Mortality and morbidity patterns in under-five children with severe acute malnutrition (SAM) in Zambia: a five-year retrospective review of hospital-based records (2009-2013).
Severe acute malnutrition has continued to be growing problem in Sub Saharan Africa. We investigated the factors associated with morbidity and mortality of under-five children admitted and managed in hospital for severe acute malnutrition. It was a retrospective quantitative review of hospital based records using patient files, ward death and discharge registers. It was conducted focussing on demographic, clinical and mortality data which was extracted on all children aged 0-60 months admitted to the University Teaching Hospital in Zambia from 2009 to 2013. Cox proportional Hazards regression was used to identify predictors of mortality and Kaplan Meier curves where used to predict the length of stay on the ward. Overall (n = 9540) under-five children with severe acute malnutrition were admitted during the period under review, comprising 5148 (54%) males and 4386 (46%) females. Kwashiorkor was the most common type of severe acute malnutrition (62%) while diarrhoea and pneumonia were the most common co-morbidities. Overall mortality was at 46% with children with marasmus having the lowest survival rates on Kaplan Meier graphs. HIV infected children were 80% more likely to die compared to HIV uninfected children (HR = 1.8; 95%CI: 1.6-1.2). However, over time (2009-2013), admissions and mortality rates declined significantly (mortality 51% vs. 35%, P < 0.0001). We find evidence of declining mortality among the core morbid nutritional conditions, namely kwashiorkor, marasmus and marasmic-kwashiorkor among under-five children admitted at this hospital. The reasons for this are unclear or could be beyond the scope of this study. This decline in numbers could be either be associated with declining admissions or due to the interventions that have been implemented at community level to combat malnutrition such as provision of "Ready to Use therapeutic food" and prevention of mother to child transmission of HIV at health centre level. Strategies that enhance and expand growth monitoring interventions at community level to detect malnutrition early to reduce incidence of severe cases and mortality need to be strengthened.


Advanced interventions for headache.
Many headache patients present when medications fail, are inadequate, are contraindicated, or are not tolerated. These are patients with severe disability. Most have daily headaches, including chronic migraine, trigeminal autonomic cephalalgias, or other primary headaches. This brief review addresses, in broad strokes, some thoughts about alternatives beyond the usual daily oral preventive therapies. Do not proceed to more invasive or elaborate approaches until the big 3 are done: diagnosis is established, onabotulinumtoxinA administered when appropriate, that is, if the patient has chronic migraine, and wean is accomplished if the patient has medication overuse headache. Large numbers of patients are helped without the need for more arcane and unproven treatments by following these initial approaches. Simple nerve blocks can be useful in the initial steps, but more invasive blocks and stimulators are not recommended until the big 3 are completed. Wean of overused medications must be absolute and may require an intravenous bridge over several days, either in an infusion unit or inpatient in a medical model. Wean should be accompanied by establishing onabotulinumtoxinA or daily prevention from the beginning. Consider referral to a structured multidisciplinary headache program. This is for patients who require an interdisciplinary approach and may be day-hospital or inpatient. Invasive blocks and stimulators may be appropriate, and the latter are currently being studied in controlled studies. The most promise, with the best balance of efficacy vs adverse event prospects, may be occipital nerve stimulators or sphenopalatine ganglion stimulators.


Unravelling dynamic changes in non-volatile and volatile metabolites of pulses during soaking: An integrated metabolomics approach.
An integrated metabolomics approach based on UPLC-QTOF-MS and HS-SPME-GC-orbitrap-MS was performed to investigate the dynamic changes of metabolite profiling in chickpeas, red speckled kidney beans, and mung beans during soaking. There were 23, 23, 16 non-volatile metabolites, and 18, 21, 22 volatile metabolites were identified as differential metabolites in chickpeas, red speckled kidney beans, and mung beans during soaking, respectively. These metabolites mainly included flavonoids, lysophosphatidylcholines (LPCs), lysophosphatidylethanolamines (LPEs), fatty acids, alcohols, aldehydes, and esters. The key time points responsible for the significant changes in metabolites and quality of the three pulses were 4, 8, and 24 h of soaking. Results revealed that the variations of some metabolites could attribute to oxidation and hydrolysis reactions. These results contribute to a better understanding of how soaking affects pulses quality, and provide useful information for determining soaking time according to nutritional and sensory requirements of their final products or dishes.


Intra-Arterial Hemodynamics to Guide the Percutaneous Treatment of a Difficult-to-Engage Transplant Renal Artery Stenosis.
Transplant renal artery stenosis (TRAS) is the most frequent vascular complication after renal transplantation. TRAS is associated with resistant hypertension and allograft dysfunction, early diagnosis and either endovascular or surgical treatment is crucial to preserve graft function. Noninvasive imaging can usually detect the underlying stenosis. In this report we present a novel technique for successful angioplasty and stent deployment in a difficult-to-engage transplant-renal artery.


Outcome of Pneumocystis jirovecii pneumonia diagnosed by polymerase chain reaction in patients without human immunodeficiency virus infection.
Pneumonia caused by Pneumocystis jirovecii (PCP) in patients without human immunodeficiency virus (HIV) infection is associated with high mortality. The diagnosis of PCP at our institution is based on detection of DNA using a polymerase chain reaction (PCR) assay. The aim of this study was to describe the clinical manifestations, outcomes and factors associated with mortality due to PCP, as diagnosed by PCR, in patients without HIV infection. Over a 6-year period, all HIV-negative immunocompromised patients suspected of having an opportunistic pulmonary infection underwent diagnostic bronchoscopy. A multigene PCR assay that detects Pneumocystis jirovecii DNA was used for the diagnosis of PCP. Patients were considered to have PCP if they had underlying immunodeficiency, compatible signs and symptoms, abnormal radiological findings, and Pneumocystis jirovecii DNA was detected in a bronchoalveolar lavage fluid sample. Data was collected retrospectively. PCP was diagnosed in 58 patients. The underlying conditions included haematological malignancies (60.3%), solid tumours (17.2%) and immunosuppressive treatment (22.4%). The most common clinical features in patients with PCP were fever (94.6%), dyspnoea (67.2%) and cough (36.2%). The overall in-hospital mortality was 17.2% (10/58). Mortality was associated with co-infections, high lactate dehydrogenase levels, female gender, and higher pneumonia severity index and acute physiology and chronic health evaluation III scores. In this study, the mortality of HIV-negative patients with PCP was low compared with previous reports. We hypothesize that this finding resulted from the increased sensitivity of a PCR-based assay, as compared with traditional methods, for the diagnosis of PCP in HIV-negative patients.


Subthreshold atrial pacing in patients with a left-sided accessory pathway: an effective new method for terminating reciprocating tachycardia.
This study investigated the possibility of terminating reciprocating atrioventricular (AV) tachycardia using subthreshold atrial pacing. Ten patients with a left-sided accessory pathway and sustained AV tachycardia underwent subthreshold atrial pacing from the coronary sinus site closest to insertion of the accessory pathway. In seven of these patients, the tachycardia could be reliably terminated with subthreshold atrial overdrive pacing. When pacing at a cycle length of 80 +/- 23% of the tachycardia cycle length, the minimal subthreshold current that was effective in tachycardia termination was 64 +/- 14% of threshold current and the maximal ineffective current was 49 +/- 17% of threshold (p less than 0.05). In all cases, the tachycardia was terminated by one or two instances of atrial capture that resulted in a premature atrial impulse (20 +/- 4% advancement of the atrial cycle) that blocked the AV node limb of the tachycardia. Anterograde conduction over the accessory pathway never occurred, either during the tachycardia or during subthreshold pacing after a return to normal sinus rhythm. No instances of atrial fibrillation were provoked by subthreshold pacing. Possible explanations for the intermittent atrial capture with critically placed subthreshold impulses include supernormal atrial conduction or summation of impulses at the atrial insertion site of the accessory pathway. It is concluded that subthreshold pacing is effective in selected patients with AV tachycardia due to an accessory pathway. Furthermore, because neither atrial fibrillation nor anterograde conduction over the accessory pathway is seen with subthreshold pacing, this modality may hold significant promise for permanent antitachycardia pacing in these patients.


Effect of one year krill oil supplementation on depressive symptoms and self-esteem of Dutch adolescents: A randomized controlled trial.
Observational studies have shown a relationship between omega-3 long-chain polyunsaturated fatty acids (n-3 LCPUFA) and depression in adolescents. However, n-3 LCPUFA supplementation studies investigating the potential improvement in depressive feelings in adolescents from the general population are missing. A one-year double-blind, randomized, placebo controlled krill oil supplementation trial was conducted in two cohorts. Cohort I started with 400 mg eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) or placebo, after three months this increased to 800 mg EPA and DHA per day, whilst cohort II started with this higher dose. Omega-3 Index (O3I) was monitored via finger-prick blood measurements. At baseline, six and 12 months participants completed the Centre for Epidemiologic Studies Depression Scale (CES-D) and the Rosenberg Self Esteem questionnaire (RSE). Adjusted mixed models were run with treatment allocation/O3I as predictor of CES-D and RSE scores. Both intention-to-treat and assessing the change in O3I analyses did not show significant effects on CES-D or RSE scores. There is no evidence for less depressive feelings, or higher self-esteem after one year of krill oil supplementation. However, due to a lack of adherence and drop-out issues, these results should be interpreted with caution.


Indicators of therapeutic effect in FIT-06, a Phase II trial of a DNA vaccine, GTU(®)-Multi-HIVB, in untreated HIV-1 infected subjects.
Combination highly active antiretroviral therapy (HAART) has significantly decreased HIV-1 related morbidity and mortality globally transforming HIV into a controllable condition. HAART has a number of limitations though, including limited access in resource constrained countries, which have driven the search for simpler, affordable HIV-1 treatment modalities. Therapeutic HIV-1 vaccines aim to provide immunological support to slow disease progression and decrease transmission. We evaluated the safety, immunogenicity and clinical effect of a novel recombinant plasmid DNA therapeutic HIV-1 vaccine, GTU(®)-multi-HIVB, containing 6 different genes derived from an HIV-1 subtype B isolate. 63 untreated, healthy, HIV-1 infected, adults between 18 and 40 years were enrolled in a single-blinded, placebo-controlled Phase II trial in South Africa. Subjects were HIV-1 subtype C infected, had never received antiretrovirals, with CD4 ≥ 350 cells/mm(3) and pHIV-RNA ≥ 50 copies/mL at screening. Subjects were allocated to vaccine or placebo groups in a 2:1 ratio either administered intradermally (ID) (0.5mg/dose) or intramuscularly (IM) (1mg/dose) at 0, 4 and 12 weeks boosted at 76 and 80 weeks with 1mg/dose (ID) and 2mg/dose (IM), respectively. Safety was assessed by adverse event monitoring and immunogenicity by HIV-1-specific CD4+ and CD8+ T-cells using intracellular cytokine staining (ICS), pHIV-RNA and CD4 counts. Vaccine was safe and well tolerated with no vaccine related serious adverse events. Significant declines in log pHIV-RNA (p=0.012) and increases in CD4+ T cell counts (p=0.066) were observed in the vaccine group compared to placebo, more pronounced after IM administration and in some HLA haplotypes (B*5703) maintained for 17 months after the final immunisation. The GTU(®)-multi-HIVB plasmid recombinant DNA therapeutic HIV-1 vaccine is safe, well tolerated and favourably affects pHIV-RNA and CD4 counts in untreated HIV-1 infected individuals after IM administration in subjects with HLA B*57, B*8101 and B*5801 haplotypes.


Intermittent hypoxic conditioning restores neurological dysfunction of mice induced by long-term hypoxia.
Central nervous system diseases are associated with hypoxia, which usually cause irreversible nerve damage, but the underlying mechanism is unclear and effective intervention strategies are lacking. This study was designed to explore the mechanism and treatment strategy of hypoxia-induced nerve injury. In this study, 13% O2 was used to treat mice for 0, 1, 3 7, and 14 days, Morris water maze and other animal behavior experiments were used to evaluate the neurological function of mice. TUNEL, BrdU, PCNA, DCX, and SOX2 staining were used to observe the apoptosis and proliferation of mouse neurons. RT-PCR and Iba1 staining were used to evaluate the release of inflammatory factors IL-1β, IL-6, and TNF-α and the activation of microglia. Short-term hypoxia promotes neurogenesis, while long-term hypoxia inhibits neurogenesis. The changes in hypoxia-induced neurogenesis were positively correlated with neurological functions, but negatively correlated with apoptosis. Moreover, intermittent hypoxic conditioning restored long-term hypoxia-induced neurological dysfunction by promoting neural stem cell generation and inhibiting the release of inflammatory factors IL-1β, IL-6, and TNF-α and the activation of microglia. Hypoxia promoted neurogenesis in a time-dependent manner, and intermittent hypoxic conditioning exerted a neuroprotective effect through promoting neural stem cell generation and suppressing inflammation induced by long-term hypoxia stress, which provided a novel concept to develop a treatment for hypoxia-related brain injury.


Additive Printed All-Cellulose Membranes with Hierarchical Structure for Highly Efficient Separation of Oil/Water Nanoemulsions.
To expand the application of commercial membranes in oily wastewater separation, in this work, all-cellulose membranes were fabricated by depositing cellulose nanocrystals onto the surface of mixed-cellulose esters via a large-scale additive printing strategy. The thickness, pore size, surface wettability, and water flux of all-cellulose membranes can be well tuned by controlling the printing cycles of cellulose nanocrystal inks. Under optimal printing conditions, the resultant all-cellulose membranes with nanoporous architecture (76-91 nm) exhibit superhydrophilicity and underwater superoleophobicity, which benefits the separation of oil/water nanoemulsions with a high water flux (>1500 L m-2 h-1 bar-1) and an ultrahigh efficiency (>99%). Moreover, these all-cellulose membranes exhibit excellent stability and reusability for long-term separation and retains their inherent properties under various acidic, basic, and salty conditions, as well as mechanical abrasion. The presented scalable additive printing is a facile, economical, and sustainable strategy to construct all-cellulose membranes with excellent separation performance for oil/water nanoemulsions.


Irisin protects against obesity-related chronic kidney disease by regulating perirenal adipose tissue function in obese mice.
Compared with typical visceral fat deposits in obesity and metabolic syndrome, perirenal adipose tissue (PRAT) dysfunction is more closely linked to obesity-related chronic kidney disease (OB-CKD). The myokine irisin reportedly promotes positive outcomes in metabolic disease. This study investigated whether irisin could reduce urinary albumin excretion and demonstrate renoprotective effects through the regulation of PRAT function in obese mice. C57BL/6 J mice received a high-fat diet (HFD) with or without concurrent administration of irisin. Glucose tolerance, plasma levels of free fatty acids, and urinary albumin excretion were assessed, along with renal morphology. The vascular endothelial growth factor and nitric oxide in glomeruli were also analyzed, in addition to PRAT function-associated proteins. Irisin administration significantly reduced the final body weight, fat mass, and free fatty acids, without reducing PRAT mass, in HFD mice. Furthermore, irisin decreased urinary albumin excretion and attenuated both renal fibrosis and lipid accumulation. Irisin administration led to increases in PRAT function-associated proteins, including sirtuin1, uncoupling protein-1, and heme-oxygenase-1. Ex vivo treatment of PRAT and glomeruli with irisin also restored PRAT function. Finally, irisin treatment restored the vascular endothelial growth factor-nitric oxide axis. Irisin attenuated metabolic disorders and protected against OB-CKD by normalizing the PRAT-kidney axis. These results suggest that agents targeting PRAT activation might be useful for treatment of OB-CKD.


Circ_0001806 relieves LPS-induced HK2 cell injury by regulating the expression of miR-942-5p and TXNIP.
Sepsis is a systemic inflammatory disease that can cause a variety of diseases, including septic acute kidney injury (AKI). Circular RNAs (circRNAs) are believed to be involved in the development of this disease. This study aims to clarify the function of circ_0001806 in lipopolysaccharide (LPS)-induced HK2 cell model and its related mechanisms. Circ_0001806 was up-regulated in septic AKI serum specimens and LPS-induced HK2 cells. Circ_0001806 knockdown promoted cell proliferation and restrained apoptosis, inflammation and oxidative stress in LPS-induced HK2 cells. In mechanism, circ_0001806 can be used as a sponge for miR-942-5p, and miR-942-5p can directly target TXNIP. Functional experiments revealed that the miR-942-5p inhibitor could reverse the alleviating effect of circ_0001806 knockdown on LPS-induced HK2 cell injury, and TXNIP addition can also reverse the inhibitory effect of miR-942-5p overexpression on LPS-induced HK2 cell injury. In addition, circ_0001806 regulated TXNIP expression through sponging miR-942-5p. Besides, exosome-derived circ_0001806 was upregulated in LPS-induced HK2 cells, while was downregulated by GW4869. The results showed that circ_0001806 knockdown could reduce LPS-induced HK2 cell injury by regulating TXNIP expression via targeting miR-942-5p, indicating that circ_0001806 might be an important biomarker for alleviating sepsis-related AKI. This might provide therapeutic strategy for the treatment of sepsis.


Relaxins enhance growth of spontaneous murine breast cancers as well as metastatic colonization of the brain.
Relaxins are known for their tissue remodeling capacity which is also a hallmark of cancer progression. However, their role in the latter context is still unclear, particularly in breast cancer. In a mouse model with spontaneously arising breast cancer due to erbB2-overexpression we show that exposure to porcine relaxin results in significantly enhanced tumour growth as compared to control animals. This is accompanied by increased serum concentrations of progesterone and estradiol as well as elevated expression of the respective receptors and the relaxin receptor RXFP1 in the tumour tissue. It is also associated with enhanced infiltration by tumour-associated macrophages which are known to promote tumour progression. Additionally, we show in an ex vivo model of metastatic brain colonization that porcine relaxin as well as human brain-specific relaxin-3 promotes invasion into the brain tissue and enhance interaction of breast cancer cells with the resident brain macrophages, the microglia. Relaxin signaling is mediated via RXFP1, since R 3/I5, a specific agonist of the relaxin-3 receptor RXFP3 in the brain, does not significantly enhance invasion. Taken together, these findings strongly support a role of relaxins in the progression of breast cancer where they foster primary tumour growth as well as metastatic colonization by direct and indirect means.


Responses of female rock lizards to multiple scent marks of males: effects of male age, male density and scent over-marking.
Scent-marked substrates may inform conspecifics on the characteristics of territorial males. Scent-marks of male Carpetan rock lizards (Iberolacerta cyreni) affect space use of females, which by selecting an area may increase the probability of mating with the male that has scent-marked that area. However, males do not hold exclusive territories, and scent-marks of different individual males are often together. This may provide complex information from multiple sources on the social structure. Here, we examined female preference in response to scent marks of various males and combinations in a laboratory experiment. Females preferred areas scent-marked by territorial old males against those scent-marked by young satellite-sneaker males. This reflected the known preference of females for mating with old males. In a second experiment, females preferred areas scent-marked by two males to areas of similar size marked by a single male. This may increase the probability of obtaining multiple copulations with different males, which may favour sperm competition and cryptic female choice, or may be a way to avoid infertile males. Finally, when we experimentally over-marked the scent-marks of an old male with scent-marks of a young male, females did not avoid, nor prefer, the over-marked area, suggesting that the quality of the old male may override the presence of a satellite male. We suggest that, irrespective of the causes underlying why a female selects a scent-marked area, this strategy may affect her reproductive success, which may have the same evolutionary consequences that "direct" mate choice decisions of other animals.


Genetic heterogeneity on sleep disorders in Parkinson's disease: a systematic review and meta-analysis.
A growing amount of evidence has indicated contributions of variants in causative genes of Parkinson's disease (PD) to the development of sleep disturbance in PD and prodromal PD stages. In this article, we aimed to investigate the role of genetics in sleep disorders in PD patients and asymptomatic carriers at prodromal stage of PD. A systematic review and meta-analysis of observational studies was conducted based on the MEDLINE, EMBASE and PsychINFO databases. A pooled effect size was calculated by odds ratio (OR) and standard mean difference (SMD). Forty studies were selected for quantitative analysis, including 17 studies on glucocerebrosidase (GBA), 25 studies on Leucine-rich repeat kinase 2 (LRRK2) and 7 on parkin (PRKN) genes, and 3 studies on alpha-synuclein gene (SNCA) were used for qualitative analysis. Patients with PD carrying GBA variants had a significantly higher risk for rapid-eye-movement behavior disorders (RBD) (OR, 1.82) and higher RBD Screening Questionnaire scores (SMD, 0.33). Asymptomatic carriers of GBA variants had higher severity of RBD during follow-up. Patients with PD carrying the LRRK2 G2019S variant had lower risk and severity of RBD compared with those without LRRK2 G2019S. Variants of GBA, LRRK2 and PRKN did not increase or decrease the risk and severity of excessive daytime sleepiness and restless legs syndrome in PD. Our findings suggest that the genetic heterogeneity plays a role in the development of sleep disorders, mainly RBD, in PD and the prodromal stage of PD.


Labeling, characterization, and in vivo localization of a new 90Y-based phosphonate chelate 2,3-dicarboxypropane-1,1-diphosphonic acid for the treatment of bone metastases: Comparison with 99mTc-DPD complex.
The goal of this investigation was to examine the possibilities for yttrium-90-labeling of the 2,3-dicarboxypropane-1,1-diphosphonic acid (DPD), which is currently labeled with technetium-99m and as a (99m)Tc-DPD clinically used as bone imaging agent. Analysis of the complex enclosed the radiochemical quality control methods, biodistribution studies, as well as the determination of pharmacokinetic parameters. The biological behavior of complexes (90)Y-DPD, (99m)Tc-DPD and (90)Y-labeled DPD-kit formulation [(90)Y-(Sn)-DPD] in animal model was compared. The labeling conditions were standardized to give the maximum yield, which ranged between 93% and 98%. The examined (90)Y complex could be easily prepared, with an outstanding yield and was also found to be very stable for at least 10h after (90)Y-labeling. Protein binding value was 4.6+/-0.7% for (90)Y-DPD complex and the complex possess a hydrophilic character. The satisfactory results of (90)Y-DPD biodistribution in healthy test animals were obtained; the uptake in the bone was 11-13%ID/g after 24h depending on the pH value during the preparation. With high skeletal uptake, a minimum uptake in soft tissues and rapid blood clearance the (90)Y-DPD complex proved to be an excellent candidate for targeting tumor therapy.


Purification, characterization, cDNA cloning, and expression of a xyloglucan endoglucanase from Geotrichum sp. M128.
A novel xyloglucan-specific endo-beta-1,4-glucanase (XEG), xyloglucanase, with a molecular mass of 80 kDa and a pI of 4.8, was isolated from the fungus Geotrichum sp. M128. It was found to be an endoglucanase active toward xyloglucan and not active toward carboxymethylcellulose, Avicel, or barley 1,3-1,4-beta-glucan. Analysis of the precise substrate specificity using various xyloglucan oligosaccharide structures revealed that XEG has at least four subsites (-2 to +2) and specifically recognizes xylose branching at the +1 and +2 sites. The full-length cDNA encoding XEG was cloned and sequenced. It consists of a 2436-bp open reading frame encoding a 776-amino acid protein. From its deduced amino acid sequence, XEG can be classified as a family 74 glycosyl hydrolase. The cDNA encoding XEG was then expressed in Escherichia coli, and enzymatically active recombinant XEG was obtained.


Interleukin 10 (IL-10) gene variants and haplotypes in Tunisian women with polycystic ovary syndrome (PCOS): a case-control study.
Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder that affects women in their child-bearing age, and is associated with insulin resistance and type 2 diabetes. The etiology of PCOS involves multiple factors including genetic, metabolic and immunological factors. Interleukin - 10 (IL-10), as an anti-inflammatory cytokine, plays a critical role in this regard. We investigated the potential role of IL-10 gene variants in the development of PCOS in Tunisian population. 115 cases and 120 controls were recruited in the current case control study. Rotterdam consensus criteria were used to diagnose PCOS patients. Genotyping for IL-10, rs1800896, rs1800871 and rs1800872 variants, was performed by real time PCR. The results obtained showed that the minor allele frequency of rs1800896, rs1800871and rs1800872 were comparable between PCOS cases and control subjects (P = 0.30, P = 0.71, and P = 0.57 respectively). The distribution analysis revealed an unsignificant association of the three tested variants, in all genetic models. Haplotype analysis identified one haplotype CCA with a protective role in PCOS development (P = 0.05; OR (95% CI) = 0.56 (0.32 - 0.99)). This association did not persist after adjustment for multiples covariates (Pc = 0.154). Our study is the first to show how ethnicity influences the association of IL-10 gene variants with PCOS susceptibility. No allelic nor genetic association were observed between the tested variants and PCOS in Tunisian women, however, a particular IL-10 haplotype with a protective effect for PCOS was identified.


First-principles, machine learning and symbolic regression modelling for organic molecule adsorption on two-dimensional CaO surface.
Data-driven methods are receiving significant attention in recent years for chemical and materials researches; however, more works should be done to leverage the new paradigm to model and analyze the adsorption of the organic molecules on low-dimensional surfaces beyond using the traditional simulation methods. In this manuscript, we employ machine learning and symbolic regression method coupled with DFT calculations to investigate the adsorption of atmospheric organic molecules on a low-dimensional metal oxide mineral system. The starting dataset consisting of the atomic structures of the organic/metal oxide interfaces are obtained via the density functional theory (DFT) calculation and different machine learning algorithms are compared, with the random forest algorithm achieving high accuracies for the target output. The feature ranking step identifies that the polarizability and bond type of the organic adsorbates are the key descriptors for the adsorption energy output. In addition, the symbolic regression coupled with genetic programming automatically identifies a series of hybrid new descriptors displaying improved relevance with the target output, suggesting the viability of symbolic regression to complement the traditional machine learning techniques for the descriptor design and fast modeling purposes. This manuscript provides a framework for effectively modeling and analyzing the adsorption of the organic molecules on low-dimensional surfaces via comprehensive data-driven approaches.


The Antioxidant Effect of Exercise: A Systematic Review and Meta-Analysis.
Physical activity has been associated with reduced oxidative stress (OS) in observational studies and clinical trials. The purpose of this systematic review and meta-analysis of controlled trials was to determine the effect of physical exercise on OS parameters. We conducted a systematic review of the literature up to March 2016 that included the following databases: PubMed, SCOPUS, and Web of Science. A keyword combination referring to exercise training and OS was included as part of a more thorough search process. We also manually searched the reference lists of the articles. From an initial 1573 references, we included 30 controlled trials (1346 participants) in the qualitative analysis, 19 of which were included in the meta-analysis. All trials were conducted in humans and had at least one exercise intervention and a paired control group. Using a standardized protocol, two investigators independently abstracted data on study design, sample size, participant characteristics, intervention, follow-up duration, outcomes, and quantitative data for the meta-analysis. Thus, the investigators independently assigned quality scores with a methodological quality assessment (MQA). The agreement level between the reviewers was 85.3 %. Discrepancies were solved in a consensus meeting. The MQA showed a total score in the quality index between 40 and 90 % and a mean quality of 55 %. Further, in a random-effects model, data from each trial were pooled and weighted by the inverse of the total variance. Physical training was associated with a significant reduction in pro-oxidant parameters (standard mean difference [SMD] -1.08; 95 % confidence interval [CI] -1.57 to -0.58; p < 0.001) and an increase in antioxidant capacity (SMD 1.45; 95 % CI 0.83-2.06; p < 0.001). The pooled analysis revealed that regardless of intensity, volume, type of exercise, and studied population, the antioxidant indicators tended to increase and pro-oxidant indicators tended to decrease after training. Therefore, we conclude that exercise training seems to induce an antioxidant effect. Thus, it is suggested that people practice some kind of exercise to balance the redox state, regardless of their health status, to improve health-related outcomes.


Prevalence of IgG diphtheria antitoxin in blood donors in Rio de Janeiro.
The lack of information on the immunity of adults in Brazil against diphtheria prompted us to analyse sera from 234 blood donors aged 18-61 years (30.3% females and 69.7% males). IgG diphtheria antitoxin levels determined by means of an ELISA, validated by toxin neutralization test in Vero cells, showed that 30.7% (95% CI 25.0-37.1) of the population was fully protected (>or=1 IU/ml). The highest percentage of subjects fully protected was in the 31-40 years age group. Most of the subjects with uncertain or no protection (<1 IU/ml) were found in the 18-30 years age group (43.8%, OR 2.18, P=0.01). Antitoxin levels were not influenced by the increase in age. Males were more protected than females (80.5%, OR 0.44, P=0.01). The prevalence of 30% of individuals fully protected against diphtheria in blood donors in Rio de Janeiro supports the fact that immunity to diphtheria among healthy Brazilian adults is inadequate. To avoid diphtheria epidemics in the future the immunity among adults should be raised in the coming years.


Microbiological aspects of a bioreactor with submerged membranes for aerobic treatment of municipal wastewater.
An aerobic membrane bioreactor treating municipal wastewater at complete biomass retention was studied in respect of microbiological parameters over a period of 380 days. The results were compared to those obtained from a conventional activated sludge wastewater treatment plant (WWTP) treating the same wastewater. Microscopically, significant changes in the structure of the flocs and of the ratio between free suspended and aggregated cells could be observed. The presence of filamentous bacteria varied from almost not present to very high numbers. With the exception of short periods after changes in operating conditions, protozoa and metazoa were rarely present in the sludge community. The rate of oxygen consumption and the cell detectability by fluorescence in situ hybridizatio (FISH) with rRNA-targeted oligonucleotide probes were used to assess the physiological state of the bacterial cells Oxygen consumption rates of sludge samples obtained from both the conventional and membrane filtration plant wer determined without and after addition of different energy and carbon sources. In contrast to the conventional activate sludge, a pronounced increase in respiration activity upon the addition of organic substrates could be observed in th membrane filtration sludge. In situ probing with the Bacteria-specific probe EUB338 visualized 40-50% of all DAPI stainable bacteria in the membrane bioreactor, compared to 80% cells detectable by FISH in the conventional activate sludge. These results suggest that bacteria present in the highly concentrated biomass of the membrane reactor use the energy supplied for their maintenance metabolism and were not in a physiological state characteristic for growth This assumption could explain the zero net biomass production observed in the reactor.


Reorganization of substrate waters between the closed and open cubane conformers during the S2 to S3 transition in the oxygen evolving complex.
A crucial step in the mechanism for oxygen evolution in the Photosystem II complex resides in the transition from the S2 state to the S3 state of Kok–Joliot's cycle, in which an additional water molecule binds to the cluster. On the basis of computational chemistry calculations on Photosystem II models, we propose a reorganization mechanism involving a hydroxyl (W2) and a μ2-oxo bridge (O5) that is able to link the closed cubane S2B intermediate conformer to the S3 open cubane structure. This mechanism can reconcile the apparent conflict between recently reported water exchange and electron paramagnetic resonance experiments, and theoretical studies.


Melkersson-Rosenthal Syndrome with Orofacial Swelling and Recurrent Lower Motor Neuron Facial Nerve Palsy: A Case Report and Review of the Literature.
Melkersson-Rosenthal Syndrome (MRS) is a rare otoneurologic condition, which is poorly understood and often underdiagnosed. Etiology and incidence are unclear, although infectious, inflammatory, and genetic causes have been implicated. Recurrent facial nerve palsy, facial swelling, and fissured tongue are the symptoms and signs of this condition. However, this triad is not typical in all patients as patients may present with one or more of the symptoms, which makes management of this condition difficult. Steroids may prove to be useful especially in patients who have facial nerve palsy. In this case report, we have described a 46 year-old Caucasian male who presented to the clinic for the evaluation of orofacial swelling and left facial deviation with a history of multiple treatments for recurrent lower motor neuron type facial nerve palsy.


Use of the International Consultation on Incontinence Questionnaire-Urinary Incontinence-Short Form (ICIQ-UI-SF) for an objective assessment of disability determination according to the Modified Katz Scale: a prospective longitudinal study.
The aim of this study was to demonstrate that the International Consultation on Incontinence Questionnaire-Urinary Incontinence-Short Form (ICIQ-UI-SF) tool can be applied for a factual score determining urinary incontinence in the Katz-6 Scale, and it is effective to identify score 2 from score 3. Functional capacity of 63 patients (14 M, 49 F aged from 70 to 99 years old) was evaluated with a Mini Mental State Examination (MMSE), Katz Index for Activities of Daily Living, and ICIQ-UI-SF questionnaire. Mean comparative analysis was performed. ICIQ-UI-SF scores were then entered as variables. These data observed in Katz continence item scored 2 and Katz continence item scored 3 were compared in a combined box-and-whisker and dot plot. Sensitivity and specificity of each variable were tested and results were evaluated using a receiver operating characteristic (ROC) curve. The best variable (ICIQ-UI-SF Score) was retained as a breach permitting to distinguish patients to be scored 2 or 3 over continence Katz item. Statistical analysis demonstrated significant difference between the sample of Katz continence item scored 2 and the sample of Katz continence item scored 3 over the ICIQ-UI-SF Score and the Katz global Score, but the difference was not significant concerning the MMSE Score. Using ROC analysis, we compared the discriminant power of the ICIQ-UI-SF Score for continence Katz item Score. Criterion values and coordinates of the ROC curve were studied and the ICIQ-UI-SF score of 13 was considered the best one. We demonstrated that the best variable (ICIQ-UI-SF Score) to retain as a breach permitting to distinguish patients to be scored 2 or 3 over continence Katz item is 13.


Patient- and population-reported outcomes in public health dentistry: oral health-related quality of life.
At present no process is in place in the United States to comprehensively monitor the national burden of oral diseases from the perspective of oral health-related quality of life (OHRQoL), yet available evidence shows that a substantial percentage of the adult population rates their oral health poorly. This article reviews applications of OHRQoL in dental public health. The authors specifically review its use, contributions, and needed advances in: (1) monitoring the impacts of oral diseases on OHRQoL at the national level, and in public health surveillance at the state and local levels; (2) treatment outcomes research and program evaluation; and (3) clinical practice.


Gastroesophageal reflux disease and odds of head and neck squamous cell carcinoma in North Carolina.
Exposure to excess gastric acid resulting from gastroesophageal reflux disease, also known as acid reflux or heartburn, might contribute to initiation of head and neck squamous cell carcinoma, particularly laryngeal cancer. Prior epidemiologic studies have reported inconsistent results. We sought to clarify this relationship using an observational study with a larger available sample size and better-characterized exposure information than most prior studies. A population-based case-control study of head and neck cancer in North Carolina with 1,340 newly diagnosed cases and 1,378 controls matched on age, race, and sex. We used unconditional logistic regression to examine associations between self-reported heartburn and development of overall head and neck cancer as well as development of cancer at specific tumor sites. Subgroup analysis by smoking and alcoholic drinking status was used to make comparisons with a previous study that used a similar study design. Overall, an increased odds of head and neck cancer was not associated with either self-reported history of heartburn symptoms (odds ratio = 0.85; 95% confidence interval 0.68, 1.06) or self-reported medical diagnosis of GERD (OR = 0.89; 95% CI 0.71, 1.11). These patterns held for specific tumor sites. For laryngopharyngeal cancer, we did not detect any associations regardless of joint smoking and alcoholic drinking status. Gastroesophageal reflux does not appear to play a role in development of head and neck cancer. 3b. Laryngoscope, 126:1091-1096, 2016.


Cardiovascular responses of the anterior claustrum; its mechanism; contribution of medial prefrontal cortex.
The anterior claustrum (CLa) has bilateral connections with the areas involved in cardiovascular regulation, though its role in cardiovascular control is not yet understood. This study was performed to find the cardiovascular responsive region of the CLa by stimulating all parts of the CLa with l-glutamate, and to find the possible mechanisms mediating its responses in urethane-anesthetized rats. We also investigated the possible involvement of the medial prefrontal cortex in the cardiovascular responses of the CLa. The effect of microinjection of l-glutamate (50-100 nl, 0.25 M) was tested throughout the Cla and only in one area at 2.7 mm rostral to bregma, 1.8-2.0 midline and 4.5-5.6mm vertical, significant decreases in arterial pressure were elicited (-21.71±2.1 mmHg, P<0.001, t-test) with no significant change in heart rate. Administration (i.v.) of the muscarinic receptor blocker, atropine, had no effect on the change in mean arterial pressure in response to glutamate stimulation, suggesting that the parasympathetic system was not involved in this response. However, administration (i.v.) of the nicotinic receptor blocker, hexamethonium dichloride abolished the depressor response to glutamate, suggesting that CLa stimulation decreases sympathetic outflow to the cardiovascular system. In addition, microinjection of the reversible synaptic blocker, cobalt chloride, into the medial prefrontal cortex greatly attenuated the depressor response elicited by microinjection of glut into the CLa. Thus for the first time, we found the cardiovascular responsive region of the anterior claustrum. Also we showed that its response is mediated through the medial prefrontal cortex.


Induction of stage-specific cell cohesion in D. discoideum by a plasma-membrane-associated moiety reactive with wheat germ agglutinin.
Dictyostelium discoideum strain JC-5 is a temperature-sensitive, cohesion-defective mutant. At the restrictive temperature, aggregates are formed and develop normally to a specific late stage, but then disperse to a lawn of noncohesive cells. The defect stems from the inability of the mutant at the restrictive temperature to accumulate or retain an adequate level of a newly arisen, plasma-membrane-associated cohesive moiety during the later stages of morphogenesis. We now report that the noncohesive mutant cells can be induced to cohere at a level of greater than 99% by addition of a fraction reactive with wheat germ agglutinin and isolated from the plasma membranes of late-stage, cohesive mutant or wild-type cells. Furthermore, the cohesivities of late-stage, cohesive mutant or wild-type cells can be significantly enhanced by the same preparations but early-stage cohesive cells remain unaffected. The cohesion-inducing activity can be recovered from two regions of a one-dimensional polyacrylamide gel electropherogram following elution and renaturation. The first is associated with a single silver-staining band (apparent molecular weight 95,000). It appears de novo at a postaggregative stage, and accumulates in a thermostable fashion in the wild-type and in a thermosensitive fashion in the mutants, concurrent with the loss of cohesivity. The second is associated with a complex of silver-staining bands (apparent molecular weights 40,000-50,000). The activity of the eluate reactive with wheat germ agglutinate is destroyed within 5 min at 100 degrees C.


Effect of cocaine in early gestation on striatal dopamine and neurotrophic activity.
Prenatal exposure to the dopamine (DA) agonist cocaine, even if limited to early gestation, is associated with impaired developmental outcome in the human infant. We investigated the possible role of neurotrophic factors in this process by evaluating 4- to 6-d-old New Zealand White rabbit pups (n = 14) born to cocaine-exposed does (30 mg/kg/d s.c. from days 7 to 15 of a 32-d gestation) and control does (sterile H2O). Cocaine exposure reduced striatal dopamine by 46% (t = 2.31; p < 0.05) and striatal 3,4-dihydroxyphenyl acetic acid by 49% (t = 2.44; p < 0.05). The number of neuron-specific enolase immunoreactive neurons in mesencephalic cultures incubated with striatal extracts from pups exposed to cocaine was reduced by 61% relative to the effect of striatal extracts from control pups (t = 4.84; p < 0.01). The present results suggest that the reduction in striatal dopamine observed may result from a cocaine-induced decrease in striatal trophic activity.


Visceral complications of electrical burn injury. A report of two cases and review of the literature.
Two patients with high voltage electrical injury involving the trunk are presented. Both injuries were complicated by visceral damage; and one patient died from sepsis secondary to bowel perforation. The rarity of this complication is examined in light of the pathophysiology of electrical injury; and its management is discussed with reference to previously published reports on this condition.


Predicting chronicity in acute back pain: validation of a French translation of the Örebro Musculoskeletal Pain Screening Questionnaire.
To establish the predictive validity of a French translation of the Örebro Musculoskeletal Pain Screening Questionnaire (OMPSQ), a screening tool assessing the risk of chronicity in patients with back pain. Prospective follow-up study. Assessment was performed at inclusion and 6 months later with the OMPSQ and the Oswestry Disability Index (ODI). Four outcome variables (pain index, two functional variables and work absence) were defined. Ninety-one patients were included, of whom 80% completed the study. Depending on the outcome variable considered, 42 to 82% of the patients recovered within 6 months. ROC AUC, a global measure of the performance of the questionnaire integrating sensitivity and specificity data, ranged from 0.73 to 0.83. When considering the functional outcome variable derived from the ODI, a low cut-off score of 71 (corresponding to 80% sensitivity) and a high cut-off score of 106 (corresponding to 80% specificity) can be used to distinguish three groups of patients: low, intermediate and high risk of chronicity. The predictive value of the French version of the OMPSQ is reasonably good, in line with the studies in other languages. This questionnaire may be particularly valuable in secondary care settings.


Real-time myocardial landmark tracking for MRI-guided cardiac radio-ablation using Gaussian Processes.
Objective.The high speed of cardiorespiratory motion introduces a unique challenge for cardiac stereotactic radio-ablation (STAR) treatments with the MR-linac. Such treatments require tracking myocardial landmarks with a maximum latency of 100 ms, which includes the acquisition of the required data. The aim of this study is to present a new method that allows to track myocardial landmarks from few readouts of MRI data, thereby achieving a latency sufficient for STAR treatments.Approach.We present a tracking framework that requires only few readouts of k-space data as input, which can be acquired at least an order of magnitude faster than MR-images. Combined with the real-time tracking speed of a probabilistic machine learning framework called Gaussian Processes, this allows to track myocardial landmarks with a sufficiently low latency for cardiac STAR guidance, including both the acquisition of required data, and the tracking inference.Main results.The framework is demonstrated in 2D on a motion phantom, andin vivoon volunteers and a ventricular tachycardia (arrhythmia) patient. Moreover, the feasibility of an extension to 3D was demonstrated byin silico3D experiments with a digital motion phantom. The framework was compared with template matching-a reference, image-based, method-and linear regression methods. Results indicate an order of magnitude lower total latency (<10 ms) for the proposed framework in comparison with alternative methods. The root-mean-square-distances and mean end-point-distance with the reference tracking method was less than 0.8 mm for all experiments, showing excellent (sub-voxel) agreement.Significance.The high accuracy in combination with a total latency of less than 10 ms-including data acquisition and processing-make the proposed method a suitable candidate for tracking during STAR treatments. Additionally, the probabilistic nature of the Gaussian Processes also gives access to real-time prediction uncertainties, which could prove useful for real-time quality assurance during treatments.


The wheat TaIQD3D-6 gene encodes a microtubule-associated protein and regulates cell morphogenesis in Arabidopsis.
A plethora of microtubule-associated proteins (MAPs) modulate the dynamics of microtubules (MTs) to ensure the proper elaboration of developmental programs in plants. Among the plant-specific MAPs are the IQ67 domain (IQD) family proteins. Despite the great progress in elucidating IQD protein functions, the majority of IQD proteins, especially IQDs in crop species, remain to be functionally explored. In this study, we identified 78 putative IQD family genes in the genome of hexaploid wheat (Triticum aestivum). Phylogenetic analysis of wheat and Arabidopsis IQDs supports the previous notion that the expansion of the IQD family coincides with plant terrestrialization. Further characterization of one TaIQD, TaIQD3D-6, revealed that TaIQD3D-6 directly binds to MTs and free tubulins in vitro and is associated with cortical MTs in interphase cells in vivo. Overexpressing TaIQD3D-6 in Arabidopsis leads to a spectrum of phenotypes that are indicative of perturbed MT homeostasis, including spiral growth, hypersensitivity to MT-destabilizing drugs, defects in cell morphogenesis, and altered organization of cMT arrays. Finally, we determined that TaIQD3D-6-GFP localizes to the expanding cell plate during cytokinesis and the overexpression of TaIQD3D-6 interferes with asymmetric cell division in the stomatal lineage in Arabidopsis. In summary, our findings establish that TaIQD3D-6 is a MAP that regulates plant cell and organ morphogenesis and provide new insights into the functions of crop IQD proteins.


Understanding the Structural Evolution and Lattice Water Movement for Rhombohedral Nickel Hexacyanoferrate upon Sodium Migration.
Prussian blue analogues (PBAs) have been regarded as prospective cathode materials for sodium-ion batteries due to tunable chemical composition and structure. Herein, a high-performance rhombohedral nickel hexacyanoferrate is synthesized via a controllable low-temperature reaction process. It can deliver impressive capacity retention of 87.8% after 10 000 cycles at 10C and high rate discharge capacity of 53 mAh g-1 at 40C. According to the structural evolution and lattice water movement, superior electrochemical performance is ascribed to small lattice alteration and high reversibility of rhombohedral-cubic transition upon Na+ insertion/extraction. The environment information of local- and long-range structure evolution is revealed by ex situ X-ray absorption spectroscopy (XAS) and in situ X-ray diffraction (XRD). Importantly, lattice water movement during cycling by Fourier transform infrared (FTIR) measurements offers an experimental validation about Na+ nonlinear migration path, as well as the accumulative lattice distortion effect from large-size Na(OH2)+ unit. The revealed mechanism points out the modified path for PBAs.


Smooth Scalar-on-Image Regression via Spatial Bayesian Variable Selection.
We develop scalar-on-image regression models when images are registered multidimensional manifolds. We propose a fast and scalable Bayes inferential procedure to estimate the image coefficient. The central idea is the combination of an Ising prior distribution, which controls a latent binary indicator map, and an intrinsic Gaussian Markov random field, which controls the smoothness of the nonzero coefficients. The model is fit using a single-site Gibbs sampler, which allows fitting within minutes for hundreds of subjects with predictor images containing thousands of locations. The code is simple and is provided in less than one page in the Appendix. We apply this method to a neuroimaging study where cognitive outcomes are regressed on measures of white matter microstructure at every voxel of the corpus callosum for hundreds of subjects.


Prospective study on metal ceramic crowns in private practice settings: 20-year results.
Posterior metal ceramic crowns are still widely used as a standard treatment. The aim of this study was to obtain long-term data on their clinical performance. Ten private practitioners participated in this prospective practice-based study. Patients were provided with two crowns each. Two groups were formed. The single crown group comprised 95 patients with 190 crowns. The retainer crown group comprised 138 patients with fixed dental prostheses and 276 retainer crowns. For the primary outcome "loss of tooth or crown," 20-year survival rates of 78.8% in the single crown group and 67.8% in the retainer crown group were found. Veneering ceramic defects occurred rather frequently, resulting in respective 20-year technical success rates of 74.2% for single crowns and 62.9% for retainer crowns. However, veneering ceramic defects causing crown losses were very rare events. The results contribute to our knowledge on long-term outcomes of treatments with metal ceramic crowns and show high survival and success rates over 20 years. Posterior metal ceramic crowns are a highly reliable option in private practice settings.


Critical residues in an SH3 domain from Sem-5 suggest a mechanism for proline-rich peptide recognition.
Src homology 3 (SH3) domains bind specific proline-rich peptide motifs. To identify interactions involved in peptide recognition, we have mutated residues on the putative binding surface of an SH3 domain from the Caenorhabditis elegans protein Sem-5. Among the most critical positions are three adjacent aromatic residues, which appear to participate in highly stereospecific packing interactions with the ligand. The co-planar arrangement of two of these residues closely matches the periodicity of a poly-proline II (PPII) helix. Thus, a model for recognition has the peptide adopting a PPII helix, with the pyrrolidine rings on one helical face interlocking with the aromatic SH3 residues.


Surpass Flow Diverter in the Treatment of Ruptured Intracranial Aneurysms-A Single-Center Experience.
Use of a Surpass flow diverter (FD) device in the treatment of acutely ruptured aneurysm has not been well studied and reported in the literature. We retrospectively reviewed patients with subarachnoid hemorrhage who were treated by Surpass FD placement at our hospital between June 2016 and March 2018. Detailed analysis of medical records was performed to obtain patient age, gender, clinical history, Hunt and Hess grade, Fisher grade, results of radiographic and procedural details including technical success and complication, clinical outcome, and follow-up angiographic results. Our search identified 16 patients with 16 aneurysms who were treated with Surpass FD, of which 13 aneurysms (81%) were in the anterior circulation and 3 (19%) were in the posterior circulation. Aneurysm size ranged from 1.1 to 16 mm, with a mean of 4 mm. The mean delay between subarachnoid hemorrhage and endovascular treatment was 5 days (range, 3-20 days). Only 1 Surpass FD was used in each patient, ranging in size from 3 × 25 mm to 4 × 50 mm. Fifteen patients (94%) achieved favorable clinical outcome (modified Rankin Scale score 0-1) at 3 months. One patient died of invasive fungal infection. Angiographic follow-up results were assessed by O'Kelly-Marotta grading scale in 15 surviving patients and showed a grade D result (no filling) in 13/15 aneurysms (87%) at 3 and 6 months. A Surpass FD device is a feasible option for the treatment of ruptured intracranial aneurysms that are difficult to treat by conventional clipping and coiling; however, larger and comparative studies with long-term follow-up are needed to confirm its safety and efficacy.


Defensive role of pleural mesothelial cell sialomucins in tumor metastasis.
Sialomucin complex (SMC) is a heterodimeric glycoprotein, and is found on the surfaces of the mesothelia of the pleura, pericardium, and peritoneum. Sialomucins play a significant role in adhesion as well as in defense. In this study, we hypothesized that pleural mesothelial cells (PMCs) express SMC and thus prevent the adherence of ovarian cancer cells (HTB-77) to the pleura. PMCs were plated, and the adherence of HTB-77 cells was observed using a cytofluor. The PMC monolayer was pretreated with sialidase, and HTB-77 adherence was observed using cytofluor. In another set of HTB-77 cells, adherence was observed when the PMC monolayer was pretreated with supernatants of HTB-77 cells. Last, supernatants of HTB-77 cells were assayed for sialidase activity. The removal of SMC by sialidase greatly increased the adherence of HTB-77 cells to the PMC monolayer, which was statistically significant (p < 0.05). Similar results were obtained when the PMC monolayer was pretreated with the supernatants of HTB-77 cells. Supernatants of HTB-77 cells showed the presence of sialidase. The presence of SMC on the PMC acts as a defense layer, and its removal by sialidase increases the susceptibility of the PMC layer to the adherence of malignant cells and to increased metastasis. HTB-77 cells also express sialidase, which by its action on the monolayer aids in the adherence of tumor cells to the pleural surface.


Balloon aortic valvuloplasty in the transcatheter aortic valve implantation era: A single-center registry.
Percutaneous balloon aortic valvuloplasty (BAV) has been limited by the risk of complications and restenosis. However, growing use of transcatheter aortic valve implantation (TAVI) has revived interest in this technique. We analyzed the current indications for BAV and outcomes in a single center. Acute results and long-term outcomes were analyzed in a retrospective single-center registry of patients undergoing BAV between January 2013 and January 2016. Twenty-three patients underwent BAV, 56.5% male, mean age 78±7 years. Indications were severe aortic stenosis and decompensated heart failure (n=5), urgent non-cardiac surgery (n=8), or bridge to definitive treatment (n=10). Peak invasive gradient decreased from a median of 54.0±19.0 mmHg to 28.5±13.8 mmHg (p=0.002). Complications included one ischemic stroke, one lower limb ischemia and one femoral pseudoaneurysm requiring surgery. During a mean follow-up of 11±10 months, eight patients underwent TAVI and two underwent surgical aortic valve replacement. Thirteen patients died, nine of non-cardiovascular causes. On Kaplan-Meier analysis mortality was significantly lower among patients undergoing definitive treatment (20.0% vs. 84.6% at two-year follow-up; p=0.005). BAV should be considered for selected patients with temporary contraindications to definitive therapy or as palliative therapy.


Pancreatoblastoma. Three original cases and review of the literature.
To describe the characteristics of pancreatoblastoma. We studied 3 cases of pancretoblastoma and reviewed another 59 cases. Parameters analyzed were tumor site, hemorrhage, capsule formation, necrosis, vascularity, production of alpha-fetoprotein (AFP), cystic changes and calcification. The diagnostic findings were as follows: pancreatic head origin (24/54, 44%), pancreatic body and tail origin (30/54, 56%), hemorrhage (16/17, 94%), capsule formation (24/26, 92%), necrosis (28/31, 90%), hypervascularity (10/14, 71%), production of AFP (19/28, 68%), cystic changes (11/16, 69%), and calcification (10/21, 48%). All neonatal cases demonstrated cystic changes. Three of them were patients with Beckwith-Wiedmann syndrome. The incidence of capsule formation and calcification was not related to the origin of the tumor. The most common features of pancreatoblastoma are hemorrhage, capsule formation and necrosis.


Flexible, Transparent, and Wafer-Scale Artificial Synapse Array Based on TiOx /Ti3 C2 Tx Film for Neuromorphic Computing.
A high-density neuromorphic computing memristor array based on 2D materials paves the way for next-generation information-processing components and in-memory computing systems. However, the traditional 2D-materials-based memristor devices suffer from poor flexibility and opacity, which hinders the application of memristors in flexible electronics. Here, a flexible artificial synapse array based on TiOx /Ti3 C2 Tx film is fabricated by a convenient and energy-efficient solution-processing technique, which realizes high transmittance (≈90%) and oxidation resistance (>30 days). The TiOx /Ti3 C2 Tx memristor shows low device-to-device variability, long memory retention and endurance, a high ON/OFF ratio, and fundamental synaptic behavior. Furthermore, satisfactory flexibility (R = 1.0 mm) and mechanical endurance (104 bending cycles) of the TiOx /Ti3 C2 Tx memristor are achieved, which is superior to other film memristors prepared by chemical vapor deposition. In addition, high-precision (>96.44%) MNIST handwritten digits recognition classification simulation indicates that the TiOx /Ti3 C2 Tx artificial synapse array holds promise for future neuromorphic computing applications, and provides excellent high-density neuron circuits for new flexible intelligent electronic equipment.


In vitro reactive oxygen species production by mitochondria from the rabbitfish Siganus fuscessens livers and the effects of Irgarol-1051.
In this study, the mitochondria from the livers of Siganus fuscessens were exposed to the Irgarol-1051with or without respiratory chain inhibitors using succinate or malate as the substrate, and the effects on mitochondrial ROS production were tested. The mitochondrial ROS production was significantly enhanced by antimycin A with an increase of more than three folds but not by rotenone and NaN3, and this may suggest complex III is the major ROS-producing site. Irgarol-1051 treatments gave a somewhat contradictory result: this chemical can inhibit the mitochondrial ROS production but the inhibition decreased with the increase of doses. These contradictory data about Irgarol-1051 may be explained by the balance between the effects of inhibition through the opening of small-size pores and stimulation through blocking electron transfer, but the mechanism laid behind needs more evidence to support. As Irgarol-1051 was continuously used in antifouling and its bio-concentration factor is up to 160 in fish, the toxic effect of Irgarol-1051 on aquatic animals should be paid more attention to.


[Early postoperative period in patients subjected to surgery for noncorrectable obesity].
The early postoperative period after jejunoileoshunting for high degree of the alimentary-constitutional obesity was found to have a number of specific features and to be an important period greatly responsible for the outcome of the operation. The very early active management of such patients was shown to improve the postoperative course and to reduce the number of pulmonary complications. In 85 patients an original technique of jejunoileoshunting was used.


Perception and adaptation strategies of forest dwellers to climate variability in the tropical rainforest in eastern Cameroon: The case of the inhabitants of the Belabo-Diang Communal Forest.
The design of appropriate adaptation strategies to the impacts of climate change requires a contextual study of local perceptions due to the non-homogeneity of climate in a given agro-ecological area. The research objective of the current study aims to examine the evolution of climate parameters from 1983 to 2019 linked to the perceptions of local populations and appropriate adaptation measures in the Belabo-Diang Communal Forest of Cameroon. The methodological approach includes collecting and analyze climate data from 1983 to 2019; and surveying existing local perceptions and adaptive strategies among 540 households using semi-structured questionnaires. A significant increase in temperature of about 1 °C over 36 years (1983-2019) and a non-significant decrease in precipitation (95.36 mm) over the same period were observed. Local perceptions related to climate change vary according to the sector of activity and are mainly associated with more heat in the dry season (90%), late onset of rains (84%), drought recurrence (82%), less rainfall during the year (80%), and increase in the duration of drought (80%). For 82-100% of households, according to the activity sector, no appropriate adaptation measures to climate change were applied depending on activities. The adaptation measures used by less than 0-20% of respondents, include mainly the abandonment or change of activity, and modification of the agricultural calendar. With the lack of appropriate and adequate adaptation measures by the riparian populations, this study appears necessary to inform policy-makers of the need to develop and implement more appropriate strategies to enable the riparian people living in forest area of Cameroon to better adapt to these effects of climate changes.


Characterization and proteomic analysis of ovarian cancer-derived exosomes.
Ovarian cancer is the most lethal type of cancer among all frequent gynecologic malignancies, because most patients present with advanced disease at diagnosis. Exosomes are important intercellular communication vehicles, released by various cell types. Here we presented firstly the protein profile of highly purified exosomes derived from two ovarian cancer cell lines, OVCAR-3 and IGROV1. The exosomes derived from ovarian cancer cell lines were round and mostly 30-100 nm in diameter when viewed under an electron microscope. The exosomal marker proteins TSG101 and Alix were detected in exosome preparations. The range of density was between 1.09 g/ml and 1.15 g/ml. A total of 2230 proteins were identified from two ovarian cell-derived exosomes. Among them, 1017 proteins were identified in both exosomes including all of the major exosomal protein markers. There were 380 proteins that are not reported in the ExoCarta database. In addition to common proteins from exosomes of various origins, our results showed that ovarian cancer-derived exosomes also carried tissue specific proteins associated with tumorigenesis and metastasis, especially in ovarian carcinoma. Based on the known roles of exosomes in cellular communication, these data indicate that exosomes released by ovarian cancer cells may play important roles in ovarian cancer progression and provide a potential source of blood-based protein biomarkers.


Prevalence of antiphospholipid antibodies in patients with subacute and chronic cutaneous lupus erythematosus.
The prevalence of antiphospholipid antibodies (APLAs) has been extensively studied in patients with systemic lupus erythematosus (SLE) but not in those with cutaneous lupus erythematosus (CLE). We determined the prevalence of APLAs among our patients with CLE, and analyzed their clinical and serologic characteristics. This retrospective study analyzed 182 patients with subacute or chronic CLE who had been in follow-up for 5 years. We selected those positive for 1 or more of the following APLAs in 2 measurements at least 12 weeks apart: lupus anticoagulant (LA), anticardiolipin antibodies (ACAs), and anti-β2-glycoprotein i (anti-β2-GPI) antibodies. In the case of ACAs and anti-β2-GPI antibodies, only patients with titers greater than or equal to 40 U/mL were selected. We obtained a series of 13 patients (4 with subacute disease and 9 with chronic disease). Seven met the diagnostic criteria for SLE and only 1 met the diagnostic criteria for antiphospholipid syndrome (APS). The prevalence of APLAs was 38% among patients with SLE and 3.65% among those without SLE. The most prevalent APLA was LA, present in 10 patients. Antinuclear antibodies (ANAs) were detected in 12 patients and anti-double-stranded DNA antibodies in 11. The prevalence of APLAs among our patients with CLE who did not meet the diagnostic criteria for SLE was similar to that reported in the general population. This, along with the strong assocation between the presence of ANAs and the presence of APLAs, would bring into question the value of determining APLAs in patients with CLE who are negative for ANAs. We also note that there was a high prevalence of discoid lesions but a low prevalence of APS among our patients with CLE who were positive for APLAs.


High 2,3-DPG blood cardioplegia and myocardial preservation during cardiopulmonary bypass.
Blood may provide superior cardioplegia compared with crystalloid cardioplegic solution. However, the results are controversial. This may be due to a leftward shift of the hemoglobin (Hb)-O2 dissociation curve induced by hypothermia, increasing the oxygen affinity for Hb. This effect may negate the potential benefit of blood cardioplegia. The oxygen affinity for Hb can be decreased by increasing the red cell 2,3-diphosphoglycerate (2,3-DPG), and hence, more oxygen can be delivered to the myocardium. The present investigation was undertaken to study the effects of 2,3-DPG-enriched blood cardioplegia on the functional recovery of the myocardium and changes in the coronary sinus red blood cell (RBC) adenosine-triphosphate (ATP), lactate, and RBC DPG after one and a half hours of reperfusion following one hour of ischemic cardiac arrest in dogs. The dogs were divided into three groups: crystalloid (CR); stored blood (SB), and high 2,3-DPG blood (HDPG) cardioplegic groups. Incubation of canine RBC in phosphoenal pyruvate (PEP) led to a 36% increase in DPG and a rightward shift in the Hb-O2 dissociation curve. There was a 4 mm Hg shift in the P50. When compared with the CR group, there was a significant decrease in the cardiac index (CI) and left ventricular work index (LVWI) and a significant increase in the total systemic vascular resistance (TSVR) in the SB group. The CI and LVWI of the HDPG group were similar to those of the CR group, but the TSVR was significantly greater in the former group. The LVWI was significantly greater and the TSVR smaller in the HDPG group as compared with those in the SB group.(ABSTRACT TRUNCATED AT 250 WORDS)


[Polytrauma in cyclists. Incidence, etiology, and injury patterns].
In our region we have noticed an increasing number of cyclists and consequently a rise in bicycle-related accidents in recent years. A large number of our polytraumatized patients are victims of bicycle-related accidents. Retrospectively we analyzed the data of our polytraumatized patients recorded between May 2003 and June 2004 for bicycle-related injuries. Of 153 polytraumatized patients treated in our emergency room 32 were cyclists (21%). The average age of our polytraumatized cyclist was 42 years, and the male-to-female ratio was 1:1. The median score on the Glasgow Coma Scale (GCS) after the accident was 8 (min. 3, max. 15), the median Injury Severity Score (ISS) was 24 (min. 18, max. 41), and the median Polytrauma Score (PTS) was 23 (min. 14, max. 51). A total of 30 patients (94%) suffered a head injury; in 28 patients (88%) the head injury was the leading diagnosis. The median score on the Abbreviated Injury Scale (AIS) Head was 4 (min. 1, max. 5), the AIS Thorax 3 (min. 2, max. 4), and the AIS Extremities 3 (min, 2, max. 5). Our data were also compared with the official injury statistics of the region and the current literature. The most frequent and most severe injury was the head injury (94%). Of the 32 polytraumatized cyclists 30 did not wear a helmet. Successful prevention could possibly be practiced if all cyclists wear helmets.


Docetaxel: a review of its use in non-small cell lung cancer.
Docetaxel, a semisynthetic member of the taxoid class of antineoplastic agents, is effective in the treatment of patients with locally advanced and metastatic non-small cell lung cancer (NSCLC). In noncomparative trials in patients with NSCLC, docetaxel 75 or 100 mg/m2 produced objective response rates of 20 to 38% and 14 to 25% as a first-line or second-line monotherapy, respectively. In Japan, docetaxel 60 mg/m2 produced objective response rates of 19 to 25% in previously untreated patients. Docetaxel 100 or 75 mg/m2 produced significantly higher response rates than either vinorelbine or ifosfamide in previously treated patients; patients treated with docetaxel 75 mg/m2 had an improved 1-year survival rate compared with those who received vinorelbine or ifosfamide. Docetaxel monotherapy in chemotherapy-naive patients produced survival rates that are similar to those reported for most platinum-containing standard combinations such as cisplatin plus vinorelbine. Combination of docetaxel with one other antineoplastic resulted in objective response rates of 20 to 54% in chemotherapy-naive patients; triple chemotherapy combinations produced responses in 51 and 60% of patients. Promising results from a few small studies and one large phase II study have also indicated a potential role for docetaxel as neoadjuvant therapy. The main dose-limiting adverse event associated with docetaxel is neutropenia, and fluid retention is common in many patients. The tolerability profile is generally acceptable in the majority of patients, although extra care has to be taken in patients with impaired liver function to minimise the risk of severe or febrile neutropenia. Conclusions. Docetaxel is generally well tolerated by patients receiving treatment for locally advanced and metastatic NSCLC, and produces response and survival rates equivalent to many current standard treatment options. Comparative studies have shown that docetaxel monotherapy provides significant survival benefits over best supportive care or treatment with vinorelbine or ifosfamide. Response and 1-year survival rates with docetaxel monotherapy are particularly encouraging in patients refractory or resistant to cisplatin or carboplatin, for whom treatment options are few. Neoadjuvant docetaxel has produced improved survival compared with local treatment alone. Combinations of docetaxel with other antineoplastic agents have produced relatively high response and 1-year survival rates; however, further comparative studies are required to confirm these benefits. In the meantime, docetaxel is a welcome addition to the options available for patients with advanced NSCLC.


Lassa hemorrhagic shock syndrome-on-a-chip.
Lack of experimental human models hinders research on Lassa hemorrhagic fever and the development of treatment strategies. Here, we report the first chip-based model for Lassa hemorrhagic syndrome. The chip features a microvessel interfacing collagen network as a simple mimic for extracellular matrix, allowing for quantitative and real-time vascular integrity assessment. Luminal infusion of Lassa virus-like particles led to a dramatic increase in vascular permeability in a viral load-dependent manner. Using this platform, we showed that Fibrin-derived peptide FX06 can be used to suppress the vascular integrity loss. This simple chip-based model proved promising in the assessment of disease severity and provides an easy-to-use platform for future investigation of Lassa pathogenesis and drug development in a human-like setting.


Pharmacologically-induced Recreational Priapism: Case Report and Review.
Priapism, a time-sensitive urologic emergency, is associated with hematologic disorders, malignancies, trauma, pharmaceuticals, and recreational drugs. A 51-year-old male presented with 36 hours of priapism after recreational use of nonprescribed pharmaceuticals including an oral phosphodiesterase inhibitor and intracorporally injected erectile medications, together with unspecified quantities of cocaine and alcohol. Venous blood gas confirmed ischemic priapism. Detumescence was achieved with intracavernosal phenylephrine injection, aspiration, and irrigation. This case highlights the risk that recreational use of vasoactive medications by patients who seek to prolong sexual activity may lead to delayed presentation for ischemic priapism.


Allele-specific genotyping by using guanine and gold electrochemical oxidation signals.
Electrochemical DNA biosensors have become strong candidates for DNA based analysis. Allele-specific genotyping is also one of the important research areas, where electrochemical approaches provide promising advances. Recently reported two methods based on electrochemical guanine and colloidal gold (Au) nanoparticle oxidation signals are reviewed and compared with the existing genotyping methods in this report.


Optimising homeothermy in neonates: a systematic review and clinical guidelines from the French Neonatal Society.
Thermal instability is harmful on the newborn infant. We sought to draw up practical guidelines on maintaining homeothermy alongside skin-to-skin contact. A systematic analysis of the literature identified relevant studies between 2000 and 2021 in the PubMed database. Selected publications were evaluated, and their level of evidence were graded, in order to underpin the development of clinical guidelines. We identified 7 meta-analyses and 64 clinical studies with a focus on newborn infants homeothermy. Skin-to-skin contact is the easiest and most rapidly implementable method to prevent body heat loss. Alongside skin-to-skin contact, monitoring the newborn infant's body temperature with a target of 37.0°C is essential. For newborn infants <32 weeks of gestation, a skullcap and a polyethylene bag should be used in the delivery room or during transport. To limit water loss, inhaled gases humidification and warming is recommended, and preterm infants weighing less than 1600 g should be nursed in a closed, convective incubator. With regard to incubators, there are no clear benefits for single vs. double-wall incubators as well as for air vs. skin servo control. Alongside skin-to-skin contact, a bundle of practical guidelines could improve the maintenance of homeothermy in the newborn infant.


Elucidating the structural variation of membrane concentrated landfill leachate during Fenton oxidation process using spectroscopic analyses.
Membrane concentrated landfill leachate (MCLL) contains large amounts of recalcitrant organic matter that cause potential hazards to the environment. Knowledge on the compositional variation of MCLL during treatment is important for a better understanding on the degradation pathway of organic pollutants. In this work, the structural change of MCLL during Fenton oxidation process was examined using spectroscopic techniques. The removal rates of COD, TOC and UV254 reached 78.9 ± 1.3%, 70.2 ± 1.4% and 90.64 ± 1.6%, respectively, under the optimal condition (i.e., dosage of H2O2 = 9.0 mL/200 mL, H2O2/Fe(II) molar ratio = 3.0, pH = 3.0, time = 40 min). Spectral analyses suggested that aromatic/CC structure and CO bonds in MCLL can be successfully destroyed by Fenton oxidation, resulting in a decrease in molecular weight. One fulvic-like and one humic-like components were identified in MCLL, both of which can be removed by Fenton treatment. In addition, two-dimensional correlation spectroscopic analyses suggested the oxidative changes of MCLL structure in the order of fulvic-like component/unsaturated conjugated bond > aromatic structure > humic-like component. The results may provide a new insight to the understanding on the structure variation of MCLL during treatment, which is beneficial for the design of cost-effective treatment strategies.


Switching between supramolecular dimer and nonthreaded supramolecular self-assembly of stilbene amide-alpha-cyclodextrin by photoirradiation.
3-trans-Stilbene amide-alpha-cyclodextrin (3-trans-Sti-alpha-CD) formed a double-threaded dimer in aqueous solutions. In contrast, the photoisomerization of the stilbene moiety in 3-Sti-alpha-CD from trans to cis leads to the structural changes from the double-threaded dimer to nonthreaded supramolecular assemblies in aqueous solutions. The structures of these supramolecular complexes have been found to be controllable by photoirradiation.


Comparison of the Copan WASPLab incorporating the BioRad expert system against the SIRscan 2000 automatic for routine antimicrobial disc diffusion susceptibility testing.
This study investigated the agreement at the categorical level between the Copan WASPLab incorporating the BioRad expert system against the SIRscan 2000 automatic for antimicrobial disc diffusion susceptibility testing. The 338 clinical strains (67 Pseudomonas aeruginosa, 19 methicillin-resistant Staphylococcus aureus, 75 methicillin-sensitive S. aureus and 177 Enterobacterales isolates) analysed in this study were non-duplicate isolates obtained from consecutive clinical samples referred to the clinical bacteriology laboratory at Geneva University Hospitals between June and August 2019. For the WASPLab the inoculum suspension was prepared in strict accordance with the manufacturer's instruction (Copan WASP srl, Brescia, Italy) by adding 2 mL of the 0.5 McFarland primary suspension used for the SIRscan analysis into a sterile tube filled with 4 mL of sterile saline (1:3 dilution). The inoculum (2 × 30 μL loop/spreader) was spread over the entire surface of Mueller-Hinton agar plates according to the AST streaking pattern defined by Copan. The antibiotic discs were dispensed by the WASP and inoculated media were loaded on conveyors for transfer to the automatic incubators. The plates were incubated for 16 h, and several digital images were acquired. Inhibition zone diameters were automatically read by the WASPLab and were adjusted manually whenever necessary. For the SIRscan 2000 automatic, the antimicrobial disc diffusion susceptibility testing was performed according to the EUCAST guidelines. The gradient strip method was used to resolve discrepancies. The overall categorical agreement between the compared methods reached 99.1% (797/804; 95% CI 98.2%-99.6%), 99.5% (1029/1034; 95% CI 98.9%-99.8%), and 98.8% (2798/2832; 95% CI 98.3%-99.1%) for P. aeruginosa, S. aureus and the Enterobacterales, respectively. WASPLab incorporating the BioRad expert system provides a fully automated solution for antimicrobial disc diffusion susceptibility testing with equal or better accuracy than other available phenotypic methods.


Fat mass and obesity-associated factor (FTO)-mediated N6-methyladenosine regulates spermatogenesis in an age-dependent manner.
N6-methyladenosine (m6A) is the most prevalent reversible RNA modification in the mammalian transcriptome. It has recently been demonstrated that m6A is crucial for male germline development. Fat mass and obesity-associated factor (FTO), a known m6A demethylase, is widely expressed in human and mouse tissues and is involved in manifold biological processes and human diseases. However, the function of FTO in spermatogenesis and male fertility remains poorly understood. Here, we generated an Fto knockout mouse model using CRISPR/Cas9-mediated genome editing techniques to address this knowledge gap. Remarkably, we found that loss of Fto in mice caused spermatogenesis defects in an age-dependent manner, resulting from the attenuated proliferation ability of undifferentiated spermatogonia and increased male germ cell apoptosis. Further research showed that FTO plays a vital role in the modulation of spermatogenesis and Leydig cell maturation by regulating the translation of the androgen receptor in an m6A-dependent manner. In addition, we identified two functional mutations of FTO in male infertility patients, resulting in truncated FTO protein and increased m6A modification in vitro. Our results highlight the crucial effects of FTO on spermatogonia and Leydig cells for the long-term maintenance of spermatogenesis and expand our understanding of the function of m6A in male fertility.


High-frequency rTMS over the supplementary motor area improves freezing of gait in Parkinson's disease: a randomized controlled trial.
Freezing of gait (FOG) contributes to falls in Parkinson's disease (PD), but robust, effective treatments remain elusive. There is evidence indicating that the supplementary motor area (SMA) plays an important role in the pathogenesis of FOG and may therefore be a potential neuromodulation target. The present study explored the clinical efficacy of high-frequency repetitive transcranial magnetic stimulation (rTMS) over the SMA on FOG in PD patients. A group of 30 PD patients with FOG were enrolled in a randomized, double-blind, sham-controlled trial. Patients were randomly allocated 2:1 to receive ten sessions of either real (N = 20) or sham (N = 10) 10 Hz rTMS over SMA. The patients were assessed at baseline (T0), after the 5th (T1) and 10th (T2) sessions, and then 2 weeks (T3) and 4 weeks (T4) after the last session. The primary clinical outcome was the Freezing of Gait Questionnaire score (FOGQ), with the Movement Disorder Society-Unified Parkinson's Disease Rating Scale motor scores (MDS-UPDRS III) and Timed Up and Go test as secondary clinical outcomes. All the assessments were carried out at the "ON" state. With a four week's follow-up, there were significant interaction effects in the FOGQ (effect of group*time, p = 0.04), MDS-UPDRS III (p = 0.02) and several gait variables (total duration, p < 0.01; cadence, p = 0.04; turn duration, p = 0.01; and turn to sit duration, p = 0.02). Post-hoc analyses revealed a significantly decreased FOGQ score at T2 and T4, and significant improvements of MDS-UPDRS III and gait variables at T1, T2, T3 and T4 in the rTMS group. No significant improvements were found in the sham group. High-frequency rTMS over SMA may ultimately serve as an add-on therapy for alleviating FOG in PD patients.


Benefits of normalizing plasma phenylalanine: impact on behaviour and health. A case report.
An elderly man with mental retardation who had never received dietary treatment for his phenylketonuria was placed on a phenylalanine-restricted diet. Social skills and walking gait improved and a new interest in the objects in his environment developed spontaneously. A 2-year analysis of diet, blood plasma phenylalanine levels and behavioural state indicated that small differences in phenylalanine intake impacted his well-being. Of significant note, leg tremor and spasm that precipitated severe self-injury were only reversible when plasma blood phenylalanine concentrations were titrated to near normal ranges and daily phenylalanine intake was strictly controlled. This case may offer a potential explanation for some of the late treatment failures that have been reported and suggest new avenues to explore in the late treatment of PKU.


Cutaneous Manifestations of Human Immunodeficiency Virus/AIDS Patients in Albania.
Dermatologic diseases are common in the human immunodeficiency virus (HIV)-infected population. Cutaneous manifestations of HIV disease may result from HIV infection itself or from opportunistic disorders secondary to the declined immunocompetence due to the disease. The aim of this study is to determine the pattern of c0utaneous manifestations in HIV in an adult HIV Clinic in Tirana. This is a retrospective study including 355 HIV-positive patients with cutaneous manifestations who referred to the Ambulatory Clinic for HIV/AIDS, at the Infective Service and Dermatology Service of University Hospital Centre "Mother Theresa," Tirana, Albania over the period 2008-2015. The mean age of patients was 43.08 (±11.8) years, with a range 15-79 years. Two hundred and forty-seven (69.6%) of patients were male and 108 (30.4%) female. Male-to-female ratio is 2.3:1. The study found a significant trend of increasing incidence of dermatological pathologies with increasing stage of the disease. Fifty-five (15.5%) of patients with cutaneous lesions were in Stage 1, 132 (37.2%) in Stage 2, and 168 (47.4%) in Stage 3 (P < 0.001). As for the HIV transmission method, the majority of patients (71%) were infected through heterosexual contact, followed by homosexual contact (16.3%), blood transfusion (3.4%), injecting drug user (2.3%), while for 7% of patients the mode of transmission was unknown. Early recognition of the cutaneous manifestation can help in better management of HIV infection in resource-poor setting, as it can indicate the progression of the disease and underlying immune status.


Cortical excitation and chronic pain.
Investigation of the basic mechanisms of chronic pain not only provides insights into how the brain processes and modulates sensory information but also provides the basis for designing novel treatments for currently intractable clinical conditions. Human brain imaging studies have revealed new roles of cortical neuronal networks in chronic pain, including its unpleasant quality, and mouse studies have provided molecular and synaptic mechanisms underlying relevant cortical plasticity. This review paper will critically examine the current literature and propose a cortical network model for chronic pain.


Erratum to: Mouse mammary tumor-like virus (MMTV) is present in human breast tissue before development of virally associated breast cancer.
[This corrects the article DOI: 10.1186/s13027-016-0113-6.].


Microarray analysis of gene expression of mouse hepatocytes of different ploidy.
Polyploidisation in hepatocytes has been associated with many physiologic and pathologic processes such as proliferation, metabolism, regeneration, aging, and cancer. We studied gene expression patterns in hepatocytes of different ploidy. Primary hepatocytes were obtained from mice of different ages: young (4-6 weeks old), adult (8-10 weeks old), and older (22-24 weeks old). Diploid (2N), tetraploid (4N), and octoploid (8N) hepatocytes were isolated for studies using a high-density mouse genome microarray. No major changes of gene expression patterns between hepatocytes of different ploidy were found. Fifty genes were identified as differentially expressed in the diploid and tetraploid populations, but the changes were less than twofold either way. Four genes (Gas2, Igfbp2, Nr1i3, and Ccne2) were differentially expressed in tetraploid and octoploid cells. This was confirmed in two age groups, "adult" and "older," but once again the factors were less than twofold and the expressions of Gas2 and Igfbp2 were more different between age groups than between ploidy classes. Our results show that polyploid hepatocytes are stable and "normal" without aberrant gene expression, unlike what is thought for cancer cells. By contrast to megakaryocytes, hepatocyte polyploidisation is not a differentiation step associated with major changes in gene expression. Our data support the hypothesis that hepatocyte polyploidisation is a protective mechanism against oxidative stress that occurs via a controlled process throughout growth and aging where binucleation is important.


XPLN is modulated by HDAC inhibitors and negatively regulates SPARC expression by targeting mTORC2 in human lung fibroblasts.
Pathogenesis of idiopathic pulmonary fibrosis (IPF) remains unclear. Secreted protein acidic and rich in cysteine (SPARC) is a matricellular protein that participates in the assembly and turnover of the extracellular matrix, whose expression is regulated by transforming growth factor (TGF)-β1 through activation of mammalian target of rapamycin complex 2 (mTORC2). Exchange factor found in platelets, leukemic, and neuronal tissues (XPLN) is an endogenous inhibitor of mTORC2. However, whether XPLN modulates SPARC expression remains unknown. Herein, we investigated the regulatory mechanisms of XPLN in human lung fibroblasts. Effect of XPLN on mTORC2 activity was evaluated by silencing XPLN in human foetal lung fibroblasts (HFL-1 cells), using small interfering RNA. SPARC expression was quantified by quantitative real-time RT-PCR and western blotting. Fibroblasts were treated with TGF-β1, histone deacetylase (HDAC) inhibitors, entinostat, or vorinostat, to assess their effects on XPLN expression. Moreover, the effect of mTORC1 inhibition on SPARC and XPLN was examined. XPLN depletion stimulated SPARC expression and Akt phosphorylation on Ser473. TGF-β1 treatment down-regulated XPLN via Smad 2/3. XPLN mRNA expression was up-regulated upon treatment with HDAC inhibitors in a concentration-dependent manner, and TGF-β1-induced SPARC expression was reversed by entinostat treatment. mTORC1 inhibition by rapamycin and Raptor depletion stimulated SPARC expression. In conclusion, this is the first study describing the involvement of XPLN in the regulation of SPARC. These findings may help uncover the regulatory mechanisms of the mTORC2-SPARC axis. The up-regulation of XPLN by HDAC inhibitors may be a novel therapeutic approach in patients with IPF.


[Studies on intestinal absorption of alkaloids in Coptis chinensis by in situ single-pass perfused rat intestinal model].
To study the absorption characteristics of alkaloids in Coptis chinensis in rat intestinal. In situ single-pass perfused rat intestinal model was used and the concentrations of berberine and palmatine were determined by HPLC, the drug absorption rate constant (K(a)) and apparent absorption coefficient (P(app)) were tested to evaluate their absorption characteristics. The absorption of berberine and palmatine in different regions of rat intestinals was significantly different. From bigness to smallness, the P(app) value of berberine at 50 mg x L(-1) were ileum, duodenum, jejunum and colon, of palmatine at 50 mg x L(-1) were ileum, colon, jejunum and duodenum. The concentration of berberine and palmatine had distinctive effect on the K(a) value of berberine and palmatine were ordered from larger to little as in Wujiwan compatibility, Coptis chinensis extractive and single compound. The berberine and palmatine were absroped at all regions of rat intestinal. The absorption characteristics of 2 alkaloids were not passive diffusion. The other ingredients in Wujiwan compatibility and Coptis chinensis extractive could promote the absorption of alkaloids.


Genotypic characterization of group A rotavirus in children < 5 years of age at tertiary care hospital in North India.
This study was undertaken to find out the positivity of rotavirus associated diarrhoea in children <5 years of age in Meerut district and to determine the genomic diversity of the circulating rotavirus strains in this geographical area. A cross-sectional study was conducted in a tertiary care hospital for a period of one year. A total of 240 stool samples were collected from children suffering from acute diarrhoea and subjected for rotavirus antigen detection by enzyme immunoassay (EIA). The EIA-positive samples were further genotyped to determine the G and P types using semi nested multiplex reverse transcriptase-polymerase chain reaction (RT-PCR). Demographic and clinical parameters were recorded in a pre-designed proforma. The rotavirus antigen positivity rate was 14.58% in Meerut district. There was male predominance and highest positivity rate was seen in children 13-24 months of age, in winter months and majority of cases belonged to moderate degree of severity. A total of 64% children in the study area were vaccinated and positivity was low in the vaccine group. G9P[4] was the predominant genotype followed by G3P[8]. Uncommon strains G12P[6] and G12P[8] were also reported as circulating genotypes in this study. The positivity rate of rotavirus associated diarrhoea has reduced in Meerut district post vaccination. G9P[4] was the most common circulating RV genotype in Meerut. Our study highlights the importance of including the emerging rotavirus strains in future multivalent RV vaccines to make the vaccines regionally more specific.


Glutathione-Dependent Formaldehyde Dehydrogenase Homolog from Bacillus subtilis Strain R5 is a Propanol-Preferring Alcohol Dehydrogenase.
Genome search of Bacillus subtilis revealed the presence of an open reading frame annotated as glutathione-dependent formaldehyde dehydrogenase/alcohol dehydrogenase. The open reading frame consists of 1137 nucleotides corresponding to a polypeptide of 378 amino acids. To examine whether the encoded protein is glutathione-dependent formaldehyde dehydrogenase or alcohol dehydrogenase, we cloned and characterized the gene product. Enzyme activity assays revealed that the enzyme exhibits a metal ion-dependent alcohol dehydrogenase activity but no glutathione-dependent formaldehyde dehydrogenase or aldehyde dismutase activity. Although the protein is of mesophilic origin, optimal temperature for the enzyme activity is 60°C. Thermostability analysis by circular dichroism spectroscopy revealed that the protein is stable up to 60°C. Presence or absence of metal ions in the reaction mixture did not affect the enzyme activity. However, metal ions were necessary at the time of protein production and folding. There was a marked difference in the enzyme activity and CD spectra of the proteins produced in the presence and absence of metal ions. The experimental results obtained in this study demonstrate that the enzyme is a bona-fide alcohol dehydrogenase and not a glutathione-dependent formaldehyde dehydrogenase.