Search

Controlling feeding practices, such as pressure to eat, are associated with a child's disinhibited eating and extremes in bodyweight. We aimed to explore which factors are associated with parent dyads' pressuring feeding practices, including how mothers and fathers perceive the sharing of household tasks such as mealtime and child feeding responsibilities. In this cross-sectional study, parent dyads (mother and father) of healthy preschool-aged children completed an identical questionnaire consisting of measures of picky eating (food fussiness subscale of Child Eating Behavior Questionnaire), parental concern for undereating, and pressure to eat (Child Feeding Questionnaire). We used separate multivariable linear regression models for mothers and fathers to assess correlates associated with pressure to eat subscale score, including slowness of eating and enjoyment of food, child BMI z-score and race/ethnicity, and household income. Separate unadjusted linear regression models for mothers and fathers were used to report the association of pressure to eat with household responsibilities. Parents (N = 88) had similar mean picky eating, concern for undereating, and pressure to eat scores; more fathers had high pressure to eat scores (36% vs 27%). Higher pressure to eat was significantly associated with lower income, non-Hispanic Black or Black race/ethnicity, slow eating, and lower enjoyment of food. Pressure was not associated with household responsibilities. While there were similar maternal and paternal perceptions of child eating behaviors, more fathers reported pressuring their child to eat. Identifying differences in parental feeding practices may assist in intervention development to improve feeding practices.

ObjectiveThe aim of the study is to investigate the effects of icodextrin on the risks of death, technique failure and the first episode of peritonitis in peritoneal dialysis (PD) patients.MethodsFrom medical records of a medical center in Taiwan, a total of 725 newly diagnosed end-stage kidney disease patients receiving PD for at least 90 days from January 1, 2007 to December 31, 2018 were identified. These patients were grouped as 190 icodextrin users and 535 non-users. Users were defined as utilization of icodextrin for ≥ 50% of their PD duration. The use of icodextrin was considered a time-varying exposure in the Cox proportional hazard model. The risks of death, technique failure and the first episode of peritonitis were compared between two cohorts by the end of 2018.ResultsCompared to the non-users, the icodextrin users had significant lower risks of mortality (6.5 vs.7.2 per 100 person-years; adjusted HR = 0.62, 95% CI = 0.42-0.91) and technique failure (12.7 vs. 15.2 per 100 person-years; adjusted HR = 0.61, 95% CI = 0.47-0.81), and the first peritonitis episode (5.0 vs. 17.0 per 100 person-years; adjusted HR = 0.22, 95% CI = 0.14-0.35). The risk of peritonitis reduced further in icodextrin users with diabetes and with cardiovascular disease.ConclusionIcodextrin was associated with lower risks of mortality, technique failure, and the first episode of peritonitis.

Commuters who spend long hours on roads are exposed to high levels of traffic related air pollutants (TRAPs). Despite some well-known multiple adverse effects of TRAPs on human health, limited studies have focused on mitigation strategies to reduce these effects. In this study, we measured fine particulate matter (PM2.5) and ultrafine particle (UFP) concentrations inside and outside 17 taxis simultaneously while they were driven on roadways. The drivers' urinary monohydroxylated polycyclic aromatic hydrocarbons (OH-PAHs) and malondialdehyde (MDA) concentrations just before and right after the driving tests were also determined. Data were collected under three driving conditions (i.e. no mitigation (NM), window closed (WC), and window closed plus using high efficiency cabin air filters (WC+HECA)) for each taxi and driver. The results show that, compared to NM, the WC+HECA reduced in-cabin PM2.5 and UFP concentrations, by 37% and 47% respectively (p < 0.05), whereas the reductions on PAH exposures were insignificant. Although nonsignificant, a reduction of 17% was also observed in the drivers' urinary MDA under WC+HECA. The MDA concentrations were found to be significantly associated with the in-cabin PM2.5 and UFP concentrations, suggesting the reduction of the drivers' lipid peroxidation can be at least partially attributed to the PM2.5 and UFP reduction by WC+HECA. Overall, these results suggest HECA filters have potential to reduce particle levels inside taxis and protect drivers' health.

Patients with hematologic malignancies have poor outcomes from COVID infection and are less likely to mount an antibody response after COVID infection. This is a retrospective study of adult lymphoma patients who received the COVID vaccine between 12/1/2020 and 11/30/2021. The primary endpoint was a positive anti-COVID spike protein antibody level following the primary COVID vaccination series. The primary vaccination series was defined as 2 doses of the COVID mRNA vaccines or 1 dose of the COVID adenovirus vaccine. Subgroups were compared using Fisher's exact test, and unadjusted and adjusted logistic regression models were used for univariate and multivariate analyses. A total of 243 patients were included in this study; 72 patients (30%) with indolent lymphomas; 56 patients (23%) with Burkitt's, diffuse large B-cell lymphoma (DLBCL), and primary mediastinal B-cell lymphoma (PMBL) combined; 55 patients (22%) with chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL); 44 patients (18%) with Hodgkin and T-cell lymphomas (HL/TCL) combined; 12 patients (5%) with mantle cell lymphoma; and 4 patients (2%) with other lymphoma types. One-hundred fifty-eight patients (65%) developed anti-COVID spike protein antibodies after completing the primary COVID vaccination series. Thirty-eight of 46 (83%) patients who received an additional primary shot and had resultant levels produced anti-COVID spike protein antibodies. When compared to other lymphoma types, patients with CLL/SLL had a numerically lower seroconversion rate of 51% following the primary vaccination series whereas patients with HL/TCL appeared to have a robust antibody response with a seropositivity rate of 77% (p = 0.04). Lymphoma patients are capable of mounting a humoral response to the COVID vaccines. Further studies are required to confirm our findings, including whether T-cell immunity would be of clinical relevance in this patient population.

Introduction Common anesthesia practice for hand surgery combines a preoperative regional anesthetic and intraoperative monitored anesthesia care (MAC). Despite adequate regional anesthesia, patients may receive doses of intraoperative sedatives which can result in oversedation and potentially avoidable complications. VR could prove to be a valuable tool for patients and providers by distracting the mind from processing noxious stimuli resulting in minimized sedative use and reduced risk of oversedation without negatively impacting patient satisfaction. Our hypothesis was that intraoperative VR use reduces sedative dosing during elective hand surgery without detracting from patient satisfaction as compared to a usual care control. Methods Forty adults undergoing hand surgery were randomized to receive either intraoperative VR in addition to MAC, or usual MAC. Patients in both groups received preoperative regional anesthesia at provider discretion. Intraoperatively, the VR group viewed programming of their choice via a head-mounted display. The primary outcome was intraoperative propofol dose per hour (mg · hr-1). Secondary outcomes included patient reported pain and anxiety, overall satisfaction, functional outcome, and post anesthesia care unit (PACU) length of stay (LOS). Results Of the 40 enrolled patients, 34 completed the perioperative portion of the trial. VR group patients received significantly less propofol per hour than the control group (Mean (±SD): 125.3 (±296.0) vs 750.6 (±334.6) mg · hr-1, pConclusion VR immersion during hand surgery led to significant reductions in intraoperative propofol dose and PACU LOS without negatively impacting key patient reported outcomes.

Introduction COVID-19 infection has been hypothesized to precipitate venous and arterial clotting events more frequently than other illnesses. Materials and methods We demonstrate this increased risk of blood clots by comparing rates of venous and arterial clotting events in 4400 hospitalized COVID-19 patients in a large multisite clinical network in the United States examined from April through June of 2020, to patients hospitalized for non-COVID illness and influenza during the same time period and in 2019. Results We demonstrate that COVID-19 increases the risk of venous thrombosis by two-fold compared to the general inpatient population and compared to people with influenza infection. Arterial and venous thrombosis were both common occurrences among patients with COVID-19 infection. Risk factors for thrombosis included male gender, older age, and diabetes. Patients with venous or arterial thrombosis had high rates of admission to the ICU, re-admission to the hospital, and death. Conclusion Given the ongoing scientific discussion about the impact of clotting on COVID-19 disease progression, these results highlight the need to further elucidate the role of anticoagulation in COVID-19 patients, particularly outside the intensive care unit setting. Additionally, concerns regarding clotting and COVID-19 vaccines highlight the importance of addressing the alarmingly high rate of clotting events during actual COVID-19 infection when weighing the risks and benefits of vaccination.

Attitudes toward aggression is a controversial phenomenon in psychiatry. This study examined and compared attitudes toward patient aggression in psychiatric hospitals from the perspectives of nurses, patients and informal caregivers and identified factors associated to these attitudes. A total of 2,424 participants completed a self-reported instrument regarding attitudes toward aggression (12-items Perception of Aggression Scale; POAS-S). We analysed data from nurses (n = 782), patients (n = 886), and informal caregivers (n = 765). Pearson's r correlations were used to examine associations between variables. Differences between group scores were analysed using ANOVA/MANOVA with post-hoc Sheffe tests. Multivariate logistic regression models and logistic regression analysis were used to examine the effects of respondents' characteristics on their attitudes toward aggression. Nurses had significantly more negative and less tolerant perceptions toward aggression (mean [SD] 47.1 [7.5], p

The 2014-2015 Ebola outbreak is the largest and most widespread to date. In order to estimate ongoing transmission in the affected countries, we estimated the weekly average number of secondary cases caused by one individual infected with Ebola throughout the infectious period for each affected West African country using a stochastic hidden Markov model fitted to case data from the World Health Organization. If the average number of infections caused by one Ebola infection is less than 1.0, the epidemic is subcritical and cannot sustain itself. The epidemics in Liberia and Sierra Leone have approached subcriticality at some point during the epidemic; the epidemic in Guinea is ongoing with no evidence that it is subcritical. Response efforts to control the epidemic should continue in order to eliminate Ebola cases in West Africa.

BackgroundPatients with symptomatic intracranial atherosclerosis (ICAS) of ≥ 70% luminal stenosis are at high risk of stroke recurrence. We aimed to evaluate the relationships between hemodynamics of ICAS revealed by computational fluid dynamics (CFD) models and risk of stroke recurrence in this patient subset.MethodsPatients with a symptomatic ICAS lesion of 70-99% luminal stenosis were screened and enrolled in this study. CFD models were reconstructed based on baseline computed tomographic angiography (CTA) source images, to reveal hemodynamics of the qualifying symptomatic ICAS lesions. Change of pressures across a lesion was represented by the ratio of post- and pre-stenotic pressures. Change of shear strain rates (SSR) across a lesion was represented by the ratio of SSRs at the stenotic throat and proximal normal vessel segment, similar for the change of flow velocities. Patients were followed up for 1 year.ResultsOverall, 32 patients (median age 65; 59.4% males) were recruited. The median pressure, SSR and velocity ratios for the ICAS lesions were 0.40 (-2.46-0.79), 4.5 (2.2-20.6), and 7.4 (5.2-12.5), respectively. SSR ratio (hazard ratio [HR] 1.027; 95% confidence interval [CI], 1.004-1.051; P = 0.023) and velocity ratio (HR 1.029; 95% CI, 1.002-1.056; P = 0.035) were significantly related to recurrent territorial ischemic stroke within 1 year by univariate Cox regression, respectively with the c-statistics of 0.776 (95% CI, 0.594-0.903; P = 0.014) and 0.776 (95% CI, 0.594-0.903; P = 0.002) in receiver operating characteristic analysis.ConclusionsHemodynamics of ICAS on CFD models reconstructed from routinely obtained CTA images may predict subsequent stroke recurrence in patients with a symptomatic ICAS lesion of 70-99% luminal stenosis.

ObjectivesThe development of a prognostic mortality risk model for hospitalized COVID-19 patients may facilitate patient treatment planning, comparisons of therapeutic strategies, and public health preparations.MethodsWe retrospectively reviewed the electronic health records of patients hospitalized within a 13-hospital New Jersey USA network between March 1, 2020 and April 22, 2020 with positive polymerase chain reaction results for SARS-CoV-2, with follow-up through May 29, 2020. With death or hospital discharge by day 40 as the primary endpoint, we used univariate followed by stepwise multivariate proportional hazard models to develop a risk score on one-half the data set, validated on the remainder, and converted the risk score into a patient-level predictive probability of 40-day mortality based on the combined dataset.ResultsThe study population consisted of 3123 hospitalized COVID-19 patients; median age 63 years; 60% were men; 42% had >3 coexisting conditions. 713 (23%) patients died within 40 days of hospitalization for COVID-19. From 22 potential candidate factors 6 were found to be independent predictors of mortality and were included in the risk score model: age, respiratory rate ≥25/minute upon hospital presentation, oxygenation ConclusionsA risk score using six variables is able to prognosticate mortality within 40-days of hospitalization for COVID-19.Trial registrationClinicaltrials.gov Identifier: NCT04347993.

BackgroundThe COVID-19 pandemic remains a significant global threat. However, despite urgent need, there remains uncertainty surrounding best practices for pharmaceutical interventions to treat COVID-19. In particular, conflicting evidence has emerged surrounding the use of hydroxychloroquine and azithromycin, alone or in combination, for COVID-19. The COVID-19 Evidence Accelerator convened by the Reagan-Udall Foundation for the FDA, in collaboration with Friends of Cancer Research, assembled experts from the health systems research, regulatory science, data science, and epidemiology to participate in a large parallel analysis of different data sets to further explore the effectiveness of these treatments.MethodsElectronic health record (EHR) and claims data were extracted from seven separate databases. Parallel analyses were undertaken on data extracted from each source. Each analysis examined time to mortality in hospitalized patients treated with hydroxychloroquine, azithromycin, and the two in combination as compared to patients not treated with either drug. Cox proportional hazards models were used, and propensity score methods were undertaken to adjust for confounding. Frequencies of adverse events in each treatment group were also examined.ResultsNeither hydroxychloroquine nor azithromycin, alone or in combination, were significantly associated with time to mortality among hospitalized COVID-19 patients. No treatment groups appeared to have an elevated risk of adverse events.ConclusionAdministration of hydroxychloroquine, azithromycin, and their combination appeared to have no effect on time to mortality in hospitalized COVID-19 patients. Continued research is needed to clarify best practices surrounding treatment of COVID-19.

Giant clams live in symbiosis with phototrophic dinoflagellates, which reside extracellularly inside zooxanthellal tubules located mainly in the colourful and extensible outer mantle. As symbiotic dinoflagellates have no access to the ambient seawater, they need to obtain inorganic carbon (Ci) from the host for photosynthesis during illumination. The outer mantle has a host-mediated and light-dependent carbon-concentrating mechanism to augment the supply of Ci to the symbionts during illumination. Iridocytes can increase the secretion of H+ through vacuolar H+-ATPase to dehydrate HCO3− present in the hemolymph to CO2. CO2 can permeate the basolateral membrane of the epithelial cells of the zooxanthellal tubules, and rehydrated back to HCO3− in the cytoplasm catalysed by carbonic anhydrase 2. This study aimed to elucidate the molecular mechanism involved in the transport of HCO3− across the apical membrane of these epithelial cells into the luminal fluid surrounding the symbionts. We had obtained the complete cDNA coding sequence of a homolog of electrogenic Na+-HCO3−cotransporter 2 (NBCe2-like gene) from the outer mantle of the fluted giant clam, Tridacna squamosa. NBCe2-like gene comprised 3,399 bp, encoding a protein of 1,132 amino acids of 127.3 kDa. NBCe2-like protein had an apical localization in the epithelial cells of zooxanthellal tubules, denoting that it could transport HCO3− between the epithelial cells and the luminal fluid. Furthermore, illumination augmented the transcript level and protein abundance of NBCe2-like gene/NBCe2-like protein in the outer mantle, indicating that it could mediate the increased transport of HCO3− into the luminal fluid to support photosynthesis in the symbionts.

There is growing interest in how exposure to videogames is associated with young children's development. While videogames may displace time from developmentally important activities and have been related to lower reading skills, work in older children and adolescents has suggested that experience with attention-demanding/fast-reaction games positively associates with attention and visuomotor skills. In the current study, we assessed 154 children aged 4-7 years (77 male; mean age 5.38) whose parents reported average daily weekday recreational videogame time, including information about which videogames were played. We investigated associations between videogame exposure and children's sustained, selective, and executive attention skills. We found that videogame time was significantly positively associated only with selective attention. Longitudinal studies are needed to elucidate the directional association between time spent playing recreational videogames and attention skills.

Given the growing evidence that a range of lifestyle factors are involved in the etiology of depression, a 'lifestyle medicine' approach can be potentially safe and cost-effective to prevent or treat depression. To examine the effects and acceptability of a group-based, integrative lifestyle medicine intervention as a standalone treatment for managing depressive symptoms, a pilot randomized controlled trial (RCT) was conducted in a Chinese adult population in 2018. Participants (n = 31) with PHQ-9 score above the cut-off of ≥ 10, which was indicative of moderate to severe depression, were recruited from the general community in Hong Kong and randomly assigned to lifestyle medicine group (LM group) or care-as-usual group (CAU group) in a ratio of 1:1. Participants in the LM group received 2-hour group sessions once per week for six consecutive weeks, which covered diet, exercise, mindfulness, psychoeducation, and sleep management. Linear mixed-effects model analyses showed that the LM group had a significant reduction in PHQ-9 scores compared to the CAU group at immediate posttreatment and 12-week posttreatment follow-up (d = 0.69 and 0.73, respectively). Moreover, there were significantly greater improvements in anxiety, stress, and insomnia symptoms (measured by DASS-21 and ISI) at all time points in the LM group (d = 0.42-1.16). The results suggests that our 6-week group-based, integrative lifestyle intervention program is effective in lowering depressive, anxiety, stress, and insomnia symptoms in the Chinese population. Further studies in clinical populations with a larger sample size and longer follow-up are warranted.

Many CRISPR/Cas platforms have been established for the detection of SARS-CoV-2. But the detection platform of the variants of SARS-CoV-2 is scarce because its specificity is very challenging to achieve for those with only one or a few nucleotide(s) differences. Here, we report for the first time that chimeric crRNA could be critical in enhancing the specificity of CRISPR-Cas12a detecting of N501Y, which is shared by Alpha, Beta, Gamma, and Mu variants of SARS-CoV-2 without compromising its sensitivity. This strategy could also be applied to detect other SARS-CoV-2 variants that differ only one or a few nucleotide(s) differences.

Background and objectiveTo develop a semi-automated, machine-learning based workflow to evaluate the ellipsoid zone (EZ) assessed by spectral domain optical coherence tomography (SD-OCT) in eyes with macular edema secondary to central retinal or hemi-retinal vein occlusion in SCORE2 treated with anti-vascular endothelial growth factor agents.MethodsSD-OCT macular volume scans of a randomly selected subset of 75 SCORE2 study eyes were converted to the Digital Imaging and Communications in Medicine (DICOM) format, and the EZ layer was segmented using nonproprietary software. Segmented layer coordinates were exported and used to generate en face EZ thickness maps. Within the central subfield, the area of EZ defect was measured using manual and semi-automated approaches via a customized workflow in the open-source data analytics platform, Konstanz Information Miner (KNIME).ResultsA total of 184 volume scans from 74 study eyes were analyzed. The mean±SD area of EZ defect was similar between manual (0.19±0.22 mm2) and semi-automated measurements (0.19±0.21 mm2, p = 0.93; intra-class correlation coefficient = 0.90; average bias = 0.01, 95% confidence interval of limits of agreement -0.18-0.20).ConclusionsA customized workflow generated via an open-source data analytics platform that applied machine-learning methods demonstrated reliable measurements of EZ area defect from en face thickness maps. The result of our semi-automated approach were comparable to manual measurements.

Hydroxychloroquine has been touted as a potential COVID-19 treatment. Tocilizumab, an inhibitor of IL-6, has also been proposed as a treatment of critically ill patients. In this retrospective observational cohort study drawn from electronic health records we sought to describe the association between mortality and hydroxychloroquine or tocilizumab therapy among hospitalized COVID-19 patients. Patients were hospitalized at a 13-hospital network spanning New Jersey USA between March 1, 2020 and April 22, 2020 with positive polymerase chain reaction results for SARS-CoV-2. Follow up was through May 5, 2020. Among 2512 hospitalized patients with COVID-19 there have been 547 deaths (22%), 1539 (61%) discharges and 426 (17%) remain hospitalized. 1914 (76%) received at least one dose of hydroxychloroquine and 1473 (59%) received hydroxychloroquine with azithromycin. After adjusting for imbalances via propensity modeling, compared to receiving neither drug, there were no significant differences in associated mortality for patients receiving any hydroxychloroquine during the hospitalization (HR, 0.99 [95% CI, 0.80-1.22]), hydroxychloroquine alone (HR, 1.02 [95% CI, 0.83-1.27]), or hydroxychloroquine with azithromycin (HR, 0.98 [95% CI, 0.75-1.28]). The 30-day unadjusted mortality for patients receiving hydroxychloroquine alone, azithromycin alone, the combination or neither drug was 25%, 20%, 18%, and 20%, respectively. Among 547 evaluable ICU patients, including 134 receiving tocilizumab in the ICU, an exploratory analysis found a trend towards an improved survival association with tocilizumab treatment (adjusted HR, 0.76 [95% CI, 0.57-1.00]), with 30 day unadjusted mortality with and without tocilizumab of 46% versus 56%. This observational cohort study suggests hydroxychloroquine, either alone or in combination with azithromycin, was not associated with a survival benefit among hospitalized COVID-19 patients. Tocilizumab demonstrated a trend association towards reduced mortality among ICU patients. Our findings are limited to hospitalized patients and must be interpreted with caution while awaiting results of randomized trials. Trial Registration: Clinicaltrials.gov Identifier: NCT04347993.

PurposeTo evaluate the correlation between the choriocapillaris (CC) flow alterations around geographic atrophy (GA) and the GA yearly growth rate (yGR) in patients with dry age-related macular degeneration (AMD).MethodsWe retrospectively reviewed and analyzed spectral domain optical coherence tomography (SD-OCT) and SD-OCT angiography images of consecutive patients with GA acquired using the Cirrus OCT at the Doheny Eye Centers between 2015 and 2017. All eligible patients had one 6 x 6 mm OCTA scan acquired during the first visit (considered as baseline) and two fovea-centered 512 x 128 macular cubes (6 x 6 mm) acquired at baseline and after a minimum of 12 months.Main outcome measuresThe fundus images from the OCT volumes were used to manually delineate the GA area and calculate the yGR after square root transformation. The en-face angiogram at the level of the CC was analyzed for the percentage of flow voids (FV) outside the atrophic lesion (FVOUT) and in the para- and peri-atrophy regions (FV500 and FV1000 respectively; two concentric 500 μm wide rings around the atrophy edge). These values, together with the difference between FV500 and FV1000 (ΔFV), were then correlated with the corresponding yGR.ResultsThirty-three eyes of 23 patients were eligible for the analysis. The mean yGR was 0.23 ± 0.17 mm/years. At baseline, the mean FVOUT was 41.86 ± 2.71%, while FV500 and FV1000 were 46.4 ± 4.17% and 42.51 ± 2.65% respectively. The mean ΔFV was 3.89 ± 2.6%. While in the univariable analysis, the yGR was significantly associated with FV500 and with ΔFV (both p < 0.001), in multivariable model the association remained significant only with ΔFV (p < 0.001).ConclusionsOur study reports a correlation between the CC flow impairment around the atrophic lesions and their yGR in patients with GA. If replicated in future longitudinal studies, the choriocapillaris FV in the para-and peri-atrophy regions may prove to be useful parameters for evaluating the prognosis of these eyes.

Anemoside A3 (AA3) is a natural triterpenoid glycoside isolated from the root of Pulsatilla chinensis (Bunge) Regel. We previously showed that AA3 exhibits cognitive-enhancing and neuroprotective properties. In the present study, we demonstrated that AA3 modulates inflammatory responses by regulating prostaglandin E receptor 4 signaling. Because prostaglandin E receptor 4 is involved in the pathophysiology of experimental autoimmune encephalomyelitis (EAE), an animal model of human multiple sclerosis (MS), we assessed the beneficial effect of AA3 in EAE mice. AA3 treatment significantly reduced clinical severity and inflammatory infiltrates in the spinal cord of EAE mice. In vitro studies revealed that AA3 inhibited the T cell response toward the encephalitogenic epitope of myelin oligodendrocyte glycoprotein (MOG). AA3 significantly downregulated the expressions of certain Th1 and Th17 cytokines in activated T cells re-stimulated by MOG. Moreover, AA3 inhibited the activation of STAT4 and STAT3, which are the transcription factors pivotal for Th1 and Th17 lineage differentiation, respectively, in activated T cells. Pharmacological analysis further suggested that AA3 reduced Th17 cell differentiation and expansion. In conclusion, AA3 exerts an immunomodulatory effect in EAE, demonstrating its potential as a therapeutic agent for MS in humans.

In countries with high tuberculosis (TB) burden, there is urgent need for rapid, large-scale screening to detect smear-positive patients. We developed a computer-aided whole smear screening system that focuses in real-time, captures images and provides diagnostic grading, for both bright-field and fluorescence microscopy for detection of acid-fast-bacilli (AFB) from respiratory specimens.To evaluate the performance of dual-mode screening system in AFB diagnostic algorithms on concentrated smears with auramine O (AO) staining, as well as direct smears with AO and Ziehl-Neelsen (ZN) staining, using mycobacterial culture results as gold standard.Adult patient sputum samples requesting for M. tuberculosis cultures were divided into three batches for staining: direct AO-stained, direct ZN-stained and concentrated smears AO-stained. All slides were graded by an experienced microscopist, in parallel with the automated whole smear screening system. Sensitivity and specificity of a TB diagnostic algorithm in using the screening system alone, and in combination with a microscopist, were evaluated.Of 488 direct AO-stained smears, 228 were culture positive. These yielded a sensitivity of 81.6% and specificity of 74.2%. Of 334 direct smears with ZN staining, 142 were culture positive, which gave a sensitivity of 70.4% and specificity of 76.6%. Of 505 concentrated smears with AO staining, 250 were culture positive, giving a sensitivity of 86.4% and specificity of 71.0%. To further improve performance, machine grading was confirmed by manual smear grading when the number of AFBs detected fell within an uncertainty range. These combined results gave significant improvement in specificity (AO-direct:85.4%; ZN-direct:85.4%; AO-concentrated:92.5%) and slight improvement in sensitivity while requiring only limited manual workload.Our system achieved high sensitivity without substantially compromising specificity when compared to culture results. Significant improvement in specificity was obtained when uncertain results were confirmed by manual smear grading. This approach had potential to substantially reduce workload of microscopists in high burden countries.

There is a significant need to develop objective measures for identifying children under the age of 8 who have anxiety and depression. If left untreated, early internalizing symptoms can lead to adolescent and adult internalizing disorders as well as comorbidity which can yield significant health problems later in life including increased risk for suicide. To this end, we propose the use of an instrumented fear induction task for identifying children with internalizing disorders, and demonstrate its efficacy in a sample of 63 children between the ages of 3 and 7. In so doing, we extract objective measures that capture the full six degree-of-freedom movement of a child using data from a belt-worn inertial measurement unit (IMU) and relate them to behavioral fear codes, parent-reported child symptoms and clinician-rated child internalizing diagnoses. We find that IMU motion data, but not behavioral codes, are associated with parent-reported child symptoms and clinician-reported child internalizing diagnosis in this sample. These results demonstrate that IMU motion data are sensitive to behaviors indicative of child psychopathology. Moreover, the proposed IMU-based approach has increased feasibility of collection and processing compared to behavioral codes, and therefore should be explored further in future studies.

This study was to investigate the prevalence of actual uptake of pre-exposure prophylaxis (PrEP), willingness to use daily oral PrEP under two cost scenarios, and potential issues related to PrEP use among men who have sex with men (MSM) with HIV negative/unknown sero-status in Hong Kong, China. Factors associated with the two measures of willingness were also investigated.403 eligible MSM completed the anonymous venue-based face-to-face interview/telephone interview.Only 1% had ever used PrEP. After being briefed about some facts of PrEP, the prevalence of willingness to use daily oral PrEP was 7.7% if they could purchase PrEP at private hospitals/clinics at HK$8,000 (US$1,032)/month (market rate) and 45.2% if free PrEP was provided by public hospitals/clinics in Hong Kong (free PrEP). After adjusted for significant background variables, significant factors of these two measures of willingness included: (1) number of correct responses to knowledge on PrEP, (2) perceived risk of HIV infection in the next six months, and (3) constructs of the Theory of Planned Behavior: positive and negative attitudes toward PrEP, perceived their significant others would support them take PrEP (perceived subjective norm), perceived number of local MSM who were willing to take PrEP (perceived descriptive norm), and confidence in using PrEP under the two scenarios (perceived behavioral control). Among all participants, 9.7% and 25.1% would start and discontinue using PrEP without consulting doctors; 26.0% would not take PrEP daily if it was provided for free, and 42.4% would not take up HIV testing every 3 months after using PrEP.Different strategies should be considered for promoting PrEP at market rate and if free PrEP is made available. Future promotion should increase their knowledge about PrEP, modify their perceptions related to HIV and PrEP, and address some potential issues related to PrEP use.

[This corrects the article DOI: 10.1371/journal.pone.0177266.].

BACKGROUND:Clostridium difficile infection (CDI) caused by ribotype 002 strain is associated with poor outcomes in Chinese patients. Fecal microbiota transplantation (FMT) is an effective but costly treatment for CDI. We aimed to examine potential cost-effectiveness of ribotype-guided FMT in Chinese patients with severe CDI. METHODS:A decision-analytic model was designed to simulate outcomes of ribotype 002-guided FMT versus vancomycin treatment in Chinese patients with severe CDI in the hospital setting. Outcome measures included mortality rate; direct medical cost; and quality-adjusted life year (QALY) loss for CDI. Sensitivity analysis was performed to examine robustness of base-case results. RESULTS:Comparing to vancomycin treatment, ribotype-guided FMT group reduced mortality (11.6% versus 17.1%), cost (USD8,807 versus USD9,790), and saved 0.472 QALYs in base-case analysis. One-way sensitivity analysis found the ribotype-guided FMT group to remain cost-effective when patient acceptance rate of FMT was >0.6% and ribotype 002 prevalence was >0.07%. In probabilistic sensitivity analysis, ribotype-guided FMT gained higher QALYs at 100% of simulations with mean QALY gain of 0.405 QALYs (95%CI: 0.400-0.410; p

Symptoms of complex illnesses such as cancer often present with a high degree of heterogeneity between patients. At the same time, there are often core symptoms that act as common drivers for other symptoms, such as fatigue leading to depression and cognitive dysfunction. These symptoms are termed bridge symptoms and when combined with heterogeneity in symptom presentation, are difficult to detect using traditional unsupervised clustering techniques. This article develops a method for identifying patient communities based on bridge symptoms termed concordance network clustering. An empirical study of breast cancer symptomatology is presented, and demonstrates the applicability of this method for identifying bridge symptoms.

p62 is a scaffolding adaptor implicated in the clearance of protein aggregates by autophagy. Reactive oxygen species (ROS) can either stimulate or inhibit NFκB-mediated gene expression influencing cellular fate. We studied the effect of hydrogen peroxide (H2O2)-mediated oxidative stress and NFκB signaling on p62 expression in the retinal pigment epithelium (RPE) and investigated its role in regulation of autophagy and RPE survival against oxidative damage. Cultured human RPE cell line ARPE-19 and primary human adult and fetal RPE cells were exposed to H2O2-induced oxidative stress. The human apolipoprotein E4 targeted-replacement (APOE4) mouse model of AMD was used to study expression of p62 and other autophagy proteins in the retina. p62, NFκB p65 (total, phosphorylated, nuclear and cytoplasmic) and ATG10 expression was assessed by mRNA and protein analyses. Cellular ROS and mitochondrial superoxide were measured by CM-H2DCFDA and MitoSOX staining respectively. Mitochondrial viability was determined using MTT activity. qPCR-array system was used to investigate autophagic genes affected by p62. Nuclear and cytoplasmic levels of NFκB p65 were evaluated after cellular fractionation by Western blotting. We report that p62 is up-regulated in RPE cells under H2O2-induced oxidative stress and promotes autophagic activity. Depletion of endogenous p62 reduces autophagy by downregulation of ATG10 rendering RPE more susceptible to oxidative damage. NFκB p65 phosphorylation at Ser-536 was found to be critical for p62 upregulation in response to oxidative stress. Proteasome inhibition by H2O2 causes p62-NFκB signaling as antioxidant pre-treatment reversed p62 expression and p65 phosphorylation when RPE was challenged by H2O2 but not when by Lactacystin. p62 protein but not RNA levels are elevated in APOE4-HFC AMD mouse model, suggesting reduction of autophagic flux in disease conditions. Our findings suggest that p62 is necessary for RPE cytoprotection under oxidative stress and functions, in part, by modulating ATG10 expression. NFκB p65 activity may be a critical upstream initiator of p62 expression in RPE cells under oxidative stress.

Na+/K+-ATPase (NKA) is essential for maintaining the Na+ and K+ gradients, and supporting the secondary active transport of certain ions/molecules, across the plasma membrane of animal cells. This study aimed to clone the NKA α-subunit (NKAα) from the inner mantle adjacent to the extrapallial fluid of Tridacna squamosa, to determine its subcellular localization, and to examine the effects of light exposure on its transcript level and protein abundance. The cDNA coding sequence of NKAα from T. squamosa comprised 3105 bp, encoding 1034 amino acids with an estimated molecular mass of 114 kDa. NKAα had a basolateral localization along the shell-facing epithelium of the inner mantle. Exposure to 12 h of light led to a significantly stronger basolateral NKAα-immunofluorescence at the shell-facing epithelium, indicating that NKA might play a role in light-enhanced calcification in T. squamosa. After 3 h of light exposure, the transcript level of NKAα decreased transiently in the inner mantle, but returned to the control level thereafter. In comparison, the protein abundance of NKAα remained unchanged at hour 3, but became significantly higher than the control after 12 h of light exposure. Hence, the expression of NKAα in the inner mantle of T. squamosa was light-dependent. It is probable that a higher expression level of NKA was needed in the shell-facing epithelial cells of the inner mantle to cope with a rise in Na+ influx, possibly caused by increases in activities of some Na+-dependent ion transporters/channels involved in light-enhanced calcification.

Uncomplicated urinary tract infections (UTI) are common in primary care. Whilst primary care physicians are called to be antimicrobial stewards, there is limited primary care antibiotic resistance surveillance and physician antibiotic prescription data available in southern Chinese primary care. The study aimed to investigate the antibiotic resistance rate and antibiotic prescription patterns in female patients with uncomplicated UTI. Factors associated with antibiotic resistance and prescription was explored. A prospective cohort study was conducted in 12 primary care group clinics in Hong Kong of patients presenting with symptoms of uncomplicated UTI from January 2012 to December 2013. Patients' characteristics such as age, comorbidity, presenting symptoms and prior antibiotic use were recorded by physicians, as well as any empirical antibiotic prescription given at presentation. Urine samples were collected to test for antibiotic resistance of uropathogens. Univariate analysis was conducted to identify factors associated with antibiotic resistance and prescription. A total of 298 patients were included in the study. E. coli was detected in 107 (76%) out of the 141 positive urine samples. Antibiotic resistance rates of E. coli isolates for ampicillin, co-trimoxazole, ciprofloxacin, amoxicillin and nitrofurantoin were 59.8%, 31.8%, 23.4%, 1.9% and 0.9% respectively. E. coli isolates were sensitive to nitrofurantoin (98.1%) followed by amoxicillin (78.5%). The overall physician antibiotic prescription rate was 82.2%. Amoxicillin (39.6%) and nitrofurantoin (28.6%) were the most common prescribed antibiotics. Meanwhile, whilst physicians in public primary care prescribed more amoxicillin (OR: 2.84, 95% CI: 1.67 to 4.85, P

African lungfishes are ammonotelic in water. They can aestivate for long periods on land during drought. During aestivation, the gills are covered with dried mucus and ammonia excretion ceases. In fishes, ammonia excretion through the gills involves Rhesus glycoproteins (RhGP/Rhgp). This study aimed to obtain the complete cDNA coding sequences of rhgp from the gills of Protopterus annectens, and to determine their branchial mRNA and protein expression levels during the induction, maintenance and arousal phases of aestivation. Three isoforms of rhgp (rhag, rhbg and rhcg) were obtained in the gills of P. annectens. Their complete cDNA coding sequences ranged between 1311 and 1398 bp, coding for 436 to 465 amino acids with estimated molecular masses between 46.8 and 50.9 kDa. Dendrogramic analyses indicated that Rhag was grouped closer to fishes, while Rhbg and Rhcg were grouped closer to tetrapods. During the induction phase, the protein abundance of Rhag, but not its transcript level, was down-regulated in the gills, suggesting that there could be a decrease in the release of ammonia from the erythrocytes to the plasma. Furthermore, the branchial transcript levels of rhbg and rhcg decreased significantly, in preparation for the subsequent shutdown of gill functions. During the maintenance phase, the branchial expression levels of rhag/Rhag, rhbg/Rhbg and rhcg/Rhcg decreased significantly, indicating that their transcription and translation were down-regulated. This could be part of an overall mechanism to shut down branchial functions and save metabolic energy used for transcription and translation. It could also be regarded as an adaptive response to stop ammonia excretion. During the arousal phase, it is essential for the lungfish to regain the ability to excrete ammonia. Indeed, the protein abundance of Rhag, Rhbg and Rhcg recovered to the corresponding control levels after 1 day or 3 days of recovery from 6 months of aestivation.

Numerous studies show that mitochondrial energy generation determines the effectiveness of immune responses. Furthermore, changes in mitochondrial function may regulate lymphocyte function in inflammatory diseases like type 2 diabetes. Analysis of lymphocyte mitochondrial function has been facilitated by introduction of 96-well format extracellular flux (XF96) analyzers, but the technology remains imperfect for analysis of human lymphocytes. Limitations in XF technology include the lack of practical protocols for analysis of archived human cells, and inadequate data analysis tools that require manual quality checks. Current analysis tools for XF outcomes are also unable to automatically assess data quality and delete untenable data from the relatively high number of biological replicates needed to power complex human cell studies. The objectives of work presented herein are to test the impact of common cellular manipulations on XF outcomes, and to develop and validate a new automated tool that objectively analyzes a virtually unlimited number of samples to quantitate mitochondrial function in immune cells. We present significant improvements on previous XF analyses of primary human cells that will be absolutely essential to test the prediction that changes in immune cell mitochondrial function and fuel sources support immune dysfunction in chronic inflammatory diseases like type 2 diabetes.

Commuters who spend long hours on roads are exposed to high levels of traffic related air pollutants (TRAPs). Despite some well-known multiple adverse effects of TRAPs on human health, limited studies have focused on mitigation strategies to reduce these effects. In this study, we measured fine particulate matter (PM2.5) and ultrafine particle (UFP) concentrations inside and outside 17 taxis simultaneously while they were driven on roadways. The drivers' urinary monohydroxylated polycyclic aromatic hydrocarbons (OH-PAHs) and malondialdehyde (MDA) concentrations just before and right after the driving tests were also determined. Data were collected under three driving conditions (i.e. no mitigation (NM), window closed (WC), and window closed plus using high efficiency cabin air filters (WC+HECA)) for each taxi and driver. The results show that, compared to NM, the WC+HECA reduced in-cabin PM2.5 and UFP concentrations, by 37% and 47% respectively (p < 0.05), whereas the reductions on PAH exposures were insignificant. Although nonsignificant, a reduction of 17% was also observed in the drivers' urinary MDA under WC+HECA. The MDA concentrations were found to be significantly associated with the in-cabin PM2.5 and UFP concentrations, suggesting the reduction of the drivers' lipid peroxidation can be at least partially attributed to the PM2.5 and UFP reduction by WC+HECA. Overall, these results suggest HECA filters have potential to reduce particle levels inside taxis and protect drivers' health.

INTRODUCTION:Mouse models are used frequently to study effects of bone diseases and genetic determinates of bone strength. Murine bones have an intracortical band of woven bone that is not present in human bones. This band is not obvious under brightfield imaging and not typically analyzed. Due to the band's morphology and location it has been theorized to be remnant bone from early in life. Furthermore, lamellar and woven bone are well known to have differing mechanical strengths. The purpose of this study was to determine (i) if the band is from early life and (ii) if the woven bone or calcified cartilage contained within the band affect whole bone strength. WOVEN BONE ORIGIN STUDIES:In twelve to fourteen week old mice, doxycycline was used to label bone formed prior to 3 weeks old. Doxycycline labeling and woven bone patterns on contralateral femora matched well and encompassed an almost identical cross-sectional area. Also, we highlight for the first time in mice the presence of calcified cartilage exclusively within the band. However, calcified cartilage could not be identified on high resolution cone-beam microCT scans when examined visually or by thresholding methods. MECHANICAL STRENGTH STUDIES:Subsequently, three-point bending was used to analyze the effects of woven bone and calcified cartilage on whole bone mechanics in a cohort of male and female six and 13 week old Balb/C mice. Three-point bending outcomes were correlated with structural and compositional measures using multivariate linear regression. Woven bone composed a higher percent of young bones than older bones. However, calcified cartilage in older bones was twice that of younger bones, which was similar when normalized by area. Area and/or tissue mineral density accounted for >75% of variation for most strength outcomes. Percent calcified cartilage added significant predictive power to maximal force and bending stress. Calcified cartilage and woven bone could have more influence in genetic models where calcified cartilage percent is double our highest value.

Shark conservation has become a focus of current international conservation efforts. However, the misunderstanding of sharks and their negative public portrayal may hinder their conservation. More importantly, the consumption of shark fin, which is very common in Chinese cultures, poses a significant threat to sharks. Hong Kong has long been the world's largest shark fin trading center. Shark conservation would become more sustainable if public understanding of this predatory fish and an appreciation of its ecological significance could be promoted. It is possible that the demand for fins could be effectively managed through long-term educational efforts targeted at younger generations. To provide essential baseline data for planning of these educational efforts, this project investigated the perceptions of 11 to 12 year-old primary school students in Hong Kong about sharks, and their understanding of ecological concepts and shark-related knowledge. The findings indicate that these students lack sufficient knowledge and possess misconceptions about sharks and their ecological significance in the marine ecosystem. The students' conceptual understanding level is strongly correlated with their perceptions. Correlational analyses further demonstrated a positive association between formal education and perceptions toward shark conservation. The students who favoured shark fin consumption did so because of its tastiness, whereas concerns about shark population decline and the cruelty of shark hunting were the main reasons for not favoring shark fin consumption. This pilot study provides preliminary but important insights into primary school education regarding the conservation of sharks.

BACKGROUND:This study aims to assess evidence for any socioeconomic gradients in childhood obesity and hypertension in a population-representative sample in Hong Kong, China. METHODS:The data of a stratified random sampled growth survey collected in 2005-2006 was matched with a population by-census. Obesity was defined using the International Obesity Task Force standard and hypertension was defined using the Hong Kong norm table. Family socioeconomic status (SES) was measured by maternal education level. Neighbourhood SES was measured by median household income of the neighbourhood. Multilevel Poisson regression models with robust standard error were used to test the association. Body mass indices of children's parents were included as potential confounders. Intra-school/neighbourhood correlations were adjusted using random factors. RESULTS:Totally 14842 children (age 6-19 years) included in the analysis, in which 16.6% of them were overweight or obese. Children whose mother only completed secondary school or below had higher risk of childhood obesity (RR 1.41, 95% CI 1.13-1.76, p = 0.003) and hypertension (RR 1.18, 95% CI 1.01-1.36, p = 0.03). Meanwhile, children in the lowest neighbourhood SES group had higher risk of childhood underweight (RR 1.61, 95% CI 1.04-2.49, p = 0.03), overweight (RR 1.35, 95% CI 1.05-1.72, p = 0.02), and obesity (RR 2.07, 95% CI 1.11-3.88, p = 0.02). CONCLUSIONS:Socioeconomic gradient in childhood obesity and hypertension existed in Hong Kong, one of the most developed cities in China. These results have implications for policymakers and public health experts and highlight the need to monitor trends in other parts of China.

We aimed to study the pathogenic roles of High-Mobility Group Box 1 (HMGB1) / Receptor-for-Advanced-Glycation-End-products (RAGE) signaling and pro-inflammatory cytokines in patients with active pulmonary tuberculosis (PTB).A prospective study was conducted among non-HIV adults newly-diagnosed with active PTB at two acute-care hospitals (n = 80); age-and-sex matched asymptomatic individuals (tested for latent TB) were used for comparison (n = 45). Plasma concentrations of 8 cytokines/chemokines, HMGB1, soluble-RAGE, and transmembrane-RAGE expressed on monocytes/dendritic cells, were measured. Gene expression (mRNA) of HMGB1, RAGE, and inflammasome-NALP3 was quantified. Patients' PBMCs were stimulated with recombinant-HMGB1 and MTB-antigen (lipoarabinomannan) for cytokine induction ex vivo.In active PTB, plasma IL-8/CXCL8 [median(IQR), 6.0(3.6-15.1) vs 3.6(3.6-3.6) pg/ml, P

This study aimed to obtain the coding cDNA sequences of voltage-gated Na+ channel (scn) α-subunit (scna) and β-subunit (scnb) isoforms from, and to quantify their transcript levels in, the main electric organ (EO), Hunter's EO, Sach's EO and the skeletal muscle (SM) of the electric eel, Electrophorus electricus, which can generate both high and low voltage electric organ discharges (EODs). The full coding sequences of two scna (scn4aa and scn4ab) and three scnb (scn1b, scn2b and scn4b) were identified for the first time (except scn4aa) in E. electricus. In adult fish, the scn4aa transcript level was the highest in the main EO and the lowest in the Sach's EO, indicating that it might play an important role in generating high voltage EODs. For scn4ab/Scn4ab, the transcript and protein levels were unexpectedly high in the EOs, with expression levels in the main EO and the Hunter's EO comparable to those of scn4aa. As the key domains affecting the properties of the channel were mostly conserved between Scn4aa and Scn4ab, Scn4ab might play a role in electrogenesis. Concerning scnb, the transcript level of scn4b was much higher than those of scn1b and scn2b in the EOs and the SM. While the transcript level of scn4b was the highest in the main EO, protein abundance of Scn4b was the highest in the SM. Taken together, it is unlikely that Scna could function independently to generate EODs in the EOs as previously suggested. It is probable that different combinations of Scn4aa/Scn4ab and various Scnb isoforms in the three EOs account for the differences in EODs produced in E. electricus. In general, the transcript levels of various scn isoforms in the EOs and the SM were much higher in adult than in juvenile, and the three EOs of the juvenile fish could be functionally indistinct.

BACKGROUND:Identifying individual correlates of infectivity of influenza virus is important for disease control and prevention. Viral shedding is used as a proxy measure of infectivity in many studies. However, the evidence for this is limited. METHODS:In a detailed study of influenza virus transmission within households in 2008-12, we recruited index cases with confirmed influenza infection from outpatient clinics, and followed up their household contacts for 7-10 days to identify secondary infections. We used individual-based hazard models to characterize the relationship between individual viral shedding and individual infectivity. RESULTS:We analyzed 386 households with 1147 household contacts. Index cases were separated into 3 groups according to their estimated level of viral shedding at symptom onset. We did not find a statistically significant association of virus shedding with transmission. Index cases in medium and higher viral shedding groups were estimated to have 21% (95% CI: -29%, 113%) and 44% (CI: -16%, 167%) higher infectivity, compared with those in the lower viral shedding group. CONCLUSIONS:Individual viral load measured by RT-PCR in the nose and throat was at most weakly correlated with individual infectivity in households. Other correlates of infectivity should be examined in future studies.

[This corrects the article DOI: 10.1371/journal.pone.0140651.].

Oleanolic acid (3β-hydroxy-olea-12-en-28-oic acid) is a natural pentacyclic triterpenoic acid found in many fruits, herbs and medicinal plants. In the past decade, increasing evidence has suggested that oleanolic acid exhibits inhibitory activities against different types of cancer including skin cancer and colon cancer, but not leukemia. We report here that a derivative of oleanolic acid, olean-12-eno[2,3-c] [1], [2], [5]oxadiazol-28-oic acid (designated OEOA) effectively blocks the proliferation of human leukemia cells. OEOA significantly reduces cell proliferation without inducing cell death in three types of leukemia cell lines, including K562, HEL and Jurket. Moreover, exposure of K562 cells to OEOA results in G1 cell cycle arrest, with a concomitant induction of cyclin-dependent kinase inhibitor p27 and downregulation of cyclins and Cdks that are essential for cell cycle progression. Interestingly, OEOA also enhances erythroid differentiation in K562 cells through suppressing the expression of Bcr-Abl and phosphorylation of Erk1/2. These findings identify a novel chemical entity for further development as therapeutics against leukemia.

This paper discusses the study of two interacting processes in which a feedback mechanism exists between the processes. The study was motivated by problems such as the circadian oscillation of gene expression where two interacting protein transcriptions form both negative and positive feedback loops with long delays to equilibrium. Traditionally, data of this type could be examined using autoregressive analysis. However, in circadian oscillation the order of an autoregressive model cannot be determined a priori. We propose a sparse multivariate autoregressive method that incorporates mixed linear effects into regression analysis, and uses a forward-backward greedy search algorithm to select non-zero entries in the regression coefficients, the number of which is constrained not to exceed a pre-specified number. A small simulation study provides preliminary evidence of the validity of the method. Besides the circadian oscillation example, an additional example of blood pressure variations using data from an intervention study is used to illustrate the method and the interpretation of the results obtained from the sparse matrix method. These applications demonstrate how sparse representation can be used for handling high dimensional variables that feature dynamic, reciprocal relationships.

Since the spread of highly pathogenic avian influenza (HPAI) H5N1 in the eastern hemisphere, numerous surveillance programs and studies have been undertaken to detect the occurrence, distribution, or spread of avian influenza viruses (AIV) in wild bird populations worldwide. To identify demographic determinants and spatiotemporal patterns of AIV infection in long distance migratory waterfowl in North America, we fitted generalized linear models with binominal distribution to analyze results from 13,574 blue-winged teal (Anas discors, BWTE) sampled in 2007 to 2010 year round during AIV surveillance programs in Canada and the United States. Our analyses revealed that during late summer staging (July-August) and fall migration (September-October), hatch year (HY) birds were more likely to be infected than after hatch year (AHY) birds, however there was no difference between age categories for the remainder of the year (winter, spring migration, and breeding period), likely due to maturing immune systems and newly acquired immunity of HY birds. Probability of infection increased non-linearly with latitude, and was highest in late summer prior to fall migration when densities of birds and the proportion of susceptible HY birds in the population are highest. Birds in the Central and Mississippi flyways were more likely to be infected compared to those in the Atlantic flyway. Seasonal cycles and spatial variation of AIV infection were largely driven by the dynamics of AIV infection in HY birds, which had more prominent cycles and spatial variation in infection compared to AHY birds. Our results demonstrate demographic as well as seasonal, latitudinal and flyway trends across Canada and the US, while illustrating the importance of migratory host life cycle and age in driving cyclical patterns of prevalence.

This study aimed to obtain the coding cDNA sequences of Na+/K+-ATPase α (nkaα) isoforms from, and to quantify their mRNA expression in, the skeletal muscle (SM), the main electric organ (EO), the Hunter's EO and the Sach's EO of the electric eel, Electrophorus electricus. Four nkaα isoforms (nkaα1c1, nkaα1c2, nkaα2 and nkaα3) were obtained from the SM and the EOs of E. electricus. Based on mRNA expression levels, the major nkaα expressed in the SM and the three EOs of juvenile and adult E. electricus were nkaα1c1 and nkaα2, respectively. Molecular characterization of the deduced Nkaα1c1 and Nkaα2 sequences indicates that they probably have different affinities to Na+ and K+. Western blotting demonstrated that the protein abundance of Nkaα was barely detectable in the SM, but strongly detected in the main and Hunter's EOs and weakly in the Sach's EO of juvenile and adult E. electricus. These results corroborate the fact that the main EO and Hunter's EO have high densities of Na+ channels and produce high voltage discharges while the Sach's EO produces low voltage discharges. More importantly, there were significant differences in kinetic properties of Nka among the three EOs of juvenile E. electricus. The highest and lowest Vmax of Nka were detected in the main EO and the Sach's EO, respectively, with the Hunter's EO having a Vmax value intermediate between the two, indicating that the metabolic costs of EO discharge could be the highest in the main EO. Furthermore, the Nka from the main EO had the lowest Km (or highest affinity) for Na+ and K+ among the three EOs, suggesting that the Nka of the main EO was more effective than those of the other two EOs in maintaining intracellular Na+ and K+ homeostasis and in clearing extracellular K+ after EO discharge.

During development, scaffold proteins serve as important platforms for orchestrating signaling complexes to transduce extracellular stimuli into intracellular responses that regulate dendritic spine morphology and function. Axin ("axis inhibitor") is a key scaffold protein in canonical Wnt signaling that interacts with specific synaptic proteins. However, the cellular functions of these protein-protein interactions in dendritic spine morphology and synaptic regulation are unclear. Here, we report that Axin protein is enriched in synaptic fractions, colocalizes with the postsynaptic marker PSD-95 in cultured hippocampal neurons, and interacts with a signaling protein Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) in synaptosomal fractions. Axin depletion by shRNA in cultured neurons or intact hippocampal CA1 regions significantly reduced dendritic spine density. Intriguingly, the defective dendritic spine morphogenesis in Axin-knockdown neurons could be restored by overexpression of the small Rho-GTPase Cdc42, whose activity is regulated by CaMKII. Moreover, pharmacological stabilization of Axin resulted in increased dendritic spine number and spontaneous neurotransmission, while Axin stabilization in hippocampal neurons reduced the elimination of dendritic spines. Taken together, our findings suggest that Axin promotes dendritic spine stabilization through Cdc42-dependent cytoskeletal reorganization.

The role of microRNAs in association with Mycobacterium tuberculosis (MTB) infection and the immunology regulated by microRNAs upon MTB infection have not been fully unravelled. We examined the microRNA profiles of THP-1 macrophages upon the MTB infection of Beijing/W and non-Beijing/W clinical strains. We also studied the microRNA profiles of the host macrophages by microarray in a small cohort with active MTB disease, latent infection (LTBI), and from healthy controls.The results revealed that 14 microRNAs differentiated infections of Beijing/W from non-Beijing/W strains (P

The 2014-2015 Ebola outbreak is the largest and most widespread to date. In order to estimate ongoing transmission in the affected countries, we estimated the weekly average number of secondary cases caused by one individual infected with Ebola throughout the infectious period for each affected West African country using a stochastic hidden Markov model fitted to case data from the World Health Organization. If the average number of infections caused by one Ebola infection is less than 1.0, the epidemic is subcritical and cannot sustain itself. The epidemics in Liberia and Sierra Leone have approached subcriticality at some point during the epidemic; the epidemic in Guinea is ongoing with no evidence that it is subcritical. Response efforts to control the epidemic should continue in order to eliminate Ebola cases in West Africa.

The African lungfish, Protopterus annectens, can undergo aestivation during drought. Aestivation has three phases: induction, maintenance and arousal. The objective of this study was to examine the differential gene expression in the liver of P. annectens after 6 months (the maintenance phase) of aestivation as compared with the freshwater control, or after 1 day of arousal from 6 months aestivation as compared with 6 months of aestivation using suppression subtractive hybridization. During the maintenance phase of aestivation, the mRNA expression of argininosuccinate synthetase 1 and carbamoyl phosphate synthetase III were up-regulated, indicating an increase in the ornithine-urea cycle capacity to detoxify ammonia to urea. There was also an increase in the expression of betaine homocysteine-S-transferase 1 which could reduce and prevent the accumulation of hepatic homocysteine. On the other hand, the down-regulation of superoxide dismutase 1 expression could signify a decrease in ROS production during the maintenance phase of aestivation. In addition, the maintenance phase was marked by decreases in expressions of genes related to blood coagulation, complement fixation and iron and copper metabolism, which could be strategies used to prevent thrombosis and to conserve energy. Unlike the maintenance phase of aestivation, there were increases in expressions of genes related to nitrogen, carbohydrate and lipid metabolism and fatty acid transport after 1 day of arousal from 6 months aestivation. There were also up-regulation in expressions of genes that were involved in the electron transport system and ATP synthesis, indicating a greater demand for metabolic energy during arousal. Overall, our results signify the importance of sustaining a low rate of waste production and conservation of energy store during the maintenance phase, and the dependence on internal energy store for repair and structural modification during the arousal phase, of aestivation in the liver of P. annectens.

Foodborne outbreaks caused by a mixed infection of Vibrio parahaemolyticus and norovirus have rarely been described. We reported a mixed outbreak of Vibrio parahaemolyticus and norovirus causing acute gastroenteritis in 99 staff members of a company in Guangdong, China, in May 2013, following consumption of roasted duck, an uncommon non-seafood vehicle for such mixed infection, in one meal served in the company's catering service. Epidemiological and laboratory findings indicated that a single asymptomatic food handler was the source of both pathogens, and the high rate of infection of both pathogens was exacerbated by the setting's suboptimal food hygiene practice.

The present study investigated whether hope and hopelessness are better conceptualized as a single construct of bipolar spectrum or two distinct constructs and whether hope can moderate the relationship between hopelessness and suicidal ideation.Hope, hopelessness, and suicidal ideation were measured in a community sample of 2106 participants through a population-based household survey.Confirmatory factor analyses showed that a measurement model with separate, correlated second-order factors of hope and hopelessness provided a good fit to the data and was significantly better than that of the model collapsing hope and hopelessness into a single second-order factor. Negative binomial regression showed that hope and hopelessness interacted such that the effect of hopelessness on suicidal ideation was lower in individuals with higher hope than individuals with lower hope.Hope and hopelessness are two distinct but correlated constructs. Hope can act as a resilience factor that buffers the impact of hopelessness on suicidal ideation. Inducing hope in people may be a promising avenue for suicide prevention.

Cyclin-dependent kinase 5 (Cdk5) is a proline-directed serine/threonine kinase, which plays critical roles in a wide spectrum of neuronal functions including neuronal survival, neurite outgrowth, and synapse development and plasticity. Cdk5 activity is controlled by its specific activators: p35 or p39. While knockout studies reveal that Cdk5/p35 is critical for neuronal migration during early brain development, functions of Cdk5/p35 have been unraveled through the identification of the interacting proteins of p35, most of which are Cdk5/p35 substrates. However, it remains unclear whether p35 can regulate neuronal functions independent of Cdk5 activity. Here, we report that a nuclear protein, nuclear hormone receptor coregulator (NRC)-interacting factor 1 (NIF-1), is a new interacting partner of p35. Interestingly, p35 regulates the functions of NIF-1 independent of Cdk5 activity. NIF-1 was initially discovered as a transcriptional regulator that enhances the transcriptional activity of nuclear hormone receptors. Our results show that p35 interacts with NIF-1 and regulates its nucleocytoplasmic trafficking via the nuclear export pathway. Furthermore, we identified a nuclear export signal on p35; mutation of this site or blockade of the CRM1/exportin-dependent nuclear export pathway resulted in the nuclear accumulation of p35. Intriguingly, blocking the nuclear export of p35 attenuated the nuclear accumulation of NIF-1. These findings reveal a new p35-dependent mechanism in transcriptional regulation that involves the nucleocytoplasmic shuttling of transcription regulators.

Patients with symptomatic intracranial atherosclerosis (ICAS) of ≥ 70% luminal stenosis are at high risk of stroke recurrence. We aimed to evaluate the relationships between hemodynamics of ICAS revealed by computational fluid dynamics (CFD) models and risk of stroke recurrence in this patient subset.Patients with a symptomatic ICAS lesion of 70-99% luminal stenosis were screened and enrolled in this study. CFD models were reconstructed based on baseline computed tomographic angiography (CTA) source images, to reveal hemodynamics of the qualifying symptomatic ICAS lesions. Change of pressures across a lesion was represented by the ratio of post- and pre-stenotic pressures. Change of shear strain rates (SSR) across a lesion was represented by the ratio of SSRs at the stenotic throat and proximal normal vessel segment, similar for the change of flow velocities. Patients were followed up for 1 year.Overall, 32 patients (median age 65; 59.4% males) were recruited. The median pressure, SSR and velocity ratios for the ICAS lesions were 0.40 (-2.46-0.79), 4.5 (2.2-20.6), and 7.4 (5.2-12.5), respectively. SSR ratio (hazard ratio [HR] 1.027; 95% confidence interval [CI], 1.004-1.051; P = 0.023) and velocity ratio (HR 1.029; 95% CI, 1.002-1.056; P = 0.035) were significantly related to recurrent territorial ischemic stroke within 1 year by univariate Cox regression, respectively with the c-statistics of 0.776 (95% CI, 0.594-0.903; P = 0.014) and 0.776 (95% CI, 0.594-0.903; P = 0.002) in receiver operating characteristic analysis.Hemodynamics of ICAS on CFD models reconstructed from routinely obtained CTA images may predict subsequent stroke recurrence in patients with a symptomatic ICAS lesion of 70-99% luminal stenosis.