and inflammatory genes. Modulation of Cx43 expression altered the phosphorylation of the NFκB subunit, p65, and inhibition of NFκB with chemical inhibitors blocked the effects of increased Cx43 expression on the mRNA levels of a subset of these catabolic and inflammatory genes. Increasing or decreasing Cx43 expression alone was sufficient to alter the levels of catabolic and inflammatory genes expressed by synovial cells. The NFκB cascade mediated the effect of Cx43 on the expression of a subset of these OA-associated genes. As such, Cx43 may be involved in joint pathology during OA, and targeting Cx43 expression or function may be a viable therapeutic strategy to attenuate the catabolic and inflammatory environment of the joint during OA.


Molecular interaction between projection neuron precursors and invading interneurons via stromal-derived factor 1 (CXCL12)/CXCR4 signaling in the cortical subventricular zone/intermediate zone.
Most cortical interneurons are generated in the subpallial ganglionic eminences and migrate tangentially to their final destinations in the neocortex. Within the cortex, interneurons follow mainly stereotype routes in the subventricular zone/intermediate zone (SVZ/IZ) and in the marginal zone. It has been suggested that interactions between invading interneurons and locally generated projection neurons are implicated in the temporal and spatial regulation of the invasion process. However, so far experimental evidence for such interactions is lacking. We show here that the chemokine stromal-derived factor 1 (SDF-1; CXCL12) is expressed in the main invasion route for cortical interneurons in the SVZ/IZ. Most SDF-1-positive cells are proliferating and express the homeodomain transcription factors Cux1 and Cux2. Using MASH-1 mutant mice in concert with the interneuron marker DLX, we exclude that interneurons themselves produce the chemokine in an autocrine manner. We conclude that the SDF-1-expressing cell population represents the precursors of projection neurons during their transition and amplification in the SVZ/IZ. Using mice lacking the SDF-1 receptor CXCR4 or Pax6, we demonstrate that SDF-1 expression in the cortical SVZ/IZ is essential for recognition of this pathway by interneurons. These results represent the first evidence for a molecular interaction between precursors of projection neurons and invading interneurons during corticogenesis.


Research network involvement and addiction treatment center staff: counselor attitudes toward buprenorphine.
The National Institute on Drug Abuse's Clinical Trials Network (CTN) aims to improve addiction treatment in the United States in part through technology transfer. Given the importance of clinicians in the technology transfer process, this research compares 561 CTN-affiliated and 1,745 non-CTN counselors' ratings of buprenorphine acceptability. CTN-affiliated counselors reported significantly greater acceptability than non-CTN counselors. This difference was not explained by controlling for counselor characteristics, but was completely attenuated by measures of buprenorphine-specific training and buprenorphine implementation. These data suggest that the CTN's impact on counselor attitudes may be attributed to the greater exposure to buprenorphine received by CTN-affiliated counselors.


Psychotropic Medication and Substance Use during Pregnancy by Women with Severe Mental Illness.
Sociodemographic factors, alcohol and drug intake, and maternal health are known to be associated with adverse outcomes in pregnancy for women with severe mental illness in addition to their use of psychotropic medication. In this study, we describe the demographic characteristics of women hospitalized for severe mental illness along with their use of medication and other drugs during the pregnancy period. A clinical case note review of women with psychosis who were hospitalized at the State Psychiatric Hospital in Western Australia during 1966-1996, gave birth between 1980 and 1992, and received psychiatric treatment during the pregnancy period. The mother's clinical information was available from the case notes and the midwives record. The demographic characteristics of the mothers were described together with their hospitalization pattern and their medication and substance use during the pregnancy period. A total of 428 mothers with a history of severe mental illness were identified who gave birth during 1980-1992. Of these, 164 mothers received psychiatric care during the pregnancy period. One hundred thirty-two had taken psychotropic medication during this period. Mothers who were married, of aboriginal status or living in regional and remote areas appeared less likely to be hospitalized during the pregnancy period, while older mothers and those with a diagnosis of schizophrenia were more likely to be hospitalized. The number of mothers taking psychotropic medication in the first trimester of pregnancy was reduced compared to the previous 6 months. The decline in the number taking substances over the same period was not significant. In all, 16% of the women attempted suicide during the pregnancy period and 10% non-suicidal self-injury. The women demonstrate a pattern of decreased use of psychotropic medication use from the period before pregnancy to the first trimester of pregnancy. Our data highlight the importance of women with severe mental illness receiving regular ongoing monitoring and support from their psychiatrist during pregnancy regarding the level of medication required as well as counseling with regard to substance use, non-suicidal self-injury, and attempted suicide.


A nucleic acid biosensor for gene expression analysis in nanograms of mRNA.
An ultrasensitive nucleic acid biosensor for direct detection of genes in mRNA extracted from animal tissues is described. It is based on amperometric detection of a target gene by forming an mRNA/redox polymer bilayer on a gold electrode. The mRNA was directly labeled with cisplatin-biotin conjugates through coordinative bonds with purine bases in the mRNA molecules. A subsequent binding of glucose oxidase-avidin conjugates to the labeled mRNA and the introduction of a poly(vinylimidazole-co-acrylamide) partially imidazole-complexed with [Os(bpy)(2)(im)] (bpy = 2,2'-bipyridine, im = imidazole) redox polymer overcoating to the electrode allowed for electrochemical detection of the oxidation current of glucose in solution. Depending on individual genes, detection limits of subfemtograms were achieved. As compared to a sandwich-type assay, the sensitivity was improved by as much as 25-fold through the incorporation of multiple enzyme labels to the mRNA molecules. Less than 2-fold gene expression difference was unambiguously differentiated in as little as 5.0 ng of mRNA. With the greatly improved sensitivity, at least 1000-fold more sensitive than fluorescence-based techniques, the amount of mRNA needed in the assay was cut down from microgram to nanogram levels.


Accumulation and risk assessment of heavy metals in water, sediments, and aquatic organisms in rural rivers in the Taihu Lake region, China.
Concentrations of heavy metals (Cd, Cr, Cu, Ni, Pb, and Zn) were measured in water, sediments, Ceratophyllum (hornwort), and Bellamya sp. (edible snail) from residential, mixed (industrial and commercial), and agricultural areas with rural rivers in the Taihu Lake region, China. Zn concentrations were the highest, whereas Cd concentrations were the lowest among the six metals in water, sediments, and aquatic organisms. Cd was mainly present in the acid-soluble fraction, Cr in the residual fraction, and Pb in the reducible fraction of sediments. Heavy metal concentrations in water, sediments, and aquatic organisms in the three areas followed the order of the mixed area > residential area > agricultural area. Heavy metal concentrations in aquatic organisms were not only related to total metal concentrations in water and sediments but also to metal speciation concentrations in sediments. In addition, the bio-concentration factor (BCF) values of Cr, Cu, Pb, and Zn for Bellamya sp. were higher than those for Ceratophyllum, whereas the BCF values of Cd and Ni for Bellamya sp. were lower than those for Ceratophyllum. An ecological risk assessment of heavy metals in sediments showed that Cd posed the highest ecological risk to the environment. A health risk assessment showed that consuming Bellamya sp. from the mixed area could cause a potential health risk.


Endogenous acetylcholine concentrations in rat iris-ciliary body.
The technique of microwave irradiation, whereby enzymes are inactivated within milliseconds, was employed to accurately determine the in vivo acetylcholine (ACh) concentration in the iris-ciliary body (ICB). Rats were sacrificed by microwave irradiation at 9.5 kW at 2,450 MHz for 0.9 seconds. The eyes were enucleated, the ICBs isolated and 10 ICBs from 10 eyes were treated as one sample. ACh levels were determined using high performance liquid chromatography in an immobilized-enzyme reactor. Endogenous ACh levels in the rat ICB were 58.8 +/- 5.0 nmoles (8.58 +/- 0.73 micrograms) per gram tissue protein (mean +/- SE, 9 samples). A single instillation of 5 microliters of 0.05% atropine in one eye of an animal lowered the ACh level in the ICB of the eye (P < 0.02).


Current role of portable MRI in diagnosis of acute neurological conditions.
Neuroimaging is an inevitable component of the assessment of neurological emergencies. Magnetic resonance imaging (MRI) is the preferred imaging modality for detecting neurological pathologies and provides higher sensitivity than other modalities. However, difficulties such as intra-hospital transport, long exam times, and availability in strict access-controlled suites limit its utility in emergency departments and intensive care units (ICUs). The evolution of novel imaging technologies over the past decades has led to the development of portable MRI (pMRI) machines that can be deployed at point-of-care. This article reviews pMRI technologies and their clinical implications in acute neurological conditions. Benefits of pMRI include timely and accurate detection of major acute neurological pathologies such as stroke and intracranial hemorrhage. Additionally, pMRI can be potentially used to monitor the progression of neurological complications by facilitating serial measurements at the bedside.


A 5-year follow-up study on one-stage implants inserted concomitantly with localized alveolar ridge augmentation.
The aim of this study was to evaluate the success of one-stage implants placed at the time of alveolar bone augmentation using simultaneous guided bone regeneration technique with a collagen barrier membrane in patients suffering from insufficient bone width. Seventeen patients were treated with 20 one-stage OSTEOFIX (Oulu, Finland) implants using simultaneous guided bone regeneration technique. Dehiscence defects were filled by bovine bone mineral Bio-Oss and covered with collagen membrane. Clinical and radiographic parameters of the peri-implant conditions were assessed at the moment of prosthesis placement and at 1- and 5-year follow-ups. Diagnostic dehiscence defect measurements after implant placement showed that the mean vertical defect varied from 3.8 mm to 10.0 mm. At the moment of prosthesis placement and at 1- and 5-year follow-ups all implants were stable, painless and without biological complications. Clinical and radiographic parameters of the peri-implant conditions remained stable during follow-up. The cumulative implant survival rate was 100% after the 5-year observation period and the success rate for all pooled implants was 90%. The present study showed predictable treatment outcomes recorded after 5 years of function for one-stage OSTEOFIX (Oulu, Finland) oral implants placed simultaneously with guided bone regeneration using collagen membrane and deproteinized bovine bone mineral.