Cytoreductive surgery with a hyperthermic intraperitoneal chemotherapy program: Safe after 40 cases, but only controlled after 140 cases.
Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC), used to treat peritoneal surface malignancies (PSM), is a complex procedure with significant major morbidity (MM). To investigate the learning curve (LC) of CRS with HIPEC in a new specialized surgical unit with a fully trained senior surgeon and individualize the variables associated with morbidity and oncological results. A total of 290 consecutive patients with PSM were included. Complete CRS with HIPEC was performed in 204 patients. A risk-adjusted sequential probability ratio test was used to assess the LC on the basis of rates of incomplete cytoreduction (IC) and MM. Complete CRS, MM, and mortality rates were 70.4%, 30.4%, and 2.5%, respectively. Tumor histotype, a high peritoneal cancer index (PCI) and the invaded region were the major independent risk factors for IC, whereas previous surgery, high PCI, stomia realization and blood transfusion were predictors of MM. RA-SPRT showed that 140 and 40 cases were needed to achieve the lowest risk of IC and MM, respectively. CRS with HIPEC to treat PSM has a steep LC. Drastic selection has to be made at the beginning, excluding high PCI, rare peritoneal disease and patients previously operated on.


Ghrelin, leptin and IGF-I levels in breast-fed and formula-fed infants in the first years of life.
To establish ghrelin, leptin and IGF-I serum levels in breastfed (BF) and formula-fed (FF) infants during the first period of life. A cross-sectional study was conducted on fasting blood venous samples obtained from exclusively BF (n=106) and FF (n=100) infants to measure total ghrelin (RIA test), leptin (RIA test) and IGF-I (chemiluminescence). Anthropometrical measurements of weight, length and cranial circumference were performed. During the first 4 mo of life, FF infants compared to BF ones showed higher ghrelin levels (2654.86 vs 2132.96 pg/ml; p<0.032), higher IGF-I levels (3.73 vs 3.15 ng/ml; p=0.00) and lower leptin levels (0.68 vs 1.16 ng/ml; p<0.04). Leptin values were higher in females than in males (0.80 vs 0.47 ng/ml; p<0.03), while no gender-related difference was found for ghrelin and IGF-I. No differences were found in anthropometrical measurements comparing the two groups of infants. A multiple regression analysis showed an inverse correlation between ghrelin and leptin values (p<0.04) and between IGF-I and leptin levels (p=0.00). Our finding suggests that breastfeeding influences hormones such as ghrelin, leptin and IGF-I in infancy, mainly during the first 4 mo of life. Further evidence is needed to confirm and clarify the role of a protective link from mother to infants as seen in our observations.


What (if anything) is wrong with residency overwork?
Long work hours during residency are a time-honored tradition. Efforts have recently been made to shorten work hours. This paper examines the main arguments supporting reform: that sleep deprivation is harmful to patients and residents and that it is exploitative. Because the data on the harms and benefits are mixed and because exploitation is difficult to prove, a stronger argument for reducing work hours is an ethical one: that overwork interferes with the development of professional values and attitudes that are an essential part of the moral curriculum of residency. Providing a climate that promotes moral growth during training is an important curricular objective that may be better achieved by shortening work hours, providing better resident supervision, and using substitute workers for some of the noneducational tasks of residency.


Recent applications of 1,3-thiazole core structure in the identification of new lead compounds and drug discovery.
1,3-Thiazole is one of the most important scaffolds in heterocyclic chemistry and drug design and discovery. It is widely found in diverse pharmacologically active substances and in some naturally-occurring compounds. Thiazole is a versatile building-block for lead generation, and is easily access of diverse derivatives for subsequent lead optimization. In the recent years, many thiazole derivatives have been synthesized and subjected to varied biological activities. In this article we intended to review the most important biological effects of thiazole-based compounds and highlight their roles in new leads identification and drug discovery. This article is also intended to help researches for finding potential future directions on the development of more potent and specific analogs of thiazole-based compounds for various biological targets.


Space occupying lesions in the fetal chest evaluated by MRI.
The most common space occupying lesions of the fetal thorax are congenital diaphragmatic hernia (CDH), congenital cystic adenomatoid malformation (CCAM), and bronchopulmonary sequestration (BPS). Although applications of prenatal MRI have been vastly improved in the recent years, its use in the assessment of space occupying lesions of the fetal chest differs among centers. To evaluate MRI findings in the diagnosis and follow-up of space-occupying lesions in the fetal chest with the review of relevant literature. The fetuses with space-occupying lesions of the chest were retrieved from our 1.5T fetal MRI database of 347 patients. MRI features including the shape, signal characteristics, feeding artery, margin, mass effect, affected organ parts and anatomic location were reviewed. The results were correlated with the pathology results, follow-up and surgical findings. Nineteen MR images of 17 fetuses (mean gestational age, 23.8 weeks) with spaceoccupying lesions (5 CCAMs including one involuted case), 2 BPSs, 2 hybrid lesions, 8 CDH) were evaluated. One case of CCAM completely involuted in utero, four newborns were operated, and the resulting 12 fetuses were terminated. The surgical and pathological findings were in accordance with MRI findings. MRI can reliably differentiate CDH from CCAM and BPS in utero. Follow-up is of utmost importance as lesions may involute or progress in utero. Prenatal MRI findings help postnatal decision-making, surgical planning and parental counseling.


Tensile water transport in a porous gel.
A Monte Carlo simulation model, which incorporates the effect of tensile forces as well as diffusion, is proposed to explain the behavior of water transport in a saturated porous gel. The algorithm is able to account for the puzzling moisture profiles, which were first observed by conventional magnetic resonance imaging and, more recently, by Overhauser imaging.


Variations in serum alkaline DNase activity in rats during growth and treatment of tumors sensitive or resistant to therapy.
Serum alkaline DNase activity (SADA) was investigated in rats receiving s.c. transplants of tumor cells sensitive or resistant to chemotherapy. Serum samples from each animal were collected before transplantation, during the development of tumors and after therapy. Within a few days after transplantation of both tumor lines (sensitive or resistant), SADA levels decreased progressively to 52% of the normal pre-transplantation level (p less than 0.01). This decrease in SADA preceded by 4 to 5 days the appearance of any palpable tumor mass. In all untreated animals as well as in treated rats bearing resistant tumors, SADA remained at a low level until death. In rats bearing tumors sensitive to therapy a progressive increase in SADA was observed after treatment, paralleling tumor regression. When tumor regression was complete, SADA resumed the levels of activity measured prior to transplantation.


Prediction of gender from longitudinal MRI data via deep learning on adolescent data reveals unique patterns associated with brain structure and change over a two-year period.
Deep learning algorithms for predicting neuroimaging data have shown considerable promise in various applications. Prior work has demonstrated that deep learning models that take advantage of the data's 3D structure can outperform standard machine learning on several learning tasks. However, most prior research in this area has focused on neuroimaging data from adults. Within the Adolescent Brain and Cognitive Development (ABCD) dataset, a large longitudinal development study, we examine structural MRI data to predict gender and identify gender-related changes in brain structure. Results demonstrate that gender prediction accuracy is exceptionally high (>97%) with training epochs > 200 and that this accuracy increases with age. Brain regions identified as the most discriminative in the task under study include predominantly frontal areas and the temporal lobe. When evaluating gender predictive changes specific to a two-year increase in age, a broader set of visual, cingulate, and insular regions are revealed. Our findings show a robust gender-related structural brain change pattern, even over a small age range. This suggests that it might be possible to study how the brain changes during adolescence by looking at how these changes are related to different behavioral and environmental factors.


Labour companionship and women's experiences of mistreatment during childbirth: results from a multi-country community-based survey.
Evidence has shown the benefits of labour companions during childbirth. Few studies have documented the relationship between the absence of labour companions and mistreatment of women during childbirth in low-income and middle-income countries using a standardised tool. We conducted a secondary analysis of the WHO multi-country study on how women are treated during childbirth, where a cross-sectional community survey was conducted with women up to 8 weeks after childbirth in Ghana, Guinea, Nigeria and Myanmar. Descriptive analysis and multivariable logistic regression were used to examine whether labour companionship was associated with various types of mistreatment. Of 2672 women, about half (50.4%) reported the presence of a labour companion. Approximately half (49.6%) of these women reported that the timing of support was during labour and after childbirth and most of the labour companions (47.0%) were their family members. Across Ghana, Guinea and Nigeria, women without a labour companion were more likely to report physical abuse, non-consented medical procedures and poor communication compared with women with a labour companion. However, there were country-level variations. In Guinea, the absence of labour companionship was associated with any physical abuse, verbal abuse, or stigma or discrimination (adjusted OR (AOR) 3.6, 1.9-6.9) and non-consented vaginal examinations (AOR 3.2, 1.6-6.4). In Ghana, it was associated with non-consented vaginal examinations (AOR 2.3, 1.7-3.1) and poor communication (AOR 2.0, 1.3-3.2). In Nigeria, it was associated with longer wait times (AOR 0.6, 0.3-0.9). Labour companionship is associated with lower levels of some forms of mistreatment that women experience during childbirth, depending on the setting. Further work is needed to ascertain how best to implement context-specific labour companionship to ensure benefits while maintaining women's choices and autonomy.


[High-dose intravenous penicillin therapy in neurosyphilis. III. Evaluation of antitreponemal antibodies of the IgM class in cerebrospinal fluid and serum].
IgM antibodies against Treponema pallidum were investigated in the serum and in the CSF of 9 patients with symptomatic neurosyphilis, before the treatment and in several occasions after the treatment. Tests used were the FTA-Abs test, the IgM-solid phase hemadsorption test and an IgM-Elisa test. Titers of reactions decreased after treatment but they were still reactive in the blood and in the CSF during the second year after the treatment.


Tight expression regulation of senataxin, linked to motor neuron disease and ataxia, is required to avert cell-cycle block and nucleolus disassembly.
The Senataxin (SETX) protein exhibits strong sequence conservation with the helicase domain of the yeast protein Sen1p, and recessive SETX mutations cause a severe ataxia, known as Ataxia with Oculomotor Apraxia type 2, while dominant SETX mutations cause Amyotrophic Lateral Sclerosis type 4. SETX is a very low abundance protein, and its expression is tightly regulated, such that large increases in mRNA levels fail to significantly increase protein levels. Despite this, transient transfection in cell culture can boost SETX protein levels on an individual cell basis. Here we found that over-expression of normal SETX, but not enzymatically-dead SETX, is associated with S-phase cell-cycle arrest in HEK293A cells. As SETX interacts with the nuclear exosome to ensure degradation of incomplete RNA transcripts, and SETX localizes to sites of collision between the DNA replication machinery and the RNAP II complex, altered dosage or aberrant function of SETX may impede this process to promote S-phase cell-cycle arrest. Because neurons are enriched for long transcripts with additional antisense regulatory transcription, collisions of RNAP II complexes may occur in such post-mitotic cells, underscoring a role for SETX in maintaining neuron homeostasis.


Charities call for staff and funds to reduce infant death levels.
'SERIOUS' STAFFING and funding shortages must be addressed urgently if the numbers of stillbirths and neonatal deaths in the UK are to be reduced, charities have urged.


The composition of the pulmonary microbiota in sarcoidosis - an observational study.
Sarcoidosis is a systemic disease of unknown etiology. The disease mechanisms are largely speculative and may include the role microbial patterns that initiate and drive an underlying immune process. The aim of this study was to characterize the microbiota of the lung of patients with sarcoidosis and compare its composition and diversity with the results from patients with other interstitial lung disease (ILD) and historic healthy controls. Patients (sarcoidosis, n = 31; interstitial lung disease, n = 19) were recruited within the PULMOHOM study, a prospective cohort study to characterize inflammatory processes in pulmonary diseases. Bronchoscopy of the middle lobe or the lingula was performed and the recovered fluid was immediately sent for analysis of the pulmonary microbiota by 16sRNA gene sequencing. Subsequent bioinformatic analysis was performed to compare the groups. There were no significant differences between patients with sarcoidosis or other ILDs with regard to microbiome composition and diversity. In addition, the abundance of the genera Atopobium, Fusobacterium, Mycobacterium or Propionibacterium were not different between the two groups. There were no gross differences to historical healthy controls. The analysis of the pulmonary microbiota based on 16sRNA gene sequencing did not show a significant dysbiosis in patients with sarcoidosis as compared to other ILD patients. These data do not exclude a microbiological component in the pathogenesis of sarcoidosis.


Inferior Vena Cava Reconstruction with Tubularized Bovine Pericardium.
A 32-year-old male presented with a large locally advanced sarcomatoid right renal cell carcinoma invading the duodenum and IVC. Due to persistent symptomatic gastrointestinal bleeding requiring repeat blood transfusion and the inability to utilize appropriate systemic chemotherapy, the patient was taken for palliative resection. En bloc pancreaticoduodenectomy, right nephrectomy and IVC resection were performed with reconstruction of the IVC with tubularized bovine pericardium. Widespread availability, ease and speed of tubularized graft creation, lack of morbidity to the patient and its inherent resistance to infection in contaminated fields make bovine pericardium an expedient reconstructive option in these challenging cases.


Ultrastructure of eggs of Paracapillaria (Crossicapillaria) philippinensis and evidence related to its life cycle.
The varied ultrastructure of the eggshell of Paracapillaria (Crossicapillaria) philippinensis, collected from a human sample, is reported from a scanning electron microscopy study. Two distinct egg shapes were identified: typical peanut-shaped and swollen peanut-shaped. Both thick and thin eggshells were detected. Thick eggshells are either fairly smooth or bear a beam-like network in relation to the pillars in their surface ultrastructure. Thin eggshells are transparent allowing visibility of the coiled larva within. Presence of the thin shell provides supportive evidence of autoinfection involved in the life cycle of this medically important parasite.


Transitional psychiatry in the Netherlands: Experiences and views of mental health professionals.
The majority of psychopathology emerges in late adolescence and continues into adulthood. Continuity of care must be guaranteed in this life phase. The current service configuration, with a distinction between child/adolescent and adult mental health services (CAMHS and AMHS), impedes continuity of care. To map professionals' experiences with and attitudes towards young people's transition from CAMHS to AMHS and the problems they encounter. An online questionnaire distributed among professionals providing mental health care to young people (15-25 years old) with psychiatric disorders. Five hundred and eighteen professionals completed the questionnaire. Decision-making regarding transition is generally based on the professional's own deliberations. The preparation was limited to discussing changes with the adolescent and parents. Most transition-related problems are experienced in CAMHS, primarily with regard to collaboration with AMHS. Respondents report that the developmental age should be leading in the transition-decision making process and that developmentally appropriate services are important in bridging the gap. Professionals in CAMHS and AMHS experience problems in the preparation of, and the collaboration during transition. The problems are related to coordination, communication and rules and regulations. Professionals attach importance to improvement through an increase in flexibility and more specialist services for youth.


Integrative analysis of summary data from GWAS and eQTL studies implicates genes differentially expressed in Alzheimer's disease.
Although genome-wide association studies (GWAS) have successfully located various genetic variants susceptible to Alzheimer's Disease (AD), it is still unclear how specific variants interact with genes and tissues to elucidate pathologies associated with AD. Summary-data-based Mendelian Randomization (SMR) addresses this problem through an instrumental variable approach that integrates data from independent GWAS and expression quantitative trait locus (eQTL) studies in order to infer a causal effect of gene expression on a trait. Our study employed the SMR approach to integrate a set of meta-analytic cis-eQTL information from the Genotype-Tissue Expression (GTEx), CommonMind Consortium (CMC), and Religious Orders Study and Rush Memory and Aging Project (ROS/MAP) consortiums with three sets of meta-analysis AD GWAS results. Our analysis identified twelve total gene probes (associated with twelve distinct genes) with a significant association with AD. Four of these genes survived a test of pleiotropy from linkage (the HEIDI test).Three of these genes - RP11-385F7.1, PRSS36, and AC012146.7 - have not yet been reported differentially expressed in the brain in the context of AD, and thus are the novel findings warranting further investigation.


Rubber additives induce oxidative stress in rainbow trout.
Several studies have demonstrated the toxicity of rubber leachate, mainly from rubber tires, to aquatic organisms. In the present study rainbow trout (Oncorhynchus mykiss) were exposed to water provided to aquaria through a rubber hose. Increased hepatic ethoxyresorufin-O-deethylase (EROD) activity, and glutathione reductase (GR) activity were observed in the exposed fish. Two common rubber additives, 2-mercaptobenzothiazole (MBT) and diphenylamine (DPA) and structurally related compounds, were identified by chemical analyses of water samples as were hydroxylated polycyclic aromatic hydrocarbons. Metabolites of these compounds were also detected in the bile of exposed fish, as were some of the parent compounds. In a following experiment, we injected rainbow trout with DPA or MBT. Both compounds affected total glutathione (tGSH) concentration in liver and MBT caused an increase in hepatic GR and glutathione S-transferase (GST) activity as well. In DPA injected fish, hydroxylated DPA was the main metabolite in the bile. Our results indicate that rubber chemicals may leach into the water surroundings where they can be taken up and metabolised by fish. Some of these chemicals can lead to up-regulation of antioxidant defences as demonstrated with DPA and MBT injections.


Racial differences in survival of women with endometrial cancer.
The hypothesis that white women with endometrial cancer survive longer than black women with this disease was evaluated in a retrospective analysis of a population-based, prospective cohort study. All female residents of metropolitan Atlanta with a first diagnosis of primary endometrial cancer from 1978 through 1982 were eligible for inclusion. The 628 white and 105 black women were followed up through June 1984 to determine survivorship. Race was evaluated as a prognostic factor with univariate, multivariate, and excess death rate analyses. Overall, an estimated 89.2% of whites and 61.6% of blacks survived 3 years from the time of diagnosis. Although black women tended to have more advanced disease at the time of diagnosis and a higher proportion of undifferentiated malignancies, the racial difference in survival persisted after adjustment for these factors. When initial therapy was considered, race remained a significant prognostic determinant among women who did not receive radiation therapy.


Empowering industrial research with shared biomedical vocabularies.
The life science industries (including pharmaceuticals, agrochemicals and consumer goods) are exploring new business models for research and development that focus on external partnerships. In parallel, there is a desire to make better use of data obtained from sources such as human clinical samples to inform and support early research programmes. Success in both areas depends upon the successful integration of heterogeneous data from multiple providers and scientific domains, something that is already a major challenge within the industry. This issue is exacerbated by the absence of agreed standards that unambiguously identify the entities, processes and observations within experimental results. In this article we highlight the risks to future productivity that are associated with incomplete biological and chemical vocabularies and suggest a new model to address this long-standing issue.


Persistent proatlantal intersegmental artery and occipital artery originating from internal carotid artery.
A case of a combined anomaly of persistent hypoglossal and proatlantal intersegmental arteries, proved on arteriogram obtained by the insertion of a needle into the common trunk of both arteries, is presented. In addition, a case of anomalous occipital artery arising from the internal carotid artery associated with an intracranial aneurysm and arteriovenous malformation is presented. Based upon analysis of the persistent proatlantal intersegmental artery and the anomalous occipital artery, we conclude that both arteries have an identical embryological origin.


Association of Estimated Glomerular Filtration Rate With Progression of Albuminuria in Individuals With Type 2 Diabetes.
To elucidate the association of glomerular filtration rate (GFR) at baseline with subsequent progression of albuminuria in individuals with type 2 diabetes. This was a single-center retrospective cohort study of 6,618 Japanese adults with type 2 diabetes and urinary albumin-to-creatinine ratio of <300 mg/g, comprising 2,459 women and 4,159 men with a mean (± SD) age of 60 ± 12 years. The exposure was baseline estimated GFR (eGFR) (mL/min/1.73 m2), treated as a categorical variable and classified into five categories: ≥90, 75-90, 60-75, 45-60, and <45, as well as a continuous variable. The outcome was progression of albuminuria category (i.e., from normoalbuminuria to micro- or macroalbuminuria or from micro- to macroalbuminuria). Hazard ratios (HRs) for the outcome were estimated using the multivariable Cox proportional hazards model. In the analysis treating baseline eGFR as a continuous variable, the multivariable-adjusted restricted cubic spline model was used. During the median follow-up period of 6.3 years, 1,190 individuals reached the outcome. When those with a baseline eGFR of 75-90 mL/min/1.73 m2 were considered the reference group, HRs (95% CIs) for the outcome in those with a baseline eGFR of ≥90, 60-75, 45-60, or <45 mL/min/1.73 m2 were 1.38 (1.14-1.66), 1.34 (1.14-1.58), 1.81 (1.50-2.20), or 2.37 (1.84-3.05), respectively. Furthermore, the inverse J-shaped curve was more clearly shown by the spline model. This study of Japanese adults with type 2 diabetes suggests that both high and low GFRs are implicated in the pathogenesis of albuminuria progression.


Fasting ketonuria is inversely associated with coronary artery calcification in non-diabetic individuals.
Increased levels of ketone bodies, an alternative fuel when glucose availability is low, may exert beneficial effects on cardiovascular disease (CVD) risk factors. Whether increased ketone bodies are associated with coronary artery calcium (CAC), a recognized and strong cardiovascular risk factor, remains unknown. We investigated the association of fasting ketonuria with CAC and its progression. Cross-sectional and longitudinal studies were conducted in adults without diabetes or CVD. Subjects underwent routine health examinations including cardiac computed tomography estimations of CAC scores. Logistic regression models were performed to compute the odds ratios (ORs), 95% confidence intervals (CIs), for prevalent CAC scores >0 according to fasting ketonuria categories (0, 1, and ≥2). Linear mixed models with random intercepts and random slopes were used to estimate CAC progression. Of 144,346 subjects, 12.3% had CAC scores >0 at baseline. Overall, higher fasting ketonuria was associated with decreased prevalence of coronary calcification than no ketonuria. Multivariable-adjusted ORs (95% CIs) for prevalent CAC by comparing ketonuria categories 1 and ≥2 with no ketonuria, were 0.94 (0.84-1.06) and 0.82 (0.71-0.95), respectively. The associations did not differ according to clinically relevant subgroups. Ketonuria was associated with lower CAC progression over time; the multivariable adjusted ratio of progression rates comparing ketonuria ≥2 versus no ketonuria was 0.976 (0.965-0.995). We found an inverse association between fasting ketonuria and subclinical coronary atherosclerosis, in both prevalence and progression. The potentially protective role of increased ketone body formation in CVD requires further investigation.


Effect of Intrathoracic or Cervical Anastomosis After Esophagectomy on Quality of Life.
We aimed to perform serial quality-of-life (QoL) evaluations and comparisons in patients after esophagectomy with intrathoracic anastomosis (IA) or cervical anastomosis (CA). Between November 2012 and March 2015, patients who underwent esophagectomy with IA or CA for mid-esophageal to distal esophageal or gastroesophageal junction cancer were followed up. QoL was measured using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) and esophagus-specific questionnaire (EORTC QLQ-OES18) before surgery, at discharge, and at 1, 6, 12, and 24 months after discharge. Linear mixed-effect models were used to assess the mean score differences (MDs) of each QoL scale between the two techniques, and changes in QoL over time. Potential confounders were adjusted. In total, 219 patients were analyzed (IA, n = 127; CA, n = 92). All patients' QoL decreased immediately after esophagectomy. Global QoL and most functioning and symptom scales exhibited a return to baseline levels within 2 years of discharge, except for physical functioning and several symptoms (dyspnea, diarrhea, dysphagia, and reflux). There was no difference in overall health score between the two groups (MD 2, 95% confidence interval [CI] - 1 to 6). Compared with IA, patients with CA reported more trouble with taste (MD - 12, 95% CI - 19 to - 4) and talking (MD - 11, 95% CI - 19 to 2) at discharge. No differences in long-term QoL were found between groups. CA was associated with more trouble with taste and talking in the short term than IA. The long-term QoL did not differ between the two approaches.


B cell epitope of human cytomegalovirus phosphoprotein 65 (HCMV pp65) induced anti-dsDNA antibody in BALB/c mice.
HCMV phosphoprotein 65 (HCMVpp65) is a putative immunogen that acts as an accelerator, inducing autoantibody and exacerbating autoimmune response in susceptible animals. The immunity to pp65336-439 instigates autoimmunity, suggesting that pp65336-439 contains crucial B cell epitope(s) for the development of nephritis. This study narrowed down the target epitope to pp65422-439 for immunization of BALB/c mice and mapping of B cell epitope. The target epitope pp65422-439 reactivity and B cell epitope mapping was examined in serum from pp65422-439-immunized mice and patients with systemic lupus erythematosus (SLE). Kidney tissue from immunized mice was examined for signs of immune complex nephritis. Anti-pp65422-439 antibody in serum either from patients with SLE or from pp65422-439-immunized mice exhibited cross-reactivity to several nuclear components such as double-stranded DNA (dsDNA). Moreover, the pp65422-439-immunized mice developed initial signs of glomerulonephritis such as deposition of immunoglobulin G/M (IgG/IgM) and third complement component (C3). With B cell epitope mapping by pp65422-439-derived decapeptides, one dominant epitope, pp65428-437, was identified in serum from pp65422-439-immunized mice and patients with SLE with anti-pp65422-439 antibody. Epitope spreading from pp65428-437 to pp65430-439 was found in pp65422-439-immunized mice in which we generated monoclonal antibodies to pp65425-434 and pp65430-439. However, dsDNA positive reactivity was exclusively observed in Crithidia luciliae stains with pp65430-439-reactive monoclonal antibody. Additionally, we observed the amelioration of autoimmunity following the elevation of IgM targeting pp65428-437. CONCLUSIONS: Our data suggest that pp65428-437 may be an autoimmune or lupus-prone B cell epitope and may catalyze further epitope spreading for inducing autoantibodies in lupus-susceptible individuals.


Clinical impact of aging on outcomes of cardioneuroablation for reflex syncope or functional bradycardia: Results from the cardionEuroabLation: patiEnt selection, imaGe integrAtioN and outComEs-The ELEGANCE multicenter study.
Cardioneuroablation (CNA) is a novel treatment for reflex syncope. The effect of aging on CNA efficacy is not fully understood. The purpose of this study was to assess the impact of aging on candidacy and efficacy of CNA for treating vasovagal syncope (VVS), carotid sinus syndrome (CSS), and functional bradyarrhythmia. The ELEGANCE (cardionEuroabLation: patiEnt selection, imaGe integrAtioN and outComEs) multicenter study assessed CNA in patients with reflex syncope or severe functional bradyarrhythmia. Patients underwent pre-CNA Holter electrocardiography (ECG), head-up tilt testing (HUT), and electrophysiological study. CNA candidacy and efficacy was assessed in 14 young (18-40 years), 26 middle-aged (41-60 years), and 20 older (>60 years) patients. Sixty patients (37 men; mean age 51 ± 16 years) underwent CNA. The majority (80%) had VVS, 8% had CSS, and 12% had functional bradycardia/atrioventricular block. Pre-CNA Holter ECG, HUT, and electrophysiological findings did not differ across age groups. Acute CNA success was 93%, without differences between age groups (P = .42). Post-CNA HUT response was negative in 53%, vasodepressor in 38%, cardioinhibitory in 7%, and mixed in 2%, without differences across age groups (P = .59). At follow-up (8 months, interquartile range 4-15), 53 patients (88%) were free of symptoms. Kaplan-Meier curves did not show differences in event-free survival between age groups (P = .29). The negative predictive value of a negative HUT was 91.7%. CNA is a viable treatment for reflex syncope and functional bradyarrhythmia in all ages, and is highly effective in mixed VVS. HUT is a key step in postablation clinical assessment.


Necrotizing retinitis caused by opportunistic virus infection in a patient with Hodgkin's disease.
A 33-year-old woman with Hodgkin's disease developed a painless progressive loss of vision in both eyes. Despite an ophthalmoscopic appearance of white-yellow retinal necrosis and retinal hemorrhage similar to that described with Hodgkin's disease, no sign of the disorder was found at autopsy. Instead, widespread evidence of Herpesviridae family virus infection was present in several organs, including the retinas. Opportunistic infection, including herpes simplex and cytomegalovirus, should be considered when retinitis complicates Hodgkin's disease.


Pretreatment Tumor Growth Rate and Radiological Response as Predictive Markers of Pathological Response and Survival in Patients with Resectable Lung Cancer Treated by Neoadjuvant Treatment.
Predictive biomarkers associated with pathological response, progression precluding surgery, and/or recurrence after surgery are needed for patients with resectable non-small cell lung carcinoma (NSCLC) treated by neoadjuvant treatment. We evaluated the clinical impact of the pretreatment tumor growth rate (TGR0) and radiological response for patients with resectable NSCLC treated with neoadjuvant therapies. Consecutive patients with resectable stage IB (≥4 cm) to IIIA NSCLC treated by neoadjuvant platinum-doublet chemotherapy with or without nivolumab at our tertiary center were retrospectively analyzed. TGR0 and RECIST objective responses were determined. Multivariable analyses identified independent predictors of event-free survival (EFS), overall survival (OS), and major pathological response (MPR). Between November 2017 and December 2022, 32 patients (mean [SD] age, 63.8 [8.0] years) were included. At a median follow-up of 54.8 months (95% CI, 42.3-60.4 months), eleven patients (34%) experienced progression or recurrence, and twelve deaths (38%) were recorded. The TGR0 cutoff of 30%/month remained the only independent factor associated with EFS (HR = 0.04; 95% CI, 0.01-0.3; p = 0.003) and OS (HR = 0.2; 95% CI, 0.03-0.7; p = 0.01). The TGR0 cut-off had a mean time-dependent AUC of 0.83 (95% CI, 0.64-0.95) and 0.80 (95% CI, 0.62-0.97) for predicting EFS and OS, respectively. Fifteen of 26 resection cases (58%) showed MPR including nine with pathological complete responses (35%). Only the objective response of the primary tumor was associated with MPR (OR = 27.5; 95% CI, 2.6-289.1; p = 0.006). Assessment of TGR0 can identify patients who should benefit from neoadjuvant treatment. A tumor objective response might be a predictor of MPR after neoadjuvant treatment, which will help to adapt surgical management.


[Influence of eating habits on caries control from viewpoint of prevention research (2)].
The author describes the influence of group standards, primary and secondary socialisation and social class on eating habits, then draws conclusions pertaining to dental health education.


Syntheses and evaluation of benzodiazaborine compounds against M. tuberculosis H37Rv in vitro.
The synthesis of six benzo[e]diazaborine compounds and thier in vitro evaluation against M. tuberculosis H37Rv is described. The compounds 1,2-dihydro-1-hydroxy-2-phenyl-2,4,1-benzo[e]diazaborin-3(4H)-one, 4, and 1,2-dihydro-1-hydroxy-2-(3-pyridyl)-2,4,1-benzo[e]diazaborin-3(4H) - thione, (5), showed the greatest inhibitory activity.


Legislating collaborative self-regulation in Canada: A comparative policy analysis.
To encourage interprofessional collaboration and to improve the regulation of healthcare providers, Ontario and Nova Scotia, Canada, have each adopted legislation calling for collaboration among the regulators of their self-regulating health professions. Ontario's legislation is "top down": it came from government and stresses the obligation of regulators to collaborate. Nova Scotia's legislation is "bottom up": it was proposed and developed by regulators and emphasizes voluntary regulatory collaboration. This article considers the theoretical strengths and weaknesses of both models. It argues that Nova Scotia's approach may be stronger because of its relative consistency with core strengths of self-regulation and interprofessionalism and its grounding in soft law and a governance approach to collaborative self-regulation and to healthcare policy more broadly.


[Clinical response to gefitinib retreatment of lung adenocarcinoma patients who benefited from an initial gefitinib therapy: a retrospective analysis].
Gefitinib is an epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) that has been widely used for the treatment of non-small cell lung cancer (NSCLC). It is most effective in women, as well as in patients who have never smoked, have pulmonary adenocarcinomas, or are of Asian origin. Several treatment options are available for NSCLC patients who responded to initial gefitinib therapy but demonstrated tumor progression, of which gefitinib readministration is the chosen therapeutic option. The present study aims to evaluate the efficacy and toxicity of gefitinib readministration. The clinical data of 18 patients with NSCLC who had shown partial response (PR) or achieved a stable disease (SD) status after gefitinib administration and were retreated with gefitinib due to failure of the initial therapy were reviewed and retrospectively analyzed. Of the 18 patients studied, 1 (6%) showed partial remission (PR), 11 (61%) achieved SD, and 6 (33%) experienced disease progression. The disease control rate was 67%, and the median progression-free survival was 5.16 months (range, 1 to 24.8 months). The median overall survival from the start of the gefitinib therapy was 39.4 months (range, 15.38 to 52.44 months). Moreover, the median overall survival from the beginning of the 2nd therapy was 12.41 months (range, 3.98 to 38.24 months). Mild toxicity was observed with the 2nd gefitinib therapy. The results of the present study indicate that patients with NSCLC may still be expected to achieve prolonged survival through gefitinib readministration if they initially responded to gefitinib and underwent various subsequent treatments.


Embryotoxicity and teratogenicity of formocresol on developing chick embryos.
White Leghorn chick embryos were used to investigate the embryotoxicity and teratogenicity of 25 and 50% Buckley's formocresol. Embryos were injected at 48 h and sacrificed on the ninth day of incubation. The percentage of mortality of sham and vehicle controls was 4.8 and 17.7%, respectively, whereas eggs injected with 25 and 50% formocresol displayed a 40 and 100% mortality rate. Gross morphological abnormalities, weights, and crown-rump lengths were determined, demonstrating that Buckley's formocresol is embryotoxic and teratogenic in chick embryos. Gross morphological changes were noted to include cranial hematomas, facial abnormalities, eye and beak deformities as well as alterations in feather germ appearance. Histological changes included alterations in the organization of the eyes, and formation of the beak, palate, vasculature, musculature, cartilage, and bone. Moreover, experimental embryos displayed a retardation of development in that they lagged behind their controls by approximately 24 to 36 h.


New Peptides Under the s(ORF)ace of the Genome.
Hundreds, perhaps thousands of previously unidentified functional small peptides could exist in most genomes, but these sequences have been generally overlooked. The discovery of genes encoding small peptides with important functions in different organisms has ignited the interest in these sequences and led to an increasing amount of effort towards their identification. Here, we review the advances, both computational and biochemical, that are leading the way in the discovery of putatively functional small open reading frame genes (smORFs), as well as the functional studies that have been carried out as a consequence of these searches. The evidence suggests that smORFs form a substantial part of our genomes, and that their encoded peptides could have a variety of important cellular functions.


Ethanol modifies differently aspartyl- and glutamyl-aminopeptidase activities in mouse frontal cortex synaptosomes.
Aminopeptidase A activity (aspartyl aminopeptidase (AspAP) and glutamyl aminopeptidase (GluAP) exerts angiotensinase activity due to its relation to the metabolism of angiotensins in the regional brain renin-angiotensin system (RAS). This activity may also modify the free amino acid pool through the release of N-terminal acidic amino acids. Ethanol (EtOH) exerts profound effects on the brain, inducing important neurological damages. Our purpose is to study the influence of EtOH on AspAP and GluAP activities on basal and K(+)-stimulated conditions, at the synapse level. We used mouse frontal cortex synaptosomes and their incubation supernatant in a Ca(2+)-containing or Ca(2+)-free artificial cerebrospinal fluid. We evaluate the possible contribution of these enzymatic activities on brain blood pressure regulation through RAS and/or the free acidic amino acid pool. The results obtained are correlated with several parameters of oxidative stress, such as free radical generation, lipid peroxidation, and protein oxidation. Under basal conditions, in synaptosomes, EtOH inhibits AspAP and GluAP activities independently of Ca(2+). In the supernatant, however, EtOH differently modulates the two enzyme activities under the various concentrations. Under K(+)-stimulated conditions, EtOH inhibits the K(+)-stimulated increase on AspAP and GluAP differently depending on the presence or absence of Ca(2+) and the concentration of EtOH used. These results invalidate the idea that excess free acidic amino acids could be released by AspAP and GluAP to induce neurodegeneration. The changes in AspAP and GluAP activities as a consequence of EtOH administration and their role in the brain RAS are discussed.


Growth kinetics of haloalkaliphilic, sulfur-oxidizing bacterium Thioalkalivibrio versutus strain ALJ 15 in continuous culture.
The chemolithoautotrophic, sulfur-oxidizing bacterium Thioalkalivibrio versutus strain ALJ 15, isolated from a soda lake in Kenya, was grown in a continuous culture, with thiosulfate or polysulfide as growth-limiting energy source and oxygen as electron acceptor, at pH 10 and at pH 0.6, 2 M and 4 M total sodium. The end product of the sulfur-compound oxidation was sulfate. Elemental sulfur and a cell-bound, polysulfide-like compound appeared as intermediates during substrate oxidation. In the thiosulfate-limited culture, the biomass yields and maximum specific growth rates decreased two and three times, respectively, with increasing sodium concentration. The apparent affinity constant measured for thiosulfate and polysulfide was in the micromolar range (Ks = 6 +/- 3 microM). The maintenance requirement (ms = 8 +/- 5 mmol S2O3(2)/g dry weight h(-1)) was in the range of values found for other autotrophic sulfur-oxidizing bacteria. The organism had a comparable maximum specific rate of oxygen uptake with thiosulfate, polysulfide, and sulfide, while elemental sulfur was oxidized at a lower rate. Glycine betaine was the main organic compatible solute. The respiration rates with different species of polysulfides (Sn2-) were tested. All polysulfide species were completely oxidized at high rates to sulfate. Overall data demonstrated efficient growth and sulfur compounds oxidation of haloalkaliphilic chemolithoautotrophic bacteria from soda lakes.


Tryptophan 2,3-dioxygenase 2 plays a key role in regulating the activation of fibroblast-like synoviocytes in autoimmune arthritis.
Abnormal kynurenine (Kyn) metabolism has been closely linked to the pathogenesis of rheumatoid arthritis (RA). The aims of this study were to investigate the role of tryptophan 2,3-dioxygenase 2 (TDO2), a rate-limiting enzyme that converts tryptophan (Trp) to Kyn, in regulating fibroblast-like synoviocyte (FLS)-mediated synovial inflammation in autoimmune arthritis. The expression of TDO2 was determined by immunohistochemistry, confocal laser scanning fluorescence microscopy, imaging flow cytometry and Western blot. TDO2 activity was tested by HPLC and colorimetric assay. TDO2 siRNA and TDO2 inhibitor 680C91 were used to inhibit TDO2 in AA-FLS function in vitro. A rat model of adjuvant-induced arthritis (AA) was used to evaluate the in vivo effect of allopurinol (Allo), a TDO2 inhibitor. TDO2 expression was strongly increased in synovial tissue and FLS of RA and AA. Immune cells were found to express high amount of TDO2 proteins at the peak stage of AA. Pharmacological inhibition or knockdown of TDO2 in AA-FLS resulted in a reduced proliferation, secretion, migration and invasion. Kyn restored the inhibitory effect of TDO2 inhibition on activation of AA-FLS. Allo treatment ameliorated the arthritis severity and decreased the activity of TDO2. Our results suggest that elevated TDO2 expression may contribute to synovial inflammation and joint destruction during arthritis. Therefore, targeting TDO2 activity and the Kyn pathway of Trp degradation may represent a potential therapeutic strategy in RA.


Ghrelin in the pilosebaceous unit: alteration of ghrelin in patients with acne vulgaris.
Ghrelin in the pilosebaceous tissues of human skin and ghrelin levels in patients with acne vulgaris have not yet been investigated. The purpose of this study was to screen ghrelin immunoreactivity by immunohistochemistry in human pilosebaceous tissues of human skin and also to determine the quantities of ghrelin in the serum of the patients with acne vulgaris. 30 patients presenting with acne vulgaris and 30 control subjects participated in this study. Ghrelin levels were determined by enzyme linked immunosorbent assay (ELISA). Human hair follicles and sebaceous glands were immunohistochemically examined. Immunohistochemistry results showed that there is a strong ghrelin immunoreactivity in the hair follicles and sebaceous glands in sections of human skin. The mean serum ghrelin levels (27.58 ・} 15.44 pg/mL) in patients with acne vulgaris was significantly lower than those of controls (35.62・}20.46 pg/mL). Ghrelin produced in hair follicles and sebaceous glands of the skin might participate in the pathogenesis of acne vulgaris and also acne vulgaris in humans might be associated with decreased serum ghrelin.


Effects of steroid anaesthesia on some liver function tests in goats.
The effect of Saffan, a steroid anaesthetic, on the liver function of goats has been studied. Forty healthy animals were divided into 4 equal groups. The first 2 groups were given 2 and 4 mg Saffan/kg b. wt respectively. A mixture of Saffan (1 mg) and Xylazine (0.1 mg)/kg b. wt was given to the third group and Xylazine alone to the fourth group (0.1 mg/kg b. wt). Serum samples from all groups were analysed for glucose, total protein, total and direct bilirubin and the level of activity of transaminases. Administration of Saffan evoked more hyperglycemia than a mixture with Xylazine, or Xylazine alone. The hyperglycemic effect of both doses of Saffan (2 and 4 mg) was equivocal beyond 2 h. The effect then differed and glucose was increased 4-fold by 2 mg and 3-fold by 4 mg Saffan. Serum total protein, conjugated and total bilirubin, and GPT and GOT were not changed in the four experimental groups. This was good evidence of a normally functioning liver during the course of steroid anaesthesia administration in goats.


Expression of peroxisome proliferator-activated receptor (PPAR) in human prostate cancer.
Recent studies have demonstrated that peroxisome proliferator activator-receptors (PPAR)-gamma is expressed in some cancer cells such as breast, lung, and gastric cancer, and its ligand induces growth arrest of these cancer cells through apoptosis. However, the expression and localization of PPARs in prostate have not been examined. In this study, PPARs expression was investigated in human prostate cancer (PC), prostatic intraepithelial neoplasia (PIN), benign prostatic hyperplasia (BPH), and normal prostate (NP) tissues. Tumor specimens were obtained from 156 patients with PC, 15 with PIN, 20 with BPH, and 12 patients with NP tissues. The expressions were investigated by RT-PCR and immunohistochemical methods. Immunoreactive PPAR-alpha and -beta were significantly apparent in PC tissues. Marked expressions of PPAR-alpha and -beta were also detected in PIN, BPH, and NP groups. However, very weak or no expression of immunoreactive PPAR-gamma was found in BPH and NP cases. In contrast, we found significant expression of immunoreactive PPAR-gamma in cancer cells in PC group and in PIN group. Our results demonstrated that PPAR-gamma is induced in PC, and suggest that PPAR-gamma ligands may mediate its own potent antiproliferative effect against PC cells through differentiation.


Socioeconomic disparities in the utilization of spine augmentation for patients with osteoporotic fractures: an analysis of National Inpatient Sample from 2011 to 2015.
Vertebral augmentation procedures are used for treatment of osteoporotic compression fractures. Prior studies have reported disparities in the treatment of patients with osteoporotic vertebral fractures, particularly with regards to the use of vertebroplasty and kyphoplasty. The purpose of this study is to report updates in racial and health insurance inequalities of spine augmentation procedures in patients with osteoporotic fractures. With the use of the National Inpatient Sample, we identified hospitalized patients with osteoporotic fractures between the period of 2011 and 2015. Patients with spine augmentation, defined by the utilization of vertebroplasty and kyphoplasty, were also identified. Our primary outcome was defined as the utilization of spine augmentation procedures across ethnic (white, hispanic, black, and asian/pacific islander) and insurance (self-pay, private insurance, Medicare, and Medicaid) groups. Variables were identified from the NIS database using International Classification of Diseases, Ninth and Tenth diagnosis codes. Univariate and multivariate regression analysis was used for statistical analysis with p value <.05 considered significant. A subgroup analysis was performed across the utilization of kyphoplasty, vertebroplasty, and Medicare coverage. We identified a total of 110,028 patients with a primary diagnosis of vertebral fracture between 2011 and 2015 (mean age: 74.4±13.6 years, 68% women). About 16,237 patients (14.8%) underwent any type of spine augmentation with over 75% of the patients receiving kyphoplasty. Multivariate analysis showed that black patients (odds ratio [OR]=0.64, 95% confidence interval [CI]: 0.58-0.70, p<.001), Hispanic patients (OR=0.79, 95% CI: 0.73-0.86, p<.001), and Asian/Pacific Islander (OR=0.79, 95% CI: 0.70-0.89, p<.001) had significantly lower odds for receiving any spine augmentation compared with white patients. Patients with Medicaid (OR=0.59, 95% CI: 0.53-0.66, p<.001), private insurance (OR=0.90, 95% CI: 0.85-0.96, p=.001), and those who self-pay (OR=0.57, 95% CI: 0.47-0.69, p<.001) had significantly lower odds of spine augmentation compared with those with Medicare. Comparative use of kyphoplasty was not significantly different between white and black patients (OR=0.85, 95% CI: 0.70-1.04, p=.12). However, Hispanic patients (OR=0.84, 95% CI: 0.71-0.99, p=.04) and Asian/Pacific Islander patients (OR=0.73, 95% CI: 0.58-0.92, p=.007) had significantly lower use of kyphoplasty compared with white patients. The comparative use of kyphoplasty among patients receiving spine augmentation was not significantly different across each insurances status when compared with patients with Medicare. Our study suggests that racial and socioeconomic disparities continue to exist with the utilization of spine augmentation procedures in hospitalized patients with osteoporotic fractures.


A gene (hur) from Streptomyces aureofaciens, conferring resistance to hydroxyurea, is related to genes encoding streptomycin phosphotransferase.
A novel gene (hur) conferring resistance to hydroxyurea (HU) in Escherichia coli has been identified in a Streptomyces aureofaciens genomic library. The expression of hur in E. coli was under the control of the external plasmid tet promoter. Sequence analysis of a minimal fragment revealed an open reading frame (ORF) encoding a protein of 340 amino acids with an M(r) of 36,049 and an average hydropathy index of 1.13. The predicted protein product was similar to streptomycin phosphotransferases from Streptomyces glaucescens and Streptomyces griseus (52.4% and 50.8% identity, respectively), but it did not confer resistance to streptomycin or to any of the other aminoglycoside antibiotics tested. It is inferred that hur encodes a phosphotransferase that inactivates HU by phosphorylation of the hydroxy group in the hydroxylamine moiety.


Synechocystis 6803 mutants expressing distinct forms of the Photosystem II D1 protein from Synechococcus 7942: relationship between the psbA coding region and sensitivity to visible and UV-B radiation.
Synechocystis PCC 6803 mutants expressing either the "low light" (D1:1) or the "high light" (D1:2) form of the Photosystem II (PSII) D1 protein from Synechococcus PCC 7942 were constructed and characterized with respect to properties of PSII and sensitivity to visible and UV-B radiation. The AI and AIII mutants (containing only the D1:1 and D1:2 forms, respectively) exhibited very similar PSII characteristics as the control strain and they differed only in the accelerated decay kinetics of flash-induced variable fluorescence measured in the presence of DCMU. However, the mutants showed increased sensitivity to photodamage induced by visible and UV-B radiation, with higher loss of PSII activity in the AI than in the AIII strain. Thus, the difference between strains containing D1:1 and D1:2 found previously in Synechococcus 7942 is maintained after transfer of corresponding psbA genes into Synechocystis 6803 and is directly related to the coding region of these genes. The higher light sensitivity of the AI mutant is caused partly by the higher rate of photodamage and partly by the less efficient PSII repair.


[Politics, actors, and interests in the process of institutional change: the creation of the Brazilian Ministry of Health in 1953].
This analysis of the 1953 creation of the Ministry of Health identifies the main actors involved, their interests, and the strategies they employed to reach their goals and influence the process of institutional change. Placing the process within the context of the era's specific political characteristics, the article identifies the predominant decision-making arena as well as emergence of this new, autonomous government agency for public health.


"We Experience What They Experience": Black Nurses' and Community Health Workers' Reflections on Providing Culturally Specific Perinatal Health Care.
Black perinatal health workers are part of a tradition of Black people fighting for the well-being of Black communities. The purpose of this article is to better understand the unique experiences of these professionals. Descriptive qualitative research was used to understand Black providers' experiences in a culturally specific perinatal public health program. A focus group was conducted with seven nurses and community health workers, and thematic analysis was used to analyze the data. Three themes emerged: (a) shared lived experience and parallel process between staff and clients; (b) navigating multiple shifting gazes between clients, public health department, and medical systems; and (c) reproductive justice and community care characterize a culturally informed approach. Findings revealed strengths and complexities facing Black nurses and community health workers in their roles. More work is needed in education, practice, and research to better prepare and support nurses and community health workers in culturally specific settings.


Backward walking and circling: behavioural responses induced by drug treatments which cause simultaneous release of catecholamines and 5-hydroxytryptamine.
1 The roles of catecholamine and 5-hydroxytryptamine (5-HT) release in mediating backward walking and circling were studied in rats. 2 These behaviours occurred in animals given 15 mg/kg intraperitoneally of (+)-amphetamine (which predominantly releases catecholamines) or either p-chloroamphetamine or fenfluramine (which predominantly release 5-HT). They also occurred when smaller doses of (+)-amphetamine (5 mg/kg) and either p-chloroamphetamine (2--5 mg/kg) or fenfluramine (5 mg/kg) were given together. 3 Characteristic dopamine-dependent behaviours (rearing, licking, gnawing) resulting from (+)-amphetamine injection were greatly reduced by p-chloroamphetamine or fenfluramine. 4 Characteristic 5-HT-dependent behaviours (wet dog shake, hind limb abduction) resulting from injection of either p-chloroamphetamine or fenfluramine were unaffected by (+)-amphetamine. 5 Fragmentary backward walking and circling resulting from levallorphan injection (50 mg/kg s.c.) were decreased by (+)-amphetamine at low dosage. 6 Results in general strengthen previous evidence that backward walking and circling are mediated by simultaneous dopamine and 5-HT release. 7 The possible relevance of the above findings to hallucinogenic activity, amphetamine psychosis, schizophrenia and abnormal movements due to L-DOPA treatment is discussed.


Mechanism of insulin production in canine bone marrow derived mesenchymal stem cells.
Insulin is a critical hormone in the regulation of blood glucose levels and is produced exclusively by pancreatic islet beta-cells. Insulin deficiency due to reduced pancreatic islet beta-cell number underlies the progression of diabetes mellitus, prompting efforts to develop beta-cell replacement therapies. However, precise information on beta-cell replacement and differentiation in canines is limited. In this study, we established insulin-producing cells from bone marrow derived mesenchymal stem cells transiently expressing canine pancreatic and duodenal homeobox 1 (Pdx1), beta cell transactivator 2 (Beta2) and V-maf avian musculoaponeurotic fibrosarcoma oncogene homolog A (Mafa) using a gene transfer technique. Real-time PCR analysis revealed an increase in insulin mRNA expression of transfected cells. And ELISA revealed that insulin protein expressed was detected in cytoplasmic fraction. Insulin immunostaining analysis was performed and observed in cytoplasmic fraction. These results suggest that co-transfection of Pdx1, Beta2 and Mafa induce insulin production in canine BMSCs. Our findings provide a clue to basic research into the mechanisms underlying insulin production in the canines.


RNF113A targeted by miR-197 promotes proliferation and inhibits autophagy via CXCR4/CXCL12/AKT/ERK/Beclin1 axis in cervical cancer.
Ring Finger Protein 113 (RNF113A), an ubiquitin E3 ligase, is genetically associated with many biological processes, including proliferation, differentiation, cell death, and neurogenesis. Recently, RNF113A has been found to be an abnormal expression in many diseases, such as X-linked trichothiodystrophy syndrome and esophageal cancer. Here, we explore the potential mechanism of RNF113A in the progression of cervical cancer (CC). In this study, we evaluated the expression level and biological function of RNF113A in CC both in vitro and in vivo by bioinformatic prediction, DIA proteomic analysis, compensation experiment, Co-IP, dual-luciferase reporter assay and nude mouse xenograft to identify the RNF113A-associated autophagy pathways involved with tumorigenesis. Consistent with the prediction from biological information analysis, we found that RNF113A was highly expressed in human CC tissues and cells. In addition, this study illustrated that the high expression of RNF113A dramatically promoted proliferation and suppressed autophagy both in vitro and in vivo. In contrast, low expression of RNF113A enhanced autophagy activities and inhibited tumor growth in CC. We also found that miRNA-197, the level of which (negative correlation with RNF113A) declined in human CC, directly restrained the expression of RNF113A. Mechanistically, proteomic and mechanistic assays uncovered that RNF113A confirmed as the direct downstream target of miR-197, promoted proliferation and restrained autophagy in CC not through direct ubiquitination degradation of autophagy marker Beclin1 but via CXCR4/CXCL12/AKT/ERK/Beclin1 signal transduction axis. In summary, we found a new miR-197/RNF113 A/CXCR4/CXCL12/AKT/ERK/Beclin1 regulation pathway that plays an important part in the survival and progression of CC.


LincRNA-ROR/miR-145/ZEB2 regulates liver fibrosis by modulating HERC5-mediated p53 ISGylation.
The tumor suppressor p53 has been implicated in the pathogenesis of liver fibrosis. HERC5-mediated posttranslational ISG modification of the p53 protein is critical for controlling its activity. Here, we demonstrated that the expression of HERC5 and ISG15 is highly elevated, whereas p53 is downregulated, in fibrotic liver tissues of mice and transforming growth factor-β1 (TGF-β1)-induced LX2 cells. HERC5 siRNA clearly increased the protein expression of p53, but the mRNA expression of p53 was not obviously changed. The inhibition of lincRNA-ROR (ROR) downregulated HERC5 expression and elevated p53 expression in TGF-β1-stimulated LX-2 cells. Furthermore, the expression of p53 was almost unchanged after TGF-β1-stimulated LX-2 cells were co-transfected with a ROR-expressing plasmid and HERC5 siRNA. We further confirmed that miR-145 is a target gene of ROR. In addition, we also showed that ROR regulates the HERC5-mediated ISGylation of p53 through mir-145/ZEB2. Together, we propose that ROR/miR-145/ZEB2 might be involved in the course of liver fibrosis by regulating ISGylation of the p53 protein.


Zirconium retention for minimizing environmental risk: Role of counterion and clay mineral.
Zr(IV) together with U(IV) are the major components of high-level radionuclide waste (HLRW) and spent nuclear fuel (SNF) from nuclear power plants. Thus, their retention in the waste disposal is of great importance for the environmental risk control. Here, the influence of clay minerals on the retention of Zr(IV), as component of the nuclear waste and as chemical analogues of U(IV), has been evaluated. Three clay minerals, two bentonites and one saponite, were hydrothermally treated with three zirconium salts. A structural study at long-range order by X-ray diffraction and short-range order by NMR was performed to evaluate the generation of new zirconium phases and degradation of the clay minerals. Three immobilization mechanisms were observed: i) cation exchange of ZrO2+ or Zr4+ by clay minerals, ii) the precipitation/crystallization of ZrO2, and, iii) the chemical interaction of zirconium with the clay minerals, with the formation of zirconium silicates.


[Antiaggregants in the prevention of ischemic cardiopathy and systemic thromboembolism].
Recent studies, carried out to prevent thromboembolism in atrial fibrillation, showed a clear benefit of anticoagulant and antiplatelet drugs. Research is now focused to evaluate the antithrombotic effect of: low dose of anticoagulants and the combination of a therapeutic range of antiplatelet drugs and low dose of anticoagulants that may not need laboratory control. For the first time we also include patients with mitral stenosis and atrial fibrillation with the intention to reduce the dose of anticoagulants in the presence of a therapeutic antiplatelet treatment.


Fabrication of oriented wrinkles on polydopamine/polystyrene bilayer films.
Wrinkles exist widely in nature and our life. In this paper, wrinkles on polydopamine (PDA)/polystyrene (PS) bilayer films were formed by thermal annealing due to the different thermal coefficients of expansion of each layer. The factors that influenced the dimensions of wrinkles were studied. We found that oriented wrinkles could be formed if the bilayer films were patterned with micro-grooves, and the degree of the orientation depended on the thickness of the PDA and the dimensions of the grooves. Combined with the strong adhesion, biocompatibility and reactivity of PDA, the oriented wrinkles on PDA/PS patterned bilayers may find potential application in diffraction gratings, optical sensors and microfluidic devices.


The rebirth of health system in Italy after COVID-19 pandemia: starting points.
After COVID-19 pandemia we have to think how to rebuild our national health care system. Balance between health measures and social consequences, reformulation of the chain of command during emergency, clear guidelines for territorial medicine, census of health system are initial points of debate to carry on.


Structure and mechanism in non-homologous end joining.
DNA double-stranded breaks (DSBs) are a particularly challenging form of DNA damage to repair because the damaged DNA must not only undergo the chemical reactions responsible for returning it to its original state, but, additionally, the two free ends can become physically separated in the nucleus and must be bridged prior to repair. In nonhomologous end joining (NHEJ), one of the major pathways of DSB repair, repair is carried out by a number of repair factors capable of binding to and directly joining DNA ends. It has been unclear how these processes are carried out at a molecular level, owing in part to the lack of structural evidence describing the coordination of the NHEJ factors with each other and a DNA substrate. Advances in cryo-Electron Microscopy (cryo-EM), allowing for the structural characterization of large protein complexes that would be intractable using other techniques, have led to the visualization several key steps of the NHEJ process, which support a model of sequential assembly of repair factors at the DSB, followed by end-bridging mediated by protein-protein complexes and transition to full synapsis. Here we examine the structural evidence for these models, devoting particular attention to recent work identifying a new NHEJ intermediate state and incorporating new NHEJ factors into the general mechanism. We also discuss the evolving understanding of end-bridging mechanisms in NHEJ and DNA-PKcs's role in mediating DSB repair.


Soluble factors released by endothelial progenitor cells promote migration of endothelial cells and cardiac resident progenitor cells.
Circulating endothelial progenitor cells (EPC) are incorporated into newly formed capillaries, enhance neovascularization after hind limb ischemia and improve cardiac function after ischemic injury. Incorporated progenitor cells may also promote neovascularization and cardiac regeneration by releasing factors, which act in a paracrine manner to support local angiogenesis and mobilize tissue residing progenitor cells. Therefore, we analyzed the expression profile of cytokines in human peripheral blood-derived EPC as opposed to human umbilical vein endothelial cells (HUVEC), human microvascular endothelial cells (HMVEC), and CD14(+) monocytes by microarray technology. A gene tree analysis revealed a distinct expression pattern of angiogenic growth factors in EPC, mature endothelial cells, and CD14(+) monocytes. VEGF-A, VEGF-B, SDF-1, and IGF-1 mRNA levels were higher in EPC as compared to HUVEC or HMVEC. The enhanced mRNA expression was paralleled by a significant release of VEGF, SDF-1, and IGF-1 protein into the cell culture supernatant of EPC. Moreover, immunohistological analysis of ischemic limbs from nude rats revealed that VEGF is also released from recruited human EPC in vivo. As a functional consequence, conditioned medium of EPC induced a strong migratory response of mature endothelial cells, which was significantly inhibited by VEGF and SDF-1 neutralizing antibodies. Finally, conditioned medium of EPC significantly stimulated the migration of cardiac resident c-kit(+) progenitor cells in vitro. Taken together, EPC exhibit a high expression of angiogenic growth factors, which enhanced migration of mature endothelial cells and tissue resident cardiac progenitor cells. In addition to the physical contribution of EPC to newly formed vessels, the enhanced expression of cytokines may be a supportive mechanism to improve blood vessel formation and cardiac regeneration after cell therapy.


Supercooling, ice inoculation and freeze tolerance in the European common lizard, Lacerta vivipara.
The European common lizard (Lacerta vivipara) is widely distributed throughout Eurasia and is one of the few Palaearctic reptiles occurring above the Arctic Circle. We investigated the cold-hardiness of L. vivipara from France which routinely encounter sub-zero temperatures within their shallow hibernation burrows. In the laboratory, cold-acclimated lizards exposed to subfreezing temperatures as low as -3.5 degrees C could remain unfrozen (supercooled) for at least 3 weeks so long as their microenvironment was dry. In contrast, specimens cooled in contact with ambient ice crystals began to freeze within several hours. However, such susceptibility to inoculative freezing was not necessarily deleterious since L. vivipara readily tolerated the freezing of its tissues, with body surface temperatures as low as -3.0 degrees C during trials lasting up to 3 days. Freezing survival was promoted by relatively low post-nucleation cooling rates (< or = 0.1 degrees C.h-1) and apparently was associated with an accumulation of the putative cryoprotectant, glucose. The cold-hardiness strategy of L. vivipara may depend on both supercooling and freeze tolerance capacities, since this combination would afford the greatest likelihood of surviving winter in its dynamic thermal and hydric microenvironment.


Interfacial molecular regulation of TiO2 for enhanced and stable cocatalyst-free photocatalytic hydrogen production.
On the basis of the inherent property limitations of commercial P25-TiO2, many surface interface modification methods have attracted substantial attention for further improving the photocatalytic properties. However, current strategies for designing and modifying efficient photocatalysts (which exhibit complicated manufacturing processes and harsh conditions) are not efficient for production that is low cost, is nontoxic, and exhibits good stability; and therefore restrict practical applications. Herein, a facile and reliable method is reported for in situ amine-containing silane coupling agent functionalization of commercial P25-TiO2 by covalent surface modification for constructing a highly efficient photocatalyst. As a consequence, a high efficiency of H2 evolution was achieved for TiO2-SDA with 0.95 mmol h-1 g-1 (AQE ∼45.6 % at 365 nm) under solar light irradiation without a co-catalyst. The amination modification broadens the light absorption range of the photocatalyst, inhibits the binding of photogenerated carriers, and improves the photocatalytic efficiency; which was verified by photochemical properties and DFT theoretical calculations. This covalent modification method ensures the stability of the photocatalytic reaction. This work provides an approach for molecularly modified photocatalysts to improve photocatalytic performance by covalently modifying small molecules containing amine groups on the photocatalyst surface.


Mechanical aspects of a multidirectional, angular stable osteosynthesis system and comparison with four conventional systems.
Following open reduction, internal fixation of fractures of the mandible is predominantly achieved using plates and screws. Today, a multitude of osteosynthesis systems are available on the market. One therapy modality, primarily developed for orthopaedic surgery, is using angular stable osteosynthesis plate systems. The dominating principle of these is the bond between screw and plate following insertion. This principle of an "internal fixateur" results in a more stable fixation of the fragments associated with less compression of the bone surfaces. A new multidirectional osteosynthesis system (TiFix=Smartlock, Hamburg - Germany) was modified to fit the maxillofacial region and compared with four other well established osteosynthesis systems developed by Mondial, Medicon, Synthes, Leibinger-Stryker, one of these (Unilock by Synthes) being also angular stable. The resistance to deformation in varying directions was investigated following fixation in four different materials. The TiFix system proved more resistant to deformation even when mounted with fewer screws than the non-angular stable systems. This system results in greater stability even when fewer screws are used. For the clinician this means smaller access incisions, less soft tissue trauma, better aesthetic results, decreased duration of operation and a reduction of costs.


Fe doped amorphous single layered vanadyl phosphate nanosheets as highly efficient electrocatalyst for water oxidation.
The search for earth-abundant water oxidation electrocatalysts with low-cost and high-performance is essential to the energy conversion field. Well defined, rational designed two-dimensional materials have attracted enormous interest in light of much more specific surface areas and unique electronic properties. Herein, we report a facile two-phase solvothermal approach for the synthesis of Fe doped amorphous single-layered (~0.85 nm) vanadyl phosphate nanosheets (Fe-Am VOPO4). The obtained electrocatalyst exhibits excellent OER electrocatalytic performance, only require overpotential of 215 mV and 270 mV to reach current densities of 10 and 100 mA cm-2 in 1.0 M KOH electrolyte, and long-term electrochemical stability of 40 h. This work strikes out a path of synthesis of graphene-like materials with amorphous phase, and explores a new type of phosphate for efficient OER electrocatalysts.


Gut Bacterial Species Distinctively Impact Host Purine Metabolites during Aging in Drosophila.
Gut microbiota impacts the host metabolome and affects its health span. How bacterial species in the gut influence age-dependent metabolic alteration has not been elucidated. Here we show in Drosophila melanogaster that allantoin, an end product of purine metabolism, is increased during aging in a microbiota-dependent manner. Allantoin levels are low in young flies but are commonly elevated upon lifespan-shortening dietary manipulations such as high-purine, high-sugar, or high-yeast feeding. Removing Acetobacter persici in the Drosophila microbiome attenuated age-dependent allantoin increase. Mono-association with A. persici, but not with Lactobacillus plantarum, increased allantoin in aged flies. A. persici increased allantoin via activation of innate immune signaling IMD pathway in the renal tubules. On the other hand, analysis of bacteria-conditioned diets revealed that L. plantarum can decrease allantoin by reducing purines in the diet. These data together demonstrate species-specific regulations of host purine levels by the gut microbiome.


Ten years of progress towards universal health coverage: has China achieved equitable healthcare financing?
This study aims to systematically evaluate vertical and horizontal equity in the Chinese healthcare financing system over the period 2008-2018 during the progress towards Universal Health Coverage (UHC), and to examine how both types of equity have changed during this period. Household information on healthcare payments was collected from 2398 households involving 7021 individuals in 2008, 3600 households involving 10 466 individuals in 2013 and 3660 households involving 11 550 individuals in 2018. Redistributive effects of healthcare financing system were decomposed into progressivity, pure horizontal inequity and reranking. Progressivity analysis and the Aronson-Johnson-Lambert decomposition method were adopted to measure the vertical equity and horizontal equity of healthcare financing. Over the period 2008-2018, healthcare financing through indirect taxes showed a slightly prorich structure and healthcare financing through direct taxes showed a propoor structure in both urban and rural areas. Urban Employee Basic Medical Insurance experienced redistribution from the poor to the rich during the period 2008-2013, but then experienced redistribution from the rich to the poor during the period 2013-2018. Urban Resident Basic Medical Insurance (URBMI), New Rural Cooperative Medical Scheme (NRCMS), Urban and Rural Resident Basic Medical Insurance (URRBMI) and out-of-pocket payments experienced redistribution from the poor to the rich over the entire period. China's healthcare financing has experienced redistribution from the poor to the rich during 10 years of progress toward the UHC. UHC improved access to and utilisation of healthcare in urban areas. The flat rate contribution mechanism should be renovated for URBMI, NRCMS and URRBMI.


Thyroglossal duct cyst: personal experience and literature review.
The thyroglossal duct cyst [TDC, or thyroglossal tract remnant (TTR)] is a well recognized developmental abnormality which arises in some 7% of the population. As a consequence, it represents the most common type of developmental cyst encountered in the neck region. It typically presents as a mobile, painless mass in the anterior midline of the neck, usually in close proximity to the hyoid bone. Less often, TDCs may present with signs and symptoms of secondary infection, or with evidence of a fistula. While TDCs are most often diagnosed in the pediatric age group, a substantial minority of patients with TDCs are over 20 years of age at the time of diagnosis. The standard surgical approach to TDC, encompassing removal of the mid-portion of the hyoid bone in continuity with the TDC and excision of a core of tissue between the hyoid bone and the foramen cecum, dates back to the late 19th and early 20th centuries and is often referred to as Sistrunk's operation. Malignancy is rarely encountered in TDCs; when such rare tumors do develop (in the order of 1% or so of patients with TDCs), they usually take the form of either papillary carcinoma of thyroid origin, or squamous carcinoma.


Mouse SCO-spondin, a gene of the thrombospondin type 1 repeat (TSR) superfamily expressed in the brain.
SCO-spondin is specifically expressed in the subcommissural organ (SCO), a secretory ependymal differentiation lining the roof of the third ventricular cavity of the brain. When released into the cerebro-spinal fluid (CSF), SCO-spondin aggregates and forms Reissner's fiber (RF), a structure present in the central canal of the spinal cord. SCO-spondin belongs to the superfamily of proteins exhibiting conserved motifs called TSRs for 'thrombospondin type 1 repeats' and involved in axonal pathfinding during development. The mouse SCO-spondin coding sequence was searched by alignement of the coding bovine SCO-spondin sequence with the mouse whole genome shotgun (WGS) supercontig (NW 000250). Compared to the bovine, mouse SCO-spondin shows 66.8% identity of amino acids. This extracellular matrix glycoprotein has a modular arrangement of several conserved domains including 25 TSRs, 10 low-density lipoprotein receptor (LDLr) type A repeats and cystein-rich regions in the -NH2 and -COOH ends. The spatio-temporal expression of SCO-spondin was analyzed using specific antisera and an homospecific SCO-spondin riboprobe. In the adult, the patterns obtained by in situ hybridization (ISH) and immunohistochemistry correlated well in the SCO, while Reissner's fiber and the ampulla caudalis were immunoreactive only. In the fetus, both the immuno and ISH reactions appeared between 14 and 15 days post coïtum (dpc) in the SCO anlage. In addition, the mouse SCO-spondin gene was located at chromosome 6, between marker D6Mit352 and D6Mit119, in a conserved syntenic region.


Effects of a new bisphosphonate (AHBuBP) on osteolysis induced by human prostate cancer cells in nude mice.
A new bisphosphonate, 4-amino-1-hydroxybutylidene-1, 1-bisphosphonate (AHBuBP), was compared with 3-amino-1-hydroxypropylidene-1, 1-bisphosphonate (AHPrBP) and 1-hydroxyethylidene-1, 1-bisphosphonate (HEBP) assessing their effects on tumor induced osteolysis using human prostate adenocarcinoma cells in nude mice. The method consisted of inoculating transplantable human prostate cancer cells subcutaneously over the calvaria in nude mice resulting in a local tumor causing fragmentation of the bone. The parameters included assessing the extent of decreased osteolysis in bone as judged by X-ray and histological examination. The results showed the following sequence of potency: AHBuBP greater than AHPrBP greater than HEBP. The compounds were active not only when administered preventively before establishment of bone resorption, but also in an inhibitory fashion once the variables were already under the influence of the tumor. This inhibition was obtained with no apparent effect on the growth of the tumor. AHBuBP appears to be an interesting new bisphosphonate for future clinical use.


Impacts of media coverage on the community stress level in Hong Kong after the tsunami on 26 December 2004.
The study investigated the prevalence and associated factors (media coverage in particular) of stress related responses to the December 2004 tsunami. An anonymous population based cross sectional telephone survey was conducted. Post-traumatic stress symptom was measured by the locally validated Chinese impact of event scale (CIES) and whether the respondent felt disturbed, apprehensive, or horrified because of the tsunami. Items related to media coverage included measures on frequency of exposure, level of distress caused by different types of images, and contents of the news messages were measured. Two summative scores, the weighted image unrest score (WIUS) and weighted content unrest score (WCUS) were formed. Hong Kong, China. A total of 604 adult Chinese respondents were interviewed. Of the respondents, 33.8% were exposed to tsunami related mass media news reports >10 times per day; 56.5% to 64.7% felt severely or very severely disturbed by the six studied types of distressful messages; 52.6% to 71.4% felt similarly because of the eight studied types of distressful contents. Of the male respondents, 30% and 5.9% respectively showed signs of mild or moderate/severe post-traumatic stress symptoms (39% and 8.7%, respectively for women). Higher WIUS and higher WCUS were associated with mild or moderate/severe post-traumatic stress symptoms (multivariate OR = 1.72 to 14.67, p<0.05). These media exposure indicators, together with some other perception variables, were significantly associated with other stress indicators. The intensive media coverage of the tsunami was consistently associated with different types of tsunami related stress indicators.


Why is everyone talking about brain state?
The rapid and coordinated propagation of neural activity across the brain provides the foundation for complex behavior and cognition. Technical advances across neuroscience subfields have advanced understanding of these dynamics, but points of convergence are often obscured by semantic differences, creating silos of subfield-specific findings. In this review we describe how a parsimonious conceptualization of brain state as the fundamental building block of whole-brain activity offers a common framework to relate findings across scales and species. We present examples of the diverse techniques commonly used to study brain states associated with physiology and higher-order cognitive processes, and discuss how integration across them will enable a more comprehensive and mechanistic characterization of the neural dynamics that are crucial to survival but are disrupted in disease.


Social factors in bird-song development: Learning to sing with friends and rivals.
Laboratory studies have revealed that social factors are key in bird-song learning. Nevertheless, little is known about how or why birds choose the songs they do learn from the many they will hear under natural conditions. We focus on various theories concerning social song learning that have been offered to date, with special attention paid to two axes of social factors. First, does song learning occur via direct interaction of the young bird with song tutors, or via social eavesdropping by the young bird on interacting singers (social modeling of song)? Social modeling, a hypothesis first proposed by Pepperberg (Zeitschrift für Tierpsychologie, 55(2), 139-160, 1981), and direct interaction are not mutually exclusive hypotheses, and the evidence we review suggests both play a role in song learning. Second, does song learning occur via interactions with rivals (territorial competitors) or with friends (mutually tolerant or even cooperative territorial neighbors). These are largely mutually exclusive hypotheses, and can really only be tested in the field. There is little evidence on this contrast to date. We review our recent study on song sparrows, which indicates that both the young bird and his primary tutor may benefit from song learning/tutoring. If this mutual benefit result is confirmed by further studies, we believe that song "tutoring" in these cases may be more than a term of convenience: that it may qualify as true teaching.


A novel mutation in RFXANK gene and low B cell count in a patient with MHC class II deficiency: a case report.
Recurrence of severe microbial infections results from a primary immunodeficiency disorder known as major histocompatibility complex class II deficiency or bare lymphocyte syndrome type II. Immunologic function is severely impaired due to the absence of MHC class II molecules on the surface of immune cells. Here, we report a 5-year-old boy with a novel homozygous mutation in RFXANK gene that negatively affects the proper expression of MHC class II molecules by antigen presenting cells. The frame shift mutations in RFXANK gene and negative HLA-DR proteins expression on peripheral blood mononuclear cells were identified and confirmed by whole exome sequencing, Sanger sequencing, and flow cytometry. The patient was referred with long-term severe prolonged diarrhea, fever, coughing, and vomiting. Also, antibiotic resistance, normal T cell, and NK cell counts with low B cell count and reduced serum immunoglobulin level were observed. The patient did not give a dramatic response to intravenous immunoglobulin infusion. The significancy of this report is the novelty of mutation and low B cell count which is not commonly expected in such patients. The final diagnosis of BLS type II is based on WES, Sanger sequencing, and flow cytometric evaluation. Moreover, it seems that the only therapeutic choice is hematopoietic stem cell transplantation.


Inflammatory response during hyperglycemia and hyperinsulinemia in a porcine endotoxemic model: the contribution of essential organs.
During euglycemia acute hyperinsulinemia diminishes the cytokine response to endotoxin [Lipopolysaccharide (LPS)] exposure. In this study we elucidated whether acute hyperglycemia and hyperinsulinemia modify the cytokine content in several organs during LPS challenge in a porcine model. Pigs (35-40 kg) were randomized to either normoglycemia (group 1, n = 8) or hyperglycemia and hyperinsulinemia (group 2, n = 8), anesthetized and mechanically ventilated. Both groups received a 180-min intravenous infusion of LPS (total 10 microg kg(-1)). Groups 1 and 2 were clamped at plasma glucose concentrations of 5 mM and 15 mM, respectively. Group 1 maintained a baseline insulin level while the hyperglycemic group exhibited increased insulin levels. Circulating cytokines, cytokine mRNA and cytokine protein content were examined in the heart, liver, kidneys, lungs, spleen, adipose and muscle tissue. After LPS exposure, in both groups vast and equal plasma cytokines were elicited by approximately 70-5000-fold. A 10-fold higher level of IL-10, IL-6 and TNF-alpha protein was found in kidney tissue compared to the other organs together with a 3-10-fold increase of TNF-alpha in adipose tissue. However, cytokine mRNAs as well as organ function were without statistical difference between the groups. Endotoxemia elicited a pronounced cytokine response in both plasma and at organ level. The kidneys and adipose tissue showed the highest cytokine protein content. Acute hyperglycemia apparently counteracts the well-established anti-inflammatory effects of insulin on the inflammatory response in a LPS challenged porcine model. Whether the observation can be extrapolated to more long-term stress-exposure remains to be clarified.


Dietary fiber chemical structures and physicochemical properties of edible Pouteria glomerata fruits, native from Brazilian Pantanal.
Pouteria glomerata is a native species from the Brazilian Pantanal, whose fruit is edible and still underexploited. The objective of this study was to carried out the chemical, nutritional and antioxidant properties of this tropical fruit, as well as to isolate e characterize the chemical strucutre of their dietary fibers. DPPH and ORAC methods were used to determine the antioxidant capacity. Minerals were quantified using inductively coupled plasma optical emission spectrometry. Soluble and insoluble dietary fiber fractions were obtained by the standard enzymatic-gravimetric method and chemically characterized by monosaccharide composition, gel permeation and NMR spectroscopy. Results showed that P. glomerata fruits presented high antioxidant capacity and high levels of vitamin C, minerals, insoluble dietary fiber, and malic acid. The soluble dietary fiber was mainly composed of uronic acids, arabinose, and galactose, and NMR analysis indicated the presence of highly methylesterified homogalacturonan, arabinan and/or arabinogalactan as pectic polysaccharides. Hemicelluloses present in insoluble dietary fiber fraction were solubilized by alkaline treatment, and characterized as (1 → 4)-β-D-xylan. The results brings new chemical information about this native fruit and may open new opportunities for using it as a potential ingredient for health improvement by human comsumption.


Spontaneous lesions in the respiratory epithelium of the Syrian golden hamster as seen by scanning electron microscopy.
The respiratory epithelium of 8, 12.5 and 17.5-month-old Syrian golden hamsters was investigated by scanning electron microscopy (SEM) and routine light microscopy (LM) of paraplast sections. In selected cases, SEM-specimens were embedded in Epon after SEM evaluation. The samples were cut in semithin sections and examined by light microscopy. The density of ciliated cells in the respiratory epithelium differs from hamster to hamster. Care must, therefore, be taken when diagnosing simple metaplasia by SEM alone unless a sufficient number of damaged cilia are present. Only 1 animal (8 months old) exhibited squamous metaplasia of the tracheal mucosa. However, surface polymorphism resembling squamous metaplasia was seen in almost every specimen. The polymorphism was caused by either submucosal calcifications or by cystic changes of hypertrophic submucosal glands. In addition, variously formed aggregations of mucus were seen protruding from duct openings of hypertrophic submucosal glands. To avoid false positive or negative diagnosis which can occur when screening is done by SEM alone, light-microscopical examination of sections cut from SEM identified lesions appears necessary.


rec-YnH enables simultaneous many-by-many detection of direct protein-protein and protein-RNA interactions.
Knowing which proteins and RNAs directly interact is essential for understanding cellular mechanisms. Unfortunately, discovering such interactions is costly and often unreliable. To overcome these limitations, we developed rec-YnH, a new yeast two and three-hybrid-based screening pipeline capable of detecting interactions within protein libraries or between protein libraries and RNA fragment pools. rec-YnH combines batch cloning and transformation with intracellular homologous recombination to generate bait-prey fusion libraries. By developing interaction selection in liquid-gels and using an ORF sequence-based readout of interactions via next-generation sequencing, we eliminate laborious plating and barcoding steps required by existing methods. We use rec-Y2H to simultaneously map interactions of protein domains and reveal novel putative interactors of PAR proteins. We further employ rec-Y2H to predict the architecture of published coprecipitated complexes. Finally, we use rec-Y3H to map interactions between multiple RNA-binding proteins and RNAs-the first time interactions between protein and RNA pools are simultaneously detected.


Biopsychosocial factors associated with a current depressive episode in diabetes: the ELSA-Brasil study.
Depression is more prevalent in people with diabetes, and is associated with worse diabetes outcomes. Depression in diabetes is more treatment resistant, and as underlying mechanisms are unknown, development of more effective treatment strategies is complicated. A biopsychosocial model may improve our understanding of the pathophysiology, and therewith help improving treatment options. Diabetes was diagnosed according to American Diabetes Association (ADA) criteria and a current depressive episode according to the International Classification of Diseases (ICD-10), based on the Clinical Interview Schedule Revised (CIS-R). From the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil), we included 455 participants without diabetes with a current depressive episode and 10 900 without either diabetes or a current depressive episode. Furthermore, 2183 participants had diabetes alone and 106 had both diabetes and a current depressive episode. Variable selection was based on their relationship with depression and/or diabetes. Multinomial multivariate logistic regression was used to determine how the models differed between participants with and without diabetes. A current depressive episode in diabetes was related to being older and female, having poorer education, financial problems, experiencing discrimination at work, home and school, higher waist circumference, albumin to creatinine ratio and insulin resistance, and the presence of hypertension and cardiovascular disease. In non-diabetes, a current depressive disorder was related to being female, not being black, low income, psychological and social factors, non-current alcohol use, lower HDL cholesterol, higher insulin resistance and the presence of cardiovascular disease. A current depressive episode in the presence compared with the absence of diabetes was related more to biological than to psychosocial factors.


Neuroendocrine Carcinoma of the Kidney and Bladder with Loss of Heterozygosity and Changes in Chromosome 3 Copy Number.
Neuroendocrine carcinomas (NECs) of the urological organs are observed occasionally, although simultaneous development in the kidney and blabber has not been reported. We report a case of a metastatic NEC of the kidney and bladder in a 77-year-old woman who underwent renal biopsy and transurethral resection of the bladder tumor. Pathological examination revealed NEC in the kidney and the bladder samples. Immunohistochemical examination revealed strongly positive staining for synaptophysin, chromogranin A, and CD56, and focally positive staining for cytokeratin AE 1/3 and Cam 5.2. Fluorescence in situ hybridization confirmed the increased chromosome 3 copy number, and loss of hybridization in 3q21, 5q22-23, 10q26, and 13q14 was detected when the tumor samples were compared with normal samples. This is a rare case of NEC-specific genetic abnormalities in a kidney-derived tumor, and is the first report to identify kidney-derived NEC that metastasized to the bladder via the urinary tract.


Experimental studies on the olfactory marker protein. V. Olfactory marker protein in the olfactory neurons transplanted within the olfactory bulb.
The olfactory mucosa of neonatal rats was transplanted within the olfactory bulb of littermates to investigate whether the olfactory bulb would have played a role in the differentiation of the olfactory neurons and whether the olfactory axons, growing out from the transplant, would have interacted with the olfactory glomeruli of the host. The observations were conducted on sections stained with Gill's hematoxylin, Loots' silver method, and the immunohistochemical technique for the demonstration of the olfactory marker protein (OMP). The olfactory neurons of the transplant (those localized in the neuroepithelium and those migrating from it into the bulbar parenchyma) could become fully differentiated but only few of them were OMP positive. Numerous sensory axons originated from the transplanted olfactory mucosa, however, they did not form ectopic glomeruli nor did they interact with the glomeruli of the host. These results indicate that the olfactory bulb, in vivo, does not affect the number of olfactory neurons expressing OMP and that the ectopically located neurons lack the cues to recognize the host glomeruli.


Peroperative ultrasonography in the diagnosis of splenic vein thrombosis.
A case of recurrent bleeding from gastric varices due to isolated splenic vein thrombosis is reported. There was no evidence of pancreatic, retroperitoneal or infectious disease. The final diagnosis was made by intraoperative ultrasonography during an emergency laparotomy for massive bleeding from a ruptured gastric vein. Splenectomy is the treatment of choice in this case. The patient was cured after splenectomy.