Hepatocellular carcinoma recurrence after liver transplantation in a Brazilian multicenter study: clinical profile and prognostic factors of survival.
Liver transplantation (LT) is the treatment of choice for patients with unresectable early hepatocellular carcinoma (HCC). Post-LT HCC recurrence rates range from 8 to 20% and still impact on overall survival (OS). The aim of our study was to evaluate the impact of HCC recurrence on post-LT survival and analyze prognostic factors among those patients with recurrence. We carried out a national, multicenter, retrospective cohort study in Brazil. Medical records of 1119 LT recipients with HCC were collected. Data from patients with post-LT HCC recurrence were analyzed and correlated with post-relapse survival. OS of the 1119 patients included in the study was 63% over 5 years. Post-LT HCC recurrence occurred in 86 (8%) patients. The mean time to recurrence was 12 months. Sites of recurrence were extrahepatic in 55%, hepatic in 27%, and both hepatic and extrahepatic in 18%. Recurrence treatment was performed in 50 (64%) cases, mostly with sorafenib. Post-relapse survival rates were 34% at 1 year and 13% at 5 years. Univariable analysis identified α-fetoprotein more than 1000 ng/ml at relapse, recurrence treatment, extrahepatic location, and time to recurrence more than 2 years as prognostic factors. In multivariable analysis, recurrence treatment, extrahepatic location, and time to recurrence more than 2 years were independent predictors of better survival. In a large Brazilian cohort of LT recipients with HCC, post-LT HCC recurrence occurred in 8% and impacted significantly on the OS. Patients with early recurrence presented a worse prognosis. However, treatment of recurrence improved outcomes, highlighting the importance of early diagnosis.


Wavy stripes and squares in zero-Prandtl-number convection.
A simple model to explain the numerically observed behavior of chaotically varying stripes and square patterns in zero-Prandtl-number convection in Boussinesq fluid is presented. The nonlinear interaction of mutually perpendicular sets of wavy rolls, via higher-order modes, may lead to a competition between the two sets of rolls. The appearance of square patterns is due to a secondary forward bifurcation from a set of wavy rolls. The statistics of the spatially averaged energy signal shows a power-law behavior.


Current Approaches to the Diagnosis of Classical form of Congenital Adrenal Hyperplasia.
Congenital adrenal hyperplasia (CAH) is one of the most common diseases transmitted in an autosomal recessive manner and is caused by mutations of enzymes which are responsible for the process of adrenal steroidogenesis. According to the impairment of enzymes involved in steroidogenesis, several types of CAH can be distinguished. The most common type is associated with mutations in the CYP21A2 gene, encoding 21-hydroxylase enzyme and has different clinical forms: Classical (in which there are two types: salt wasting and simple virilization) and non-classical, characterized by less severe symptoms and late onset. CAH is characterized by a strong correlation between the genotype and the phenotype. Mutations in the CYP21A2 gene can cause different degrees of loss of 21-hydroxylase enzyme activity which result in a wide spectrum of clinical pictures. Several methods used to diagnose CAH (such as determining steroids in serum or urine) have been known from the 70's. Modern diagnosis of CAH is based primarily on the use of genetic testing, which is the subject of numerous constantly updated patents. In this paper the most recent patents on the diagnosis of CAH were assessed.


3D-MEDNEs: an alternative "in silico" technique for chemical research in toxicology. 1. prediction of chemically induced agranulocytosis.
A novel approach to molecular negentropy from the point of view of Markov models is introduced. Stochastic negentropies (MEDNEs) are used to develop a linear discriminant analysis. The discriminant analysis produced a set of two discriminant functions, which gave rise to a very good separation of 93.38% of 151 chemicals (training series) into two groups. The total predictability (86.67%, i.e., 52 compounds out of 60) was tested by means of an external validation set. Randić's orthogonalization procedures allowed interpretation of the model while avoiding collinearity descriptors. On the other hand, factor analysis was used to suggest the relation of MEDNEs with other molecular descriptors and properties into a property space. Three principal factors (related to three orthogonal MEDNEs) can be used to explain approximately 90% of the variance of different molecular parameters of halobenzenes including bulk, energetic, dipolar, molecular surface-related, and hydrophobic parameters. Finally, preliminary experimental results coincide with a theoretical prediction when agranulocytosis induction by G-1, a novel microcidal that presents Z/E isomerism, is not detected.


Effect of neuromuscular electrical stimulation associated with swallowing-related muscle training for post-stroke dysphagia: A protocol for systematic review and meta-analysis.
Swallowing dysfunction is a common dysfunction after stroke, and its incidence exceeds 50%. Aspiration pneumonia and malnutrition induced by dysphagia not only cause psychological shock to patients after stroke, but also burden the medical payment. Neuromuscular electrical stimulation, which stimulates the cortex and cortical bulb pathways to improve swallowing function, has been one of the emerging treatments for the post-stroke deglutition disorder. These therapy operators require the proficiency in professional knowledge, limiting clinical large sample studies, so there is an absence of evidence-based medicine. The research is to evaluate the effectiveness of neuromuscular electrical stimulations combined with swallowing-related muscle training to treat swallowing dysfunction after stroke. Computer retrieval performed in the 9 databases, including PubMed, Embase, Web of science, Cochrane Library, ClinicalTrials, China Biomedical Literature Database (CBM), China Knowledge Network Database (CNKI), Wanfang Database (WanFang), and China VIP Database (VIP). Taking the published literature from the establishment of the database until December 20, 2020. Literature searching is related to neuromuscular electrical stimulation randomized controlled trials on the effect of swallowing in stroke. In addition, we will do the manual search in Baidu Academic and Google Academic database as a supplementary search. The correlative randomized controlled clinical studies retrieval time range from the establishment of the database to December 20, 2020. Two investigators will screen the literature according to the inclusion and exclusion criteria independently, during that period they will evaluate the quality of the included studies and extract data from studies. The extracted data are dichotomous data will be represented by relative risk, continuous data will be represented by mean difference or standard mean deviation. If there exists heterogeneity and the final data summary analysis select random effect model. On the contrary, the fixed effect model is selected. Then, RevMan5.3 software was used when analyzing included literature. Meanwhile, the analysis results were illustrated by drawing. This review will summarize available trials aimed at providing a comprehensive estimation of effectiveness of neuromuscular electrical stimulation associated with swallowing muscle training for post-stroke dysphagia. This review based on a comprehensive analysis of currently published randomized controlled trials on post-stroke dysphagia, that provide reliable evidence-based medicine evidence for the efficacy of neuromuscular electrical stimulation associated with swallowing rehabilitation training. INPLASY202110009.


New Cytotoxic Natural Products from the Red Sea Sponge Stylissa carteri.
Bioactivity-guided isolation supported by LC-HRESIMS metabolic profiling led to the isolation of two new compounds, a ceramide, stylissamide A (1), and a cerebroside, stylissoside A (2), from the methanol extract of the Red Sea sponge Stylissa carteri. Structure elucidation was achieved using spectroscopic techniques, including 1D and 2D NMR and HRMS. The bioactive extract's metabolomic profiling showed the existence of various secondary metabolites, mainly oleanane-type saponins, phenolic diterpenes, and lupane triterpenes. The in vitro cytotoxic activity of the isolated compounds was tested against two human cancer cell lines, MCF-7 and HepG2. Both compounds, 1 and 2, displayed strong cytotoxicity against the MCF-7 cell line, with IC50 values at 21.1 ± 0.17 µM and 27.5 ± 0.18 µM, respectively. They likewise showed a promising activity against HepG2 with IC50 at 36.8 ± 0.16 µM for 1 and IC50 30.5 ± 0.23 µM for 2 compared to the standard drug cisplatin. Molecular docking experiments showed that 1 and 2 displayed high affinity to the SET protein and to inhibitor 2 of protein phosphatase 2A (I2PP2A), which could be a possible mechanism for their cytotoxic activity. This paper spreads light on the role of these metabolites in holding fouling organisms away from the outer surface of the sponge, and the potential use of these defensive molecules in the production of novel anticancer agents.


Programmed Site-Selective Palladium-Catalyzed Arylation of Thieno[3,2-b]thiophene.
Mono-, di-, tri-, and tetraarylated thieno[3,2-b]thiophenes were synthesized by direct site-selective Pd-catalyzed C-H activation reactions with various aryl bromides in the presence of a phosphine-free Pd(OAc)2 /KOAc catalyst system in N,N-dimethylacetamide (DMAc). The arylation of 2-arylthieno[3,2-b]thiophene took place at the C3 position if the 2-aryl substituents possessed electron-withdrawing groups and at the C5 position if they were bulky and possessed electron-donating groups.


Five-year follow-up results of a randomized controlled trial comparing bipolar plasmakinetic and monopolar transurethral resection of the prostate.
To report the 5-year follow-up results of a randomized controlled trial comparing bipolar transurethral resection of the prostate (TURP) with standard monopolar TURP for the treatment of benign prostatic obstruction (BPO). A total of 220 patients were randomized to bipolar plasmakinetic TURP (PK-TURP) or monopolar TURP (M-TURP). Catheterization time was the primary endpoint of this study. Secondary outcomes included operation time, hospital stay, as well as decline in postoperative serum sodium and hemoglobin levels. All patients were assessed preoperatively and followed-up at 1, 6, 12, 24, 36, 48, and 60 months postoperatively. Parameters assessed included quality of life, transrectal ultrasound, serum prostate-specific antigen level, postvoid residual urine volume, maximum urinary flow rates (Q(max)), and International Prostate Symptom Score. Patient baseline characteristics, perioperative data including complications, and postoperative outcomes were compared. Complication occurrence was graded according to the modified Clavien classification system. PK-TURP was significantly superior to M-TURP in terms of operation time, intraoperative irrigation volume, resected tissue weight, decreases in hemoglobin and sodium, postoperative irrigation volume and time, catheterization time, and hospital stay. At 5 years postoperatively, efficacy was comparable between arms. No differences were detected in safety outcomes except that the clot retention rate was significantly greater after M-TURP. Our results indicate that PK-TURP is equally as effective in the treatment of BPO, but has a more favorable safety profile in comparison to M-TURP. The clinical efficacy of PK-TURP is long-lasting and comparable with M-TURP.


Inhibitions of mast cell-derived histamine release by different Flos Magnoliae species in rat peritoneal mast cells.
Flos Magnoliae (FM) is a commonly used Chinese medicinal herb for symptomatic relief of allergic rhinitis, sinusitis and headache. A number of FM species have been used as substitutes or adulterants for clinical application, although the differences in their pharmacological actions have not been reported. The present study investigated the effects of six identified FM species M. biondii, M. denudata, M. kobus, M. liliflora, M. sargentiana and M. sprengeri, as well as the marker compounds magnolin and fargesin on compound 48/80-induced histamine release in rat peritoneal mast cells (RPMC) in vitro. Ethanolic extracts of all FM species produced a concentration-dependent inhibition of compound 48/80-induced histamine release in RPMC. The rank order of the IC(50)s was M. biondii<M. kobus<M. liliflora<M. denudata<M. sprengeri<M. sargentiana. The marker compound magnolin, but not fargesin, only slightly inhibited the histamine release. The contents of magnolin and fargesin, determined by using RP-HPLC, varied significantly among these FM species. Magnolin was found in M. biondii, M. kobus and M. liliflora, but not in M. denudate, M. sprengeri and M. sargentiana, while fargesin was only found in M. biondii and M. kobus. These findings provide the first evidence of differences in pharmacological actions of different FM species on mast cell-derived histamine release in vitro. In addition, the marker compounds magnolin and fargesin may not play a major role in the observed pharmacological actions of FM species.


Heterogeneity of CD80 gene transcription by human keratinocytes to allergens and irritants: relevance to allergic contact dermatitis in vivo.
Using an in vitro assay for CD80 promoter activity, the transcriptional response of primary cultured human keratinocytes from different donors in response to allergens and irritants was studied. The CD80 promoter activity was increased reproducibly after exposure to certain chemicals. The epithelial cell lines HeLa and HaCaT also increased CD80 transcriptional activity in response to exposure to a panel of different allergens and irritants. Normal or immortalized keratinocytes responded reproducibly with a unique pattern to a panel of chemicals in which the culture increases CD80 transcription after exposure to certain chemicals and has no increase in CD80 transcription after exposure to other chemicals. Some keratinocyte cultures responded positively to certain chemicals whereas others did not respond to the same chemicals. Cultured keratinocytes from 16 of 20 adult donors (80%) responded to nitrochlorobenzene in vitro by increasing CD80 transcriptional activity, thus predicting subsequent sensitization to this same hapten (chi2= 7.2, P <0.0073). Thus, a keratinocyte CD80 gene expression assay exhibits good sensitivity in predicting allergic contact dermatitis for sensitizers such as dinitrochlorobenzene. These data suggest that there is a rationale for developing the use of gene-transcription-based predictive assays to identify individual susceptibility to cutaneous reactivity after exposure to allergens and irritants.


[Doses of epirubicin used in oily chemoembolization of hepatocellular carcinoma].
Epirubicin (EPIR), an anticancer agent, has recently been used with increasing frequency in transcatheter oily chemoembolization (TOCE) of hepatocellular carcinoma. We conducted a dose-finding study of EPIR with regard to its safety. One hundred thirty-four patients were divided into five groups according to the EPIR doses (mg/m2), Group A (< 30 mg/m2), Group B (> or = 30 - < 40 mg/m2), Group C (> or = 40 - < 50 mg/m2), Group D (> or = 50 - < 60 mg/m2), and Group E (> or = 60 mg/m2). The number of leukocytes decreased at 2 weeks but recovered at 4 weeks with no significant differences among the groups. However, there were significantly fewer leukocytes in Group E than in Groups A to D. There were no significant differences among the groups in either the number of erythrocytes or platelets. The number of platelets tended to remain at increased levels even at 4 weeks. Liver function as represented by GOT, GPT, LDH, and total bilirubin was not aggravated, but tended to improve. GOT and LDH in Groups D and E, in particular, improved significantly at 4 weeks, probably because of the antitumor effect of TOCE. These results suggest that EPIR can be administered up to 50 mg/m2 for TOCE.


Effects of medical male circumcision (MC) on plasma HIV viral load in HIV+ HAART naïve men; Rakai, Uganda.
Medical male circumcision (MC) of HIV-infected men may increase plasma HIV viral load and place female partners at risk of infection. We assessed the effect of MC on plasma HIV viral load in HIV-infected men in Rakai, Uganda. 195 consenting HIV-positive, HAART naïve men aged 12 and above provided blood for plasma HIV viral load testing before surgery and weekly for six weeks and at 2 and 3 months post surgery. Data were also collected on baseline social demographic characteristics and CD4 counts. Change in log10 plasma viral load between baseline and follow-up visits was estimated using paired t tests and multivariate generalized estimating equation (GEE). Of the 195 men, 129 had a CD4 count ≧ 350 and 66 had CD4 <350 cells/mm3. Men with CD4 counts <350 had higher baseline mean log10 plasma viral load than those with CD4 counts ≧ 350 cells/mm3 (4.715 vs 4.217 cps/mL, respectively, p = 0.0005). Compared to baseline, there was no statistically significant increase in post-MC HIV plasma viral loads irrespective of CD4. Multivariate analysis showed that higher baseline log10 plasma viral load was significantly associated with reduction in mean log10 plasma viral load following MC (coef. = -0.134, p<0.001). We observed no increase in plasma HIV viral load following MC in HIV-infected, HAART naïve men.


[Composition of cerebrospinal fluid protein in children with nervous system diseases according to disc-electrophoresis in polyacrylamide gel].
The author studied the fractional content of proteins in the CSF in 105 children with different disorders of the nervous system and 35 children of a control group (aged 2-13 years) with the aid of disc-electrophoresis in polyacrylamide gel. The proteins of the CSF were studied in encephalitis, polyradiculoneuritis, cerebral arachnoiditis, brain tumors and epilepsy. The content of total proteins in the CSF in 42% of the studied children did not differ significantly from the usual age norm. More distinct changes were found in proteinogramms of the CSF where 14 protein fractions were singled out. It was established that a change in the content of separate fractions, their intercorrelation depended on the character of the pathological process.


Cutaneous photosensitivity to medications.
Photosensitivity induced by exogenous agents accounts for an increasing portion of the total undesirable effects caused by environmental chemicals. The exponential increase in the number of new drugs each year is responsible for a significant rise in the incidence of and disability caused by these reactions. An extensive drug history must be taken whenever a patient presents with a reaction limited to or accentuated in light-exposed areas. These reactions may present with a wide morphologic spectrum ranging from sunburn-like responses to eczematous, lichenoid, and even bullous lesions resembling porphyria cutanea tarda.


Enhancement of lamina cribrosa visibility in optical coherence tomography images using adaptive compensation.
We improved the visibility of the lamina cribrosa (LC), including its posterior boundary, in optical coherence tomography (OCT) images of the human optic nerve head (ONH). An adaptive compensation algorithm was developed to overcome a limitation of our standard compensation algorithm, that is the overamplification of noise at high depth. Such limitation currently hampers our ability to distinguish the posterior LC boundary. In adaptive compensation, standard compensation operations are performed until an energy threshold is reached, at which stage the compensation process is stopped to limit noise overamplification in the deeper portion of the OCT image. The performance of adaptive compensation was compared to that of standard compensation using OCT images of 5 human ONHs. Adaptive compensation significantly reduced the intralayer contrast (a measure of pixel intensity uniformity) in the deeper portion of the OCT images (from 0.62 ± 0.11-0.30 ± 0.03, P < 0.001), indicating successful removal of noise overamplification. Furthermore, adaptive compensation significantly increased the interlayer contrast (a measure of boundary visibility) across the posterior LC boundary (from 0.29 ± 0.13-0.61 ± 0.21, P < 0.001), indicating improved posterior LC boundary visibility. Adaptive compensation provided significant improvement compared to standard compensation by eliminating noise overamplification at high depth and improving the visibility of the posterior LC boundary. These improvements were performed while maintaining all other benefits of compensation, such as shadow removal and contrast enhancement. Adaptive compensation will help further our efforts to characterize in vivo ONH biomechanics for the diagnosis and monitoring of glaucoma.


Comparative Immune Response in Children and Adults with H. pylori Infection.
Helicobacter pylori (H. pylori) infection is generally acquired during early childhood; therefore, the immune response which usually takes place at this age may influence or even determine susceptibility to the infection contributing to the clinical outcomes in adulthood. Several cytokines including IL-6, IL-10, and TGF-β1 as well as Foxp3(+) cell numbers have been shown to be higher; however, some other cytokines consisting of IL-1β, IL-17A, and IL-23 are lower in infected children than in infected adults. Immune response to H. pylori infection in children is predominant Treg instead of Th17 cell response. These results indicate that immune system responses probably play a role in persistent H. pylori infection. Childhood H. pylori infection is also associated with significantly lower levels of inflammation and ulceration compared with adults. This review, therefore, aimed to provide critical findings of the available literature about comparative immune system in children and adults with H. pylori infection.


Angiotensin converting enzyme inhibitory activity of SCH 33844 (spirapril) in rats, dogs and monkeys.
SCH 33844 is a new non-sulfhydryl-containing angiotensin converting enzyme (ACE) inhibitor. SCH 33844 diacid inhibited hydrolysis of the synthetic substrate hippuryl-histidyl-leucine by rabbit lung ACE in vitro with an IC50 (concentration inhibiting enzyme by 50%) of 0.81 nM. The ester was 83 times less active. Intravenous administration of SCH 33844 and its diacid inhibited pressor responses to angiotensin I (AI) in anesthetized rats with calculated ID50's of 16 and 8 micrograms/kg, respectively. Oral administration of SCH 33844 (0.03-1 mg/kg) inhibited AI pressor responses in conscious rats with a duration of 24 hr at the highest dose. The diacid was inactive. Intravenous administration of SCH 33844 (100-1000 micrograms/kg) or its diacid (30 micrograms/kg) to anesthetized dogs inhibited AI pressor activity and potentiated the depressor response to bradykinin. SCH 33844 inhibited AI responses in conscious dogs following oral administration of 0.3-3 mg/kg. Oral administration of SCH 33844 (1 mg/kg) to conscious monkeys inhibited AI pressor responses for the 4 hr duration of study. In conclusion, SCH 33844 is a potent, orally effective ACE inhibitor in rats, dogs and monkeys.


Pigment production by filamentous fungi on agro-industrial byproducts: an eco-friendly alternative.
The search for new sources of natural pigments has increased, mainly because of the toxic effects caused by synthetic dyes used in food, pharmaceutical, textile, and cosmetic industries. Fungi provide a readily available alternative source of natural pigments. In this context, the fungi Penicillium chrysogenum IFL1 and IFL2, Fusarium graminearum IFL3, Monascus purpureus NRRL 1992, and Penicillium vasconiae IFL4 were selected as pigments producers. The fungal identification was performed using ITS and part of the β-tubulin gene sequencing. Almost all fungi were able to grow and produce water-soluble pigments on agro-industrial residues, with the exception of P. vasconiae that produced pigments only on potato dextrose broth. The production of yellow pigments was predominant and the two strains of P. chrysogenum were the largest producers. In addition, the production of pigments and mycotoxins were evaluated in potato dextrose agar using TOF-MS and TOF-MS/MS. Metabolites as roquefortine C, chrysogine were found in both extracts of P. chrysogenum, as well fusarenone X, diacetoxyscirpenol, and neosolaniol in F. graminearum extract. In the M. purpureus extract, the pigments monascorubrin, rubropunctatin, and the mycotoxin citrinin were found. The crude filtrates have potential to be used in the textile industry; nevertheless, additional pigment purification is required for food and pharmaceutical applications.


Effect of endurance training on fatty acid metabolism: local adaptations.
Older studies of humans seem to suggest a correlation between free fatty acid (FFA) turnover and oxidation on the one hand and plasma FFA concentration on the other hand during submaximal exercise. However, recent studies, in which higher concentrations of plasma FFA have been reached during prolonged submaximal exercise, have revealed a levelling off in net uptake in spite of increasing plasma FFA concentrations. Furthermore, this relationship between FFA concentration and FFA uptake and oxidation is altered by endurance training. These recent findings in humans support the notion from other cell types that transmembrane fatty acid transport is not only by simple diffusion, but predominantly carrier-mediated. During prolonged submaximal knee-extension exercise it has been demonstrated that the total oxidation of fatty acids was approximately 60% higher in trained subjects than in nontrained subjects. The training-induced adaptations responsible for this increased utilization of plasma fatty acids by the muscle could be located at several steps from the mobilization of fatty acids to skeletal muscle metabolism in the mitochondria. In this paper regulation at the transport steps and also at various metabolic steps is discussed.


Hydrothermal carbonization of dry toilet residues as an added-value strategy - Investigation of process parameters.
Human faeces from a dry toilet are converted via hydrothermal carbonization to obtain a sterilized carbonaceous material. During this process the original material undergoes consecutively hydrolysis, water elimination and polymerization reactions. Consequently, the oxygen content is reduced, leading to a material with a better dewaterability and an attractive higher heating value (HHV = 22-28 MJ kg-1). The influence of pH-value, set by the addition of citric acid, the reaction time and the reaction temperature are investigated. By thermogravimetric analysis it is shown that especially higher acid concentration as well as higher reaction temperatures and longer reaction times are necessary to fully convert the feedstock into a stable carbon-rich material. As pathogens are destroyed by hydrothermal carbonization, nutrient recovery becomes a relevant aspect. The analysis shows that alkali salts such as sodium and potassium are dissolved in the aqueous phase, but an important proportion of the phosphorus and nitrogen remain in the hydrochar. This finding is the basis for phosphorus recycling or to produce an organic fertilizer.


IRF and STAT Transcription Factors - From Basic Biology to Roles in Infection, Protective Immunity, and Primary Immunodeficiencies.
The induction and action of type I interferon (IFN) is of fundamental importance in human immune defenses toward microbial pathogens, particularly viruses. Basic discoveries within the molecular and cellular signaling pathways regulating type I IFN induction and downstream actions have shown the essential role of the IFN regulatory factor (IRF) and the signal transducer and activator of transcription (STAT) families, respectively. However, the exact biological and immunological functions of these factors have been most clearly revealed through the study of inborn errors of immunity and the resultant infectious phenotypes in humans. The spectrum of human inborn errors of immunity caused by mutations in IRFs and STATs has proven very diverse. These diseases encompass herpes simplex encephalitis (HSE) and severe influenza in IRF3- and IRF7/IRF9 deficiency, respectively. They also include Mendelian susceptibility to mycobacterial infection (MSMD) in STAT1 deficiency, through disseminated measles infection associated with STAT2 deficiency, and finally staphylococcal abscesses and chronic mucocutaneous candidiasis (CMC) classically described with Hyper-IgE syndrome (HIES) in the case of STAT3 deficiency. More recently, increasing focus has been on aspects of autoimmunity and autoinflammation playing an important part in many primary immunodeficiency diseases (PID)s, as exemplified by STAT1 gain-of-function causing CMC and autoimmune thyroiditis, as well as a recently described autoinflammatory syndrome with hypogammaglobulinemia and lymphoproliferation as a result of STAT3 gain-of-function. Here I review the infectious, inflammatory, and autoimmune disorders arising from mutations in IRF and STAT transcription factors in humans, highlightning the underlying molecular mechanisms and immunopathogenesis as well as the clinical/therapeutic perspectives of these new insights.


Neobladder after cystectomy: an Indian experience.
A continent urinary reservoir was constructed from an ileocolonic segment and anastomosed to the urethra in 30 males after radical cystectomy for infiltrating bladder cancer. A small cuff of the prostate was retained for anastomosis with the reservoir and ureteric anastomosis was done from within the reservoir by the "pull through" method. Complete continence was achieved in 29 patients, all of whom had an adequate reservoir capacity exceeding 400 ml; they were able to empty the reservoirs satisfactorily as judged by the residual urine (< 50 ml). Urodynamic study revealed an intra-abdominal pressure < 30 cm of water at rest and at reservoir capacity of 500 ml. Early post-operative complications included urinary leaks in 3 patients, intestinal obstruction in 3 and a faecal fistula in 1. Deterioration of the upper tracts was noted in 5 cases. Twenty-seven patients are alive after a mean follow-up of 36 months.


Solitary adult xanthogranuloma: a case report with new observation on lipid droplet formation.
A case of solitary xanthogranuloma was studied by optical and electron microscopy. The tumor parenchyma cells were composed mainly of multilocular lipid droplets together with rough-surfaced endoplasmic reticulum, a few mitochondria, glycogen particles, and fine filaments sparsely scattered throughout the cytoplasm. The parenchyma cells bore a close structural resemblance to Ito's "fat-storing cells" which are situated in Disse's space, contain lipid droplets and are thought to be the only cells participating in intralobular fibrillogenesis in the liver. Another notable finding was that the lipid droplets of the tumor parenchyma cells originated directly from rough-surfaced endoplasmic reticulum. Thus, the tumor morphology was incompatible with the currently favored concept of a benign, reactive non-neoplastic process of prominently histiocyte cells, being characterized instead by prominently fibroblastic cells.


Left Ventricular Outflow Tract Obstruction and Systolic Anterior Motion of the Mitral Valve in the Absence of Hypertrophic Cardiomyopathy.
Systolic anterior motion of the mitral valve is a mechanism for the development of left ventricular outflow tract (LVOT) obstruction. While often associated with left ventricular hypertrophy (LVH), a case is reported of symptomatic LVOT obstruction due to intrinsic mitral valve pathology in the absence of hypertrophy or cardiomyopathy. This case highlights the importance of recognizing isolated mitral valve pathology as a treatable cause of LVOT obstruction.


Monocyte chemoattractant protein (MCP)-1 production via functionally reconstituted Fcalpha receptor (CD89) on glomerular mesangial cells.
Fc alpha receptor (FcalphaR; CD89) is the receptor for Fc portion of IgA in various cells, and displays various immunological responses on binding. It is important to analyze the mesangial functions via FcalphaR in the pathogenesis of IgA nephropathy. However, it is still controversial whether FcalphaR is expressed on mesangial cells. To assess biological functions of FcalphaR on the mesangial cells, we established mesangial transfectants that expressed FcalphaR with or without FcRgamma chain that is a common signaling molecule of FcRs. The production of monocyte chemoattractant protein-1 (MCP-1) by mesangial cells is known to contribute to cellular infiltration into glomeruli and subsequent glomerular injuries. Murine mesangial cell lines (SV40 MES 13) were transfected with cDNA of the human FcalphaR. Furthermore, we co-transfected some of the FcalphaR transfectants with cDNA of human FcRgamma chain. The tyrosine phosphorylation of the intra-mesangial proteins after FcalphaR cross-linking was examined by immunoprecipitation. MCP-1 production from each transfectant stimulated with heat aggregated IgA was determined by sandwich ELISA. Two kinds of mesangial transfectants stably expressed human FcalphaR with or without FcRgamma chain (FcalphaR(+), FcalphaR(+)/gamma(+)). Phosphorylation of FcRgamma chain and syk kinase was detected in FcalphaR(+) and FcalphaR(+)/gamma(+) cells, but not in untransfected cells. Aggregated IgA induced significantly higher MCP-1 production in FcalphaR(+)/gamma(+) than those in FcalphaR(+) or untransfected control. Present study demonstrated that FcalphaR and FcRgamma chain could be reconstituted in mesangial cells and mediated MCP-1 production by aggregated IgA in a dose-dependent manner. Current data would argue that FcalphaR can be activated in mesangial cells through their own machinery, although underlying mechanisms for FcalphaR induction in mesangial cells remain unclear.


Multiphasic survival response of a radioresistant lepidopteran insect cell line.
TN-368 lepidopteran insect cells display a multiphasic survival response in both air and nitrogen. In each case the survival curve is characterized by an initial small- shouldered component having a steep slope, a plateau or broad- shouldered region near the 0.1 survival level, and finally a shallow slope component. The D0, Dq, and n values for the initial steep slope component in air and nitrogen are, respectively, 65.7 Gy, 9.0 Gy, and 1.2, and 104.4 Gy, 28.8 Gy, and 1.3. The oxygen enhancement ratio (OER) for this portion of the curve is 1.6. The D0, Dq, and n values for the shallow slope component in air and nitrogen are, respectively, 130.2 Gy,--36.1 Gy, and 0.8, and 226.8 Gy, 121.0 Gy, and 1.7. The OER for this portion of the curve is 1.7. The D0 values for each slope and the width of the plateau region all increase proportionally for the nitrogen curve over that of air, the OER being approximately the same for both curve components. A similar multiphasic response was observed at dose rates of 202, 49.6, and 9.1 Gy/min. In addition, the survival of cells which had previously been irradiated with a dose well into the logarithmic region of the more resistant shallow slope portion of the curve retained a multiphasic response. Although cell cycle variations in radiosensitivity may contribute slightly to the response, an inducible or activated repair process would be consistent with the results.


Ester Bonds for Modulation of the Mechanical Properties of Protein Hydrogels.
Hydrogels are soft materials constructed of physically or chemically crosslinked polymeric net-works with abundant water. The crosslinkers, as the mechanophores that bear and respond to mechanical forces, play a critical role in determining the mechanical properties of hydrogels. Here, we use a polyprotein as the crosslinker and mechanophore to form covalent polymer hydrogels in which the toughness and fatigue fracture are controlled by the mechanical unfolding of polyproteins. The protein Parvimonas sp. (ParV) is super stable and remains folded even at forces > 2 nN; however, it can unfold under loading forces of ~100 pN at basic pH values or low calcium concentrations due to destabilization of the protein structures. Through tuning the protein unfolding by pH and calcium concentrations, the hydrogel exhibits differences in modulus, strength, and anti-fatigue fracture. We found that due to the partially unfolding of ParV, the Young's modulus decreased at pH 9.0 or in the presence of EDTA (Ethylene Diamine Tetraacetic Acid), moreover, because partially unfolded ParV can be further completely unfolded due to the mechanically rupture of ester bond, leading to the observed hysteresis of the stretching and relaxation traces of the hydrogels, which is in line with single-molecule force spectroscopy experiments. These results display a new avenue for designing pH- or calcium-responsive hydrogels based on proteins and demonstrate the relationship between the mechanical properties of single molecules and macroscopic hydrogel networks.


Acetaminophen induces a caspase-dependent and Bcl-XL sensitive apoptosis in human hepatoma cells and lymphocytes.
Acetaminophen is a widely used analgesic and antipyretic drug that exhibits toxicity at high doses to the liver and kidneys. This toxicity has been attributed to cytochrome P-450-generated metabolites which covalently modify target proteins. Recently, acetaminophen, in its unmetabolized form, has been shown to affect a variety of cells and tissues, for instance, testicular and lymphoid tissues and lymphocyte cell lines. The effects on cell viability of acetaminophen at a concentration comparable to that achieved in plasma during acetaminophen toxicity have now been examined with a hepatoma cell line SK-Hep1, primary human peripheral blood lymphocytes and human Jurkat T cells. Acetaminophen reduced cell viability in a time-dependent manner. Staining of cells with annexin-V also revealed that acetaminophen induced, after 8 hr of treatment, a loss of the asymmetry of membrane phospholipids, which is an early event associated with apoptosis. Acetaminophen triggered the release of cytochrome c from mitochondria into the cytosol, activation of caspase-3, 8, and 9, cleavage of poly(ADP-ribose) polymerase, and degradation of lamin B1 and DNA. Whereas cleavage of DNA into internucleosomal fragments was apparent in acetaminophen treated SK-Hep1 and primary lymphocytes, DNA was only degraded to 50-kb fragments in treated Jurkat cells. Overexpression of the antiapoptotic protein Bcl-XL prevented these various apoptotic events induced by acetaminophen in Jurkat cells. Caspase-8 activation was a postmictochondrial event and occurred in a Fas-independent manner. These results demonstrate that acetaminophen induces caspases-dependent apoptosis with mitochondria as a primary target. These results also reiterate the potential role of apoptosis in acetaminophen hepatic and extrahepatic toxicity.


retrospective analysis of topoisomerase IIa amplifications and deletions as predictive markers in primary breast cancer patients randomly assigned to cyclophosphamide, methotrexate, and fluorouracil or cyclophosphamide, epirubicin, and fluorouracil: Danish Breast Cancer Cooperative Group.
The aim of the study was to evaluate the predictive value of HER2 and topoisomerase IIalpha gene (TOP2A) for the efficacy of epirubicin in the adjuvant setting of breast cancer patients. In the Danish Breast Cancer Cooperative Group trial 89D, 980 pre- and postmenopausal primary patients were randomly allocated to either CMF (cyclophosphamide, methotrexate, and fluorouracil; n = 500) or CEF (cyclophosphamide, epirubicin, and fluorouracil; n = 480) times 9, between January 1990 and November 1999. Tumor tissue was retrospectively identified from 805 patients and was analyzed for HER2-positivity and for TOP2A-amplifications and deletions. HER2-positivity was found in 33% of the 805 investigated tumors and was not a predictive marker for epirubicin sensitivity. TOP2A changes were identified in 23% of the 773 investigated tumors: 12% had TOP2A amplifications and 11% had TOP2A deletions. We found that patients with TOP2A amplification had an increased recurrence-free (RFS; hazard ratio [HR], 0.43; 95% CI, 0.24 to 0.78) and overall survival (OS; HR, 0.57; 95% CI, 0.29 to 1.13), respectively if treated with CEF compared with CMF, and that patients with TOP2A deletions had an almost identical hazard ratio (RFS: HR, 0.63; 95% CI, 0.36 to 1.11; OS: HR, 0.56; 95% CI, 0.30 to 1.04). This is in contrast to patients with a normal TOP2A genotype for whom similar outcome was observed in both treatment arms (RFS: HR, 0.90; 95% CI, 0.70 to 1.17; OS: HR, 0.88; 95% CI, 0.66 to 1.17). TOP2A amplification-and possibly deletion-seems to be predictive markers for the effect of adjuvant epirubicin containing therapy in primary breast cancer, but a final conclusion has to await a confirmative study or a meta-analysis.


[Emergency surgery making use of video-assisted thoracoscopy--2 case reports].
We recently experienced two emergency operating cases using video-assisted thoracoscopy. First case was a 17-year-old male with foreign body and pneumothorax in the right thorax. He was emergencilly treated by means of video-assisted thoracoscopic surgery. The operation was carried out using double-lumen endotracheal anesthesia. Short trocars were inserted through the right intercostal spaces to introduce a flexible video thoracoscope and surgical instruments. Foreign body was looked for easily and removed out. Second case was a 22-year-old male with hemo-pneumothorax at the right side. He was treated using video-assisted thoracoscopy emergencilly. Bleeding point was searched and hemostasis was done by the electrical mess and the clip. Bulla was removed out with surgical instruments. These were good adaptation of emergency operation using video-assisted thoracoscope. The advantages of this thoracoscopic surgery are: less operative invasion and postoperative pain, early recovery and short hospital stay, and cosmetic preservation.


Management of trauma to primary and developing teeth.
Traumatic dental injuries to the young child can present both diagnostic and therapeutic challenges. Luxation injuries to the primary dentition are the most common injuries. Yet, they are the most controversial with regard to definitive treatment, prognosis, and sequelae. Damage to the developing teeth subsequent to primary tooth injury is often unavoidable and has permanent effects on the dentition. Diagnostic criteria, treatment options, and outcomes are presented in this article; however, treatment decisions are often based on patient behavior.


Innate Immune System Orchestrates Metabolic Homeostasis and Dysfunction in Visceral Adipose Tissue During Obesity.
Arising incidence of metabolic disorders and related diseases caused by obesity is a global health concern. Elucidating the role of the immune system in this process will help to understand the related mechanisms and develop treatment strategies. Here, we have focused on innate immune cells in visceral adipose tissue (VAT) and summarized the roles of these cells in maintaining the homeostasis of VAT. Furthermore, this review reveals the importance of quantitative and functional changes of innate immune cells when the metabolic microenvironment changes due to obesity or excess lipids, and confirms that these changes eventually lead to the occurrence of chronic inflammation and metabolic diseases of VAT. Two perspectives are reviewed, which include sequential changes in various innate immune cells in the steady state of VAT and its imbalance during obesity. Cross-sectional interactions between various innate immune cells at the same time point are also reviewed. Through delineation of a comprehensive perspective of VAT homeostasis in obesity-induced chronic inflammation, and ultimately metabolic dysfunction and disease, we expect to clarify the complex interactive networks among distinct cell populations and propose that these interactions should be taken into account in the development of biotherapeutic strategies.


The 14-3-3 protein forms a molecular complex with heat shock protein Hsp60 and cellular prion protein.
The 14-3-3 protein family consists of acidic 30-kDa proteins composed of 7 isoforms expressed abundantly in neurons and glial cells of the central nervous system (CNS). The 14-3-3 protein identified in the cerebrospinal fluid provides a surrogate marker for premortem diagnosis of Creutzfeldt-Jakob disease, although an active involvement of 14-3-3 in the pathogenesis of prion diseases remains unknown. By protein overlay and mass spectrometric analysis of protein extract of NTera2-derived differentiated neurons, we identified heat shock protein Hsp60 as a 14-3-3-interacting protein. The 14-3-3zeta and gamma isoforms interacted with Hsp60, suggesting that the interaction is not isoform-specific. Furthermore, the interaction was identified in SK-N-SH neuroblastoma, U-373MG astrocytoma, and HeLa cervical carcinoma cells. The cellular prion protein (PrPC) along with Hsp60 was coimmunoprecipitated with 14-3-3 in the human brain protein extract. By protein overlay, 14-3-3 interacted with both recombinant human Hsp60 and PrPC produced by Escherichia coli, indicating that the molecular interaction is phosphorylation-independent. The 14-3-3-binding domain was located in the N-terminal half (NTF) of Hsp60 spanning amino acid residues 27-287 and the NTF of PrPC spanning amino acid residues 23-137. By immunostaining, the 14-3-3 protein Hsp60 and PrPC were colocalized chiefly in the mitochondria of human neuronal progenitor cells in culture, and were coexpressed most prominently in neurons and reactive astrocytes in the human brain. These observations indicate that the 14-3-3 protein forms a molecular complex with Hsp60 and PrPC in the human CNS under physiological conditions and suggest that this complex might become disintegrated in the pathologic process of prion diseases.


Single-Crystalline Diluted Magnetic Semiconductor GaN:Mn Nanowires.
Single-crystalline diluted magnetic semiconductor GaN:Mn nanowires with controlled Mn concentrations have been successfully synthesized and incorporated into devices. These nanowires exhibit Curie temperatures above room temperature, magnetoresistances near room temperature, and spin-dependent transport. The nanowires are used as building blocks for the fabrication of GaN:Mn/n-SiC based light-emitting diodes.


Characterization of serotonergic receptors in rabbit, porcine and human conjunctivae.
To characterize the serotonin (5-HT) receptors linked to the modulation of adenylyl cyclase activity in rabbit, porcine and human conjunctivae. Serotonin receptor-subtype expression was examined using reverse transcription-polymerase chain reaction (RT-PCR) and receptor subtype-specific polyclonal antibodies for the immunofluorescent labeling of conjunctival cryosections. In addition, measurements of the effects of serotonergics on the short-circuit current (I(sc)) across rabbit and porcine conjunctivae were contrasted. RT-PCR assays indicated the expression of 5-HT(1B ) and 5-HT(1D) receptors, subtypes negatively coupled to adenylyl cyclase, in the rabbit conjunctiva. This approach also suggested the co-expression of 5-HT(1B), 5-HT(1D), 5-HT(1F), 5-HT(4) and 5-HT(7) mRNA's in the porcine conjunctiva, and 5-HT( 1D), 5-HT(1F) and 5-HT(7) in the human conjunctiva. Since the 5-HT(4) and 5-HT(7) receptors are positively linked to adenylyl cyclase, these results implied that the porcine and human tissues exhibited subtypes both positively and negatively linked to the enzyme. However, immunohistochemical observations, using currently available antibodies solely localized the 5-HT(7) moiety in the porcine and human epithelia, suggested that the 1B/1D forms may be minor elements. Consistent with this prospect, 5-HT was a stimulant of the transepithelial I(sc) across the porcine conjunctiva, an opposite response from earlier findings that demonstrated inhibitory effects by 5-HT on the rabbit I(sc), which are now explained by the localization of the 1B/1D receptors in the rabbit stratified epithelium. The 5-HT receptors expressed by mammalian conjunctivae are not identical. In terms of 5-HT receptor expression, the porcine tissue may be a more appropriate model for human, than is the rabbit, in that 5-HT may serve as a secretagogue in the human epithelium.


Strain Selection and Optimization of Mixed Culture Conditions for Lactobacillus pentosus K1-23 with Antibacterial Activity and Aureobasidium pullulans NRRL 58012 Producing Immune-Enhancing β-Glucan.
Lactobacillus pentosus K1-23 was selected from among 25 lactic acid bacterial strains owing to its high inhibitory activity against several pathogenic bacteria, including Escherichia coli, Salmonella typhimurium, S. gallinarum, Staphylococcus aureus, Pseudomonas aeruginosa, Clostridium perfringens, and Listeria monocytogenes. Additionally, among 13 strains of Aureobasidium spp., A. pullulans NRRL 58012 was shown to produce the highest amount of β-glucan (15.45 ± 0.07%) and was selected. Next, the optimal conditions for a solid-phase mixed culture with these two different microorganisms (one bacterium and one yeast) were determined. The optimal inoculum sizes for L. pentosus and A. pullulans were 1% and 5%, respectively. The appropriate inoculation time for L. pentosus K1-23 was 3 days after the inoculation of A. pullulans to initiate fermentation. The addition of 0.5% corn steep powder and 0.1% FeSO₄ to the basal medium resulted in the increased production of lactic acid bacterial cells and β-glucan. The following optimal conditions for solid-phase mixed culture were also statistically determined by using the response surface method: 37.84°C, pH 5.25, moisture content of 60.82%, and culture time of 6.08 days for L. pentosus; and 24.11°C, pH 5.65, moisture content of 60.08%, and culture time of 5.71 days for A. pullulans. Using the predicted optimal conditions, the experimental production values of L. pentosus cells and β-glucan were 3.15 ± 0.10 × 10⁸ CFU/g and 13.41 ± 0.04%, respectively. This mixed culture may function as a highly efficient antibiotic substitute based on the combined action of its anti-pathogenic bacterial and immune-enhancing activities.


[Periodontal status of labially inversely impacted maxillary central incisor in mixed dentition after orthodontic treatment].
To study the periodontal status of labially inversely impacted maxillary central incisor in mixed dentition after orthodontic treatment. Sixteen patients with labially inversely impacted maxillary central incisor in mixed dentition and treated by guided rod appliance and conventional fixed appliance were enrolled in this study. Periodontal examinations were performed and cone-beam CT (CBCT) was taken approximately 2 years post treatment. Central incisors were divided into impacted and contralateral incisor groups. Clinical examinations included plaque index (PLI), gingival index (GI), probing depth (PD), width of attached gingiva (AW) and clinical crown length (CL); Mimics 16.0 software was used to measure the length of alveolar bone around the root (ha and fc), the length from the alveolar bone crest to cemento-enamel junction(CEJ) (ab and cd) on both the labial and palatal side of the central incisors as well as the labial and palatal bone support proportion (LBP and PBP) of the root and tipping of central incisor (U1-SN). The data were analyzed using paired sample t tests with SPSS 17.0 software package. There was no significant difference in PLI, GI, PD, U1-SN; the value of AW, ha,fc, LBP, PBP was significantly smaller in impacted groups(P<0.01); the value of CL, ab and cd was significantly larger in impacted groups (P<0.01). The periodontal status of the impacted central incisor was on good condition without teeth mobility and inflammation, although a little worse than the contralateral homonymous teeth. There may be a need for periodontal bone grafting and gingival surgery in the future for the asymmetric morphology of gingiva.


An updated meta-analysis of the Fc receptor-like 3 -169T/C polymorphism and rheumatoid arthritis risk.
Published studies have shown conflicting results concerning the association between the -169T/C promoter polymorphism in the Fc receptor-like 3 (FCRL3) gene and rheumatoid arthritis (RA). In this study we conducted an up-to-date meta-analysis to examine the relationship. We searched the PubMed database for all papers published up to 20 April 2012. Overall, 18 case-control studies with 12 620 cases and 12 613 controls were retrieved based on the search criteria for RA susceptibility related to the FCRL3 -169T/C polymorphism. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of this association. Publication bias was assessed using the Egger test. We found that the FCRL3 -169T/C polymorphism increased the risk for RA overall in genetic models (allelic contrast: OR 1.09, 95% CI 1.03-1.14, p = 0.001; homozygote comparison: OR 1.20, 95% CI 1.08-1.34, p = 0.001; dominant genetic model: OR 1.03, 95% CI 1.01-1.05, p = 0.001). Stratified analysis by race also showed a significant positive association with Asians and Caucasians. Subgroup analysis of rheumatoid factor (RF) revealed a slightly positive relationship between the FCRL3 -169T/C polymorphism and RF-positive RA risk. No obvious evidence of publication bias was detected in the overall analysis. Our study indicates that the FCRL3 -169T/C polymorphism is significantly associated with increased RA risk.


In vivo exposure of murine dendritic cell and macrophage bone marrow progenitors to the phosphorylcholine-containing filarial nematode glycoprotein ES-62 polarizes their differentiation to an anti-inflammatory phenotype.
We have previously shown in an in vitro study that the filarial nematode phosphorylcholine (PC)-containing glycoprotein ES-62 promotes a murine dendritic cell (DC) phenotype that induces T helper type 2 (Th2) responses. We now show that, in addition to directly priming Th2 responses, ES-62 can act to dampen down the pro-inflammatory DC responses elicited by lipopolysaccharide. Furthermore, we also demonstrate that murine DCs and macrophages derived ex vivo from bone marrow cells exposed in vivo to ES-62 by release from osmotic pumps are hyporesponsive to subsequent stimulation with lipopolysaccharide. These effects can be largely mimicked by exposure to the PC moiety of ES-62 conjugated to an irrelevant protein. The data we provide are, as far as we aware, the first to show that a defined pathogen product can modulate the developmental pathway of bone marrow cells of the immune system in vivo. Such a finding could have important implications for the use of pathogen products or their derivatives for immunotherapy.


Inhibition of type I and type II phospholipase A2 by phosphatidyl-ethanolamine linked to polymeric carriers.
We have previously shown that cell surface proteoglycans protect the cell membrane from the action of extracellular phospholipase A2 (PLA2) enzymes [Dan, P., Nitzan, D. W., Dagan, A., Ginsburg, I., and Yedgar, S. (1996) FEBS Lett. 383, 75-78]. Cell-impermeable PLA2 inhibitors (ExPLIs) were prepared by linking phosphatidylethanolamine (PE) to polymeric carriers, specifically, carboxymethylcellulose, heparin, or hyaluronic acid. The structure of these inhibitors enables the incorporation of their PE moiety into the membrane while the polymer remains at the membrane surface. In the present study, we show that the ExPLIs are effective inhibitors of the hydrolysis of different phospholipids in biological (Escherichia coli) and model (phospholipid vesicle) membranes, by diverse types of PLA2 enzymes, specifically human recombinant synovial fluid and C. atrox (type II), as well as Naja mocambique and porcine pancreatic (type I) PLA2. It is proposed that the external polymers of the ExPLIs, which are anchored to the membrane by the PE, mimic the naturally occurring cell surface proteoglycans and similarly protect membranes from the action of exogenous PLA2.


A polymeric cobalt(II) complex derived from citric acid (H4cit) and 2,6-diaminopurine (dap): {[Co4(cit)2(dap)4(H2O)4]·6.35H2O}n.
Poly[[tetraaquadi-μ4-citrato-tetrakis(2,6-diaminopurine)tetracobalt(II)] 6.35-hydrate], {[Co4(C6H4O7)2(C5H6N6)4(H2O)4]·6.35H2O}n, presents three different types of Co(II) cations in the asymmetric unit, two of them lying on symmetry elements (one on an inversion centre and the other on a twofold axis). The main fragment is further composed of one fully deprotonated citrate (cit) tetraanion, two 2,6-diaminopurine (dap) molecules and two aqua ligands. The structure is completed by a mixture of fully occupied and disordered solvent water molecules. The two independent dap ligands are neutral and the cit tetraanion provides for charge balance, compensating the 4+ cationic charge. There are two well defined coordination geometries in the structure. The simplest is mononuclear, with the Co(II) cation arranged in a regular centrosymmetric octahedral array, coordinated by two aqua ligands, two dap ligands and two O atoms from the β-carboxylate groups of the bridging cit tetraanions. The second, more complex, group is trinuclear, bisected by a twofold axis, with the metal centres coordinated by two cit tetraanions through their α- and β-carboxylate and α-hydroxy groups, and by two dap ligands bridging through one of their pyridine and one of their imidazole N atoms. The resulting coordination geometry around each metal centre is distorted octahedral. Both groups are linked alternately to each other, defining parallel chains along [201], laterally interleaved and well connected via hydrogen bonding to form a strongly coupled three-dimensional network. The compound presents a novel μ4-κ(5)O:O,O':O',O'',O''':O'''' mode of coordination of the cit tetraanion.


Phase II study of rubitecan in recurrent or metastatic head and neck cancer.
Rubitecan is an oral camptothecin analogue that has shown activity against a broad spectrum of human tumor xenografts and has been tested in several diseases. In the present study, 19 patients with incurable, recurrent or metastatic head and neck cancer were treated with rubitecan at the initial dose of 1.5 mg/m(2) x 5 days per week. An appropriate dose modification program was set up according to the observed toxicities. Thirteen out of the 19 treated patients were formally evaluable for tumor response. Ten patients had a disease progression and three patients had a stabilization of disease as their best response. The mean duration of stable disease was 141 days. Median survival was 16 weeks (range 2-22 weeks). Three patients died during the study or less than a month after their last dose of study medication. Hematologic toxicity was serious in this study since four patients discontinued their participation because of severe anemia. The drug was also associated with grade 1-4 neutropenia, and with 1-3 thrombocytopenia. We conclude that rubitecan is not effective as a single-agent in recurrent or metastatic head and neck cancer with the doses and schedule used in this study.


Discharges in human muscle receptor afferents during block grasping.
Human grasping relies on feedforward control that is monitored and corrected on-line by means of sensory feedback. While much of the sensory mechanisms underpinning hand-object interaction are known, information has been lacking about muscle receptor responses during the phases before and after actual object contact. We therefore let subjects use their thumb and fingers to grasp blocks presented to them while we recorded muscle afferents from the thumb and finger extensor muscles along with wrist and digit kinematics, and electromyographic activity. The kinematics of the task was indistinguishable from "normal" grasping. None of the afferents encoded either object contact or finger apposition. Both primary and secondary afferents were more phase advanced on the parent muscle lengths than expected from previous studies as well as from their responses to imposed length changes of their parent muscles. Thus, the discharges of both primary and secondary afferents were well correlated to the tendon velocity of their parent muscles and that of primary afferents also to acceleration whereas neither appeared to encode muscle length as such. Decoding the velocity of muscle length changes were significantly improved if the discharge of Golgi tendon organ afferents were taken into account along with that of the muscle spindle afferents. We propose that these findings may be explained by the biomechanical properties of contracting muscles. Moreover, we conclude that it seems unlikely that the muscle spindle afferents recorded in this task have any role in providing "proprioceptive" information pertaining to the size of an object grasped.


C-shaped root canal configuration in maxillary first molars.
This clinical report presents the endodontic treatment of two maxillary first molars and the anatomical study of two additional maxillary first molars with a C-shaped distally located root canal system. This configuration is not a common finding. According to the endodontic literature, the C-shaped root canal is most frequently seen in the mandibular second molar. The occurrence of C-shapes in maxillary first molars, however, has only been described in a limited number of case reports. We observed this configuration in two out of 2175 root-filled maxillary first molars treated at the Department of Endodontology, Ghent University Hospital, during the last 10 years. In order to study and visualize this particular aberration, cross-sections in two additional two-rooted maxillary first molars were made. From these cross sections it can be concluded that the C-shaped canal configuration is the result of a fusion of the distobuccal and the palatal roots.


Weather-based prediction of Plasmodium falciparum malaria in epidemic-prone regions of Ethiopia II. Weather-based prediction systems perform comparably to early detection systems in identifying times for interventions.
Timely and accurate information about the onset of malaria epidemics is essential for effective control activities in epidemic-prone regions. Early warning methods that provide earlier alerts (usually by the use of weather variables) may permit control measures to interrupt transmission earlier in the epidemic, perhaps at the expense of some level of accuracy. Expected case numbers were modeled using a Poisson regression with lagged weather factors in a 4th-degree polynomial distributed lag model. For each week, the numbers of malaria cases were predicted using coefficients obtained using all years except that for which the prediction was being made. The effectiveness of alerts generated by the prediction system was compared against that of alerts based on observed cases. The usefulness of the prediction system was evaluated in cold and hot districts. The system predicts the overall pattern of cases well, yet underestimates the height of the largest peaks. Relative to alerts triggered by observed cases, the alerts triggered by the predicted number of cases performed slightly worse, within 5% of the detection system. The prediction-based alerts were able to prevent 10-25% more cases at a given sensitivity in cold districts than in hot ones. The prediction of malaria cases using lagged weather performed well in identifying periods of increased malaria cases. Weather-derived predictions identified epidemics with reasonable accuracy and better timeliness than early detection systems; therefore, the prediction of malarial epidemics using weather is a plausible alternative to early detection systems.


Malignant conjunctival T cell lymphoma diagnosed by punch biopsy as a primary manifestation of systemic cancer.
This report documents a case of T cell lymphoma manifesting only with a conjunctival mass. A 67-year-old man underwent a diagnostic punch biopsy, histopathological examination, and immunohistochemical study for a pink-yellow colored mass infiltrating the bulbar conjunctiva in the lower fornix of the eyelid. A biopsy specimen of the conjunctival mass was found histopathologically to be a malignant T cell lymphoma. Systemic involvement was diagnosed within four weeks after the initial diagnosis by computed tomography, showing evidence of extension at the level of the ethmoidal cells, optic nerve, periorbital tissue, and pancreas. T cell lymphoma of the conjunctiva as a primary manifestation of systemic cancer is an uncommon entity. Punch biopsy may be the first diagnostic pathway useful to initiate a search for systemic involvement of a malignant lymphoid tumor of T cell lineage.


Psychological parameters of psoriasis.
Psoriasis is a chronic, inflammatory scaling dermatosis. The marked visible appearance of the lesions have a negative impact on body image that leads to decreased self-esteem, hence seriously compromising the patient's quality of life. The clinical picture critically affects the social well-being of the patient since the disease is commonly misunderstood and feared by the social environment as being contagious. The patient feels stigmatized and this further intensifies their lack of self-confidence and self-esteem. Feelings of shame and guilt increase the tendency toward suicidal ideation. The poor quality of life of psoriatic patients has been associated with excessive alcohol consumption, increased smoking and greater use of tranquilizers, sedatives and antidepressants. As far as mental impairment is concerned, a correlation has been found between psychological stress and the clinical severity of symptoms: the more mentally affected the patient, the more severe the dermatologic lesions. Similarly, stressful life events constitute a major risk for the occurrence and recurrence, exacerbating the severity and duration of the symptoms. Depression and anxiety can worsen the disease or cause resistance to treatment or patient's indifference, which in turn can lead to expensive and prolonged treatment. Not least, the disease itself contributes to anxiety, depression and psychological stress, thus creating a "vicious circle" that is difficult to manage. Given that women seem to invest more in their personal appearance than men, it is hardly surprising that female psoriatic patients report higher levels of depression. Similarly, the risk of mental disorders is also higher in younger patients for whom body image plays an equally significant role. The severity of the disease, side effects of therapy and mental disorders are among the causes that have been attributed to sexual dysfunction reported by some psoriatic patients. At the social level, stigma, social rejection, feelings of shame, embarrassment and lack of confidence provoked by the disease often lead to the discontinuation of daily activities and social withdrawal. This review attempts to describe the prevalence of psychological stress and its negative social impact on patients with psoriasis. The recognition and treatment of these psychosocial problems may contribute to improving the quality of life for patients and reduce treatment costs. The collaboration between the psychiatrist and the dermatologist is a fundamental prerequisite toward addressing these issues.


Anomalous Coronary Anatomy with Fistula Diagnosed on Coronary Computed Tomography Angiography.
Anomalous coronary vasculature is a rare finding among the general population. Identifying such cases is important for preventing adverse outcomes such as sudden cardiac death. We present two rare cases of aberrant coronary anatomy. In Case 1, a 4-year-old male who presented with non-exertional chest pain was found to have anomalous coronary architecture on echocardiogram. Coronary computed tomography angiogram (CCTA) confirmed an anomalous origin of the left coronary artery from the right coronary sinus with a malignant interarterial course and myocardial bridging of the left anterior descending (LAD) artery. The patient underwent a successful surgical correction of the defects. In Case 2, a full-term infant female was born with a hypoplastic right ventricle and pulmonary atresia. CCTA showed a large fistula originating from the coronary sinus on the left that drained into the superior aspect of the mid right ventricular cavity, an anomalous bridge between the left and right atrial appendages, and five fistulous connections between various vessels. The patient was transferred to another facility for cardiac transplant.


Inherited factor II deficiency with paradoxical hypercoagulability: a case report.
: Congenital deficiency of factor II is a very rare autosomal recessive disorder that can result in a bleeding diathesis. Genotypically, individuals are either homozygous for a defective prothrombin gene or a compound heterozygote with different mutated prothrombin genes inherited from each parent. Phenotypically, it is characterized by either a low production of normal prothrombin or a near-normal production of dysfunctional prothrombin. Treatment is aimed at restoring normally functioning factor II circulating levels to sufficient concentration for hemostasis. Paradoxical thrombosis in patients born from a nonconsanguineous marriage with factor II deficiency has not been reported. A woman with known congenital factor II deficiency confirmed by history and hemostatic laboratory analysis presented with an unprovoked spontaneous thrombosis of the common femoral vein detected on color Doppler. Venous thrombosis can occur in congenital deficiency of factor II and inferior vena cava filter can be life-saving.


Identification of plasmid-mediated AmpC beta-lactamases in Escherichia coli, Klebsiella spp., and proteus species can potentially improve reporting of cephalosporin susceptibility testing results.
The goal of this study was to determine if the interpretations of extended-spectrum and advanced-spectrum cephalosporins (ESCs and ASCs, respectively) for isolates of Enterobacteriaceae would be impacted by the results of aminophenylboronic acid (APBA) testing. Fifty-three isolates of Escherichia coli, 21 Klebsiella species, and 6 Proteus species that were resistant to at least one ESC were tested by disk diffusion with ceftazidime and cefotetan disks with and without APBA. Ceftazidime disks with and without clavulanic acid (CLAV) were also tested to confirm extended-spectrum beta-lactamase (ESBL) carriage. Twenty-nine (36.3%) isolates were only APBA test positive, 27 were only CLAV test positive, 2 were positive with both substrates, and 22 were negative with both substrates. Thirteen (41.9%) of the 31 APBA-test-positive isolates (all E. coli) tested susceptible to cefotaxime, ceftriaxone, or ceftazidime. Since clinical data suggest that AmpC-producing isolates should be reported as resistant to all ESCs, APBA testing can be helpful in identifying such organisms. Screening for AmpC-producing organisms using nonsusceptibility to cefoxitin and amoxicillin-clavulanate was less specific than APBA testing; it identified ESBL as well as AmpC-producing organisms. Only 18 of 31 APBA-positive isolates were positive by PCR for an AmpC beta-lactamase gene. Thus, testing with APBA could improve the accuracy of reporting ESCs, especially for E. coli. However, results of APBA and CLAV testing did not correlate well for isolates containing both AmpC beta-lactamases and ESBLs. Thus, additional data are needed before formal recommendations can be made on changing the reporting of ASC test results.


Central glucagon like peptide-1 inhibits reflex swallowing elicited by the superior laryngeal nerve via caudal brainstem in the rat.
The effects of glucagon like peptide-1 (GLP-1) on reflex swallowing were examined using anaesthetized rats. GLP-1 was injected into the dorsal vagal complex (DVC) using glass micropipettes. Swallowing was induced by repeated electrical stimulation of the central cut end of the superior laryngeal nerve (SLN) and was identified by the electromyogram lead penetrated in the mylohyoide muscle through bipolar electrodes. Microinjection of GLP-1 into the medial DVC (M-DVC) increased the frequency of swallowing during the electrical stimulation of the SLN and extended the latency of the first swallowing. Microinjection of GLP-1 into the lateral DVC (L-DVC) did not change the frequency of swallowing or the latency of the first swallowing. Neither the injection of vehicle into the M-DVC nor L-DVC affected swallowing frequency. Pre-injection of exendin (5-39), a GLP-1 receptor antagonist, attenuated the degree of suppression of swallowing frequency induced by the administration of GLP-1 in addition to shortening the latency of the first swallowing. To identify the effective site of GLP-1, lesion experiments were performed. Electrical lesion of the commissural part of the NTS (cNTS) and the vacuum removal of the area postrema (AP) did not affect the inhibition of reflex swallowing induced by the injection of GLP-1 into the M-DVC. Electrical lesion of the medial nucleus of the NTS (mNTS) and its vicinity abolished the inhibitory effects of swallowing induced by the injection of GLP-1. These results suggest that GLP-1 inhibits reflex swallowing via the mNTS in the dorsal medulla.


[The Community Care as a model of social and health integration at the local level].
The article develops a hypothesis for improving primary care services through health care solutions that can exceed the models in use (essentially hierarchical and based on tasks) in favor of new relational, multi-sectoral and network approaches that could privilege the integration of social and health services at the regional and district level (Community care). A qualitative methodological approach which analyzes the role of social networks in Community care, some national and international experiences of primary care models and the evaluation of the different role given to primary care both in the hierarchical-pyramidal approach and in the horizontal one (network approach). Some Italian regions are experimenting effective organizational models of care such as Primary Care Teams, Primary Care Units, Regional teams, Departments of Primary Care, Houses of Health ... At international level, it should be mentioned the Chronic Care Model (CCM), recently identified by WHO as a reference model, and adopted by the Tuscany Region (Italy). People-centered health care projects need shared interventions by competent and functional multiprofessional teams: the best outcome for the patient depends on the good interaction between individuals. It's necessary that relationships between members of the group are based on interdependence, integration and consistency to avoid risks of group illusion.


Pros & cons of some popular extreme weight-loss diets.
Obesity has now become a huge public health issue not only in the developed world but also in developing countries. In view of the health hazards associated with obesity and more importantly for cosmetic reasons, many people, particularly the youth, have started resorting to 'extreme' weight-loss diets to achieve a rapid reduction in weight. These extreme diets are either very low in carbohydrate or very low in fat. Such extreme diets not only make the diet unbalanced but also have safety issues. Moreover, these are not sustainable in the long run. The weight that is lost is regained within a short period of time when people go off these extreme diets. This explains why the popularity of most extreme diets peaks as well as wanes rapidly. Instead of resorting to such extreme diets, correction of obesity is best achieved with balanced, healthy, nutritious diets which are low in calories, combined with adequate physical activity (exercise). Motivational counselling can also help people to initiate weight loss and sustain this weight loss over longer periods of time.


Social representations of pregnant women about high-risk pregnancy: repercussions for prenatal care.
To analyze the Social Representations of pregnant women about high-risk pregnancy and its repercussions for prenatal care. Qualitative study, based on the procedural aspect of the Theory of Social Representations, carried out with 62 high-risk prenatal pregnant women at a High Complexity Maternity, in Belém, PA, Brazil. Data from semi-structured interviews were processed by the software Interface de R pour les Analyzes Multidimensionnelles de Textes et de Questionnaires. Four categories emerged, in which three dimensions of the Theory composing the genesis of Social Representations are considered: the affective dimension, the biological dimension and the sociocultural dimension. Affects, negative feelings, and adaptations were revealed, with high-risk pregnancy being represented as an unusual and uncomfortable event, influenced by common sense and science, communication means, and dialogues with health professionals, with family support being considered of paramount importance. and prenatal care a propitious moment for establishing bonds with the health professional, seen as essential for their adherence to the care offered.


Longitudinal Household Trends in Access to Improved Water Sources and Sanitation in Chi Linh Town, Hai Duong Province, Viet Nam and Associated Factors.
This study aims to characterize household trends in access to improved water sources and sanitaton in Chi Linh Town, Hai Duong Province, Vietnam, and to identify factors affecting those trends. Data were extracted from the Chi Linh Health and Demographic Surveillance System (CHILILAB HDSS) database from 2004-2014, which included household access to improved water sources, household access to improved sanitation, and household demographic data. Descriptive statistical analysis and multinominal logistic regression were used. The results showed that over a 10-year period (2004-2014), the proportion of households with access to improved water and improved sanitation increased by 3.7% and 28.3%, respectively. As such, the 2015 Millennium Development Goal targets for safe drinking water and basic sanitation were met. However, 13.5% of households still had unimproved water and sanitation. People who are retired, work in trade or services, or other occupations were 1.49, 1.97, and 1.34 times more likely to have access to improved water and sanitation facilities than farming households, respectively (p < 0.001). Households living in urban areas were 1.84 times more likely than those living in rural areas to have access to improved water sources and improved sanitation facilities (OR =1.84; 95% CI = 1.73-1.96). Non-poor households were 2.12 times more likely to have access to improved water sources and improved sanitation facilities compared to the poor group (OR = 2.12; 95% CI = 2.00-2.25). More efforts are required to increase household access to both improved water and sanitation in Chi Linh Town, focusing on the 13.5% of households currently without access. Similar to situations observed elsewhere in Vietnam and other low- and middle- income countries, there is a need to address socio-economic factors that are associated with inadequate access to improved water sources and sanitation facilities.


Unsupervised learning of Probabilistic Grammar-Markov Models for object categories.
We introduce a Probabilistic Grammar-Markov Model (PGMM) which couples probabilistic context free grammars and Markov Random Fields. These PGMMs are generative models defined over attributed features and are used to detect and classify objects in natural images. PGMMs are designed so that they can perform rapid inference, parameter learning, and the more difficult task of structure induction. PGMMs can deal with unknown 2D pose (position, orientation, and scale) in both inference and learning, different appearances, or aspects, of the model. The PGMMs can be learnt in an unsupervised manner where the image can contain one of an unknown number of objects of different categories or even be pure background. We first study the weakly supervised case, where each image contains an example of the (single) object of interest, and then generalize to less supervised cases. The goal of this paper is theoretical but, to provide proof of concept, we demonstrate results from this approach on a subset of the Caltech dataset (learning on a training set and evaluating on a testing set). Our results are generally comparable with the current state of the art, and our inference is performed in less than five seconds.


Immunochemistry of cytochrome c. Identification of antigenic determinants through the study of hybrid molecules.
Antibodies elicited in rabbits against horse cytochrome c cross-react in varying degree with the cytochromes c of other species. Radioimmunoassay experiments are described in which 23% of the immunoglobulin shown to bind to horse cytochrome c fails to react with beef cytochrome c, and 14% of that bound by beef cytochrome c does not react with rabbit cytochrome c. Studies of hybrid cytochromes, prepared by a reconstitution procedure involving the cleavage and re-formation of peptide bond 65-66, show that these differences result from single amino acid replacements, Beef cytochrome c differs in binding capacity from horse cytochrome c as a result of the substitution of a glycine for a lysine residue in sequence position 60, and the difference between rabbit cytochrome c and beef cytochrome c reflects the substitution of a valine for a proline residue in position 44. Reconstituted horse cytochrome c and reconstituted beef cytochrome c have binding capacities indistinguishable from those of the parent proteins. The presence of a homoserine rather than a methionine residue in position 65 results, in the case of the reconstituted horse molecule, in a slightly lower affinity for the antibody population directed against the lysine-60 region. A corresponding difference is not observed in the case of beef cytochrome c and its reconstitution product, which do not bind the population in question.


Physical and functional interaction between Hck tyrosine kinase and guanine nucleotide exchange factor C3G results in apoptosis, which is independent of C3G catalytic domain.
The hematopoietic cell kinase Hck is a Src family tyrosine kinase expressed in cells of myelomonocytic lineage, B lymphocytes, and embryonic stem cells. To study its role in signaling pathways we used the Hck-SH3 domain in protein interaction cloning and identified C3G, the guanine nucleotide exchange factor for Rap1 and R-Ras, as a protein that associated with Hck. This interaction was direct and was mediated partly through the proline-rich region of C3G. C3G could be co-immunoprecipitated with Hck from Cos-1 cells transfected with Hck and C3G. C3G was phosphorylated on tyrosine 504 in cells when coexpressed with Hck but not with a catalytically inactive mutant of Hck. Phosphorylation of endogenous C3G at Tyr-504 was increased by treatment of human myelomonocytic THP-1 cells with mercuric chloride, which is known to activate Hck tyrosine kinase specifically. Coexpression of Hck with C3G induced a high level of apoptosis in many cell lines by 30-42 h of transfection. Induction of apoptosis was not dependent on Tyr-504 phosphorylation or the catalytic domain of C3G but required the catalytic activity of Hck. Using dominant negative constructs of caspases we found that caspase-1, -8, and -9 are involved in this apoptotic pathway. These results suggest that C3G and Hck interact physically and functionally in vivo to activate kinase-dependent and caspase-mediated apoptosis, which is independent of catalytic domain of C3G.


Dietary Management of Hyperthyroidism in a Dog.
An 8 yr old female spayed golden retriever presented for a routine exam during which ventral cervical soft tissue masses were identified. History included weight loss, increased activity and appetite, gagging, and occasional diarrhea. Exam findings included a body condition score of 4/9 and palpable ventral cervical nodules. A serum thyroxine (T4) value was 8.0 ug/dL (normal = 0.8-3.5ug/dL). Doppler systolic blood pressure readings ranged from 200-210 mmHg (normal systolic blood pressure <150 mmHg). The diagnosis was hyperthyroidism due to active thyroid masses. Due to financial constraints, the owner elected conservative management. Initial treatment with methimazole resulted in a decreased T4 value of 5.0 ug/dL at approximately 4 mo after initiation of treatment. A commercially available iodine-restricted feline diet was fed and this resulted in further reduction in serum T4 levels, improved sleeping cycles, reduced anxiety, and reduced systolic blood pressure. A temporary suspension of iodine-restricted feline diet for 2 mo resulted in increases in serum T4 concentrations, which, subsequently, decreased with re-introduction of the diet. Roughly 10 mo after initiation of the therapeutic diet and 16 mo after intial diagnosis, the dog remains relatively normal clinically despite active growing cervical masses with T4 concentration of 2.3 ug/dL.


A prospective 4-year study of insulin resistance and adipokines in morbidly obese diabetic and non-diabetic patients after gastric banding.
There are insufficient data regarding the changes in adipokine levels after laparoscopic adjustable gastric banding (LAGB) in diabetic and non-diabetic patients and their effects on insulin resistance and type 2 diabetes remission. To assess leptin, adiponectin, and insulin resistance changes after LAGB in diabetic and non-diabetic morbidly obese patients. One hundred and three patients (37 with and 66 without type 2 diabetes) underwent LAGB from January 2009 to January 2010. Glycated hemoglobin, insulin, adipokine levels and insulin resistance were evaluated preoperatively, and 1 and 4 years after LAGB. The mean patient age was 45.9 ±11.7 years and mean preoperative body mass index was 47.5 ±7.3 kg/m2. A total of 80 of 103 patients (77.6%) completed the 4-year follow-up. After 4 years the mean excess weight loss was 38.8% and 39.5% in diabetic and non-diabetic patients respectively. Leptin levels decreased significantly in both groups at 1 year, but after 4 years this was noted only in non-diabetic patients. After 1 year adiponectin levels increased significantly only in non-diabetic patients (p = 0.003) and remained almost the same at 4 years. A significant decrease in insulin resistance was noted in both groups 1 year after LAGB and diabetes remission was observed in 23 (62.1%) patients. There was a negative correlation between preoperative insulin resistance and adiponectin levels throughout the follow-up period. Leptin levels positively correlated with BMI throughout the study period (baseline r = 0.45; p < 0.001; after 1 year r = 0.71; p < 0.001; after 4 years r = 0.68; p < 0.001). There was no significant correlation between leptin and adiponectin concentrations preoperatively or after 1 year; however, at 4 years it was significant (r = 0.27; p < 0.02). The most significant metabolic changes occurred within 1 year after LAGB. The 4-year follow-up revealed stabilization in metabolic indices rather than significant improvement.


Genetic influences on adolescent eating habits.
Behavioral genetic research shows that variation in eating habits and food consumption is due to genetic and environmental factors. The current study extends this line of research by examining the genetic contribution to adolescent eating habits. Analysis of sibling pairs drawn from the National Longitudinal Study of Adolescent Health (Add Health) revealed significant genetic influences on variance in an unhealthy eating habits scale (h(2) = .42), a healthy eating habits scale (h(2) = .51), the number of meals eaten at a fast-food restaurant (h(2) = .33), and the total number of meals eaten per week (h(2) = .26). Most of the remaining variance was due to nonshared environmental factors. Additional analyses conducted separately for males and females revealed a similar pattern of findings. The authors note the limitations of the study and offer suggestions for future research.


Writing and publishing clinical articles: a practical guide.
The sharing of knowledge among nurses and clinicians can strengthen the healthcare professions. In this context, many clinicians underestimate the relevance and importance of what they can contribute, and find the idea of writing for publication daunting. This article presents a practical approach to writing clinical articles for publication in professional journals such as Emergency Nurse. It covers the characteristics of clinical articles, their structure, choosing a journal and how the editorial process should be understood.


New insights from a high-resolution look at gastrulation in the sea urchin, Lytechinus variegatus.
Gastrulation is a complex orchestration of movements by cells that are specified early in development. Until now, classical convergent extension was considered to be the main contributor to sea urchin archenteron extension, and the relative contributions of cell divisions were unknown. Active migration of cells along the axis of extension was also not considered as a major factor in invagination. Cell transplantations plus live imaging were used to examine endoderm cell morphogenesis during gastrulation at high-resolution in the optically clear sea urchin embryo. The invagination sequence was imaged throughout gastrulation. One of the eight macromeres was replaced by a fluorescently labeled macromere at the 32 cell stage. At gastrulation those patches of fluorescent endoderm cell progeny initially about 4 cells wide, released a column of cells about 2 cells wide early in gastrulation and then often this column narrowed to one cell wide by the end of archenteron lengthening. The primary movement of the column of cells was in the direction of elongation of the archenteron with the narrowing (convergence) occurring as one of the two cells moved ahead of its neighbor. As the column narrowed, the labeled endoderm cells generally remained as a contiguous population of cells, rarely separated by intrusion of a lateral unlabeled cell. This longitudinal cell migration mechanism was assessed quantitatively and accounted for almost 90% of the elongation process. Much of the extension was the contribution of Veg2 endoderm with a minor contribution late in gastrulation by Veg1 endoderm cells. We also analyzed the contribution of cell divisions to elongation. Endoderm cells in Lytechinus variagatus were determined to go through approximately one cell doubling during gastrulation. That doubling occurs without a net increase in cell mass, but the question remained as to whether oriented divisions might contribute to archenteron elongation. We learned that indeed there was a biased orientation of cell divisions along the plane of archenteron elongation, but when the impact of that bias was analyzed quantitatively, it contributed a maximum 15% to the total elongation of the gut. The major driver of archenteron elongation in the sea urchin, Lytechinus variagatus, is directed movement of Veg2 endoderm cells as a narrowing column along the plane of elongation. The narrowing occurs as cells in the column converge as they migrate, so that the combination of migration and the angular convergence provide the major component of the lengthening. A minor contributor to elongation is oriented cell divisions that contribute to the lengthening but no more than about 15%.


Light therapy of late luteal phase dysphoric disorder: an extended study.
Nineteen patients with late luteal phase dysphoric disorder (LLPDD) and 11 healthy comparison subjects underwent a 3-month crossover trial of bright (more than 2500 lux) white morning, bright white evening, and placebo dim (less than 10 lux) red evening light, administered daily for 1 week during the premenstrual phase of the menstrual cycle. All light treatments significantly reduced depressive ratings from baseline levels.


Explaining differences in hepatitis C between U.S. veterans and nonveterans in treatment for substance abuse: results from a regression decomposition.
Hepatitis C virus (HCV) infection is common among people with substance abuse histories and a burden for U.S. veterans in particular. This study compares self-reported HCV between 1,652 veterans and 48,013 nonveterans who received public-sector substance abuse treatment in Los Angeles between 2006 and 2010. A higher percentage of veterans than nonveterans reported HCV (6.5% vs. 3.8%, p < .0001). Homelessness and mental illness explained, respectively, 8.6% and 7.1% of the difference in HCV between the two groups, adjusting for other variables. Reducing homelessness and mental illness among veterans may also help reduce the excess burden of HCV in this population.


Rapid identification of Escherichia coli by Fluorocult media and positive indole reaction.
To assess the specificity and sensitivity of Fluorocult media for the identification of Escherichia coli, the beta-glucuronidase activities of 1,258 bacterial strains, as well as 20 strains of Candida spp., were investigated. Fluorescence of colonies combined with positive indole reaction resulted in specificities of 99.6 to 99.8%. Sensitivities were 59.1% (MacConkey agar), 69.9% (brolacin agar), 85.5% (Columbia agar), and 85.8% (ECD agar).


C3 rho-inhibitor for targeted pharmacological manipulation of osteoclast-like cells.
The C3 toxins from Clostridium botulinum (C3bot) and Clostridium limosum (C3lim) as well as C3-derived fusion proteins are selectively taken up into the cytosol of monocytes/macrophages where the C3-catalyzed ADP-ribosylation of Rho results in inhibition of Rho-signalling and characteristic morphological changes. Since the fusion toxin C2IN-C3lim was efficiently taken up into and inhibited proliferation of murine macrophage-like RAW 264.7 cells, its effects on RAW 264.7-derived osteoclasts were investigated. C2IN-C3lim was taken up into differentiated osteoclasts and decreased their resorption activity. In undifferentiated RAW 264.7 cells, C2IN-C3lim-treatment significantly decreased their differentiation into osteoclasts as determined by counting the multi-nucleated, TRAP-positive cells. This inhibitory effect was concentration- and time-dependent and most efficient when C2IN-C3lim was applied in the early stage of osteoclast-formation. A single-dose application of C2IN-C3lim at day 0 and its subsequent removal at day 1 reduced the number of osteoclasts in a comparable manner while C2IN-C3lim-application at later time points did not reduce the number of osteoclasts to a comparable degree. Control experiments with an enzymatically inactive C3 protein revealed that the ADP-ribosylation of Rho was essential for the observed effects. In conclusion, the results indicate that Rho-activity is crucial during the early phase of osteoclast-differentiation. Other bone cell types such as pre-osteoblastic cells were not affected by C2IN-C3lim. Due to their cell-type selective and specific mode of action, C3 proteins and C3-fusions might be valuable tools for targeted pharmacological manipulation of osteoclast formation and activity, which could lead to development of novel therapeutic strategies against osteoclast-associated diseases.


Amino acid transport in Mycoplasma.
The uptake of l-histidine by Mycoplasma fermentans and l-methionine by M. hominis was found to be dependent on temperature and pH and to follow saturation kinetics. Several metabolic inhibitors inhibited this uptake. The transport system for l-methionine was highly specific. The l-histidine transport system was less specific, and the uptake was competitively inhibited by l-arginine and l-lysine. l-Histidine accumulated in the intracellular pool of M. fermentans at a concentration about 200 times that found in the medium. Efflux of accumulated l-histidine was demonstrated at 37 C, but not at 0 C. The rate of efflux was greatly accelerated by addition of l-histidine to the medium. The findings indicate that the Mycoplasma cell membrane contains specific transport systems resembling the permease systems of other microorganisms.


Rapid multi sample DNA amplification using rotary-linear polymerase chain reaction device (PCRDisc).
Multiple sample DNA amplification was done by using a novel rotary-linear motion polymerase chain reaction (PCR) device. A simple compact disc was used to create the stationary sample chambers which are individually temperature controlled. The PCR was performed by shuttling the samples to different temperature zones by using a combined rotary-linear movement of the disc. The device was successfully used to amplify up to 12 samples in less than 30 min with a sample volume of 5 μl. A simple spring loaded heater mechanism was introduced to enable good thermal contact between the samples and the heaters. Each of the heater temperatures are controlled by using a simple proportional-integral-derivative pulse width modulation control system. The results show a good improvement in the amplification rate and duration of the samples. The reagent volume used was reduced to nearly 25% of that used in conventional method.


Pararhodonellum marinum gen. nov., sp. nov., isolated from deep-sea sediment.
A Gram-stain-negative, non-motile bacterial strain, designated SW124T, was isolated from a deep-sea sediment sample collected from the Indian Ocean. SW124T was aerobic and catalase-positive. The strain grew at 4-40 °C (optimum, 30 °C), at pH 5.0-8.6 (optimum, pH 7.0) and in the presence of 0.5-9.5 % (w/v) NaCl (optimum, 3.0%). The results of comparative analyses of the 16S rRNA gene sequence indicated that SW124T was grouped in the vicinity of the genus Rhodonellum in the family Cyclobacteriaceae. The quinone system contained menaquinone MK-7. The predominant cellular fatty acids were iso-C15 : 0, iso-C17 : 0 3-OH and summed feature 3 (comprising C16 : 1ω7c and/or C16 : 1ω6c). SW124T contained phosphatidylethanolamine (PE) as the major polar lipid. The genomic DNA G+C content of SW124T was 41.7 mol%. On the basis of its phenotypic characteristics and phylogenetic data, we propose that strain SW124T (=CGMCC 1.16171T=KCTC 82235T) represents a novel species of a novel genus, with the name Pararhodonellum marinum gen. nov., sp. nov.