Boron-Functionalized Graphene Oxide-Organic Frameworks for Highly Efficient CO2 Capture.
The capture and storage of CO2 have been suggested as an effective strategy to reduce the global emissions of greenhouse gases. Hence, in recent years, many studies have been carried out to develop highly efficient materials for capturing CO2 . Until today, different types of porous materials, such as zeolites, porous carbons, N/B-doped porous carbons or metal-organic frameworks (MOFs), have been studied for CO2 capture. Herein, the CO2 capture performance of new hybrid materials, graphene-organic frameworks (GOFs) is described. The GOFs were synthesized under mild conditions through a solvothermal process using graphene oxide (GO) as a starting material and benzene 1,4-diboronic acid as an organic linker. Interestingly, the obtained GOF shows a high surface area (506 m2 g-1 ) which is around 11 times higher than that of GO (46 m2 g-1 ), indicating that the organic modification on the GO surface is an effective way of preparing a porous structure using GO. Our synthetic approach is quite simple, facile, and fast, compared with many other approaches reported previously. The synthesized GOF exhibits a very large CO2 capacity of 4.95 mmol g-1 at 298 K (1 bar), which is higher those of other porous materials or carbon-based materials, along with an excellent CO2 /N2 selectivity of 48.8.


BK virus associated nephropathy and severe pneumonia in a kidney transplanted adolescent with Schimke immuneosseous- dysplasia.
Düzova A, Gülhan B, Topaloğlu R, Özaltın F, Cengiz AB, Yetimakman AF, Doğru D, Güçer Ş, Beşbaş N. BK virus associated nephropathy and severe pneumonia in a kidney transplanted adolescent with Schimke immune-osseous-dysplasia. Turk J Pediatr 2019; 61: 111-116. Patients with juvenile onset Schimke immune-osseous-dysplasia (SIOD) have less severe symptoms and can survive in the second and third decade of life. We present an 18 year-old adolescent with juvenile onset SIOD who was diagnosed after renal transplantation and developed BK virus associated nephropathy (BKVAN) and severe pneumonia during follow-up. The patient developed nephrotic syndrome, unresponsive to immunosuppressives, at the age of 8 years. He had a history of meningitis, short stature, microcephaly, prominent ears, and bilateral cryptorchidism. A renal transplantation was performed at the age of 15 years. During follow-up, he suffered from leucopenia, urinary tract infections, herpes labialis, and candida esophagitis. Sanger sequencing of SMARCAL1 revealed a missense mutation on exon 11 (R586W). A renal biopsy performed after a sharp increase in serum creatinine (without significant viremia) revealed BKVAN which responded to sirolimus monotherapy and cidofovir. Three months later, he suffered from productive cough and dyspnea with diffuse ground glass pulmonary infiltrates. His clinical situation deteriorated and non-invasive mechanical ventilation was started. Cidofovir (2 mg/kg) was re-started weekly for a possible BKV pneumonia with intravenous immunoglobulin. After 5 doses of cidofovir and intense antibiotic regime, his dyspnea resolved with stable graft functions. In our case; BKVAN, which developed without significant viremia, and possibly associated pneumonia were treated successfully with cidofovir and sirolimus monotherapy.


Factors associated with hospital admission in hereditary angioedema attacks: a multicenter prospective study.
Acute attacks of hereditary angioedema are characterized by recurrent localized edema. These attacks can be life threatening and are associated with substantial morbidity and mortality. To determine factors associated with hospital admission of patients with an acute attack of hereditary angioedema presenting at the emergency department. This was a multicenter prospective observational study of consecutive patients (January 2011 through December 2013) experiencing an acute hereditary angioedema attack and presenting at the emergency department at 1 of 4 French reference centers for bradykinin-mediated angioedema. Attacks requiring hospital admission were compared with those not requiring admission. Of 57 attacks in 29 patients, 17 (30%) led to hospital admission. In multivariate analysis, laryngeal and facial involvements were associated with hospital admission (odds ratio 18.6, 95% confidence interval 3.9-88; odds ratio 7.7, 95% confidence interval 1.4-43.4, respectively). Self-injection of icatibant at home was associated with non-admission (odds ratio 0.06, 95% confidence interval 0.01-0.61). The course was favorable in all 57 cases. No upper airway management was required. Most patients attended the emergency department because they were running out of medication and did not know that emergency treatment could be self-administered. Risk factors associated with hospital admission were laryngeal and facial involvement, whereas self-injection of icatibant was associated with a return home.


Daily negative affect and smoking after a self-set quit attempt: The role of dyadic invisible social support in a daily diary study.
Social support receipt from one's partner is assumed to be beneficial for successful smoking cessation. However, support receipt can have costs. Recent research suggests that the most effective support is unnoticed by the receiver (i.e., invisible). Therefore, this study examined the association between everyday levels of dyadic invisible emotional and instrumental support, daily negative affect, and daily smoking after a self-set quit attempt in smoker-non-smoker couples. Overall, 100 smokers (72.0% men, mean age M = 40.48, SD = 9.82) and their non-smoking partners completed electronic diaries from a self-set quit date on for 22 consecutive days, reporting daily invisible emotional and instrumental social support, daily negative affect, and daily smoking. Same-day multilevel analyses showed that at the between-person level, higher individual mean levels of invisible emotional and instrumental support were associated with less daily negative affect. In contrast to our assumption, more receipt of invisible emotional and instrumental support was related to more daily cigarettes smoked. The findings are in line with previous results, indicating invisible support to have beneficial relations with affect. However, results emphasize the need for further prospective daily diary approaches for understanding the dynamics of invisible support on smoking cessation. Statement of contribution What is already known on this subject? Social support receipt from a close other has proven to have emotional costs. According to current studies, the most effective social support is unnoticed by the receiver (i.e., invisible). There is empirical evidence for beneficial effects of invisible social support on affective well-being. What does this study add? Confirming benefits of invisible social support for negative affect in a health behaviour change setting Providing first evidence for detrimental effects of invisible social support on smoking.


"I just wish that everything is in one place": facilitators and barriers to continuity of care among HIV-positive, postpartum women with a non-communicable disease in South Africa.
HIV and non-communicable diseases (NCD) are co-epidemics in South Africa. Comorbid individuals must engage in lifelong care. Postpartum HIV-positive women in South Africa are at high risk of dropping out of HIV care. We explored healthcare utilization among postpartum women requiring chronic management of HIV and NCD. From August - December 2016, we enrolled 25 women in Soweto, South Africa, and conducted one-time interviews. All participants were adult (≥18 years), HIV-positive, postpartum, and diagnosed with a NCD that required further evaluation after delivery. We developed a conceptual model that describes how maternal factors, interaction with environments, and social networks influence follow up engagement. Barriers to follow-up included separate visit days, increased time commitment, transportation and logistics, unfamiliar clinic environments, and disrespectful staff. Factors facilitating patient engagement included social support and partner disclosure. Women were more likely to turn to friends and family for advice regarding HIV or the NCD, rather than a clinic. Women prioritized infant care after delivery, suggesting that baby care may be an entry point for improving maternal care after delivery. Our results support advocating for better integration of services at the primary care level as a method to improve continuity of care for both women and children.


A slow-onset, long-duration indanamine monoamine reuptake inhibitor as a potential maintenance pharmacotherapy for psychostimulant abuse: effects in laboratory rat models relating to addiction.
Slow-onset, long-lasting dopamine reuptake blockers with reduced abuse potential have been suggested as maintenance therapies for cocaine addiction. We have synthesized a series of 3-(3',4'-dichlorophenyl)-1-indanamine monoamine reuptake inhibitors as candidates for such maintenance pharmacotherapy. The initial lead compound, the N,N-dimethyl analogue 30,640 was then subjected to testing in addiction-relevant animal models. Compound 30,640 (2 mg/kg i.p.) produced a pronounced slow-onset, long-lasting increase (300-400%) in extracellular nucleus accumbens dopamine levels, as measured by in vivo brain microdialysis in awake laboratory rats. Slow-onset, long-lasting decreases (40-80%) in the dopamine metabolites 3,4-dihydroxyphenylacetic acid and homovanillic acid, and the serotonin metabolite 5-hydroxyindoleacetic acid were also seen. Compound 30,640 (3 or 5 mg/kg i.p.) also produced a significant (approximately 30%) slow-onset, long-lasting enhancement of electrical brain-stimulation reward, which was additive with that of cocaine (5 mg/kg i.p.). When given to cocaine-administering rats, 30,640 (2.5, 3, 5, or 10 mg/kg i.p.) significantly inhibited (30-60%) intravenous cocaine self-administration, with a pronounced long-lasting profile. In sum, 30,640 showed cocaine-like effects, but with a marked slow-onset, long-lasting profile. We conclude that the prodrug strategy employed in the design of 30,640 achieved its goal. We suggest that such compounds may be useful as maintenance pharmacotherapies for psychostimulant addiction.


Development of radiographic and microscopic techniques for the characterization of bacterial transport in intact sediment cores from Oyster, Virginia.
The objective of this study was to ascertain the physical and mineralogical properties responsible for the retention of bacteria in subsurface sediments. The sediment core chosen for this study was a fine-grained, quartz-rich sand with minor amounts of Fe and Al hydroxides. A bacterial transport experiment was performed using an intact core collected from a recent excavation of the Butler's Bluff member of the Nassawadox formation in the borrow pit at Oyster, VA. and a 14C-labeled bacterial strain OYS2-A was selected for its relatively low adhesion. After the bacterial breakthrough was observed in the effluent, the intact core was dissected to determine the internal distribution of the injected bacteria retained in the sediment. The sediment was dried, epoxy fixed, and thin sectioned. The distribution of 14C activity in the thin sections was mapped using a phosphor screen and X-ray film. The remainder of the core was subsampled and the 14C activity of the subsamples was determined by liquid scintillation counting. The phosphor imaging technique was capable of directly imaging the distribution of radiolabeled bacteria in thin sections, because of its high sensitivity and linear response over a large activity range. The phosphor imaging signal intensity was utilized as a measure of bacterial concentration. The distribution of bacteria at the millimeter scale in the thin sections was compared to the grain size, porosity, and mineralogy as measured by scanning electron microscopy (SEM) and energy dispersive spectrum (EDS) analyses. No apparent correlation was observed between the retention or collision efficiency of bacteria in the sediment and the amount of Fe and Al hydroxides. This apparent lack of correlation can be qualitatively explained by combination of several factors including a nearly neutral surface charge of the bacterial strain, and texture of the Fe and Al hydroxides in the sediment. The combination of phosphor imaging with SEM-EDS proved to be a robust method for relating the physical and mineralogical microscopic properties of poorly indurated sediment to the distribution of adsorbed bacteria, allowing bacterial retention mechanisms to be unambiguously unraveled.


Asbestos content of lung tissue in asbestos associated diseases: a study of 110 cases.
Diseases associated with asbestos exposure include asbestosis, malignant mesothelioma, carcinoma of the lung, and parietal pleural plaques. In this study the asbestos content of lung tissue was examined in groups of cases representing each of these diseases and in several cases with non-occupational idiopathic pulmonary fibrosis. Asbestos bodies (AB), which are the hallmark of asbestos exposure, were present in the lungs of virtually everyone in the general population and present at increased levels in individuals with asbestos associated diseases. The highest numbers of AB occurred in individuals with asbestosis, all of whom had levels greater than or equal to 2000 ABs/g wet lung tissue. Every case with a content of 100,000 ABs/g or higher had asbestosis. Intermediate levels occurred in individuals with malignant mesothelioma and the lowest levels in patients with parietal pleural plaques. There was no overlap between the asbestos content of lung tissue from patients with asbestosis and those with idiopathic pulmonary fibrosis. Lung cancer was present in half the patients with asbestosis, and the distribution of histological patterns did not differ from that in patients with lung cancer without asbestosis. The asbestos body content in patients with lung cancer was highly variable. Control cases had values within our previously established normal range (0-20 ABs/g). There was a significant correlation (p less than 0.001) between AB counted by light microscope and AB and uncoated fibres counted by scanning electron microscopy. The previous observation that the vast majority of asbestos bodies isolated from human tissues have an amphibole core was confirmed.


IL-5 receptor-mediated tyrosine phosphorylation of SH2/SH3-containing proteins and activation of Bruton's tyrosine and Janus 2 kinases.
Interleukin 5 (IL-5) induces proliferation and differentiation of B cells and eosinophils by interacting with its receptor (IL-5R) which consists of two distinct polypeptide chains, alpha and beta (beta c). Although both IL-5R alpha and beta c lack a kinase catalytic domain, IL-5 is capable of inducing tyrosine phosphorylation of cellular proteins. We investigated the role of IL-5R alpha in tyrosine phosphorylation of molecules involved in IL-5 signal transduction, using an IL-5-dependent early B cell line, Y16 and transfectants expressing intact or mutant IL-5R alpha together with intact beta c. The results revealed that the transfectants expressing truncated IL-5R alpha, which entirely lacks a cytoplasmic domain, together with beta c, showed neither protein-tyrosine phosphorylation nor proliferation in response to IL-5. This confirms that IL-5R alpha plays a critical role in protein-tyrosine phosphorylation which triggers cell growth. IL-5 stimulation results in rapid tyrosine phosphorylation of beta c and proteins containing Src homology 2 (SH2) and/or SH3 domains such as phosphatidyl-inositol-3 kinase, Shc, Vav, and HS1, suggesting their involvement in IL-5-mediated signal transduction. IL-5 stimulation significantly enhanced activities of Janus 2 and B cell-specific Bruton's tyrosine kinases (JAK2 and Btk) and increased the tyrosine phosphorylation of JAK2 kinase. These results and recent data on signaling of growth factors taken together, multiple biochemical pathways driven by tyrosine kinases such as JAK2 and Btk are involved in IL-5 signal transduction.


Histone H3 Ser10 phosphorylation-independent function of Snf1 and Reg1 proteins rescues a gcn5- mutant in HIS3 expression.
Gcn5 protein is a prototypical histone acetyltransferase that controls transcription of multiple yeast genes. To identify molecular functions that act downstream of or in parallel with Gcn5 protein, we screened for suppressors that rescue the transcriptional defects of HIS3 caused by a catalytically inactive mutant Gcn5, the E173H mutant. One bypass of Gcn5 requirement gene (BGR) suppressor was mapped to the REG1 locus that encodes a semidominant mutant truncated after amino acid 740. Reg1(1-740) protein does not rescue the complete knockout of GCN5, nor does it suppress other gcn5- defects, including the inability to utilize nonglucose carbon sources. Reg1(1-740) enhances HIS3 transcription while HIS3 promoter remains hypoacetylated, indicating that a noncatalytic function of Gcn5 is targeted by this suppressor protein. Reg1 protein is a major regulator of Snf1 kinase that phosphorylates Ser10 of histone H3. However, whereas Snf1 protein is important for HIS3 expression, replacing Ser10 of H3 with alanine or glutamate neither attenuates nor augments the BGR phenotypes. Overproduction of Snf1 protein also preferentially rescues the E173H allele. Biochemically, both Snf1 and Reg1(1-740) proteins copurify with Gcn5 protein. Snf1 can phosphorylate recombinant Gcn5 in vitro. Together, these data suggest that Reg1 and Snf1 proteins function in an H3 phosphorylation-independent pathway that also involves a noncatalytic role played by Gcn5 protein.


Etiopathophysiological assessment of cases with chronic daily headache: A functional magnetic resonance imaging included investigation.
Chronic daily headache (CDH) has gained little attention in functional neuro-imaging. When no structural abnormality is found in CDH, defining functional correlates between activated brain regions during headache bouts may provide unique insights towards understanding the pathophysiology of this type of headache. We recruited four CDH cases for comprehensive assessments, including history taking, physical examinations and neuropsychological evaluations (The Addenbrooke's Cognitive Evaluation, Beck's Anxiety and Depression Inventories, Pittsburg Sleep Quality Index and Epworth Sleepiness Scale). Visual analogue scale (VAS) was used to self-rate the intensity of headache. Patients then underwent electroencephalography (EEG), transcranial Doppler (TCD) and functional magnetic resonance imaging (fMRI) evaluations during maximal (VAS = 8-10/10) and off-headache (VAS = 0-3/10) conditions. Data were used to compare in both conditions. We also used BOLD (blood oxygen level dependent) -group level activation map fMRI to possibly locate headache-related activated brain regions. General and neurological examinations as well as conventional MRIs were unremarkable. Neuropsychological assessments showed moderate anxiety and depression in one patient and minimal in others. Unlike three patients, maximal and off-headache TCD evaluation in one revealed increased middle cerebral artery blood flow velocity, at the maximal pain area. Although with no seizure history, the same patient's EEG showed paroxysmal epileptic discharges during maximal headache intensity, respectively. Group level activation map fMRI showed activated classical pain matrix regions upon headache bouts (periaqueductal grey, substantia nigra and raphe nucleus), and markedly bilateral occipital lobes activation. The EEG changes were of note. Furthermore, the increased BOLD signals in areas outside the classical pain matrix (i.e. occipital lobes) during maximal headaches may suggest that activation of these areas can be linked to the increased neural activity or visual cortex hyperexcitability in response to visual stimuli. These findings can introduce new perspective towards more in-depth functional imaging studies in headaches of poorly understood pathophysiology.


Calibration of the great american interchange.
From radioisotopic (potassium-argon) age determinations of tuffs and magnetostratigraphy of Late Tertiary mammal-bearing beds in Catamarca Province, northwest Argentina, refined estimates have been obtained for the durations and boundaries of beds of Chasicoan (Middle Miocene) through Chapadmalalan (Pliocene) age. An age of 9.0 million years is tentatively accepted for the Chasicoan-Huayquerian boundary, 5.0 million years for the Huayquerian-Montehermosan boundary, and 3.0 million years for the Montehermosan-Chapadmalalan boundary. Procyonids (raccoons and their allies), a group of North American origin, are first recorded in South America in a level immediately below a unit dated at 6.0 million years. Cricetine rodents of the tribe Sigmodontini are first recorded in South America in beds of Montehermosan age in Argentina. Ground sloths, a group of South American origin, first appear in North America in Early Hemphillian time in beds dated between 9.5 and 9.0 million years. The Panamanian land bridge was established by 3.0 million years ago, and an interchange of the terrestrial faunas was well under way by Late Blancan time (around 2.5 million years before present) in North America and by Chapadmalalan time in South America.


Biomarkers of oxidative stress and risk of developing colorectal cancer: a cohort-nested case-control study in the European Prospective Investigation Into Cancer and Nutrition.
Oxidative stress has been shown to play an important role in carcinogenesis, but prospective evidence for an association between biomarkers of oxidative stress and colorectal cancer (CRC) risk is limited. The authors investigated the association between prediagnostic serum levels of oxidative stress indicators (i.e., reactive oxygen metabolites (ROM) and ferric reducing ability of plasma (FRAP)) and CRC risk. This was examined in a nested case-control study (1,064 CRC cases, 1,064 matched controls) in the European Prospective Investigation Into Cancer and Nutrition cohort (1992-2003). Incidence rate ratios and 95% confidence intervals were calculated using conditional logistic regression analyses. ROM were associated with overall CRC risk (highest tertile vs. lowest: adjusted incidence rate ratio (IRR(adj)) = 1.91, 95% confidence interval (CI): 1.47, 2.48), proximal (IRR(adj) = 1.89, 95% CI: 1.06, 3.36) and distal (IRR(adj) = 2.31, 95% CI: 1.37, 3.89) colon cancer, and rectal cancer (IRR(adj) = 1.69, 95% CI: 1.05, 2.72). When results were stratified by tertile of follow-up time, the association remained significant only in participants with less than 2.63 years of follow-up (IRR(adj) = 2.28, 95% CI: 1.78, 2.94; P-heterogeneity < 0.01). FRAP was not associated with CRC risk. In conclusion, prediagnostic serum ROM levels were associated with increased risk of CRC. However, this association was seen only in subjects with relatively short follow-up, suggesting that the association results from production of reactive oxygen species by preclinical tumors.


Executive functioning: developmental consequences on adolescents with histories of maltreatment.
Research suggests that children exposed to maltreatment have deficits in executive functioning (EF) but few studies have focused on the adolescent age group. We investigated whether maltreated adolescents had lower EF abilities compared to a group of non-maltreated adolescents. Forty adolescents with histories of child maltreatment, together with a comparison group of 40 non-maltreated adolescents matched for age, completed a comprehensive battery of EF tasks. Hierarchical multiple regression analyses, controlling for IQ, were carried out using each of the EF measures as dependent variables to examine group differences. Maltreated adolescents had significantly lower performance than non-maltreated adolescents on tasks assessing executive loaded working memory, fluency, and inhibition, although switching was not impaired. Emotional and behavioural difficulties (EBD) were included in additional regression analyses to examine whether these variables would explain the group differences. The inclusion of EBD variables had some effect on group differences, as expected, but did not eliminate them. These findings support the theory that impairments in EF may be one underlying reason why adolescents with histories of maltreatment struggle to cope both inside and outside the classroom.


Catecholaminergic modulation of indices of cognitive flexibility: A pharmaco-tDCS study.
Dopaminergic activity within the dorsolateral prefrontal cortex (dlPFC) has been implicated in the control of cognitive flexibility. Much of the evidence for a causative relationship between cognitive flexibility and dopamine has come from animal studies, whilst human data have largely been correlational. The current study examines whether changes in dopamine levels through tyrosine administration and suppression of dlPFC activity via cathodal tDCS could be causally related to cognitive flexibility as measured by task switching and reversal learning. Using a crossover, double-blind, sham controlled, counterbalanced, randomized trial, we tested the effects of combining cathodal tDCS with tyrosine, a catecholaminergic precursor, with appropriate drug and tDCS placebo controls, on two measures of cognitive flexibility: probabilistic reversal learning, and task switching. While none of the manipulations had an effect on task switching, there was a significant main effect of cathodal tDCS and tyrosine on reversal learning. Reversal learning performance was significantly worsened by cathodal tDCS compared with sham tDCS, whilst tyrosine significantly improved performance compared with placebo. However, there was no significant tDCS × drugs interaction. Interestingly, and as predicted by our model, the combined administration of tyrosine with cathodal tDCS resulted in performance that was equivalent to the control condition (i.e. tDCS sham + placebo). Our results suggest a causative role for dopamine signalling and dorsolateral prefrontal cortex activity in regulating indices of cognitive flexibility in humans.


Classifying hand sensorimotor functions of the chronic kidney disease patients using novel manual tactile test and pinch-holding-up activity.
Hand function deterioration brings about inconvenience to the daily lives of the chronic kidney disease patients. However, a full spectrum of hand function examination is absent. Therefore, this study aimed to classify the hand sensorimotor functions of the chronic kidney disease patients using the novel sensorimotor assessment tools, manual tactile test (MTT) and pinch-holding-up activity (PHUA) test, and explore the feasibility in comparison with traditional evaluations in the clinical practice. 68 stage-5 chronic kidney disease patients and 50 healthy subjects were recruited in this study. A series of conventional evaluations and two novel hand function tools, manual tactile test and pinch-holding-up activity test were conducted from the perspective of hand dexterity, sensory input threshold, force generation and sensorimotor control. Independent t-test was used to find out group differences and the receiver operating characteristic curve was used to determine accuracy of the tests. In our results, significant reduction of hand dexterity, sensory input, force generation and sensorimotor control was found in patients from an overall perspective. This trend was discovered to be the same when dividing the subjects into the old and young age group. From the receiver operator characteristic curves, nearly all the areas under the curve of all tests were over 0.8. The novel evaluation tools, the manual tactile test and pinch-holding-up activity, were found to have comparable or even better accuracy than the traditional ones. The shape and weight subtests of the manual tactile test displayed the highest accuracy. To sum up, by incorporating the novel and conventional assessment tests, this study built up the fundamental understanding of the hand functions in multiple dimensions and consolidate the clinical merits of applying the two novel tools, manual tactile test and pinch-holding-up activity, on chronic kidney disease patients.


Interim guidance: preexposure prophylaxis for the prevention of HIV infection in men who have sex with men.
An estimated 56,000 human immunodeficiency virus (HIV) infections occur each year in the United States. Men who have sex with men (MSM) account for 53% of the estimated incident infections, and surveillance data suggest that the annual number of new HIV infections among MSM has been rising since the mid-1990s. Strategies for reducing acquisition of HIV infection by MSM have included 1) expanded HIV testing so that infected persons can be treated and their risk for transmitting infection minimized; 2) individual, small-group, and community-level behavioral interventions to reduce risk behaviors; 3) promotion of condom use; 4) detection and treatment of sexually transmitted infections; and 5) mental health and substance abuse counseling when needed. On November 23, 2010, investigators for the Pre-Exposure Prophylaxis Initiative (iPrEX) study announced results from a multinational, randomized, double-blind, placebo-controlled, phase III clinical trial of daily oral antiretrovirals (tenofovir disoproxil fumarate [TDF] and emtricitabine [FTC]) to prevent acquisition of HIV infection among uninfected but exposed MSM. This report provides interim guidance to health-care providers based on the reported results of that trial, which indicated that TDF plus FTC taken orally once a day as preexposure prophylaxis (PrEP) is safe and partially effective in reducing HIV acquisition among MSM when provided with regular monitoring of HIV status and ongoing risk-reduction and PrEP medication adherence counseling.


Mercury exposure, nutritional deficiencies and metabolic disruptions may affect learning in children.
Among dietary factors, learning and behavior are influenced not only by nutrients, but also by exposure to toxic food contaminants such as mercury that can disrupt metabolic processes and alter neuronal plasticity. Neurons lacking in plasticity are a factor in neurodevelopmental disorders such as autism and mental retardation. Essential nutrients help maintain normal neuronal plasticity. Nutritional deficiencies, including deficiencies in the long chain polyunsaturated fatty acids eicosapentaenoic acid and docosahexaenoic acid, the amino acid methionine, and the trace minerals zinc and selenium, have been shown to influence neuronal function and produce defects in neuronal plasticity, as well as impact behavior in children with attention deficit hyperactivity disorder. Nutritional deficiencies and mercury exposure have been shown to alter neuronal function and increase oxidative stress among children with autism. These dietary factors may be directly related to the development of behavior disorders and learning disabilities. Mercury, either individually or in concert with other factors, may be harmful if ingested in above average amounts or by sensitive individuals. High fructose corn syrup has been shown to contain trace amounts of mercury as a result of some manufacturing processes, and its consumption can also lead to zinc loss. Consumption of certain artificial food color additives has also been shown to lead to zinc deficiency. Dietary zinc is essential for maintaining the metabolic processes required for mercury elimination. Since high fructose corn syrup and artificial food color additives are common ingredients in many foodstuffs, their consumption should be considered in those individuals with nutritional deficits such as zinc deficiency or who are allergic or sensitive to the effects of mercury or unable to effectively metabolize and eliminate it from the body.


Relative metabolite concentrations and ratios determined by use of 3-T region-specific proton magnetic resonance spectroscopy of the brain of healthy Beagles.
To determine relative concentrations of selected major brain tissue metabolites and their ratios and lobar variations by use of 3-T proton (hydrogen 1 [(1)H]) magnetic resonance spectroscopy (MRS) of the brain of healthy dogs. 10 healthy Beagles. 3-T (1)H MRS at echo times of 144 and 35 milliseconds was performed on 5 transverse slices and 1 sagittal slice of representative brain lobe regions. Intravoxel parenchyma was classified as white matter, gray matter, or mixed (gray and white) and analyzed for relative concentrations (in arbitrary units) of N-acetylaspartate (NAA), choline, and creatine (ie, height at position of peak on MRS graph) as well as their ratios (NAA-to-choline, NAA-to-creatine, and choline-to-creatine ratios). Peak heights for metabolites were compared between echo times. Peak heights for metabolites and their ratios were correlated and evaluated among matter types. Yield was calculated as interpretable voxels divided by available lobar voxels. Reference ranges of the metabolite concentration ratios were determined at an echo time of 35 milliseconds (NAA-to-choline ratio, 1.055 to 2.224; NAA-to-creatine ratio, 1.103 to 2.161; choline-to-creatine ratio, 0.759 to 1.332) and 144 milliseconds (NAA-to-choline ratio, 0.687 to 1.788; NAA-to-creatine ratio, 0.984 to 2.044; choline-to-creatine ratio, 0.828 to 1.853). Metabolite concentration ratios were greater in white matter than in gray matter. Voxel yields ranged from 43% for the temporal lobe to 100% for the thalamus. Metabolite concentrations and concentration ratios determined with 3-T (1)H MRS were not identical to those in humans and were determined for clinical and research investigations of canine brain disease.


Neither ischemic parenchymal volume nor severe grade complication correlate transient high transaminase elevation after liver resection.
To clarify whether high transient elevation of serum transaminase predicts severe complications and is related to the ischemic area on CT. Postoperative laboratory data and ischemia area on CT were analyzed on the basis of the presence of high transaminase elevation (aspartate aminotransferase (AST) > 1,000 IU/L within postoperative day (POD) 2 after liver resection. In the high elevation group, volume of ischemic areas was assessed by CT on POD2. The 538 patients were divided into a high transaminase group (n = 51) and a control group (n = 487). Median operation time (527 min vs. 360 min, p < 0.01) and liver ischemia time (121 min vs. 70 min, p < 0.01) were significantly longer, and intraoperative blood loss (478 mL [85-1572 mL] vs. 269 mL [5-4491 mL], p < 0.01) was significantly greater in the high transaminase group. No significant differences observed in frequency of severe complications (Clavien-Dindo classification Grade III or more) or postoperative hospitalization. Operation time (> 500 min; odds ratio (OR), 4.86; 95% confidence interval (CI), 2.40-9.89; p < 0.01) and liver ischemia time (> 120 min; OR, 3.47; 95%CI, 1.67-7.17; p < 0.01) were independent predictors of high transaminase elevation. No relationship was observed between degree of transaminase elevation and ischemic area (correlation coefficients: AST, R2 < 0.001; alanine aminotransferase, R2 = 0.005) CT volumetry on POD2. In conclusions, high transaminase elevations do not predict severe complications or reflect remnant ischemic area.


Global survey of the diagnostic evaluation and management of cryptogenic ischemic stroke.
About 25% of ischemic strokes are categorized as cryptogenic (i.e. of unknown cause), but few data exist about the extent of diagnostic testing or treatment. We undertook an international survey to characterize current diagnostic evaluation and antithrombotic management of patients with cryptogenic ischemic stroke in 2014. To determine the type of diagnostic evaluation undertaken for cryptogenic ischemic stroke and antithrombotic management and to compare across global regions. An 18-question online survey was sent to 995 physicians involved in stroke care in 61 countries. Countries were separated into World Bank global regions and income groups. Diagnostic tests were considered routine if performed in >75% of patients at a center. Three hundred one completed surveys were received from 48 countries (response rate ∼30%). The majority (82%) of hospitals were from high-income countries and mainly from Europe and Central Asia (56%) and North America (19%). For ischemic stroke patients, magnetic resonance imaging is routinely obtained at 36% of hospitals (highest in North America, 58%). Among cryptogenic stroke patients, transesophageal echocardiography is routinely performed in 17% of hospitals. More than 24 hour cardiac rhythm monitoring is done routinely at relatively few (17%) hospitals (highest in North America, 33%). Intracranial arterial imaging is done routinely at 70% of hospitals, with no significant regional differences. Antiplatelet therapies are routinely prescribed for secondary prevention at 94% of hospitals. Based on self-selected respondents from a large number of international stroke centers, transesophageal echocardiography and prolonged (>24 h) cardiac rhythm monitoring are not routinely performed in cryptogenic stroke patients, even in high-income countries. Antiplatelet therapy is the global standard for secondary prevention of cryptogenic stroke.


ANNarchy: a code generation approach to neural simulations on parallel hardware.
Many modern neural simulators focus on the simulation of networks of spiking neurons on parallel hardware. Another important framework in computational neuroscience, rate-coded neural networks, is mostly difficult or impossible to implement using these simulators. We present here the ANNarchy (Artificial Neural Networks architect) neural simulator, which allows to easily define and simulate rate-coded and spiking networks, as well as combinations of both. The interface in Python has been designed to be close to the PyNN interface, while the definition of neuron and synapse models can be specified using an equation-oriented mathematical description similar to the Brian neural simulator. This information is used to generate C++ code that will efficiently perform the simulation on the chosen parallel hardware (multi-core system or graphical processing unit). Several numerical methods are available to transform ordinary differential equations into an efficient C++code. We compare the parallel performance of the simulator to existing solutions.


Increasing utilisation of perinatal services: estimating the impact of community health worker program in Neno, Malawi.
By 2015, Malawi had not achieved Millennium Development Goal 4, reducing maternal mortality by about 35% from 675 to 439 deaths per 100,000 livebirths. Hypothesised reasons included low uptake of antenatal care (ANC), intrapartum care, and postnatal care. Involving community health workers (CHWs) in identification of pregnant women and linking them to perinatal services is a key strategy to reinforce uptake of perinatal care in Neno, Malawi. We evaluated changes in uptake after deployment of CHWs between March 2014 and June 2016. A CHW intervention was implemented in Neno District, Malawi in a designated catchment area of about 3100 women of childbearing age. The pre-intervention period was March 2014 to February 2015, and the post-intervention period was March 2015 to June 2016. A 5-day maternal health training package was delivered to 211 paid and supervised CHWs. CHWs were deployed to identify pregnant women and escort them to perinatal care visits. A synthetic control method, in which a "counterfactual site" was created from six available control facilities in Neno District, was used to evaluate the intervention. Outcomes of interest included uptake of first-time ANC, ANC within the first trimester, four or more ANC visits, intrapartum care, and postnatal care follow-up. Women enrolled in ANC increased by 18% (95% Credible Interval (CrI): 8, 29%) from an average of 83 to 98 per month, the proportion of pregnant women starting ANC in the first trimester increased by 200% (95% CrI: 162, 234%) from 10 to 29% per month, the proportion of women completing four or more ANC visits increased by 37% (95% CrI: 31, 43%) from 28 to 39%, and monthly utilisation of intrapartum care increased by 20% (95% CrI: 13, 28%) from 85 to 102 women per month. There was little evidence that the CHW intervention changed utilisation of postnatal care (- 37, 95% CrI: - 224, 170%). In a rural district in Malawi, uptake of ANC and intrapartum care increased considerably following an intervention using CHWs to identify pregnant women and link them to care.


Designing artificial 3D helicates: unprecedented self-assembly of homo-octanuclear tetrapods with europium.
Herein, we report on the rational design, preparation and characterization of a novel homo-octanuclear helicate, which results from a spatial extension of the central tetranuclear platform. The 3D supramolecular assembly is obtained by complexing europium(III) with a new hexatopic tripodal ligand. The isolated octanuclear helicate is fully characterized by different methods clearly evidencing the structure predicted with molecular modelling. The ligand preorganization plays a crucial role in a successful self-assembly process and induces the formation of a well-defined triple-stranded helical structure. This prototypal octanuclear edifice accommodating functional lanthanides within a 3D scaffold offers attractive perspectives for further applications.


The dynamical consequences of seasonal forcing, immune boosting and demographic change in a model of disease transmission.
The impact of seasonal effects on the time course of an infectious disease can be dramatic. Seasonal fluctuations in the transmission rate for an infectious disease are known mathematically to induce cyclical behaviour and drive the onset of multistable and chaotic dynamics. These properties of forced dynamical systems have previously been used to explain observed changes in the period of outbreaks of infections such as measles, varicella (chickenpox), rubella and pertussis (whooping cough). Here, we examine in detail the dynamical properties of a seasonally forced extension of a model of infection previously used to study pertussis. The model is novel in that it includes a non-linear feedback term capturing the interaction between exposure and the duration of protection against re-infection. We show that the presence of limit cycles and multistability in the unforced system give rise to complex and intricate behaviour as seasonal forcing is introduced. Through a mixture of numerical simulation and bifurcation analysis, we identify and explain the origins of chaotic regions of parameter space. Furthermore, we identify regions where saddle node lines and period-doubling cascades of different orbital periods overlap, suggesting that the system is particularly sensitive to small perturbations in its parameters and prone to multistable behaviour. From a public health point of view - framed through the 'demographic transition' whereby a population׳s birth rate drops over time (and life-expectancy commensurately increases) - we argue that even weak levels of seasonal-forcing and immune boosting may contribute to the myriad of complex and unexpected epidemiological behaviours observed for diseases such as pertussis. Our approach helps to contextualise these epidemiological observations and provides guidance on how to consider the potential impact of vaccination programs.


Differential narrow focusing of immunodominant human immunodeficiency virus gag-specific cytotoxic T-lymphocyte responses in infected African and caucasoid adults and children.
Cytotoxic T-lymphocyte (CTL) activity plays a central role in control of viral replication and in determining outcome in cases of human immunodeficiency virus type 1 (HIV-1) infection. Incorporation of important CTL epitope sequences into candidate vaccines is, therefore, vital. Most CTL studies have focused upon small numbers of adult Caucasoid subjects infected with clade-B virus, whereas the global epidemic is most severe in sub-Saharan African populations and predominantly involves clade-C infection in both adults and children. In this study, sensitive enzyme-linked immunospot (elispot) assays have been utilized to identify the dominant Gag-specific CTL epitopes targeted by adults and children infected with clade-B or -C virus. Cohorts evaluated included 44 B-clade-infected Caucasoid American and African American adults and children and 37 C-clade-infected African adults and children from Durban, South Africa. The results show that 3 out of 46 peptides spanning p17(Gag) and p24(Gag) sequences tested contain two-thirds of the dominant Gag-specific epitopes, irrespective of the clade, ethnicity, or age group studied. However, there were distinctive differences between the dominant responses made by Caucasoids and Africans. Dominant responses in Caucasoids were more often within p17(Gag) peptide residues 16 to 30 (38 versus 12%; P < 0.01), while p24(Gag) peptide residues 41 to 60 contained the dominant Gag epitope more often in the African subjects tested (39 versus 4%; P < 0.005). Within this 20-mer p24(Gag), an epitope presented by both B42 and B81 is defined which represents the dominant Gag response in >30% of the total infected population in Durban. This epitope is closely homologous with dominant HIV-2 and simian immunodeficiency virus Gag-specific CTL epitopes. The fine focusing of dominant CTL responses to these few regions of high immunogenicity is of significance to vaccine design.


Heterochronic detection through a function for the ontogenetic variation of bone shape.
Heterochrony, evolutionary modifications in the rates and/or the timing of development, is widely recognized as an important agent of evolutionary change. In this paper, we are concerned with the detection of this evolutionary mechanism through the analysis of long bone growth. For this, we provide a function sigma (t) for the ontogenetic variation of bone shape by taking the ratio of two Gompertz curves explaining, respectively, the relative contribution to long bone growth of (a) endochondral ossification and (b) periosteal ossification. The significance of the fitting of this function to empirical data was tested in Anas platyrhynchos (Anseriformes). In this function sigma (t), the time t(m) at which periosteal growth rate first equalizes endochondral growth rate was taken as the timing parameter to be compared between taxa. On the other hand, the maximum rate of ontogenetic change in bone shape (maximum slope, beta) from hatching to t(m) was taken as the rate parameter to be compared. Comparisons of these parameters between the plesiomorphic condition and the derived character state would provide evidence for hypomorphosis (earlier occurrence of t(m)), hyper-morphosis (delayed occurrence of t(m)), deceleration (smaller beta) or acceleration (higher beta). Regarding the phylogenetic context, the ancestral condition for the character of interest should be estimated to polarize the direction of the heterochronic change. We have quantified the influence of the phylogenetic history on the variation of adult bone shape in a sample of 13 species of Anseriformes and 17 species from other neornithine orders of birds by using permutational phylogenetic regressions. Phylogenetic effects are significant, and this fact allows the optimization of bone shape onto a phylogenetic tree of Anseriformes to estimate the ancestral condition for Anas platyrhynchos.


Survey of undergraduate medical students on their understanding and attitude towards the discipline of radiotherapy.
The discipline of radiotherapy (RT) in India is considered a low priority subject. Postgraduate (PG) students rarely choose RT as a career option. The possible reasons could be: 1) limited availability of PG course training centers, 2) limited job prospects, etc. We decided to conduct a survey of undergraduate (UG) medical students to find out their awareness, understanding, and attitude toward the subject of RT. A simple 12-point questionnaire was designed to assess the level of awareness, understanding, and attitude. It was handed over personally or sent by e-mail or post to UG students of various medical colleges in India. The data provided by respondents was analyzed. During the period from January to June 2008, 400 questionnaires were distributed. A total of 155 respondents sent their responses. Twenty-eight of them (18%) opined that RT is not a part of the bachelor of medicine and bachelor of surgery (MBBS) curriculum at their institute. About 84% replied that not more than 10 theory lectures/practical classes are assigned to RT during the entire UG period. About one-third of the respondents stated that there are no separate clinical postings for RT. According to 54% of the respondents, RT is still a low priority subject in the PG setting and the majority (70%) thought that inadequate exposure at the UG level and lack of awareness about the current prospects of RT are the main reasons for this. The results of our survey indicate that the RT is still a low priority subject in India, mainly due to the poor exposure to the discipline and low awareness of the subject of RT during the UG program. The Medical Council of India (MCI) needs to ensure that adequate importance is given to RT in the MBBS curriculum so as to enhance awareness regarding the subject and increase exposure to this specialty.


Non-rhinovirus enteroviruses associated with respiratory infections in Peru (2005-2010).
Enteroviruses (EVs) are a common cause of respiratory tract infections and are classified into seven species (EVA-D and rhinoviruses [RHVs] A-C) with more than 200 different serotypes. Little is known about the role of non-RHV EVs in respiratory infections in South America. The aim of this study was to describe the epidemiology of non-RHV EVs detected in patients with influenza-like illness enrolled in a passive surveillance network in Peru. Throat swabs and epidemiological data were collected from participants after obtaining verbal consent. Viral isolation was performed in cell culture and identified by immunofluorescence assay. Serotype identification of EV isolates was performed using commercial monoclonal antibodies. Identification of non-serotypeable isolations was carried out by reverse transcriptase-PCR, followed by sequencing. Between 2005 and 2010, 24,239 samples were analyzed, and 9,973 (41.1%) possessed at least one respiratory virus. EVs were found in 175 samples (0.7%). Our results revealed a clear predominance of EVB species, 90.9% (159/175). No EVDs were isolated. The mean and median ages of EV-positive subjects were 9.1 and 4.0 years, respectively, much younger than the population sampled, 17.6 and 12.0 years. Sixteen serotypes were identified, four EVA, 11 EVB, and one EVC species. The most common serotypes were coxsackievirus B1, coxsackievirus B2, coxsackievirus B5, and coxsackievirus B3. This study provides data about the serotypes of EVs circulating in Peru and sets the need for further studies.


Preterm birth and future risk of maternal cardiovascular disease - is the association independent of smoking during pregnancy?
While the association of preterm birth and the risk of maternal cardiovascular disease (CVD) has been well-documented, most studies were limited by the inability to account for smoking during pregnancy - an important risk factor for both preterm birth and CVD. This study aimed to determine whether the increased future risk of maternal cardiovascular disease (CVD) associated with preterm birth is independent of maternal smoking during pregnancy. A population-based record linkage study of 797,056 women who delivered a singleton infant between 1994 and 2011 in New South Wales, Australia was conducted. Birth records were linked to the mothers' subsequent hospitaliation or death from CVD. Preterm births were categorised as late (35-36 weeks), moderate (33-34 weeks), or extreme (≤32 weeks); and as spontaneous or indicated. Cox proportional hazard regression was used to estimate adjusted hazard ratios (AHR) [95 % CI]. During the study period, 59,563 women (7.5 %) had at least one preterm birth. After adjustment for CVD risk factors other than smoking, AHR [95 % CI] of CVD among women who ever had a preterm birth was 1.78 [1.61-1.96]. Associations were greater for extreme (AHR = 1.98 [1.63-2.42]) and moderate (AHR = 2.06 [1.69-2.51]) than late preterm birth (AHR = 1.63 [1.44-1.85]), for indicated (AHR = 2.04 [1.75-2.38]) than spontaneous preterm birth (AHR = 1.65 [1.47-1.86]), and for having ≥ two (AHR = 2.29[1.75-2.99]) than having one preterm birth (AHR = 1.73[1.57-1.92]). A further adjustment for maternal smoking attenuated, but did not eliminate, the associations. Smoking during pregnancy was also independently associated with maternal CVD risks, with associations being stronger for mothers who smoked during last pregnancy (AHR = 2.07 [1.93-2.23]) than mothers who smoked during a prior pregnancy (AHR = 1.64 [1.41-1.90]). Associations of preterm birth and maternal CVD risk are independent of maternal smoking during pregnancy. This underscores the importance of smoking cessation in reducing CVD and suggests that a history of preterm delivery (especially if severe, indicated or recurrent) identifies women who could be targeted for CVD screening and preventative therapies.


Influence of overlay restorative materials and load cusps on the fatigue resistance of endodontically treated molars.
To assess the influence of restorative materials and load cusps on the fatigue resistance of endodontically treated molars. Thirty extracted molars received root canal treatment followed by a standardized tooth preparation (3-mm cuspal reduction and immediate dentin sealing). Twenty Cerec 3 overlays (Sirona Dental Systems) were milled in the ceramic Vita MKII block (Vident; groups MKIIGL and MKIIGL-Z, oven-glazed), and 10 restorations were duplicated with a composite resin (Miris 2, Coltane/Whaledent; group M2). The fitting surfaces of the restorations were hydrofluoric acid etched (porcelain only) and silanated. Preparations were airborne-particle abraded and etched. All restorations were luted with preheated Filtek Z100 (3M ESPE) and subjected to cyclic isometric chewing (5 Hz) starting at 200 N (5,000 cycles), followed by stages of 400, 600, 800, 1,000, 1,200, and 1,400 N at a maximum of 30,000 cycles each. A stainless steel load sphere was used for groups MKIIGL and M2, while a composite resin load sphere was used in group MKIIGL-Z. All samples were loaded until fracture or to a maximum of 185,000 cycles. Groups were compared using the Kaplan-Meier survival curves (P = .05). None of the molars restored with porcelain withstood all 185,000 loading cycles (survival = 0%). The mean fracture load for MKIIGL was 1,060 N and for MKIIGL-Z, 1,280 N. In group M2, the survival rate was 50%. The rate of fracture below the CEJ was 40%, 30%, and 20% for MKIIGL, MKIIGL-Z, and M2, respectively. Miris 2 overlays showed higher fatigue resistance than MKII porcelain (P = .01) when loaded with a stainless steel antagonist.


Effect of chronic exposure to prometryne on oxidative stress and antioxidant response in early life stages of common carp (Cyprinus carpio L.).
The aim of the study was to investigate effects of the triazine herbicide prometryne on early life stages of common carp Cyprinus carpio as indicated by oxidative stress and antioxidant indices. Toxicity tests were performed according to OECD 210 methodologies. Common carp larvae and embryos exposed for 35 days to prometryne at three concentrations, 0.51 (reported concentration in Czech rivers), 80 (1% 96 h LC50), and 1200 (15% 96 h LC50) μg/l, were compared to carp in a non-treated control group. Activity of superoxide dismutase (SOD), catalase (CAT), and glutathione reductase (GR), as well as levels of thiobarbituric acid reactive substances (TBARS) were assessed. Chronic exposure of early life stages of carp to prometryne showed no effect on growth and mortality rates. Levels of oxidative damage in fish test groups showed no significant differences from the controls. Glutathione reductase activity at exposure 0.51 μg/l was significantly increase (p<0.01) compared with controls and other exposures. The chronic exposure to prometryne showed no influence on oxidative stress. Differences from control fish was observed in GR activity in exposure prometryne 0.51 μg/l.


Social stress in young people with specific language impairment.
Social interactions can be a source of social stress for adolescents. Little is known about how adolescents with developmental difficulties, such as specific language impairment (SLI), feel when interacting socially. Participants included 28 adolescents with SLI and 28 adolescents with typical language abilities (TL). Self-report measures of social stress, social skills and social acceptance were obtained. Participants with SLI reported experiencing significantly more social stress than did participants with TL. Both groups judged themselves as having adequate social skills and positive social acceptance. Expressive language ability was negatively associated with social stress, but did not predict social stress when social factors were included in the regression model. Perceived social skills and social acceptance scores predicted social stress, in that poorer scores predicted more social stress. Despite perceiving themselves as having adequate social skills and as being socially accepted, social interactions are nonetheless a source of stress for adolescents with SLI.


Recombinant OmpA protein fragments mediate interleukin-17 regulation to prevent Escherichia coli meningitis.
Neonates are at a higher risk for bacterial meningitis than children of other age groups. Although the mortality rates have decreased over the past few decades, neonatal meningitis is still a severe disease with high morbidity. For bacterial meningitis, antibiotic therapy is the primary choice for management. However, neurologic complications often cannot be averted; ∼40% of survivors exhibit neurological sequelae. Escherichia coli infection is the common cause of neonatal meningitis. Previously, we have demonstrated that the recombinant loop 1-3, loop 2-3, and loop 2-4 fragments of OmpA protein can protect mice from death after intracerebral E. coli infection. In this study, the protective effects of the recombinant OmpA protein fragments in E. coli intracerebral infections were investigated. The effects of E. coli intracerebral infection on cytokine and chemokine expression were determined. We also used various recombinant fragments of the OmpA protein to investigate the effects of these recombinant OmpA protein fragments on cytokine and chemokine expression. In this study, we demonstrated that the expression of interleukin-17 and other cytokines, chemokines, inducible nitric oxide synthase, and cyclooxygenase-2 are involved in the inflammatory processes of intracerebral E. coli infection. We also demonstrated that specific recombinant OmpA protein fragments (L1-3, L2-3, L2-4, and L3) can regulate cytokine, chemokine, nitric oxide synthase, and cyclooxygenase-2 expression and, subsequently, protect mice from death caused by intracerebral infection of E. coli. This finding indicates the potential for developing a new therapeutic approach to improve the prognosis of bacterial meningitis.


Resilience in patients with psychotic disorder.
The recovery movement differentiated clinical, which is related to disorder's symptoms, from personal recovery, which is outlined by a subjectively defined wellness state, characterised by hope and self-management. Schizophrenia research has long focused on risk factors and symptoms. The recovery movement triggered a focus shift from psychopathology towards better adjustment and growth despite living with schizophrenia. The recovery movement flourished parallel with positive psychology, the scientific study of ordinary human strengths and virtues investigating human motives and potentials. Understanding of human strengths could contribute to prevention or lessening of psychiatric disorders' devastating consequences, since optimism, sense of personal control and many other positive processes promote psychological health. Lately, the concepts of positive psychology have been implemented in schizophrenia research. Positive self-appraisals moderated suicidal ideation, even when patients experienced high levels of hopelessness.1 Additionally, among other factors, better self-images, internal locus of control (i.e. the perception that events in one's life relate to one's actions) and emphasis on personal efforts predicted a more favourable outcome in functioning of unmedicated patients.2 The concept of "resilience" is closely related to positive psychology. The American Psychological Association defines resilience as ''the process of adapting well in the face of adversity, trauma, threats or significant sources of stress''. The concept of resilience includes rebound from adversity.3 Determinants of resilience include biological, psychological, social and cultural factors that interact in a complex manner. The major manifestations of personal resilience are social competence, problem solving, autonomy and sense of purpose.5 Personality strengths that relate to resilience include high self-esteem, extroversion and optimism. Internal assets and personal competencies comprise the so called "phenomenological resilience" that can be measured by scales.4,5 Originally, research focused on resilience in relation to post-traumatic stress disorder and depression. Recently, resilience was proven a significant predictor of depressive episode recurrence in bipolar disorder.6 Low resilience levels were also established in individuals at clinical high risk state for development of psychosis. Interestingly, individuals at high risk that developed a full-blown psychosis had shown significantly lower resilience levels compared with non-converters. Additionally, high resilience levels in individuals at high risk for psychosis related to less severe negative, anxiety and depressive symptoms, as well as higher social functioning.7,8 Schizophrenia patients with higher resilience levels and optimism showed higher levels of happiness that associated in turn with lower perceived stress and higher personal mastery,9 while resilience was a significant predictor of functioning in a subgroup of non-medicated schizophrenia patients.10 In light of evidence supporting a positive association between resilience and schizophrenia outcome and based on the fact that resilience is modifiable and could improve with treatment,5 resilience studies are particularly meaningful, specifically within the first 3-5 years after schizophrenia onset,11 and could lead to interventions that aim at harnessing resilience during this "critical period". Diverse positive psychology interventions aim at improving psychological well-being by developing and nourishing positive feelings, behaviours and cognitions. Lately, positive psychotherapy was adapted for schizophrenia patients and was proven a feasible intervention that might contribute to improvement in functioning.12 Conclusively, sustained improvement in social and occupational functioning remains the most important indicator of recovery from schizophrenia. Still, such an improvement may not be accomplished in all patients by currently available pharmacological treatment alone. Studies that implement resilience and other positive psychology concepts reinforce schizophrenia research shift from risk to protective factors, reverse the question "which factors associate with relapse and chronicity" to "which factors promote recovery" and are promising for the development of additional therapeutic approaches.


Increased longevity in older users of postmenopausal estrogen therapy: the Leisure World Cohort Study.
To examine the effect of postmenopausal estrogen therapy (ET), including duration and recency of use, on all-cause mortality in older women. As part of a prospective cohort study of residents of a California retirement community begun in the early 1980s, Leisure World Cohort women (median age, 73 y) completed a postal health survey including details on ET use and were followed up for 22 years (1981-2003). Age- and multivariate-adjusted risk ratios (RR) and 95% CIs were calculated using proportional hazard regression. Of the 8,801 women, 6,626 died during follow-up (median age, 88 y). ET users had an age-adjusted mortality rate of 52.9 per 1,000 person-years compared with 56.5 among lifetime nonusers (RR = 0.91; 95% CI, 0.87-0.96). Risk of death decreased with both increasing duration of ET and decreasing years since last use (P for trend < 0.001). The risk was lowest among long-term (≥15 y) users (RR = 0.83; 95% CI, 0.74-0.93 for 15-19 y and RR = 0.87; 95% CI, 0.80-0.94 for 201 y). For long-term users, the age-adjusted mortality rate was 50.4 per 1,000 person-years. Lower-dose users (≤0.625 mg) had a slightly better survival rate than higher-dose users (RR = 0.84; 95% CI, 0.78-0.91 vs RR = 0.91; 95% CI, 0.83-0.97). Risk did not differ by route of administration (P = 0.56). Further adjustment for potential confounders had little effect on the observed RRs for ET. Long-term ET is associated with lower all-cause mortality in older women.


A systematic review of economic evaluations of CHW interventions aimed at improving child health outcomes.
Evidence of the cost-effectiveness of community health worker interventions is pertinent for decision-makers and programme planners who are turning to community services in order to strengthen health systems in the context of the momentum generated by strategies to support universal health care, the post-2015 Sustainable Development Goal agenda.We conducted a systematic review of published economic evaluation studies of community health worker interventions aimed at improving child health outcomes. Four public health and economic evaluation databases were searched for studies that met the inclusion criteria: National Health Service Economic Evaluation Database (NHS EED), Cochrane, Paediatric Economic Evaluation Database (PEED), and PubMed. The search strategy was tailored to each database.The 19 studies that met the inclusion criteria were conducted in either high income countries (HIC), low- income countries (LIC) and/or middle-income countries (MIC). The economic evaluations covered a wide range of interventions. Studies were grouped together by intended outcome or objective of each study. The data varied in quality. We found evidence of cost-effectiveness of community health worker (CHW) interventions in reducing malaria and asthma, decreasing mortality of neonates and children, improving maternal health, increasing exclusive breastfeeding and improving malnutrition, and positively impacting physical health and psychomotor development amongst children.Studies measured varied outcomes, due to the heterogeneous nature of studies included; a meta-analysis was not conducted. Outcomes included disease- or condition -specific outcomes, morbidity, mortality, and generic measures (e.g. disability-adjusted life years (DALYs)). Nonetheless, all 19 interventions were found to be either cost-effective or highly cost-effective at a threshold specific to their respective countries.There is a growing body of economic evaluation literature on cost-effectiveness of CHW interventions. However, this is largely for small scale and vertical programmes. There is a need for economic evaluations of larger and integrated CHW programmes in order to achieve the post-2015 Sustainable Development Goal agenda so that appropriate resources can be allocated to this subset of human resources for health. This is the first systematic review to assess the cost-effectiveness of community health workers in delivering child health interventions.


Profiling of gender-regulated gene transcripts in the filarial nematode Brugia malayi by cDNA oligonucleotide array analysis.
Microarray technology permits high-throughput comparisons of gene expression in different parasite stages or sexes and has been used widely. We report the first use of this technology for analysis of gene expression in filarial male and female worms. The slide array (comprised of 65-mer oligos representing 3569 EST clusters) was spotted with sequences selected from the extensive Brugia malayi EST database (). Arrays were hybridized with Cy dye labeled male and female cDNA. The experimental design included both biological and technical (dye-flip) replicates. The data were normalized for background and probe intensity, and the relative abundance of hybridized cDNA for each spot was determined. Genes showing two-fold or greater differences with P<0.05 were considered gender-regulated candidates. One thousand one hundred and seventy of 2443 clusters (48%) with signals above threshold in at least one sex were considered as gender-regulated gene candidates. This included 520 and 650 clusters up-regulated in male and female worms, respectively. Fifty of 53 (94%) gender-regulated candidate genes identified by microarray analysis were confirmed by real-time RT-PCR. Approximately 61% of gender-regulated genes had significant similarity to known genes in other organisms such as Caenorhabditis elegans. Many C. elegans homologues of these genes have been reported to have reproductive phenotypes (sterility or abnormal embryo development) by RNA interference. This study has provided the first broad view of gender-regulated gene expression in B. malayi; this should lead to improved understanding of reproduction in filarial nematodes. More generally, this approach holds great promise as a means of studying stage-specific or tissue-specific gene expression in parasitic nematodes.


Increased Lipolysis, Diminished Adipose Tissue Insulin Sensitivity, and Impaired β-Cell Function Relative to Adipose Tissue Insulin Sensitivity in Obese Youth With Impaired Glucose Tolerance.
Despite evidence of insulin resistance and β-cell dysfunction in glucose metabolism in youth with prediabetes, the relationship between adipose tissue insulin sensitivity (ATIS) and β-cell function remains unknown. We investigated whole-body lipolysis, ATIS, and β-cell function relative to ATIS (adipose disposition index [DI]) in obese youth with impaired glucose tolerance (IGT) versus normal glucose tolerance (NGT). Whole-body lipolysis (glycerol appearance rate [GlyRa], [2H5]glycerol at baseline and during a hyperinsulinemic-euglycemic clamp), lipid oxidation (indirect calorimetry), insulin secretion (2-h hyperglycemic clamp), and body composition (dual-energy X-ray absorptiometry) were examined. Adipose DI was calculated as ATIS: (1/GlyRa × fasting insulin) × first-phase insulin secretion. Despite similar percent body fat, youth with IGT versus NGT had higher GlyRa, lower ATIS at baseline and during hyperinsulinemia, and higher lipid oxidation. Adipose DI was ∼43% lower in youth with IGT and correlated positively with glucose DI. The lower ATIS and diminished adipose DI in IGT versus NGT is in line with the compromised glucose metabolism reflected in impaired β-cell function relative to peripheral insulin resistance. We conclude that youth with IGT manifest a global decline in insulin sensitivity, including impaired insulin action in suppressing lipolysis and lipid oxidation, accompanied by β-cell dysfunction in fat and glucose metabolism, enhancing their risk of type 2 diabetes.


Prediction of invasion from the early stage of an epidemic.
Predictability of undesired events is a question of great interest in many scientific disciplines including seismology, economy and epidemiology. Here, we focus on the predictability of invasion of a broad class of epidemics caused by diseases that lead to permanent immunity of infected hosts after recovery or death. We approach the problem from the perspective of the science of complexity by proposing and testing several strategies for the estimation of important characteristics of epidemics, such as the probability of invasion. Our results suggest that parsimonious approximate methodologies may lead to the most reliable and robust predictions. The proposed methodologies are first applied to analysis of experimentally observed epidemics: invasion of the fungal plant pathogen Rhizoctonia solani in replicated host microcosms. We then consider numerical experiments of the susceptible-infected-removed model to investigate the performance of the proposed methods in further detail. The suggested framework can be used as a valuable tool for quick assessment of epidemic threat at the stage when epidemics only start developing. Moreover, our work amplifies the significance of the small-scale and finite-time microcosm realizations of epidemics revealing their predictive power.


Cloning and functional characterization of human SMCT2 (SLC5A12) and expression pattern of the transporter in kidney.
Recently, we cloned two Na(+)-coupled lactate transporters from mouse kidney, a high-affinity transporter (SMCT1 or slc5a8) and a low-affinity transporter (SMCT2 or slc5a12). Here we report on the cloning and functional characterization of human SMCT2 (SLC5A12) and compare the immunolocalization patterns of slc5a12 and slc5a8 in mouse kidney. The human SMCT2 cDNA codes for a protein consisting of 618 amino acids. When expressed in mammalian cells or Xenopus oocytes, human SMCT2 mediates Na(+) -coupled transport of lactate, pyruvate and nicotinate. The affinities of the transporter for these substrates are lower than those reported for human SMCT1. Several non-steroidal anti-inflammatory drugs inhibit human SMCT2-mediated nicotinate transport, suggesting that NSAIDs interact with the transporter as they do with human SMCT1. Immunofluorescence microscopy of mouse kidney sections with an antibody specific for SMCT2 shows that the transporter is expressed predominantly in the cortex. Similar studies with an anti-SMCT1 antibody demonstrate that SMCT1 is also expressed mostly in the cortex. Dual-labeling of SMCT1 and SMCT2 with 4F2hc (CD98), a marker for basolateral membrane of proximal tubular cells in the S1 and S2 segments of the nephron, shows that both SMCT1 and SMCT2 are expressed in the apical membrane of the tubular cells. These studies also show that while SMCT2 is broadly expressed along the entire length of the proximal tubule (S1/S2/S3 segments), the expression of SMCT1 is mostly limited to the S3 segment. These studies suggest that the low-affinity transporter SMCT2 initiates lactate absorption in the early parts of the proximal tubule followed by the participation of the high-affinity transporter SMCT1 in the latter parts of the proximal tubule.


Impact of upper limb complex regional pain syndrome type 1 on everyday life measured with a novel upper limb-activity monitor.
Complex regional pain syndrome type 1 (CRPS1) often leads to serious activity limitations in everyday life. To date, however, limitations in patients with CRPS1 of an upper limb have not been objectively measured.Therefore, the aim of this study was to determine the long-term impact of upper limb CRPS1 on general mobility and upper limb usage during everyday life, as measured with a novel upper limb-activity monitor (ULAM). In ten female chronic CRPS1 patients and ten healthy control subjects, 24-h activity patterns were measured with the ULAM. This ULAM consists of body-fixed acceleration sensors, connected to a recorder worn around the waist. The ULAM automatically detects upper limb activity during mobility-related activities. Several outcome measures related to general mobility and upper limb usage were compared between patients and controls. The results showed that CRPSI in the dominant upper limb had modest impact on general mobility; i.e. on the percentages spent in body positions and body motions and on mean intensity of body activity. For upper limb usage outcome measures during sitting, there was a marked difference between CRPS1 patients and controls. Especially patients with dominant side involvement clearly showed less activity of their involved limb during sitting, indicated by significant differences for the mean intensity (P=0.014), percentage (P=0.004), and proportion (P=0.032) of upper limb activity. It is concluded that these ten chronic CRPS1 patients still had limitations in upper limb usage during everyday life, 3.7 years (average) after the causative event.


Synthesis of Non-Racemic Pyrazolines and Pyrazolidines by [3+2] Cycloadditions of Azomethine Imines.
Asymmetric [3+2] cycloadditions of azomethine imines comprise a useful synthetic tool for the construction of pyrazole derivatives with a variable degree of saturation and up to three stereogenic centers. As analogues of pyrrolidines and imidazolidines that are abundant among natural products, pyrazoline and pyrazolidine derivatives represent attractive synthetic targets due to their extensive applications in the chemical and medicinal industries. Following the increased understanding of the mechanistic aspect of metal-catalyzed and organocatalyzed [3+2] cycloadditions of 1,3-dipoles gained over recent years, significant strides have been taken to design and develop new protocols that proceed efficiently under mild synthetic conditions and duly benefit from superior functional group tolerance and selectivity. In this review, we represent the current state of the art in this field and detailed methods for the synthesis of non-racemic pyrazolines and pyrazolidines via [3+2] metal and organocatalyzed transformations reported since the seminal work of Kobayashi et al. and Fu et al. in 2002 and 2003 up to the end of year 2017.


Calmodulin-binding transcription activator 1 (CAMTA1) alleles predispose human episodic memory performance.
Little is known about the genes and proteins involved in the process of human memory. To identify genetic factors related to human episodic memory performance, we conducted an ultra-high-density genome-wide screen at > 500 000 single nucleotide polymorphisms (SNPs) in a sample of normal young adults stratified for performance on an episodic recall memory test. Analysis of this data identified SNPs within the calmodulin-binding transcription activator 1 (CAMTA1) gene that were significantly associated with memory performance. A follow up study, focused on the CAMTA1 locus in an independent cohort consisting of cognitively normal young adults, singled out SNP rs4908449 with a P-value of 0.0002 as the most significant associated SNP in the region. These validated genetic findings were further supported by the identification of CAMTA1 transcript enrichment in memory-related human brain regions and through a functional magnetic resonance imaging experiment on individuals matched for memory performance that identified CAMTA1 allele-specific upregulation of medial temporal lobe brain activity in those individuals harboring the 'at-risk' allele for poorer memory performance. The CAMTA1 locus encodes a purported transcription factor that interfaces with the calcium-calmodulin system of the cell to alter gene expression patterns. Our validated genomic and functional biological findings described herein suggest a role for CAMTA1 in human episodic memory.


Comparison of serological and molecular tests for detection of Trypanosoma evansi in domestic animals from Ghardaïa district, South Algeria.
Trypanosoma evansi (T. evansi) is a hemoflagellate parasite that affects a broad range of mammalian hosts and that causes a disease called surra. Diagnosis of surra based on clinical symptoms alone is inaccurate. Therefore, a variety of serological and molecular diagnostic tests are used to assist in the detection of T. evansi infections. The aim of this study was to compare the diagnostic performance of four serological tests (CATT/T.evansi, immune trypanolysis, ELISA with purified variant surface glycoprotein RoTat 1.2 and with whole cell lysate) and two molecular PCR tests targeting sequences within the ribosomal genes locus (ITS1 TD PCR and 18S qPCR). Tests were carried out on blood samples from 161 dromedary camels, 93 horses, 129 goats, 168 sheep, 127 bovines and 76 dogs. Latent class analysis was carried out to calculate the sensitivity and specificity of each diagnostic test. Cohen's Kappa test was used to assess the concordance between the different diagnostic tests. Overall positivity rates observed with the serological tests were as follows: 3.1 % with CATT/T.evansi, 4.9 % with ELISA/RoTat 1.2, 3.4 % with ELISA/whole lysate and 2.0 % with immune trypanolysis (TL). Among the 754 samples tested with the molecular tests, 1.7 % were positive with 18S qPCR and 1.3 % with ITS1 TD PCR. Cohen's Kappa test showed agreement ranging from fair to substantial (k = 0.2-0.8) between serological diagnostic tests. However, it showed a perfect agreement (k = 0.868) between molecular diagnostic tests. Latent class analysis showed that all serological tests were 100 % sensitive, in contrast to the molecular tests with 47 % sensitivity. All tests, though, were highly specific (≥ 97 %). Given the persistence of circulating antibodies after cure, detectable by serological tests, it is recommend combining a serological and a molecular diagnostic test for accurate diagnosis of infection with T. evansi in domestic animals.


Transformation of tetrachloromethane to dichloromethane and carbon dioxide by Acetobacterium woodii.
Five anaerobic bacteria were tested for their abilities to transform tetrachloromethane so that information about enzymes involved in reductive dehalogenations of polychloromethanes could be obtained. Cultures of the sulfate reducer Desulfobacterium autotrophicum transformed some 80 microM tetrachloromethane to trichloromethane and a small amount of dichloromethane in 18 days under conditions of heterotrophic growth. The acetogens Acetobacterium woodii and Clostridium thermoaceticum in fructose-salts and glucose-salts media, respectively, degraded some 80 microM tetrachloromethane completely within 3 days. Trichloromethane accumulated as a transient intermediate, but the only chlorinated methanes recovered at the end of the incubation were 8 microM dichloromethane and traces of chloromethane. Desulfobacter hydrogenophilus and an autotrophic, nitrate-reducing bacterium were unable to transform tetrachloromethane. Reduction of chlorinated methanes was thus observed only in the organisms with the acetyl-coenzyme A pathway. Experiments with [14C]tetrachloromethane were done to determine the fate of this compound in the acetogen A. woodii. Radioactivity in an 11-day heterotrophic culture was largely (67%) recovered in CO2, acetate, pyruvate, and cell material. In experiments with cell suspensions to which [14C]tetrachloromethane was added, 14CO2 appeared within 20 s as the major transformation product. A. woodii thus catalyzes reductive dechlorinations and transforms tetrachloromethane to CO2 by a series of unknown reactions.


Effectiveness of self-testing kits availability on improving HIV testing frequency for chinese men who have sex with men and their sexual partners: a protocol for a multicenter randomised controlled trial.
HIV epidemic is increasing among men who have sex with men (MSM) in China, yet HIV testing uptake remains low. As an emerging approach, HIV self-testing (HIVST) has the potential to promote HIV testing coverage and frequency in this population. However, evidence of the effectiveness on implementation of HIVST among Chinese MSM and their sexual partners is scarce. The randomised controlled trial will be performed in Changsha, Changde, Shaoyang and Yiyang, Hunan province, China, recruiting 184 recent testers (men who had at least one HIV test within the past 2 years) and 26 non-recent testers (men who did not have HIV tests within 2 years or never had an HIV test). Eligible men will be randomly divided 1:1 into two groups: intervention (with free HIVST kits plus site-based HIV testing services) and control (site-based HIV testing services only). Participants in the intervention group will be provided with two free finger-prick-based HIVST kits, and can apply for two to four kits every 3 months for 1 year.Participants in both groups will complete questionnaires via WeChat at five separate times: baseline, third, sixth, ninth and twelfth month. The primary outcome is the mean number of HIV tests for MSM over the 12-month study period. The secondary outcome is the mean number of HIV tests for sexual partners of MSM over the 12-month study period. The tertiary outcomes are the self-reported proportion of consistent condom usage for anal sex, and the numbers of sexual partners during the 12-month study period. The study has been approved by the Institutional Review Board of Behavioural and Nursing Research in Xiangya School of Nursing of Central South University, China (2018002). Study results will be disseminated through conferences and academic journals. ChiCTR1800015584; Pre-results.


Increased prevalence of cysticercosis and taeniasis among professional fried pork vendors and the general population of a village in the Peruvian highlands. Cysticercosis Working Group in Peru.
Two different populations in Saylla, a Peruvian village near Cusco, known for chicharrones, a local pork dish, were surveyed by serology and stool examination to determine the prevalence and epidemiologic characteristics of Taenia solium infection. Group I (n=43), the chicharroneros, were members of families professionally devoted to the making and selling of chicharrones, and Group II (n=102) was a sample of the general population of the same village. Unlike people in Group I, general villagers only occasionally prepare or sell this food product, and then only to their neighbors or relatives. The prevalence of taeniasis was extremely high (8.6%) for the chicharroneros and 3% for the general villagers. Seroprevalence for cysticercosis by immunoblot was similarly high in both groups (23.3% and 23.8%, respectively). Being female, older than 30, and having daily contact with pork were factors strongly associated with a positive serologic result for cysticercosis in the chicharroneros, whereas males were more frequently seropositive in the general villagers group. Antibody reaction to more antigen bands in immunoblots and neurologic symptoms were more common among the chicharroneros. Also, in the general villagers group, seroprevalence increased with each exposure factor, ranging from 9.4% in individuals who did not raise pigs to 50% in the small subgroup that raised pigs, butchered their own animals, sold pork, and sold chicharrones, suggesting that these activities are related to increased risk for tapeworm or larval infection.


[Evaluation of the effect of tobacco on trandolapril tolerance].
The objective of this study was to evaluate the impact of smoking habits on safety of trandolapril assessed by interrogation and by visual analogue scales (VAS). A total of 3402 hypertensive smokers (> or = 1 cigarette/d for at least 6 months) and non-smokers (no smoking or ceased at least 6 months previously) received trandolapril 2 mg/d for 4 weeks. The safety profile of trandolapril was assessed by both interrogation and by VAS. The VAS completed by the patients at D0 and D28 explored the following symptoms: asthenia, nausea, cough, headaches and dizziness. A significant change in cough VAS was previously defined by an at least 19 mm change. VAS analysis was performed on 2840 patients (1296 smokers and 1544 non-smokers), mean age 59 +/- 12 years. Smokers and non-smokers were significantly different for age 56 +/- 12 years vs. 62 +/- 12 years, sex ratio 74 per cent males vs. 45 per cent, history of hypertension 4.5 +/- 6.1 years vs. 5.3 +/- 6.5 years and cough VAS score at D0 35 +/- 26 mm vs. 20 +/- 21 mm. In the total population, 214 adverse events were reported by 177 patients (5.2 per cent). The most frequent adverse events were a cough (2.1 per cent), bronchitis (0.6 per cent), headaches (0.5 per cent), rhinitis (0.4 per cent), nausea (0.4 per cent) and asthenia (0.3 per cent). Cough was reported by 23 smokers (1.5 per cent) and by 49 (2.6 per cent) non-smokers (p = 0.02). In the VAS population, 151 adverse events were reported by 130 patients, 47 smokers (3.6 per cent) and 83 non-smokers (5.4 per cent, p = 0.03). The difference between the two groups was mainly due to a cough: 15 smokers (1.2 per cent) reported a cough vs. 38 non-smokers (2.5 per cent, p = 0.01) and 77 smokers (5.9 per cent) presented a significant change of cough VAS score vs. 124 non-smokers (8.0 per cent, p = 0.03). In this large scale study, 1.9 per cent of patients treated with trandolapril exhibited a cough. Smokers were less likely to present a cough. Use of VAS confirmed this trend.


The severity of pandemic H1N1 influenza in the United States, from April to July 2009: a Bayesian analysis.
Accurate measures of the severity of pandemic (H1N1) 2009 influenza (pH1N1) are needed to assess the likely impact of an anticipated resurgence in the autumn in the Northern Hemisphere. Severity has been difficult to measure because jurisdictions with large numbers of deaths and other severe outcomes have had too many cases to assess the total number with confidence. Also, detection of severe cases may be more likely, resulting in overestimation of the severity of an average case. We sought to estimate the probabilities that symptomatic infection would lead to hospitalization, ICU admission, and death by combining data from multiple sources. We used complementary data from two US cities: Milwaukee attempted to identify cases of medically attended infection whether or not they required hospitalization, while New York City focused on the identification of hospitalizations, intensive care admission or mechanical ventilation (hereafter, ICU), and deaths. New York data were used to estimate numerators for ICU and death, and two sources of data--medically attended cases in Milwaukee or self-reported influenza-like illness (ILI) in New York--were used to estimate ratios of symptomatic cases to hospitalizations. Combining these data with estimates of the fraction detected for each level of severity, we estimated the proportion of symptomatic patients who died (symptomatic case-fatality ratio, sCFR), required ICU (sCIR), and required hospitalization (sCHR), overall and by age category. Evidence, prior information, and associated uncertainty were analyzed in a Bayesian evidence synthesis framework. Using medically attended cases and estimates of the proportion of symptomatic cases medically attended, we estimated an sCFR of 0.048% (95% credible interval [CI] 0.026%-0.096%), sCIR of 0.239% (0.134%-0.458%), and sCHR of 1.44% (0.83%-2.64%). Using self-reported ILI, we obtained estimates approximately 7-9 x lower. sCFR and sCIR appear to be highest in persons aged 18 y and older, and lowest in children aged 5-17 y. sCHR appears to be lowest in persons aged 5-17; our data were too sparse to allow us to determine the group in which it was the highest. These estimates suggest that an autumn-winter pandemic wave of pH1N1 with comparable severity per case could lead to a number of deaths in the range from considerably below that associated with seasonal influenza to slightly higher, but with the greatest impact in children aged 0-4 and adults 18-64. These estimates of impact depend on assumptions about total incidence of infection and would be larger if incidence of symptomatic infection were higher or shifted toward adults, if viral virulence increased, or if suboptimal treatment resulted from stress on the health care system; numbers would decrease if the total proportion of the population symptomatically infected were lower than assumed.


Functional properties of a unique subset of cytotoxic CD3+ T lymphocytes that express Fc receptors for IgG (CD16/Leu-11 antigen).
A subset of peripheral blood T lymphocytes coexpressing CD3 and IgG Fc receptors (FcR) (CD16/Leu-11 antigen) have been identified, isolated, and functionally characterized. The CD3+, CD16+ cells were established in short-term culture using growth medium containing interleukin 2 (IL-2). Both the freshly isolated cells and the cultured cell line stably expressed the CD3+, CD16+ phenotype. Furthermore, a majority of these T cells lacked either CD4 or CD8 expression. Like in vitro-activated cytotoxic T lymphocytes and natural killer (NK) cells, the CD3+, CD16+ cells showed numerous azurophilic granules. Although these cells failed to mediate significant levels of NK cell-mediated cytotoxicity even after stimulation with IL-2, they efficiently functioned as effectors of antibody-dependent cellular cytotoxicity (ADCC). The Ig isotype specificity of the ADCC was analyzed using an isotype switch-variant family of a murine anti-HLA monoclonal antibody (mAb). Similar to the CD3-, CD16+ NK cell population, the CD3+, CD16+ T cells preferentially used the IgG2a antibody to mediate ADCC. The CD3+, CD16+ cells demonstrated a proliferative response when cocultured with either a NK-sensitive tumor cell line, K562, or a NK-insensitive B lymphoblastoid cell line, CCRF-SB. The response against CCRF-SB was significantly inhibited by anti-IL-2 receptor antibody, whereas the response against K562 was only partially diminished. Cytotoxicity was also induced in the CD3+, CD16+ population by the presence of anti-CD3 mAb, indicating that cytotoxicity can be triggered by stimulation via the CD3-T cell antigen receptor complex. By isolating these CD3+, CD16+ cells from the peripheral blood of a normal, healthy individual, it has been possible to extensively study the morphology, antigenic phenotype, and functional behavior of this unique subset of T lymphocytes expressing IgG FcR.


Bioavailability of vitamin D2 from enriched mushrooms in prediabetic adults: a randomized controlled trial.
Based on the growing evidence of risk reduction from fresh fruit and vegetable consumption and an inverse relationship between serum 25-hydroxyvitamin D (25OHD) and the risk of type 2 diabetes (T2D), we determined the benefits of regularly consuming vitamin D-enriched mushrooms in a prediabetic cohort. Exposing edible mushrooms to ultraviolet B (UVB) light increases vitamin D2 (D2) and raises serum 25OHD2 in healthy young adults; however, their benefit to deficient prediabetics and glucose metabolism remains untested. Forty-three prediabetic, D-deficient adults (25OHD≤20 ng/ml), BMI>25 were randomized to four groups consuming daily entrées containing 100 g fresh sliced cooked mushrooms prepared by a chef for 16 weeks. Two groups were fed UVB-treated mushrooms initially containing: 600 IU D2 or 4000 IU D2; each one also received one capsule of placebo daily. Two control groups were fed untreated mushrooms and D3 dietary supplements at two label doses: 600 IU D3 and 4000 IU D3. D2 and D3 content were analyzed in mushrooms, before and after cooking and in over-the-counter supplements. After 16 weeks, both D2-UVB-mushroom entrée doses, which were significantly lower after cooking, produced modest or no increases in 25OHD2 or total 25OHD relative to the positive control subjects who actually consumed about 1242 and 7320 IU per day of D3 (higher than stated on the label). Unanticipated D2 cooking loss from fresh UVB mushrooms and probable low absorption and/or hydroxylation may explain the smaller increase in 25OHD2 in our prediabetic overweight/obese cohort compared with past findings in younger, healthy subjects. Moreover, no dose or vitamin D source was associated with modifying T2D risk factors.


Cardiopulmonary exercise capacity and preoperative markers of inflammation.
Explanatory mechanisms for the association between poor exercise capacity and infections following surgery are underexplored. We hypothesized that aerobic fitness-assessed by cardiopulmonary exercise testing (CPET)-would be associated with circulating inflammatory markers, as quantified by the neutrophil-lymphocyte ratio (NLR) and monocyte subsets. The association between cardiopulmonary reserve and inflammation was tested by multivariable regression analysis with covariates including anaerobic threshold (AT) and malignancy. In a first cohort of 240 colorectal patients, AT was identified as the sole factor associated with higher NLR (P = 0.03) and absolute and relative lymphopenia (P = 0.01). Preoperative leukocyte subsets and monocyte CD14(+) expression (downregulated by endotoxin and indicative of chronic inflammation) were also assessed in two further cohorts of age-matched elective gastrointestinal and orthopaedic surgical patients. Monocyte CD14(+) expression was lower in gastrointestinal patients (n = 43) compared to age-matched orthopaedic patients (n = 31). The circulating CD14(+)CD16(-) monocyte subset was reduced in patients with low cardiopulmonary reserve. Poor exercise capacity in patients without a diagnosis of heart failure is independently associated with markers of inflammation. These observations suggest that preoperative inflammation associated with impaired cardiorespiratory performance may contribute to the pathophysiology of postoperative outcome.


Chlorproguanil/dapsone for uncomplicated Plasmodium falciparum malaria in young children: pharmacokinetics and therapeutic range.
The disposition of chlorproguanil/dapsone (one daily dose for 3 d of 1.2 and 2.4 mg/kg respectively) has been studied in young children with Plasmodium falciparum malaria, to provide data complementary to a clinical trial of this drug combination. Unbound concentrations of chlorcycloguanil (the active metabolite of chlorproguanil) and dapsone in clinical samples have been related to the unbound drug concentrations which produced defined outcomes in tests in vitro of drug efficacy and toxicity. Twelve children with uncomplicated malaria were treated: all cleared parasitaemia within 72 h and made uneventful recoveries. After the first dose of chlorproguanil/dapsone the maximum unbound chlorcycloguanil concentration in clinical samples (19 ng/mL [about 60 nM]) was 2 orders of magnitude above the 50% inhibitory concentration (IC50) value for this drug against the K39 stain of P. falciparum, while falling 2 orders of magnitude below its IC50 against human bone marrow cells; the maximum unbound dapsone concentration in clinical samples (160 ng/mL [about 645 nM]) was 10-fold higher than its IC50 against the K39 strain. However, because of the rapid elimination of chlorproguanil from the body (half-life 12.6 +/- 6.3 h), the minimum fractional inhibitory concentrations of unbound chlorcycloguanil/dapsone against the K39 strain were probably exceeded for no more than 6 d. These data, together with the clinical trial, will be helpful in deciding whether current chlorproguanil/dapsone doses are optimal for the treatment of falciparum malaria.