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Background: Despite the growth and popularity of gig work, limited information exists about the occupational health and safety concerns faced by individuals who are employed through ridesharing online applications. In this qualitative study, we characterized the perceived health and safety concerns of drivers employed by rideshare companies. Methods: During September–October 2019, we requested car rides, using digital rideshare platforms. During the ride, drivers responded verbally to a brief closed-end sociodemographic and work characteristics survey. A semi-structured interview script was used to collect rideshare driver perceptions on health and safety risks. Findings: A total of 35 rideshare drivers of group mean age of 43.1 ± 11.2 years were interviewed, of whom 77.1% were male and 82.9% identified as Latino. Sixty percent of participants reported rideshare as their primary job, working an average of 47.9 ± 19.6 hours weekly (minimum = 6 hours, maximum = 84 hours). Drivers enjoyed job autonomy yet faced stressors such as passenger risky behavior, car accidents, and lack of policies that protect the driver. Rideshare drivers also raised concerns about their current health status, economic pressures, and worker safety. Conclusion/Application to Practice: Drivers are forced to extend work hours to support themselves financially, exacerbating their current health concerns and safety risks as it means more time spent working in their sedentary job, compromising their mental and physical health as well as their safety. Occupational health and safety programs geared toward workers in the gig economy are needed.

OBJECTIVES: Characterize occupational cancer risk perceptions and attitudes towards cancer prevention practices among firefighters in the Dominican Republic. METHODS: Focus group discussions and key informant interviews were conducted in June 2019 among firefighters from three fire departments. Themes were inductively created using a qualitative descriptive approach. RESULTS: Thirty-seven firefighters were interviewed with a group mean age of 36.2 ±10.3 years, of which 97.3% were male, and 37.1% worked at least 10 years. Six themes emerged: 1) availability of personal protective equipment (PPE); 2) constant toxic exposure during fire suppression; 3) occupational stress due to emergency response experiences; 4) lack of workplace health promotion activities and policies at the fire department level; 5)firefighters attribute Dominican Culture for not engaging in medical checkups; and 6) expensive medical copays limits healthcare access. CONCLUSION: Dominican firefighters are willing to adopt cancer prevention practices, however organizational barriers (i.e., PPE availability, cultural barriers, health promotion practices) limit engagement.

OBJECTIVES We use a qualitative method to gain further insight into women firefighters' experiences, perceptions of cancer, health, and safety risks in the fire service. METHODS We conducted six focus groups with U.S. women firefighters. Participants engaged in a 60 to 75-minute, semi-structured discussion and completed a sociodemographic questionnaire. A qualitative descriptive approach was used to inductively create themes. Data collection concluded when saturation was met. RESULTS Forty-nine women firefighters participated. Qualitative results indicated the main health concerns include: occupational cancer risks including, risks related to hazardous exposures, sleep disruption and stress; and women's health concerns including, cancer, pregnancy and breastfeeding, and lack of resources. CONCLUSIONS Women firefighters are concerned about their risk for cancer due to their occupation and identify a lack of resources specific to health and safety needs of women firefighters.

BACKGROUND Fishing industry workers are exposed to hazardous working conditions, engage in strenuous labor, and work long hours in variable weather conditions. Despite these known employment challenges, little is known of their perceived occupational health and safety concerns. In this pilot study, we: (1) describe fishermen's perceptions on worker- and organizational-level characteristics that impact occupational health and safety; and (2) estimate environmental exposure to polycyclic aromatic hydrocarbons (PAHs) encountered during fishing activities. METHODS We collected both qualitative and quantitative data from Mississippi and Florida fishermen. Using an ethnographic approach, the study team conducted 1-h key informant interviews, administered a one-page demographic survey, and collected objective measurements to PAHs using silicone-based passive sampling wristbands. RESULTS Study participants (n = 17) had a mean age of 50.9 years (SD = 11.7), 88.2% were male, 94.1% white, 100.0% non-Hispanic/Latino, and 52.9% were married. Approximately, 87.5% reported fishing as their primary job, with a mean of 26.4 years in the industry (SD = 15.3). Four broad themes describing the culture of the fishing industry, common workplace exposures that impact fishermen's safety and health, and facilitators and barriers to safety while working in the fishing industry were documented. Deckhands had the lowest mean exposure to PAHs (8.3 ppb), followed by crew members (11.0 ppb), captains (82.64 ppb), and net makers (208.1 ppb). CONCLUSIONS Gulf coast fishermen expressed specific occupational health and safety concerns and were exposed to carcinogenic PAHs during regular work. Opportunities exist and strategies are needed for health protection and health promotion interventions among Gulf fishermen.

ObjectiveAltered bacterial composition is associated with disease progression in cirrhosis but the role of virome, especially phages, is unclear.DesignCross-sectional and pre/post rifaximin cohorts were enrolled. Cross-sectional: controls and cirrhotic outpatients (compensated, on lactulose (Cirr-L), on rifaximin (Cirr-LR)) were included and followed for 90-day hospitalisations. Pre/post: compensated cirrhotics underwent stool collection pre/post 8 weeks of rifaximin. Stool metagenomics for bacteria and phages and their correlation networks were analysed in controls versus cirrhosis, within cirrhotics, hospitalised/not and pre/post rifaximin.ResultsCross-sectional: 40 controls and 163 cirrhotics (63 compensated, 43 Cirr-L, 57 Cirr-LR) were enrolled. Cirr-L/LR groups were similar on model for end-stage liver disease (MELD) score but Cirr-L developed greater hospitalisations versus Cirr-LR (56% vs 30%, p=0.008). Bacterial alpha/beta diversity worsened from controls through Cirr-LR. While phage alpha diversity was similar, beta diversity was different between groups. Autochthonous bacteria linked negatively, pathobionts linked positively with MELD but only modest phage-MELD correlations were seen. Phage–bacterial correlation network complexity was highest in controls, lowest in Cirr-L and increased in Cirr-LR. Microviridae and Faecalibacterium phages were linked with autochthonous bacteria in Cirr-LR, but not Cirr-L hospitalised patients had greater pathobionts, lower commensal bacteria and phages focused on Streptococcus, Lactococcus and Myoviridae. Pre/post: No changes in alpha/beta diversity of phages or bacteria were seen postrifaximin. Phage–bacterial linkages centred around urease-producing Streptococcus species collapsed postrifaximin.ConclusionUnlike bacteria, faecal phages are sparsely linked with cirrhosis characteristics and 90-day outcomes. Phage and bacterial linkages centred on urease-producing, ammonia-generating Streptococcus species were affected by disease progression and rifaximin therapy and were altered in patients who experienced 90-day hospitalisations.

Objective We aim to non-invasively facilitate activation of spared neural circuits after cervical spinal cord injury (SCI) and amyotrophic lateral sclerosis (ALS). We developed and tested a novel configuration for cervical transcutaneous spinal stimulation (cTSS). Methods cTSS was delivered via electrodes placed over the midline at ~T2-T4 levels posteriorly and ~C4-C5 levels anteriorly. Electromyographic responses were measured in arm and hand muscles across a range of stimulus intensities. Double-pulse experiments were performed to assess homosynaptic post-activation depression (PAD). Safety was closely monitored. Results More than 170 cTSS sessions were conducted without major safety or tolerability issues. A cathode-posterior, 2 ms biphasic waveform provided optimal stimulation characteristics. Bilateral upper extremity muscle responses were easily obtained in subjects with SCI and ALS. Resting motor threshold at the abductor pollicis brevis muscle ranged from 5.5 to 51.0 mA. As stimulus intensity increased, response latencies to all muscles decreased. PAD was incomplete at lower stimulus intensities, and decreased at higher stimulus intensities. Conclusions Posteroanterior cTSS has the capability to target motor neurons both trans-synaptically via large-diameter afferents and non-synaptically via efferent motor axons. Significance Posteroanterior cTSS is well tolerated and easily activates upper extremity muscles in individuals with SCI and ALS.

ObjectivesTo understand and characterise the construct of ‘near misses’ from the perspective of temporary construction workers and to describe the safety and health risks associated with and contributing to near misses and injuries in temporary workers in the construction industry.MethodsSix semistructured language-sensitive (ie, English and Spanish) focus group discussions were conducted with workers (n=43) employed with temporary staffing agencies in South Florida. This convenience sample completed a demographic questionnaire prior to the focus group discussion. A general inductive approach was used to examine near misses in the construction industry and the unique safety and health concerns of temporary workers.ResultsFour broad themes describing near misses, reporting practices and workplace safety hazards in the construction industry were derived from the group discussions: (1) non-standard workers in the construction industry draw a clear distinction between near misses and injury and believe their best protections from both occur at the worker level; (2) social network structure on construction worksites is an effective way to protect workers against injury and near misses; (3) safety and health priorities and policies at the organisational level differ from those at the worker level, which contributes to workplace injury; and (4) reporting of safety concerns and near misses is influenced by injury severity.ConclusionsTemporary workers in the construction industry are familiar with near misses but have limited resources to protect themselves against potential health and safety hazards. These non-standard workers addressed unique barriers to staying safe at work and identified potential improvements.

Dysbiosis of the intestinal microbiota has been shown to result in altered immune responses and increased susceptibility to infection; as such, the state of the intestinal microbiome may have profound implications in the perioperative setting. In this first-in-class study, we used 16s ribosomal RNA sequencing and analysis in a mouse model of general anesthesia to investigate the effects of volatile anesthetics on the diversity and composition of the intestinal microbiome. After 4-hour exposure to isoflurane, we observed a decrease in bacterial diversity. Taxonomic alterations included depletion of several commensal bacteria including Clostridiales. These data identify volatile anesthetics as potential contributors to microbial dysbiosis in the postoperative patient.

Despite known individual-level facilitators of cancer screening, the impact of work-related organizational-level characteristics on cancer screening is unknown particularly in the firefighter workforce who is experiencing a disproportionate burden of cancer. We examine the association between fire service organizational-level factors and implementation of cancer screening activities within Florida fire departments. We used a cross-sectional observational study design to survey fire department leaders attending the Florida Fire Chiefs' Association Health and Safety conference about cancer screening activities implemented by their fire departments. Measures assessing organizational-level characteristics include: fire department workforce size, total health and safety officers, fire department geographic location, employment type, leadership support and capacity. Among the 126 fire departments participating (response rate = 47.7%), approximately 44% reported some type of cancer screening activity in the 12 months prior to survey administration. The proportion of fire departments with two or more health and safety officers was significantly greater among those with cancer screening activities as compared with departments without cancer screening activities (46.3% vs. 24.2%; P = 0.016). There were no statistical differences noted for cancer screening activities among all other organizational-level characteristics including workforce size, fire department geographic location, employment type, leadership support, and individual capacity measures. Most organizational-level characteristics of a fire department evaluated in this study were not associated with cancer screening activities; however, having two or more dedicated health and safety officers supports the delivery of cancer screening activities. These officers may be a key to improving availability of cancer screening activities at work.

Background Fructose consumption has been linked to nonalcoholic fatty liver disease (NAFLD) in children. However, the effect of high-fructose corn syrup (HFCS) compared with sucrose in pediatric NAFLD has not been investigated. Objectives We tested whether the isocaloric substitution of dietary sucrose by HFCS would increase the severity of NAFLD in juvenile pigs, and whether this effect would be associated with changes in gut histology, SCFA production, and microbial diversity. Methods Iberian pigs, 53-d-old and pair-housed in pens balanced for weight and sex, were randomly assigned to receive a mash diet top-dressed with increasing amounts of sucrose (SUC; n = 3 pens; 281.6-486.8 g/kg diet) or HFCS (n = 4; 444.3-724.8 g/kg diet) during 16 wk. Diets exceeded the animal's energy requirements by providing sugars in excess, but met the requirements for all other nutrients. Animals were killed at 165 d of age after blood sampling, and liver, muscle, and gut were collected for histology, metabolome, and microbiome analyses. Data were analyzed by multivariate and univariate statistics. Results Compared with SUC, HFCS increased subcutaneous fat, triacylglycerides in plasma, and butyrate in colon (P ≤ 0.05). In addition, HFCS decreased UMP and short-chain acyl carnitines in liver, and urea nitrogen and creatinine in serum (P ≤ 0.05). Microbiome analysis showed a 24.8% average dissimilarity between HFCS and SUC associated with changes in SCFA-producing bacteria. Body weight gain, intramuscular fat, histological and serum markers of liver injury, and circulating hormones, glucose, and proinflammatory cytokines did not differ between diets. Conclusions Fructose consumption derived from HFCS promoted butyrate synthesis, triglyceridemia, and subcutaneous lipid deposition in juvenile Iberian pigs, but did not increase serum and histological markers of NAFLD compared with a sucrose-enriched diet. Longer studies could be needed to observe differences in liver injury among sugar types.

Background: Firefighters suffer from a disproportionally high burden of chronic diseases that could be prevented from regular bouts of physical activity (PA). The goal(s) of this pilot study were to (a) describe typical PA levels in professional paid firefighters, and (b) assess their ability to estimate their own levels of PA. Methods: A repeated measures study design was used to assess self-reported and objectively measured levels of PA from a non-probabilistic sample of firefighters ( n = 18) over 1 week. Objective measures of PA, measured by accelerometry were defined as the number of minutes spent in sedentary, light, moderate, and vigorous PA. Firefighters completed a follow-up questionnaire recording their self-reported levels of PA. Results: Obese (body mass index [BMI] > 30 kg/m2) firefighters spent 8,033 ± 2,543 minutes/week in sedentary activity, overweight (BMI = 25–29 kg/m2) firefighters 6,533 ± 1,587 minutes/week, and healthy weight (BMI = 18.5–24.9 kg/m2) firefighters 5,846 ± 1,160 minutes/week. The difference in self-reported weekly minutes spent in light, moderate, and vigorous activity and objectively measured minutes in activity was calculated. Healthy weight firefighters reported the least difference (1,924 minutes/week), followed by the overweight (3,884 minutes/week) and obese (5,749 minutes/week). Conclusion/Application to Practice: Firefighters poorly estimated their true level of PA compared with their objectively measured PA and obese firefighters reported the greatest inconsistency. Occupational health nurses should aim to support firefighters in achieving PA levels that assist firefighters to achieve a healthy weight and educate them about what it means to be engaged in each level of PA.

ObjectivesWe estimate the point seroprevalence of SARS-CoV-2 antibodies in the frontline firefighter/paramedic workforce of a South Florida fire department located in the epicentre of a State outbreak.MethodsA cross-sectional study design was used to estimate the point seroprevalence of SARS-CoV-2 antibodies using a rapid immunoglobulin (Ig)M-IgG combined point-of-care lateral flow immunoassay among frontline firefighters/paramedics collected over a 2-day period, 16–17 April 2020. Fire department personnel were emailed a survey link assessing COVID-19 symptoms and work exposures the day prior to the scheduled drive-through antibody testing at a designated fire station. Off-duty and on-duty firefighter/paramedic personnel drove through the fire station/training facility in their personal vehicles or on-duty engine/rescue trucks for SARS-CoV-2 antibody testing.ResultsAmong the 203 firefighters/paramedics that make up the fire department workforce, 18 firefighters/paramedics (8.9%) tested positive for SARS-CoV-2 antibodies, of which 8 firefighters/paramedics (3.9%) were IgG positive only, 8 (3.9%) were IgM positive only and 2 (0.1%) were IgG/IgM positive. The positive predictive value (PPV) of the serological test is estimated to be 33.2% and the negative predictive value is 99.3%. The average number of COVID-19 case contacts (ie, within 6 feet of an infected person (laboratory-confirmed or probable COVID-19 patient) for ≥15 min) experienced by firefighters/paramedics was higher for those with positive serology compared with those with negative (13.3 cases vs 7.31 cases; p=0.022). None of the antibody positive firefighters/paramedics reported receipt of the annual influenza vaccine compared with firefighters/paramedics who tested negative for SARS-CoV-2 antibodies (0.0% vs 21.0%; p=0.027).ConclusionRapid SARS-CoV-2 IgM-IgG antibody testing documented early-stage and late-stage infection in a firefighter workforce providing insight to a broader medical surveillance project on return to work for firefighters/paramedics. Given the relatively low PPV of the serological test used in this study back in April 2020, caution should be used in interpreting test results.

Laparoscopic sacral colpopexy (LSC) is the gold standard treatment for apical pelvic organ prolapse (POP). Artificial urinary sphincter (AUS) has a high success rate in treating recurrent stress urinary incontinence (SUI).To describe the first simultaneous LSC and AUS implantation through a vesicovaginal approach to the bladder neck.Operation is performed through a transperitoneal approach. The rectovaginal space is created and the posterior mesh is fixed. The vesicovaginal and both laterovesical spaces are dissected. The vesicovaginal space is connected to both lateral spaces. This is main step of the procedure because it let us place the cuff around the bladder neck in a non-blind fashion. The anterior mesh is fixed to the vagina. The anterior side of the bladder neck is dissected and the cuff implanted. Both meshes are fixed to the promontory. Pressure-regulating balloon is inserted, the pump is placed in the labia majora and the components are connected. Peritoneum is closed.Surgical time was 180 minutes, bladder catheter was removed at 5th postoperative day, hospital stay was 5 days. The AUS was activated 6 weeks after surgery. No perioperative complications occurred. After 12 months the patient is pad-free and prolapse was objectively and subjectively cured.Vesicovaginal dissection is a shared step in this technique of LSC and AUS implantation. This approach could minimize the risk of bladder neck injury. We propose this technique in selected cases of prolapse and recurrent SUI.

Prior studies have shown that high-fat diet (HFD) can have profound effects on the gastrointestinal (GI) tract microbiome and also demonstrate that bacteria in the GI tract can affect metabolism and lean/obese phenotypes. We investigated whether the composition of viral communities that also inhabit the GI tract are affected by shifts from normal to HFD. We found significant and reproducible shifts in the content of GI tract viromes after the transition to HFD. The differences observed in virome community membership and their associated gene content suggest that these altered viral communities are populated by viruses that are more virulent toward their host bacteria. Because HFD also are associated with significant shifts in GI tract bacterial communities, we believe that the shifts in the viral community may serve to drive the changes that occur in associated bacterial communities., Alterations in diet can have significant impact on the host, with high-fat diet (HFD) leading to obesity, diabetes, and inflammation of the gut. Although membership and abundances in gut bacterial communities are strongly influenced by diet, substantially less is known about how viral communities respond to dietary changes. Examining fecal contents of mice as the mice were transitioned from normal chow to HFD, we found significant changes in the relative abundances and the diversity in the gut of bacteria and their viruses. Alpha diversity of the bacterial community was significantly diminished in response to the diet change but did not change significantly in the viral community. However, the diet shift significantly impacted the beta diversity in both the bacterial and viral communities. There was a significant shift away from the relatively abundant Siphoviridae accompanied by increases in bacteriophages from the Microviridae family. The proportion of identified bacteriophage structural genes significantly decreased after the transition to HFD, with a conserved loss of integrase genes in all four experimental groups. In total, this study provides evidence for substantial changes in the intestinal virome disproportionate to bacterial changes, and with alterations in putative viral lifestyles related to chromosomal integration as a result of shift to HFD. IMPORTANCE Prior studies have shown that high-fat diet (HFD) can have profound effects on the gastrointestinal (GI) tract microbiome and also demonstrate that bacteria in the GI tract can affect metabolism and lean/obese phenotypes. We investigated whether the composition of viral communities that also inhabit the GI tract are affected by shifts from normal to HFD. We found significant and reproducible shifts in the content of GI tract viromes after the transition to HFD. The differences observed in virome community membership and their associated gene content suggest that these altered viral communities are populated by viruses that are more virulent toward their host bacteria. Because HFD also are associated with significant shifts in GI tract bacterial communities, we believe that the shifts in the viral community may serve to drive the changes that occur in associated bacterial communities.

To investigate the role of bile acids (BAs) in the pathogenesis of diet-induced nonalcoholic steatohepatitis (NASH), we fed a “Western-style diet” [high fructose, high fat (HFF)] enriched with fructose, cholesterol, and saturated fat for 10 wk to juvenile Iberian pigs. We also supplemented probiotics with in vitro BA deconjugating activity to evaluate their potential therapeutic effect in NASH. Liver lipid and function, cytokines, and hormones were analyzed using commercially available kits. Metabolites, BAs, and fatty acids were measured by liquid chromatography-mass spectrometry. Histology and gene and protein expression analyses were performed using standard protocols. HFF-fed pigs developed NASH, cholestasis, and impaired enterohepatic Farnesoid-X receptor (FXR)-fibroblast growth factor 19 (FGF19) signaling in the absence of obesity and insulin resistance. Choline depletion in HFF livers was associated with decreased lipoprotein and cholesterol in serum and an increase of choline-containing phospholipids in colon contents and trimethylamine- N-oxide in the liver. Additionally, gut dysbiosis and hyperplasia increased with the severity of NASH, and were correlated with increased colonic levels of choline metabolites and secondary BAs. Supplementation of probiotics in the HFF diet enhanced NASH, inhibited hepatic autophagy, increased excretion of taurine and choline, and decreased gut microbial diversity. In conclusion, dysregulation of BA homeostasis was associated with injury and choline depletion in the liver, as well as increased biliary secretion, gut metabolism and excretion of choline-based phospholipids. Choline depletion limited lipoprotein synthesis, resulting in hepatic steatosis, whereas secondary BAs and choline-containing phospholipids in colon may have promoted dysbiosis, hyperplasia, and trimethylamine synthesis, causing further damage to the liver.NEW & NOTEWORTHY Impaired Farnesoid-X receptor (FXR)-fibroblast growth factor 19 (FGF19) signaling and cholestasis has been described in nonalcoholic fatty liver disease (NAFLD) patients. However, therapeutic interventions with FXR agonists have produced contradictory results. In a swine model of pediatric nonalcoholic steatohepatitis (NASH), we show that the uncoupling of intestinal FXR-FGF19 signaling and a decrease in FGF19 levels are associated with a choline-deficient phenotype of NASH and increased choline excretion in the gut, with the subsequent dysbiosis, colonic hyperplasia, and accumulation of trimethylamine- N-oxide in the liver.

Background Measurement of skin involvement is essential for the diagnosis and assessment of prognosis and disease progression in systemic sclerosis (SSc). The modified Rodnan skin score (mRSS) is the gold standard measure of skin thickness, but it has been criticised for the lack of objectivity, poor inter-observer reproducibility and lack of sensitivity to change. Recently, shear-wave elastography (SWE) emerged as a promising tool for the objective and quantitative assessment of the skin in SSc patients. However, no studies have evaluated its sensitivity to change over time. Objective To assess changes in skin stiffness in SSc patients using SWE during a 5-year follow-up. Methods Skin stiffness [i.e. shear-wave velocity values (SWV) in metres per second] was assessed by SWE ultrasound (using virtual touch image quantification) at the 17 sites of the mRSS, in each participant, at baseline and follow-up. mRSS was performed at both time points. Differences between groups were analysed using the related-samples Wilcoxon signed-rank test and the Mann–Whitney U test. Results We included 21 patients [85.7% females; mean age 56.3 (10.4) years at baseline, 57.1% with limited SSc] and 15 healthy controls [73.3% females; mean age 53.6 (14.1) years)]. The median follow-up was 4.9 (0.4) years. Skin stiffness decreased significantly at all Rodnan sites (p ≤ 0.001) (except in the fingers), in SSc patients, over time. The same phenomenon occurred in controls, but to a lesser degree, in terms of percentage change. The percentage reduction in skin stiffness varied in the different Rodnan sites and in different phases of the disease. In addition, SWV values also decreased significantly in 15/16 skin sites with local normal Rodnan at baseline, whereas local Rodnan skin score only changed significantly in the upper arm (p = 0.046) and forearm (p = 0.026). Conclusion This study provides first-time evidence suggesting that skin SWV values are more sensitive to change over time than mRSS and reduce significantly over time in SSc and normal controls.

In 2017, approximately 5 million Americans were living with Alzheimer’s disease (AD), and it is estimated that by 2050 this number could increase to 16 million. In this study, we apply mathematical optimization to approach microarray analysis to detect differentially expressed genes and determine the most correlated structure among their expression changes. The analysis of {"type":"entrez-geo","attrs":{"text":"GSE4757","term_id":"4757"}}GSE4757 microarray dataset, which compares expression between AD neurons without neurofibrillary tangles (controls) and with neurofibrillary tangles (cases), was casted as a multiple criteria optimization (MCO) problem. Through the analysis it was possible to determine a series of Pareto efficient frontiers to find the most differentially expressed genes, which are here proposed as potential AD biomarkers. The Traveling Sales Problem (TSP) model was used to find the cyclical path of maximal correlation between the expression changes among the genes deemed important from the previous stage. This leads to a structure capable of guiding biological exploration with enhanced precision and repeatability. Ten genes were selected (FTL, GFAP, HNRNPA3, COX1, ND2, ND3, ND4, NUCKS1, RPL41, and RPS10) and their most correlated cyclic structure was found in our analyses. The biological functions of their products were found to be linked to inflammation and neurodegenerative diseases and some of them had not been reported for AD before. The TSP path connects genes coding for mitochondrial electron transfer proteins. Some of these proteins are closely related to other electron transport proteins already reported as important for AD.

No treatment is available for patients with spinal cord injury (SCI). Patients often arrive to the hospital hours after SCI suggesting the need of a therapy that can be used on a clinically relevant window. Previous studies showed that Tamoxifen (TAM) treatment 24 hours after SCI benefits locomotor recovery in female rats. Tamoxifen exerts beneficial effects in male and female rodents but a gap of knowledge exists on: the therapeutic window of TAM, the spatio-temporal mechanisms activated and if this response is sexually dimorphic. We hypothesized that TAM will favor locomotor recovery when administered up-to 24 hours after SCI in male Sprague-Dawley rats. Rats received a thoracic (T10) contusion using the MACSIS impactor followed by placebo or TAM (15mg/21 days) pellets in a therapeutic window of 0, 6, 12, or 24 hours. Animals were sacrificed at 2, 7, 14, 28 or 35 days post injury (DPI) to study the molecular and cellular changes in the acute and chronic stages. Immediate or delayed therapy (t=6 hours) improved locomotor function, increased white matter spared tissue, and neuronal survival. TAM reduced reactive gliosis during chronic stages and increased the expression of Olig-2. A significant difference was observed in estrogen receptor alpha between male and female rodents from 2–28 DPI suggesting a sexually dimorphic characteristic that could be related to the behavioral differences observed in the therapeutic window of TAM. This study supports the use of TAM in the SCI setting due to its neuroprotective effects but with a significant sexually dimorphic therapeutic window.

Intragastric balloon therapy is a temporary, minimally invasive method for inducing weight loss. Any balloon with a volume of 400mL induces satiety and delayed gastric emptying. The aim of the present study was to demonstrate its safety and efficacy.We analyzed the safety and effectiveness of balloon placement in relation to weight loss in 128patients. Subgroups were compared through the Student's t test, ANOVA test, and the chi-square test, depending on the type of variable and the number of groups evaluated. Statistical significance was set at a P≤.05 to evaluate weight loss.Mean weight loss after balloon therapy was 10.7kg, with only 2 cases of complications due to oral feeding intolerance. Mean length of time with the balloon was 8months. There were no complications after 6months, but no further weight loss either (P=.540). Final weight loss versus initial weight loss was significant (P=.000). There was greater weight loss in the group that attended the bimonthly control appointments than in the group that did not: 12.7kg vs. 7.26kg (P=.000).The rates of the adverse events of intolerance and complications were very low in our study, compared with results in the literature: 1.6% vs. 4.7% and 0% vs. 3%, respectively. Intragastric balloon placement had better results when the patients attended the control appointments. Intragastric balloon therapy is a safe and efficacious method for reducing weight in patients with overweight and obesity.

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Background and purpose Spared fibers after spinal cord injury (SCI) tend to consist predominantly of subcortical circuits that are not under volitional (cortical) control. We aim to improve function after SCI by using targeted physical exercises designed to simultaneously stimulate cortical and spared subcortical neural circuits. Methods Participants with chronic motor-incomplete SCI enrolled in a single-center, prospective interventional crossover study. Participants underwent 48 sessions each of weight-supported robotic-assisted treadmill training and a novel combination of balance and fine hand exercises, in randomized order, with a 6-week washout period. Change post-intervention was measured for lower extremity motor score, soleus H-reflex facilitation; seated balance function; ambulation; spasticity; and pain. Results Only 9 of 21 enrolled participants completed both interventions. Thirteen participants completed at least one intervention. Although there were no statistically significant differences, multimodal training tended to increase short-interval H-reflex facilitation, whereas treadmill training tended to improve dynamic seated balance. Discussion The low number of participants who completed both phases of the crossover intervention limited the power of this study to detect significant effects. Other potential explanations for the lack of significant differences with multimodal training could include insufficient engagement of lower extremity motor cortex using skilled upper extremity exercises; and lack of skill transfer from upright postural stability during multimodal training to seated dynamic balance during testing. To our knowledge, this is the first published study to report seated posturography outcomes after rehabilitation interventions in individuals with SCI. Conclusion In participants with chronic incomplete SCI, a novel mix of multimodal exercises incorporating balance exercises with skilled upper extremity exercises showed no benefit compared to an active control program of body weight-supported treadmill training. To improve participant retention in long-term rehabilitation studies, subsequent trials would benefit from a parallel group rather than crossover study design.

Introduction: After a large outbreak of dengue virus (DENV) serotype-3 in Saint Kitts and Nevis (SKN) in 2008, we performed a cross-sectional study to determine the prevalence of anti-DENV immunoglobulin G (IgG) antibodies in expatriate and local persons affiliated with an American veterinary school there. Methodology: This campus community comprised mostly expatriate students and faculty and Kittitian administrative staff. In 2009, a stratified random sample of students, faculty and staff was invited to complete an electronic survey to assess risk factors for DENV and provide blood for testing for anti-DENV IgG antibodies by an enzyme-linked immunosorbent assay. IgG-positive specimens were also tested by a 90% plaque reduction neutralization test (PRNT90) to determine immunoreactivity to DENV (1-4) serotypes and West Nile virus. Risk factors for anti-DENV IgG seropositivity were determined using simple and adjusted logistic regression. Results: Of the 118 participants, the overall prevalence of DENV IgG antibodies was 44.1% (95% confidence interval [CI]: 35.1-53.0%), ranging from 30.1% in students, 100.0% in staff and 57.9% in faculty (p < 0.001). Duration of residence in St. Kitts was the only variable significantly associated with seropositivity on multiple logistic regression (adjusted odds ratio [95% CI]: 1.21 [1.07-1.37]). The serotype of DENV was determined in 11 persons: DENV-1 (n = 4), DENV-2 (n = 3), and DENV-3 (n = 4). Conclusions: Expatriate students and faculty moving to St. Kitts from non-endemic areas were at high risk of DENV infection. There is a need for increased emphasis on pre-travel mosquito-borne virus prevention education for persons moving to St. Kitts to study and work.

OBJECTIVE We characterize and compare the self-reported physical exposures, work tasks, and OSHA-10 training in a non-probabilistic sample of temporary and payroll construction workers. METHODS In June 2016, a total of 250 payroll and temporary general laborers employed at Florida construction sites completed a survey at the job site as part of the falls reported among minority employees (FRAME) study. RESULTS Workers employed through temp agencies (57.1%) were significantly more likely to report moving or lifting materials more than 100 pounds than payroll workers (38.5%; P

Maintenance Electroconvulsive Therapy (mECT) is a biological long-term treatment in which patients receive ECT on periods from 2 to 4 weeks, during a variable period of time, usually for more than 6 months. Recent studies showed the efficacy of mECT in prevention of relapse and recurrences. Our study wants to demostrate the effectivity and cost-effectivity of this therapy in the naturalistic conditions of our area.Retrospective longitudinal study, with mirror analysis in naturalistic conditions.Patients attended at the Corporació Sanitària Parc Taulí (Sabadell, Catalonia), and included in the mECT program during more than six months. We performed diagnostic following DSM-IV criteria, subdividing the sample in three groups: patients affected of Recurrent Major Depression, Bipolar Disorder and Schizophrenia and Related Disorders.Number and duration of hospitalizations for the previous three years before the beginning of mECT, compared with the same data for the next three years following the beginning of mECT. Comparative analysis of direct hospitalization costs, costs of the mECT and pharmacologic costs. Statistic: Descriptive and non- parametric tests.Sample of 35 patients (1997-2008). There is a significative reduction the number of hospitalizations and days of hospitalization in the total sample and also in each of the three subgroups. The direct total cost decreased but it was only significant in the Bipolar Disorder subgroup, due to the increased pharmacological costs.mECT in our area is an effective and costeffective treatment with a great impact on the reduction of clinical decline and hospitalizations.

Objectives To assess the consumption of ultra-processed foods among inmates in a women’s prison in the State of São Paulo, Brazil. Methods We conducted a cross-sectional study in 2012/2013 with 1,013 female inmates. A structured interview questionnaire was used to collect socio-demographic, self-reported morbidity and healthy lifestyles and health-related behaviors data. The inmates’ usual diet was assessed with a food frequency questionnaire. Foods were classified as either natural or minimally processed, processed or ultra-processed. Results Inmates age ranged from 18 to 65 years, 51.7% were black, 80.3% had children, 69.5% smoked, 47% were overweight/obese and half of them had high blood triglycerides. The prevalence of daily consumption of natural or minimally processed foods (rice, beans and cassava flour) was 87.7%. The prevalence of daily consumption of green leafy and other vegetables was 63.7%. Almost two-thirds reported consuming milk and fried chicken frequently. A high prevalence of daily consumption of ultra-processed foods was observed in this study. Hot dog bread and sweet bread with margarine were consumed by 86.5% of the interviewees on a daily basis; sugar sweetened beverages by 68.4%, and biscuits as well as candies by 77.1%. Conclusions The women’s diet in the prison is of low quality, and may lead to metabolic alterations, obesity and other comorbidities. It is recommended that the prison’s Food Evaluation Committee considers improvements to the quality of the prisoners’ diets.

17β-Estradiol is a multi-active steroid that imparts neuroprotection via diverse mechanisms of action. However, its role as a neuroprotective agent after spinal cord injury (SCI), or the involvement of the estrogen receptor-alpha (ER-α) in locomotor recovery, is still a subject of much debate. In this study, we evaluated the effects of estradiol and of Tamoxifen (an estrogen receptor mixed agonist/antagonist) on locomotor recovery following SCI. To control estradiol cyclical variability, ovariectomized female rats received empty or estradiol filled implants, prior to a moderate contusion to the spinal cord. Estradiol improved locomotor function at 7, 14, 21, and 28 days post injury (DPI), when compared to control groups (measured with the BBB open field test). This effect was ER-α mediated, because functional recovery was blocked with an ER-α antagonist. We also observed that ER-α was up-regulated after SCI. Long-term treatment (28 DPI) with estradiol and Tamoxifen reduced the extent of the lesion cavity, an effect also mediated by ER-α. The antioxidant effects of estradiol were seen acutely at 2 DPI but not at 28 DPI, and this acute effect was not receptor mediated. Rats treated with Tamoxifen recovered some locomotor activity at 21 and 28 DPI, which could be related to the antioxidant protection seen at these time points. These results show that estradiol improves functional outcome, and these protective effects are mediated by the ER-α dependent and independent-mechanisms. Tamoxifen’s effects during late stages of SCI support the use of this drug as a long-term alternative treatment for this condition.

A prospective cohort epidemiological pilot study was performed at three tropical beaches with point- and non-point-sources of fecal pollution to characterize the risk of illness among swimmers and non-swimmers. There was an increased risk of illness in swimmers as compared to non-swimmers, even when waters met current microbial standards for recreational water quality. Illnesses included gastrointestinal (GI), skin and respiratory symptoms, earache and fever. Odds ratios (ORs) ranged from 0.32 to 42.35 (GI illness), 0.69 to 3.12 (skin infections), 0.71 to 3.21 (respiratory symptoms), 0.52 to 15.32 (earache) and 0.80 to 1.68 (fever), depending on the beach sampled. The indicators that better predicted the risks of symptoms (respiratory) in tropical recreational waters were total (somatic and male-specific) coliphages (OR = 1.56, p < 0.10, R2 = 3.79%) and Escherichia coli (OR = 1.38, p < 0.10, R2 = 1.97%). The present study supports the potential of coliphages as good predictors of risks of respiratory illness in tropical recreational waters. This is the first study that has determined risks of illness after exposure to tropical recreational waters with point- and non-point sources of fecal contamination. The results give an opportunity to perform epidemiological studies in tropical recreational waters in Puerto Rico which can include more participants and other indicators and detection techniques.

Background Obstructive sleep apnea syndrome (OSAS) and allergic rhinitis (AR) are common coexisting disorders. Upper airway, specifically al resistance, is thought to increase during exacerbations of AR and nonallergic rhinitis (NAR), as well as in OSAS. The study objective was to determine if a correlation exists between clinical control of rhinitis and OSAS. Methods This prospective study followed 43 patients with concurrent OSAS and AR or NAR. OSAS was diagnosed by polysomnography, and AR or NAR was diagnosed by history, skin testing, serum-specific IgE, and total IgE levels. Measurements of control of OSAS included the Epworth Sleepiness Scale (ESS) survey and compliance with continuous positive airway pressure (CPAP) device. Measurements of rhinitis control included Assessment of Nasal Symptom Severity and Assessment of Nonnasal Symptom Severity (NSS refers to both) and Global Assessment of Nasal and Nonnasal Symptom Severity surveys (GSS). Higher NSS scores correlate with more rhinitis symptoms, whereas higher GSS scores correlate with less symptoms. Results All patients completed the study. There was a positive correlation between ESS and NSS scores (p < 0.001), inverse correlation between ESS and GSS scores (p < 0.001), inverse correlation between CPAP compliance and NSS scores (p < 0.001), and positive correlation between CPAP compliance and GSS scores (p < 0.001). There was no statistically significant difference between the AR, NAR, and AR/NAR groups. Conclusion Our study showed a statistically significant positive correlation between clinical control of rhinitis symptoms and clinical control of OSAS. This study emphasizes the importance of achieving concurrent optimal control of both OSAS and AR/NAR.

The concept of the human oral microbiome was applied to understand health and disease, lifestyles, and dietary habits throughout part of human history. In the present study, we augment the understanding of ancient oral microbiomes by characterizing human dental calculus samples recovered from the ancient Abbey of Badia Pozzeveri (central Italy), with differences in socioeconomic status, time period, burial type, and sex. Samples dating from the Middle Ages (11th century) to the Industrial Revolution era (19th century) were characterized using high-throughput sequencing of the 16S ribosomal RNA (rRNA) gene V4 region. Consistent with previous studies, individuals from Badia Pozzeveri possessed commensal oral bacteria that resembled modern oral microbiomes. These results suggest that members of the oral microbiome are ubiquitous despite differences in geographical regions, time period, sex, and socioeconomic status. The presence of fecal bacteria could be in agreement with poor hygiene practices, consistent with the time period. Respiratory tract, nosocomial, and other rare pathogens detected in the dental calculus samples are intriguing and could suggest subject-specific comorbidities that could be reflected in the oral microbiome.

In 2009, an increased proportion of suspected dengue cases reported to the surveillance system in Puerto Rico were laboratory negative. As a result, enhanced acute febrile illness (AFI) surveillance was initiated in a tertiary care hospital. Patients with fever of unknown origin for 2-7 days duration were tested for Leptospira, enteroviruses, influenza, and dengue virus. Among the 284 enrolled patients, 31 dengue, 136 influenza, and 3 enterovirus cases were confirmed. Nearly half (48%) of the confirmed dengue cases met clinical criteria for influenza. Dengue patients were more likely than influenza patients to have hemorrhage (81% versus 26%), rash (39% versus 9%), and a positive tourniquet test (52% versus 18%). Mean platelet and white blood cell count were lower among dengue patients. Clinical diagnosis can be particularly difficult when outbreaks of other AFI occur during dengue season. A complete blood count and tourniquet test may be useful to differentiate dengue from other AFIs.

A commercial anti-dengue virus (anti-DENV) indirect IgG enzyme-linked immunosorbent assay (ELISA) for serological diagnosis was evaluated for its utility in determining previous DENV exposure in U.S. travelers. The Boston Area Travel Medicine Network clinics used Focus Diagnostics anti-DENV IgG ELISA to measure anti-DENV IgG antibodies in 591 pretravel specimens from U.S. residents who had traveled to countries where dengue is endemic. When using the manufacturer's index cutoff value for this ELISA, false-positive results were observed that overestimated the perceived past DENV exposure in U.S. travelers. Validation of 121 of these anti-DENV IgG results by plaque reduction neutralization test (PRNT) was used for receiver operating characteristic (ROC) curve optimization of the index cutoff value from 1 to 3.0, improving the specificity of the anti-DENV IgG ELISA from 24% to 95.7%. Additionally, previous vaccination with yellow fever virus contributed to 52.8% of the false-positive rate in the anti-DENV IgG ELISA results. Optimization of the cutoff value of the anti-DENV IgG ELISA provided better interpretation and confidence in the results and eliminated the need for confirmation by PRNT. The travel history of U.S. travelers was also useful for categorizing these travelers into groups for analysis of previous DENV exposure.

Spinal cord injury (SCI) is a condition with no available cure. The initial physical impact triggers a cascade of molecular and cellular events that generate a nonpermissive environment for cell survival and axonal regeneration. Spinal cord injured patients often arrive at the clinic hours after the initial insult. This indicates the need to study and develop treatments with a long therapeutic window of action and multiactive properties, which target the complex set of events that arise after the initial trauma. We provide evidence that tamoxifen (TAM), a drug approved by the Food and Drug Administration, exerts neuroprotective effects in an animal model when applied up-to 24 h after SCI. We hypothesized that continuous TAM administration will improve functional locomotor recovery by favoring myelin preservation and reducing secondary damage after SCI. Adult female Sprague-Dawley rats (∼230 g) received a moderate contusion to the thoracic (T9-T10) spinal cord, using the MASCIS impactor device. To determine the therapeutic window available for TAM treatment, rats were implanted with TAM pellets (15 mg) immediately or 24 h after SCI. Locomotor function (Basso, Beattie, Bresnahan open field test, grid walk, and beam crossing tests) was assessed weekly for 35 days post-injury. TAM-treated rats showed significant functional locomotor recovery and improved fine movements when treated immediately or 24 h after SCI. Further, TAM increased white matter preservation and reduced secondary damage caused by astrogliosis, axonal degeneration, and cell death after trauma. These results provide evidence for TAM as a potential therapeutic agent to treat SCI up to 24 h after the trauma.

17β-Estradiol (17βE) regulates glucose homeostasis in part by centrally mediated mechanisms. In female rodents, the influence of the ovarian cycle on hypoglycemia counterregulation and glucose tolerance is unclear. We found previously that in prepubertal females, 17βE modulates glucose sensing in nonadapting glucose-inhibited (GI) and adapting GI (AdGI) neurons within the ventrolateral portion of the ventromedial nucleus (VL-VMN). Nonadapting GI neurons persistently decrease their activity as glucose increases while AdGI neurons transiently respond to a glucose increase. To begin to understand if endogenous fluctuations in estrogen levels across the estrous cycle impact hypothalamic glucose sensing and glucose homeostasis, we assessed whether hypoglycemia counterregulation and glucose tolerance differed across the phases of the estrous cycle. We hypothesized that the response to insulin-induced hypoglycemia (IIH) and/or glucose tolerance would vary throughout the estrous cycle according to changes in 17βE availability. Moreover, that these changes would correlate with estrous-dependent changes in the glucose sensitivity of VL-VMN glucose-sensing neurons (GSNs).These hypotheses were tested in female mice by measuring the response to IIH, glucose tolerance and the glucose sensitivity of VL-VMN GSNs during each phase of the estrous cycle. Furthermore, a physiological brain concentration of 17βE seen during proestrus was acutely applied to brain slices isolated on the day of diestrous and the response to low glucose in VL-VMN GSNs was assayed.The response to IIH was strongest during diestrous. The response of nonadapting GI and AdGI neurons to a glucose decrease from 2.5 to 0.5mM also peaked during diestrous; an effect which was blunted by the addition of 17βE. In contrast, the glucose sensitivity of the subpopulation of GSNs which are excited by glucose (GE) was not affected by estrous phase or exogenous 17βE application.These data suggest that physiological fluctuations in circulating 17βE levels across the estrous cycle lead to changes in hypothalamic glucose sensing and the response to IIH.

Background Antibiotics are a mainstay of treatment for bacterial infections worldwide, yet the effects of typical antibiotic prescriptions on human indigenous microbiota have not been thoroughly evaluated. We examined the effects of the two most commonly prescribed antibiotics (amoxicillin and azithromycin) in the USA to discern whether short-term antibiotic courses may have prolonged effects on human microbiota. Results We sampled the feces, saliva, and skin specimens from a cohort of unrelated, cohabitating individuals over 6 months. An individual in each household was given an antibiotic, and the other a placebo to discern antibiotic impacts on microbiota, as well as determine whether antibiotic use might reshape the microbiota of each household. We observed household-specific patterns of microbiota on each body surface, which persevered despite antibiotic perturbations. While the gut microbiota within an individual became more dissimilar over time, there was no evidence that the use of antibiotics accelerated this process when compared to household members. There was a significant change in microbiota diversity in the gut and mouth in response to antibiotics, but analogous patterns were not observed on the skin. Those who received 7 days of amoxicillin generally had greater reductions in diversity compared to those who received 3 days, in contrast to those who received azithromycin. Conclusions As few as 3 days of treatment with the most commonly prescribed antibiotics can result in sustained reductions in microbiota diversity, which could have implications for the maintenance of human health and resilience to disease. Electronic supplementary material The online version of this article (doi:10.1186/s40168-016-0187-9) contains supplementary material, which is available to authorized users.

Infection by Toxoplasma gondii affects around one-third of world population and the treatment for patients presenting toxoplasmosis clinically manifested disease is mainly based by a combination of sulfadiazine, pyrimethamine, and folinic acid. However, this therapeutic protocol is significantly toxic, causing relevant dose-related bone marrow damage. Thus, it is necessary to improve new approaches to investigate the usefulness of more effective and non-toxic agents for treatment of patients with toxoplasmosis. It has been described that lectins from plants can control parasite infections, when used as immunological adjuvants in vaccination procedures. This type of lectins, such as ArtinM and ScLL is able to induce immunostimulatory activities, including efficient immune response against parasites. The present study aimed to evaluate the potential immunostimulatory effect of ScLL and ArtinM for treatment of T. gondii infection during acute phase, considering that there is no study in the literature accomplishing this issue. For this purpose, bone marrow-derived macrophages (BMDMs) were treated with different concentrations from each lectin to determine the maximum concentration without or with lowest cytotoxic effect. After, it was also measured the cytokine levels produced by these cells when stimulated by the selected concentrations of lectins. We found that ScLL showed high capacity to induce of pro-inflammatory cytokine production, while ArtinM was able to induce especially an anti-inflammatory cytokines production. Furthermore, both lectins were able to increase NO levels. Next, we evaluated the treatment effect of ScLL and ArtinM in C57BL/6 mice infected by ME49 strain from T. gondii. The animals were infected and treated with ScLL, ArtinM, ArtinM plus ScLL, or sulfadiazine, and the following parameters analyzed: Cytokines production, brain parasite burden and survival rates. Our results demonstrated that the ScLL or ScLL plus ArtinM treatment induced production of pro-inflammatory and anti-inflammatory cytokines, showing differential but complementary profiles. Moreover, when compared with non-treated mice, the parasite burden was significantly lower and survival rates higher in mice treated with ScLL or ScLL plus ArtinM, similarly with sulfadiazine treatment. In conclusion, the results demonstrated the suitable potential immunotherapeutic effect of ScLL and ArtinM lectins to control acute toxoplasmosis in this experimental murine model.

Some receptors that block axonal regeneration or promote cell death after spinal cord injury (SCI) are localized in membrane rafts. Flotillin-2 (Flot-2) is an essential protein associated with the formation of these domains and the clustering of membranal proteins, which may have signaling activities. Our hypothesis is that trauma will change Flot-2 expression and interference of this lipid raft marker will promote functional locomotor recovery after SCI. Analyses were conducted to determine the spatio-temporal profile of Flot-2 expression in adult rats after SCI, using the MASCIS impactor device. Immunoblots showed that SCI produced a significant decrease in the level of Flot-2 at 2 days post-injury (DPI) that increased until 28 DPI. Confocal microscopy revealed Flot-2 expression in neurons, reactive astrocytes and oligodendrocytes specifically associated to myelin structures near or close to the axons of the cord. In the open field test and grid walking assays, to monitor locomotor recovery of injured rats infused intrathecally with Flot-2 antisense oligonucleotides for 28 days showed significant behavioral improvement at 14, 21 and 28 DPI. These findings suggest that Flot-2 has a role in the non-permissive environment that blocks locomotor recovery after SCI by clustering unfavorable proteins in membrane rafts.

Dengue, endemic in Puerto Rico, is a major public health problem. Vaccines are thought the best means to prevent dengue because vector control alone has been largely ineffective. We implemented qualitative studies in 2006 and 2010 to determine the acceptability of conducting placebo-controlled dengue vaccine efficacy trials in Puerto Rican children. Key informant interviews and focus groups with parents and children were conducted in municipalities with high dengue incidence. We used structured open-ended questions to determine motivators and attitudes regarding vaccine trial participation. Knowledge about dengue risk and prevention, and knowledge, attitudes, and beliefs regarding vaccines and vaccine trials were assessed. Using grounded theory, we conducted content analysis and established categories and sub-categories of participant responses. All participants were knowledgeable about dengue prevention and perceived children as most affected age groups. Participants were aware of vaccines benefits and they thought a vaccine could prevent dengue. However, most would not allow their children to participate in a placebo-controlled vaccine trial. Barriers included lack of trust in new vaccines and vaccine trial procedures; fear of developing dengue or side effects from the vaccine and lack of information about candidate dengue vaccines. Participants thought information, including results of previous trials might overcome barriers to participation. Motivators for participation were altruism, protection from dengue, free medical attention, and compensation for transportation and participation. Parents would consider children participation if accurate vaccine trial information is provided.

Lung cancer is the leading cause of cancer death for both men and women worldwide. Since most of the symptoms found for lung cancer are nonspecific, diagnosis is mostly done at late and progressed stage with the consecutive poor therapy outcome. Effective early detection techniques are sorely needed. The emerging field of salivary diagnostics could provide scientifically credible, easy-to-use, non-invasive and cost-effective detection methods. Recent advances have allowed us to develop discriminatory salivary biomarkers for a variety of diseases from oral to systematic diseases. In this study, salivary transcriptomes of lung cancer patients were profiled and led to the discovery and pre-validation of seven highly discriminatory transcriptomic salivary biomarkers (BRAF, CCNI, EGRF, FGF19, FRS2, GREB1, and LZTS1). The logistic regression model combining five of the mRNA biomarkers (CCNI, EGFR, FGF19, FRS2, and GREB1) could differentiate lung cancer patients from normal control subjects, yielding AUC value of 0.925 with 93.75 % sensitivity and 82.81 % specificity in the pre-validation sample set. These salivary mRNA biomarkers possess the discriminatory power for the detection of lung cancer. This report provides the proof of concept of salivary biomarkers for the non-invasive detection of the systematic disease. These results poised the salivary biomarkers for the initiation of a multi-center validation in a definitive clinical context.

Failure of axon regeneration after traumatic spinal cord injury (SCI) is attributable in part to the presence of inhibitory molecular interactions. Recent evidence demonstrates that activation of Eph signaling pathways leads to modulation of growth cone dynamics and repulsion through the activation of ephexin, a novel guanine nucleotide exchange factor (GEF). However, little is known about the expression and modulation of Eph molecular targets in the injured spinal cord. In this study, we determined the expression profile of ephexin after a moderate spinal cord contusion at thoracic level (T10) in young adult rats. Western Blot studies showed increased protein expression in injured rats at 4, and 7 days post-injury (DPI) when compared to control animals. The protein levels returned to normal at 14 DPI and remained steady until 28 DPI. However, immunoprecipitation studies of the phosphorylated ephexin demonstrated that this protein is activated by day 2 until 14 DPI. Expression of ephexin was noticeable in neurons, axons, microglia/macrophages and reactive astrocytes, and co-localized with EphA3, A4 and A7. These results demonstrate the presence of ephexin in the adult spinal cord, and its activation after SCI. Therefore, we show, for the first time, the spatio-temporal pattern of ephexin expression and activation after contusive spinal cord injury. Collectively, our data supports our previous findings on the putative non-permissive roles of Eph receptors after spinal cord injury, and the possible involvement of ephexin in the intracellular cascade of events.

Spinal cord injury (SCI) triggers the re-expression of inhibitory molecules present in early stages of development, contributing to prevention of axonal regeneration. Upregulation of EphA receptor tyrosine kinases after injury suggest their involvement in the nervous system's response to damage. However, the expression profile of their ephrinA ligands after SCI is unclear. In this study, we determined the expression of ephrinA ligands after contusive SCI. Adult Sprague-Dawley female rats were injured using the MASCIS impactor device at the T10 vertebrae, and levels of ephrinA mRNA and protein determined at different time points. Identification of the cell phenotype expressing the ephrin ligand and colocalization with Eph receptors was performed with immunohistochemistry and confocal microscopy. Behavioral studies were made, after blocking ephrinA1 expression with antisense (AS) oligonucleotides, to assess hindlimb locomotor activity. Real-time PCR demonstrated basal mRNA levels of ephrin (A1, A2, A3, and A5) in the adult spinal cord. Interestingly, ephrinA1 was the only ligand whose mRNA levels were significantly altered after SCI. Although ephrinA1 mRNA levels increased after 2 weeks and remain elevated, we did not observe this pattern at the protein level as revealed by western blot analysis. Immunohistochemical studies showed ephrinA1 expression in reactive astrocytes, axons, and neurons and also their colocalization with EphA4 and A7 receptors. Behavioral studies revealed worsening of locomotor activity when ephrinA1 expression was reduced. This study suggests that ephrinA1 ligands play a role in the pathophysiology of SCI.

Background.Carbapenem-resistantKlebsiella pneumoniae(CRKP) is resistant to almost all antimicrobial agents, and CRKP infections are associated with substantial morbidity and mortality.Objective.To describe an outbreak of CRKP in Puerto Rico, determine risk factors for CRKP acquisition, and detail the successful measures taken to control the outbreak.Design.Two case-control studies.Setting.A 328-bed tertiary care teaching hospital.Patients.Twenty-six CRKP case patients identified during the outbreak period of February through September 2008, 26 randomly selected uninfected control patients, and 26 randomly selected control patients with carbapenem-susceptibleK. pneumoniae(CSKP) hospitalized during the same period.Methods.We performed active case finding, including retrospective review of the hospital's microbiology database and prospective perirectal surveillance culture sampling in high-risk units. Case patients were compared with each control group while controlling for time at risk. We sequenced theblaKPCgene with polymerase chain reaction for 7 outbreak isolates and subtyped these isolates with pulsed-field gel electrophoresis.Results.In matched, multivariable analysis, the presence of wounds (hazard ratio, 19.0 [95% confidence interval {CI}, 2.5-142.0]) was associated with CRKP compared with noK. pneumoniae.Transfer between units (adjusted odds ratio [OR], 7.5 [95% CI, 1.8-31.1]), surgery (adjusted OR, 4.0 [95% CI, 1.0-15.7]), and wounds (adjusted OR, 4.9 [95% CI, 1.1-21.8]) were independent risk factors for CRKP compared to CSKP. A novelK. pneumoniaecarbapenemase variant (KPC-8) was present in 5 isolates. Implementation of active surveillance for CRKP colonization and cohorting of CRKP patients rapidly controlled the outbreak.Conclusions.Enhanced surveillance for CRKP colonization and intensified infection control measures that include limiting the physical distribution of patients can reduce CRKP transmission during an outbreak.

Dengue infection can be challenging to diagnose early in the course of infection before severe manifestations develop, but early diagnosis can improve patient outcomes and promote timely public health interventions. We developed age-based predictive models generated from 2 years of data from an enhanced dengue surveillance system in Puerto Rico. These models were internally validated and were able to differentiate dengue infection from other acute febrile illnesses with moderate accuracy. The accuracy of the models was greater than either the current World Health Organization case definition for dengue fever or a proposed modification to this definition, while requiring the collection of fewer data. In young children, thrombocytopenia and the absence of cough were associated with dengue infection; for adults, rash, leucopenia, and the absence of sore throat were associated with dengue infection; in all age groups, retro-orbital pain was associated with dengue infection.

Dengue is a potentially fatal acute febrile illness caused by the mosquito-borne dengue viruses (DENV-1 to -4). To estimate DENV seroincidence in school-aged children, a 1-year prospective cohort study was conducted in Patillas, Puerto Rico; 10- to 18-year-olds (N = 345) were randomly selected from 13 public schools. At enrollment, 49.8% of the entire cohort had DENV immunoglobulin G (IgG) anti-DENV antibodies, and there were individuals with neutralizing antibodies specific to each of the four DENV. The mean age of participants with incident DENV infection was 13.4 years. The 1-year seroincidence rate was 5.6%, and 61.1% of infections were inapparent. Having IgG anti-DENV at enrollment was associated with seroincidence (risk ratio = 6.8). Acute febrile illnesses during the study period were captured by a fever diary and an enhanced and passive surveillance system in the municipios of Patillas and Guayama. In summary, at enrollment, nearly one-half of the participants had a prior DENV infection, with the highest incidence in the 10- to 11-year-olds, of which most were inapparent infections, and symptomatic infections were considered mild.

OBJECTIVE—Multiple daily injection (MDI) therapy of bolus insulin aspart and basal insulin glargine was compared with continuous subcutaneous insulin infusion (CSII) with aspart in type 1 diabetic patients previously treated with CSII. RESEARCH DESIGN AND METHODS—One hundred patients were enrolled in a randomized, multicenter, open-label, crossover study. After a 1-week run-in period with aspart by CSII, 50 subjects were randomly assigned to MDI therapy (aspart immediately before each meal and glargine at bedtime) and 50 subjects continued CSII. After 5 weeks of the first treatment, subjects crossed over to the alternate treatment for 5 weeks. During the last week of each treatment period, subjects wore a continuous glucose monitoring system for 48–72 h. RESULTS—Mean serum fructosamine levels were significantly lower after CSII therapy than after MDI therapy (343 ± 47 vs. 355 ± 50 μmol/l, respectively; P = 0.0001). Continuous glucose monitoring profiles over a 24-h time period showed that glucose exposure was 24 and 40% lower for CSII than MDI as measured by area under the curve (AUC) glucose ≥80 mg/dl (1,270 ± 742 vs. 1,664 ± 1,039 mg · h · dl−1; P < 0.001) and AUC glucose ≥140 mg/dl (464 ± 452 vs. 777 ± 746 mg · h · dl−1, CSII vs. MDI, respectively; P < 0.001). Similar percentages of subjects reported hypoglycemic episodes (CSII: 92%, MDI: 94%) and nocturnal (12:00 a.m. to 8:00 a.m.) hypoglycemic episodes (CSII: 73%, MDI: 72%). Major hypoglycemia was infrequent (CSII: two episodes, MDI: five episodes). CONCLUSIONS—In a trial of short duration, CSII therapy with insulin aspart resulted in lower glycemic exposure without increased risk of hypoglycemia, as compared with MDI with insulin aspart and glargine.

Nasal resistance contributes to negative airway pressure during breathing. We sought to define normal patterns of nasal flow and the effects of mechanical dilatation and splinting of the nares on flow during forced inspiration and expiration. Maximal inspiratory and expiratory flow volume loops (FVL) were determined in 17 normal subjects. Oral FVL were obtained with nares clamped and nasal FVL through a mask with and without dilatation of nares using a plastic splint (Nozovent). Oral FVL were normal in all. Two patterns of nasal FVL were observed: one indicating 'variable' extrathoracic obstruction, the other indicating 'fixed' extrathoracic obstruction. Maximal inspiratory flow at 50% of vital capacity (FiF50) was improved by the Nozovent only in those with a 'variable' pattern (FIF50 (L/sec): 1.54 +/- 0.3 to 2.86 +/- 0.5; P0.05, versus 1.92 +/- 0.3 to 2.21 +/- 0.3: P = 0.5). In subjects with a fixed pattern, failure of dilatation of the nares to increase flow suggests that the site of inspiratory flow limitation is within the bony nostril.

Pentalogy of Cantrell is a rare condition with a varied expression and a high mortality. We present a patient with the classic pentad (type 1), but with a previously undescribed constellation of cardiac manifestations including ectopia cordis totalis, total anomalous pulmonary venous return, and tetralogy of Fallot. This case reminds us of the challenges associated with the management of various forms of this condition. We discuss the prenatal diagnosis, genetic basis, postnatal evaluation, and management of this entity.

To investigate the efficacy and safety of creatine supplementation in fibromyalgia patients.A 16-week, randomized, double-blind, placebo-controlled, parallel-group trial was conducted. Fibromyalgia patients were randomly assigned to receive either creatine monohydrate or placebo in a double-blind manner. The patients were evaluated at baseline and after 16 weeks. Muscle function, aerobic conditioning, cognitive function, quality of sleep, quality of life, kidney function, and adverse events were assessed. Muscle phosphorylcreatine content was measured through (31) P magnetic resonance spectroscopy.After the intervention, the creatine group presented higher muscle phosphorylcreatine content when compared with the placebo group (+80.3% versus -2.7%; P = 0.04). Furthermore, the creatine group presented greater muscle strength than the placebo group in the leg press and chest press exercises (+9.8% and +1.2% for creatine versus -0.5% and -7.2% for placebo, respectively; P = 0.02 and P = 0.002, respectively). Isometric strength was greater in the creatine group than in the placebo group (+6.4% versus -3.2%; P = 0.007). However, no general changes were observed in aerobic conditioning, pain, cognitive function, quality of sleep, and quality of life. Food intake remained unaltered and no side effects were reported.Creatine supplementation increased intramuscular phosphorylcreatine content and improved lower- and upper-body muscle function, with minor changes in other fibromyalgia features. These findings introduce creatine supplementation as a useful dietary intervention to improve muscle function in fibromyalgia patients.