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Background: Self-administered questionnaires provide a better alternative to disclose sensitive information in sexual health research. We describe the factors that determine the positive response (initial recruitment) to an initial invitation and subsequent completion of study to a postal questionnaire on sexual dysfunction. Methods: South Asians (SA) and Europids with and without diabetes (DM) were recruited from GP clinics in UK. Men who returned the properly filled consent form ('recruited-group') were sent the questionnaire and those who returned it were considered asthe'completed-group'. Index of Multiple Deprivation Scores (IMDs) were generated using UK postcodes. We calculated the recruitment rate and completion rate of the recruited and the study-completed groups respectively. Results: Total approached sample was 9100 [DM: 2914 (32 %), SA: 4563 (50.1 %)]. Recruitment rate was 8.8 % and was higher in Europids and in patients with DM. Mean IMDs for the recruited group was 20.9 ± 11.9, and it was higher among recruited SA compared to Europids (p < 0.001). Mean IMDs was higher in the recruited group compared to non-recruited (p < 0.01). All four recruited groups (SA/Europid and DM/non-DM) had lower IMDs compared to non-recruited. Completion rate was 71.5 % (n 544) (SA: 62.3 %, Europids: 77.4 %; p < 0.05). Conclusion: Recruitment for postal sexual health surveys is positively influenced by presence of investigated disease, older age, being from lesser deprived areas and Europid ethnicity. Furthermore, Europids were more likely to complete survey than South Asians irrespective of disease status. [ABSTRACT FROM AUTHOR]

We present a patient with severe hypothyroidism complicated by paralytic ileus and acute kidney injury. A 65 year old male patient, diagnosed with hypothyroidism one year ago was transferred to our unit in a state of drowsiness and confusion. He was severely hypothyroid and had paralytic ileus and impaired renal function at the time of transfer. Hypokalaemia was present, and was likely to have contributed to the paralytic ileus and this together with dehydration was likely to have contributed to renal injury. Nonetheless, hypothyroidism is very likely to have been the principal precipitant of both these complications, and both paralytic ileus and acute kidney injury improved with thyroxine replacement. Unfortunately, the patient died unexpectedly eight days after admission to the unit. Hypothyroidism may induce de novo acute kidney injury or it may exacerbate ongoing chronic kidney disease. This rare complication is assumed to be due to the hypodynamic circulatory state created by thyroid hormone deficiency. Paralytic ileus is an even rarer fatal manifestation of hypothyroidism and is thought to be due to an autonomic neuropathy affecting the intestines that is reversible with thyroxine replacement. To our knowledge, both these complications have not been observed in a single patient so far. It is important that clinicians are aware of these rare manifestations of hypothyroidism as in most occasions, thyroxine deficiency may be missed, and treatment can reverse the complications. [ABSTRACT FROM AUTHOR]

Background: Dengue fever is a common infection with increasing numbers of patients affected. Muscle haematomas are a rare complication of dengue fever. In most cases haematomas resolve spontaneously.Case Presentation: We report a case of spontaneous psoas muscle haematoma, formed during the critical phase of dengue haemorrhagic fever. A 28-year-old gentleman presented with features of severe dengue and was admitted to the Dengue High Dependency Unit. He was treated with intravenous fluid therapy and supportive measures, and gradually improved initially. However, as the critical phase ended, he suddenly developed pain in the left groin and inguinal region and physical examination was normal. Ultrasound scan revealed a left psoas haematoma. As the patient deteriorated haemodynamically blood was transfused. He recovered without further complication and was discharged home.Conclusions: Dengue fever is a common tropical infection. Recognizing serious complications such as psoas haematoma presenting as simple complaints such as back pain and inguinal pain are important to prevent mortality. [ABSTRACT FROM AUTHOR]

Introduction: Enteral nutrition (EN) with eicosapentaenoic acid (EPA)/γ-linolenic acid (GLA) is recommended for mechanically ventilated patients with severe lung injury. EPA/GLA has anti-inflammatory benefits, as evidenced by its association with reduction in pulmonary inflammation, improvement in oxygenation and improved clinical outcomes in patients with severe forms of acute lung injury. This study was a prospective, multicenter, randomized, double-blinded, controlled trial designed to investigate whether EPA/GLA could have an effective role in the treatment of patients with early sepsis (systemic inflammatory response syndrome with confirmed or presumed infection and without any organ dysfunction) by reducing the progression of the disease to severe sepsis (sepsis associated with at least one organ failure) or septic shock (sepsis associated with hypotension despite adequate fluid resuscitation). Secondary outcomes included the development of individual organ failure, increased ICU and hospital length of stay, need for mechanical ventilation and 28-day all-cause mortality.Methods: Randomization was concealed, and patients were allocated to receive, for seven days, either an EPA/GLA diet or an isocaloric, isonitrogenous control diet not enhanced with lipids. Patients were continuously tube-fed at a minimum of 75% of basal energy expenditure × 1.3. To evaluate the progression to severe sepsis and/or septic shock, daily screening for individual organ failure was performed. All clinical outcomes were recorded during a 28-day follow-up period.Results: A total of 115 patients in the early stages of sepsis requiring EN were included, among whom 106 were considered evaluable. Intention-to-treat (ITT) analysis demonstrated that patients fed the EPA/GLA diet developed less severe sepsis and/or septic shock than patients fed the control diet (26.3% versus 50%, respectively; P = 0.0259), with similar results observed for the evaluable patients (26.4% versus 50.9% respectively; P = 0.0217). The ITT analysis demonstrated that patients in the study group developed cardiovascular failure (36.2% versus 21%, respectively; P = 0.0381) and respiratory failure (39.6% versus 24.6%, respectively; P = 0.0362) less often than the control group. Similarly, when considering only the evaluable patients, fewer patients developed cardiovascular failure (20.7% versus 37.7%, respectively; P = 0.03) and respiratory failure (26.4% versus 39.6%, respectively; P = 0.04). The percentage of patients fed the EPA/GLA diet requiring invasive mechanical ventilation was reduced compared with controls (ITT patients: 18.9% versus 33.9%, respectively; P = 0.394; evaluable patients: 17.5% versus 34.5%, respectively; P = 0.295). Patients nourished with the EPA/GLA diet remained in the ICU fewer days than the control population (ITT patients: 21.1 ICU-free days versus 14.7 ICU-free days, respectively; P < 0.0001; evaluable patients: 20.8 ICU-free days versus 14.3 ICU-free days, respectively; P < 0.0001) and fewer days at the hospital (ITT patients: 19.5 hospital-free days versus 10.3 hospital-free days, respectively; P < 0.0001; evaluable patients: 19.1 hospital-free days versus 10.2 hospital-free days, respectively; P < 0.001) (all numbers expressed as means). No significant differences in 28-day all-cause mortality were observed (ITT patients: 26.2% EPA/GLA diet versus 27.6% control diet, respectively; P = 0.72; evaluable: 26.4 EPA/GLA diet versus 30.18 control diet, respectively; P = 0.79).Conclusions: These data suggest that EPA/GLA may play a beneficial role in the treatment of enterally fed patients in the early stages of sepsis without associated organ dysfunction by contributing to slowing the progression of sepsis-related organ dysfunction, especially with regard to cardiovascular and respiratory dysfunction.Trial Registration: ClinicalTrials.gov: NCT00981877. [ABSTRACT FROM AUTHOR]

Background: Despite important improvements in available prevention and treatment, cardiovascular diseases (CVD) remain an important cause of morbidity and mortality. Not all high-risk patients and patients with CVD have healthy lifestyles and receive the best possible healthcare. Internationally comparative data are needed to compare cardiovascular risk management in different countries, and to examine the impact of improvement programs and others factors.Objectives: This study aims to provide internationally comparative data on cardiovascular risk management provided in primary care and on health-related lifestyles of patients in Europe. The study will also explore the views of doctors and patients on innovative preventive services for CVDs.Design and Methods: An observational cross-sectional study is planned. In 10 European countries, stratified samples of 36 practices per country will be recruited. In each practice, three samples of 15 patients each will be sampled: patients with coronary heart disease, patients at high risk for CVD, and healthy adult patients. The quality of cardiovascular risk management has been specified in terms of 44 performance indicators that resulted from an international Delphi-procedure with general practitioners. Most indicators are based on medical records, and some on a structured interview with a contact person of the practice. Lifestyle (smoking, physical exercise, diet) will be measured with previously validated questionnaires that are completed by patients. Additional measures include practice characteristics and exposure to programs to improve cardiovascular care. [ABSTRACT FROM AUTHOR]

Wildland fires contribute significantly to the ambient air pollution burden worldwide, causing a range of adverse health effects in exposed populations. The toxicity of woodsmoke, a complex mixture of gases, volatile organic compounds, and particulate matter, is commonly studied in vitro using isolated exposures of conventionally cultured lung cells to either resuspended particulate matter or organic solvent extracts of smoke, leading to incomplete toxicity evaluations. This study aimed to improve our understanding of the effects of woodsmoke inhalation by building an advanced in vitro exposure system that emulates human exposure of the airway epithelium. We report the development and characterization of an innovative system that permits live-cell monitoring of the intracellular redox status of differentiated primary human bronchial epithelial cells cultured at an air-liquid interface (pHBEC-ALI) as they are exposed to unfractionated woodsmoke generated in a tube furnace in real time. pHBEC-ALI exposed to freshly generated woodsmoke showed oxidative changes that were dose-dependent and reversible, and not attributable to carbon monoxide exposure. These findings show the utility of this novel system for studying the molecular initiating events underlying woodsmoke-induced toxicity in a physiologically relevant in vitro model, and its potential to provide biological plausibility for risk assessment and public health measures., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background: Changes in serum metabolites in individuals with altered cardiac function and morphology may exhibit information about cardiovascular disease (CVD) pathway dysregulations and potential CVD risk factors. We aimed to explore associations of cardiac function and morphology, evaluated using magnetic resonance imaging (MRI) with a large panel of serum metabolites., Methods: Cross-sectional data from CVD-free individuals from the population-based KORA cohort were analyzed. Associations between 3T-MRI-derived left ventricular (LV) function and morphology parameters (e.g., volumes, filling rates, wall thickness) and markers of carotid plaque with metabolite profile clusters and single metabolites as outcomes were assessed by adjusted multinomial logistic regression and linear regression models., Results: In 360 individuals (mean age 56.3 years; 41.9% female), 146 serum metabolites clustered into three distinct profiles that reflected high-, intermediate- and low-CVD risk. Higher stroke volume (relative risk ratio (RRR): 0.53, 95%-CI [0.37; 0.76], p-value < 0.001) and early diastolic filling rate (RRR: 0.51, 95%-CI [0.37; 0.71], p-value < 0.001) were most strongly protectively associated against the high-risk profile compared to the low-risk profile after adjusting for traditional CVD risk factors. Moreover, imaging markers were associated with 10 metabolites in linear regression. Notably, negative associations of stroke volume and early diastolic filling rate with acylcarnitine C5, and positive association of function parameters with lysophosphatidylcholines, diacylphosphatidylcholines, and acylalkylphosphatidylcholines were observed. Furthermore, there was a negative association of LV wall thickness with alanine, creatinine, and symmetric dimethylarginine. We found no significant associations with carotid plaque., Conclusions: Serum metabolite signatures are associated with cardiac function and morphology even in individuals without a clinical indication of CVD., (© 2024. The Author(s).)

Background: With the increasing proportion of older adults in India, it becomes essential to get an insight into the various influencing factors of successful ageing. However, the literature on successful ageing is minuscule in the Indian context. The present study attempted to understand successful ageing in terms of active and productive ageing by exploring their determining factors., Methods: The data were extracted from the Longitudinal Ageing Study in India (LASI) Wave-1 (2017-2018). We utilized self-reported time use information from the experimental module of the LASI. A total of 7837 ageing adults were included in the study. We employed descriptive statistics, bivariate analysis and a multinominal logistic regression model to examine the prevalence and the determinants of active and productive ageing., Results: The prevalence of inactive ageing was higher among the Indian ageing population (57.47%), followed by active ageing (29.59%) and productive ageing (12.94%). Poor sleep quality and the prevalence of morbidity and disability limited the ageing population from attaining active and productive ageing. Engagement in physical activity was significantly associated with active and productive ageing (β = 0.83, 99% CI: -0.72-0.94 and β = 0.82, 99% CI: 0.66-0.98), respectively. Rural ageing adults were more likely to attain active ageing and less likely to attain productive ageing., Conclusion: Engagement in physical activities among the ageing population shall be promoted to attain active and productive ageing. Since the rural ageing population were less likely to attain productive ageing than their urban counterparts, opportunities to participate in more formal economic activities in rural areas could be promoted for the wellbeing of the second demographic dividend., (© 2023. The Author(s).)

Background: Approximately nine million adults in the United States are living with chronic obstructive pulmonary disease (COPD), and positive associations between short-term air pollution exposure and increased risk of COPD hospitalizations in older adults are consistently reported. We examined the association between short-term PM 2.5 exposure and hospitalizations and assessed if there is modification by long-term exposure in a cohort of individuals with COPD., Methods: In a time-referent case-crossover design, we used a cohort of randomly selected individuals with electronic health records from the University of North Carolina Healthcare System, restricted to patients with a medical encounter coded with a COPD diagnosis from 2004-2016 (n = 520), and estimated ambient PM 2.5 concentrations from an ensemble model. Odds ratios and 95% confidence intervals (OR (95%CI)) were estimated with conditional logistic regression for respiratory-related, cardiovascular (CVD), and all-cause hospitalizations. Exposures examined were 0-2 and 0-3 day lags of PM 2.5 concentration, adjusting for daily census-tract temperature and humidity, and models were stratified by long-term (annual average) PM 2.5 concentration at the median value., Results: We observed generally null or low-magnitude negative associations with short-term PM 2.5 exposure and respiratory-related (OR per 5 µg/m 3 increase in 3-day lag PM 2.5 : 0.971 (0.885, 1.066)), CVD (2-day lag: 0.976 (0.900, 1.058) and all-cause (3 day lag: 1.003 (0.927, 1.086)) hospitalizations. Associations between short-term PM 2.5 exposure and hospitalizations were higher among patients residing in areas with higher levels of annual PM 2.5 concentrations (OR per 5 µg/m 3 in 3-day lag PM 2.5 for all-cause hospitalizations: 1.066 (0.958, 1.185)) than those in areas with lower annual PM 2.5 concentrations (OR per 5 µg/m 3 in 3-day lag PM 2.5 for all-cause hospitalizations: 0.914 (0.804, 1.039))., Concluisons: Differences in associations demonstrate that people in areas with higher annual PM 2.5 exposure may be associated with higher risk of hospitalization during short-term increases in PM 2.5 exposure., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background: Despite many efforts, preterm birth (PTB) is poorly understood and remains a major public health problem in the United States. Toxicological work suggests gestational parent (GP) diet may modify the effect of ambient pollutants on birth outcomes. We assessed risk of PTB in humans in relation to fine particulate matter (PM 2.5 ), ozone (O 3 ), and nitrogen dioxide (NO 2 ) and variation by diet., Methods: 684 GP-singleton infant pairs in the Newborn Epigenetics Study prospective birth cohort were attributed ambient air pollutant exposures for each trimester based on residence. Total energy intake, percent of energy intake from saturated fat, and percent of energy intake from total fat were dichotomized at the 75th percentile. >We used log binomial regressions to estimate risk ratios (RR (95%CI)) for PTB by pollutant interquartile ranges, adjusting for GP age, pre-pregnancy body mass index, GP race/ethnicity, GP education, season of conception, household income, and each diet factor. We assessed departure from additivity using interaction contrast ratios (ICRs). We addressed missing covariate data with multiple imputation., Results: Point estimates suggest that O 3 may be inversely associated with PTB when exposure occurs in trimester 2 (min RR: 0.77, 95% CI: 0.39, 1.49), but may be harmful when exposure occurs in trimester 3 (max RR: 1.51, 95% CI: 0.62, 3.64). Additionally, PM 2.5 may be inversely associated with PTB when considered with total fat and saturated fat in trimester 2. Imprecise ICRs suggest departure from additivity (evidence of modification) with some pollutant-diet combinations., Conclusions: While confidence intervals are wide, we observed potential modification of pollutant associations by dietary factors. It is imperative that large cohorts collect the required data to examine this topic, as more power is necessary to investigate the nuances suggested by this work., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background: Cubital tunnel syndrome is the second most common entrapment neuropathy of the upper extremity. Surgical decompression of the ulnar nerve aims to improve complaints and prevent permanent damage to the nerve. Open and endoscopic release of the cubital tunnel are both used in common practice, but none has proven to be superior. This study assesses patient reported outcome and experience measures (PROMs and PREMs respectively), in addition to objective outcomes of both techniques., Methods: A prospective single-center open randomized non-inferiority trial will take place at the Plastic Surgery Department in the Jeroen Bosch Hospital, the Netherlands. 160 patients with cubital tunnel syndrome will be included. Patients are allocated to endoscopic or open cubital tunnel release by randomization. The surgeon and patients are not blinded for treatment allocation. The follow-up time will take 18 months., Discussion: Currently, the choice for one of the methods is based on surgeon's preferences and degree of familiarity with a particular technique. It is assumed that the open technique is easier, faster and cheaper. The endoscopic release, however, has better exposure of the nerve and reduces the chance of damaging the nerve and might decrease scar discomfort. PROMs and PREMs have proven potential to improve the quality of care. Better health care experiences are associated with better clinical outcome in self-reported post-surgical questionnaires. Combining subjective measures with objective outcomes, efficacy, patient treatment experience and safety profile could help differentiating between open and endoscopic cubital tunnel release. This could aid clinicians in evidence based choices towards the best surgical approach in patients with cubital tunnel syndrome., Trial Registration: This study is registered prospectively with the Dutch Trial Registration under NL9556. Universal Trial Number (WHO-UTN) U1111-1267-3059. Registration date 26-06-2021. The URL: https://www.trialregister.nl/trial/9556., (© 2023. The Author(s).)

Background: Early-evening and outdoor-biting mosquitoes may compromise the effectiveness of frontline malaria interventions, notably insecticide-treated nets (ITNs). This study aimed to evaluate the efficacy of low-cost insecticide-treated eave ribbons and sandals as supplementary interventions against indoor-biting and outdoor-biting mosquitoes in south-eastern Tanzania, where ITNs are already widely used., Methods: This study was conducted in three villages, with 72 households participating (24 households per village). The households were divided into four study arms and assigned: transfluthrin-treated sandals (TS), transfluthrin-treated eave ribbons (TER), a combination of TER and TS, or experimental controls. Each arm had 18 households, and all households received new ITNs. Mosquitoes were collected using double net traps (to assess outdoor biting), CDC light traps (to assess indoor biting), and Prokopack aspirators (to assess indoor resting). Protection provided by the interventions was evaluated by comparing mosquito densities between the treatment and control arms. Additional tests were done in experimental huts to assess the mortality of wild mosquitoes exposed to the treatments or controls., Results: TERs reduced indoor-biting, indoor-resting and outdoor-biting Anopheles arabiensis by 60%, 73% and 41%, respectively, while TS reduced the densities by 18%, 40% and 42%, respectively. When used together, TER & TS reduced indoor-biting, indoor-resting and outdoor-biting An. arabiensis by 53%, 67% and 57%, respectively. Protection against Anopheles funestus ranged from 42 to 69% with TER and from 57 to 74% with TER & TS combined. Mortality of field-collected mosquitoes exposed to TER, TS or both interventions was 56-78% for An. arabiensis and 47-74% for An. funestus., Conclusion: Transfluthrin-treated eave ribbons and sandals or their combination can offer significant household-level protection against malaria vectors. Their efficacy is magnified by the transfluthrin-induced mortality, which was observed despite the prevailing pyrethroid resistance in the study area. These results suggest that TER and TS could be useful supplementary tools against residual malaria transmission in areas where ITN coverage is high but additional protection is needed against early-evening and outdoor-biting mosquitoes. Further research is needed to validate the performance of these tools in different settings, and assess their long-term effectiveness and feasibility for malaria control., (© 2023. The Author(s).)

Background: Acute kidney injury (AKI) is frequently associated with COVID-19, and the need for kidney replacement therapy (KRT) is considered an indicator of disease severity. This study aimed to develop a prognostic score for predicting the need for KRT in hospitalised COVID-19 patients, and to assess the incidence of AKI and KRT requirement., Methods: This study is part of a multicentre cohort, the Brazilian COVID-19 Registry. A total of 5212 adult COVID-19 patients were included between March/2020 and September/2020. Variable selection was performed using generalised additive models (GAM), and least absolute shrinkage and selection operator (LASSO) regression was used for score derivation. Accuracy was assessed using the area under the receiver operating characteristic curve (AUC-ROC)., Results: The median age of the model-derivation cohort was 59 (IQR 47-70) years, 54.5% were men, 34.3% required ICU admission, 20.9% evolved with AKI, 9.3% required KRT, and 15.1% died during hospitalisation. The temporal validation cohort had similar age, sex, ICU admission, AKI, required KRT distribution and in-hospital mortality. The geographic validation cohort had similar age and sex; however, this cohort had higher rates of ICU admission, AKI, need for KRT and in-hospital mortality. Four predictors of the need for KRT were identified using GAM: need for mechanical ventilation, male sex, higher creatinine at hospital presentation and diabetes. The MMCD score had excellent discrimination in derivation (AUROC 0.929, 95% CI 0.918-0.939) and validation (temporal AUROC 0.927, 95% CI 0.911-0.941; geographic AUROC 0.819, 95% CI 0.792-0.845) cohorts and good overall performance (Brier score: 0.057, 0.056 and 0.122, respectively). The score is implemented in a freely available online risk calculator ( https://www.mmcdscore.com/ )., Conclusions: The use of the MMCD score to predict the need for KRT may assist healthcare workers in identifying hospitalised COVID-19 patients who may require more intensive monitoring, and can be useful for resource allocation., (© 2022. The Author(s).)

Background: Chronic pain after cardiac surgery, whether or not related to the operation, is common and has negative impact on health related quality of life (HRQL). Frailty is a risk factor for adverse surgical outcomes, but its relationship with chronic pain after cardiac surgery is unknown. This study aimed to address the association between frailty and chronic pain following cardiac surgery., Methods: This sub-study of the Anesthesia Geriatric Evaluation study included 518 patients ≥ 70 years undergoing elective cardiac surgery. Pain was evaluated with the Short-Form 36 questionnaire prior to and one year after surgery. Associations between chronic postoperative pain and frailty domains, including medication use, nutritional status, mobility, physical functioning, cognition, HRQL, living situation and educational level, were investigated with multivariable regression analysis., Results: Chronic pain one year after cardiac surgery was reported in 182 patients (35%). Medication use, living situation, mobility, gait speed, Nagi's physical functioning and preoperative HRQL were frailty domains associated with chronic pain after surgery. For patients with chronic pain physical HRQL after one year was worse compared to patients without chronic pain (β -10.37, 99% CI -12.57 - -8.17)., Conclusions: Preoperative polypharmacy, living alone, physical frailty and lower mental HRQL are associated with chronic pain following cardiac surgery. Chronic postoperative pain is related to worse physical HRQL one year after cardiac surgery. These findings may guide future preoperative interventions to reduce chronic pain and poor HRQL after cardiac surgery in older patients., Trial Registration: This trial has been registered before initiation under number NCT02535728 at clinicaltrials.gov., (© 2022. The Author(s).)

Background: Cigarette smoking is a risk factor for interstitial lung abnormalities (ILAs) and interstitial lung diseases (ILDs). Investigation defining the relationships between ILAs/ILDs and clinical, radiographic, and pathologic findings in smokers have been incomplete. Employing a cohort undergoing surgical resection for lung nodules/masses, we (1) define the prevalence of ILAs/ILDs, (2) delineate their clinical, radiographic and pathologic predictors, and (3) determine their associations with mortality., Methods: Patients undergoing resection of lung nodules/masses between 2017 and 2020 at a rural Appalachian, tertiary medical center were retrospectively investigated. Predictors for ILAs/ILDs and mortality were assessed using multivariate logistic regression analysis., Results: In the total study cohort of 352 patients, radiographic ILAs and ILDs were observed in 35.2% and 17.6%, respectively. Among ILA patterns, subpleural reticular changes (14.8%), non-emphysematous cysts, centrilobular (CL) ground glass opacities (GGOs) (8% each), and mixed CL-GGO and subpleural reticular changes (7.4%) were common. ILD patterns included combined pulmonary fibrosis emphysema (CPFE) (3.1%), respiratory bronchiolitis (RB)-ILD (3.1%), organizing pneumonitis (2.8%) and unclassifiable (4.8%). The group with radiographic ILAs/ILDs had a significantly higher proportion of ever smokers (49% vs. 39.9%), pack years of smoking (44.57 ± 36.21 vs. 34.96 ± 26.22), clinical comorbidities of COPD (35% vs. 26.5%) and mildly reduced diffusion capacity (% predicated 66.29 ± 20.55 vs. 71.84 ± 23). Radiographic centrilobular and paraseptal emphysema (40% vs. 22.2% and 17.6% vs. 9.6%, respectively) and isolated traction bronchiectasis (10.2% vs. 4.2%) were associated with ILAs/ILDs. Pathological variables of emphysema (34.9% vs. 18.5%), any fibrosis (15.9% vs. 4.6%), peribronchiolar metaplasia (PBM, 8% vs. 1.1%), RB (10.3% vs. 2.5%), and anthracosis (21.6% vs. 14.5%) were associated with ILAs/ILDs. Histologic emphysema showed positive correlations with any fibrosis, RB, anthracosis and ≥ 30 pack year of smoking. The group with ILAs/ILDs had significantly higher mortality (9.1% vs. 2.2%, OR 4.13, [95% CI of 1.84-9.25])., Conclusions: In a rural cohort undergoing surgical resection, radiographic subclinical ILAs/ILDs patterns were highly prevalent and associated with ever smoking and intensity of smoking. The presence of radiographic ILA/ILD patterns and isolated honeycomb changes were associated with increased mortality. Subclinical ILAs/ILDs and histologic fibrosis correlated with clinical COPD as well as radiographic and pathologic emphysema emphasizing the co-existence of these pulmonary injuries in a heavily smoking population., (© 2022. The Author(s).)

Background: The use of systems science methodologies to understand complex environmental and human health relationships is increasing. Requirements for advanced datasets, models, and expertise limit current application of these approaches by many environmental and public health practitioners., Methods: A conceptual system-of-systems model was applied for children in North Carolina counties that includes example indicators of children's physical environment (home age, Brownfield sites, Superfund sites), social environment (caregiver's income, education, insurance), and health (low birthweight, asthma, blood lead levels). The web-based Toxicological Prioritization Index (ToxPi) tool was used to normalize the data, rank the resulting vulnerability index, and visualize impacts from each indicator in a county. Hierarchical clustering was used to sort the 100 North Carolina counties into groups based on similar ToxPi model results. The ToxPi charts for each county were also superimposed over a map of percentage county population under age 5 to visualize spatial distribution of vulnerability clusters across the state., Results: Data driven clustering for this systems model suggests 5 groups of counties. One group includes 6 counties with the highest vulnerability scores showing strong influences from all three categories of indicators (social environment, physical environment, and health). A second group contains 15 counties with high vulnerability scores driven by strong influences from home age in the physical environment and poverty in the social environment. A third group is driven by data on Superfund sites in the physical environment., Conclusions: This analysis demonstrated how systems science principles can be used to synthesize holistic insights for decision making using publicly available data and computational tools, focusing on a children's environmental health example. Where more traditional reductionist approaches can elucidate individual relationships between environmental variables and health, the study of collective, system-wide interactions can enable insights into the factors that contribute to regional vulnerabilities and interventions that better address complex real-world conditions., (© 2022. The Author(s).)

Aims: Ulnar-sided wrist pain has historically been equated to lower-back pain of wrist surgery. Little is known about the relationship between psychosocial profile and the manifestation of ulnar-sided wrist pathology and their treatment outcomes. This study aimed to determine the impact of pain catastrophising, psychological distress, illness perception, and patients' outcome expectations on patient-reported pain and hand function before and one year after surgery for ulnar-sided wrist pathology., Patients and Methods: We included patients who underwent surgical treatment for ulnar-sided wrist pathology. Before surgery, patients completed the Pain Catastrophising Scale (PCS), Patient Health Questionnaire (PHQ), Brief-Illness Perception Questionnaire (B-IPQ), and Credibility/Expectancy Questionnaire (CEQ). Pain and dysfunction were assessed before (n = 423) and one year after surgery (n = 253) using the Patient Rated Wrist/Hand Evaluation (PRWHE). Hierarchical linear regression was used to assess the relationship between psychosocial factors and the preoperative PRWHE score, postoperative PRWHE score, and change in PRWHE., Results: Psychosocial variables explained an additional 35% of the variance in preoperative PRWHE scores and 18% on postoperative scores. A more negative psychosocial profile was associated with higher (worse) preoperative PRWHE scores (PCS: B = 0.19, CI = [0.02-0.36]; B-IPQ Consequences: B = 3.26, CI = 2.36-4.15; and B-IPQ Identity, B = 1.88 [1.09-2.67]) and postoperative PRWHE scores (PCS: B = 0.44, CI = [0.08-0.81]) but not with the change in PRWHE after surgery. Higher treatment expectations were associated with a lower (better) postoperative PRWHE score (CEQ expectancy: B = -1.63, CI = [-2.43;-0.83]) and a larger change in PRWHE scores (B =|1.62|, CI = [|0.77; 2.47|])., Conclusion: A more negative psychosocial profile was associated with higher pain levels and dysfunction preoperatively and postoperatively. However, these patients showed similar improvement as patients with a more feasible psychosocial profile. Therefore, patients should not be withheld from surgical treatment based on their preoperative psychosocial profile alone. Boosting treatment expectations might further improve treatment outcomes., Level of Evidence: III (Cohort study)., (© 2022. The Author(s).)

Background: The occurrence of cyanobacterial blooms in freshwater presents a threat to human health. However, epidemiological studies on the association between cyanobacterial blooms in drinking water sources and human health outcomes are scarce. The objective of this study was to evaluate if cyanobacterial blooms were associated with increased emergency room visits for gastrointestinal (GI), respiratory and dermal illnesses., Methods: Satellite-derived cyanobacteria cell concentrations were estimated in the source of drinking water for the Greater Boston area, during 2008-2011. Daily counts of hospital emergency room visits for GI, respiratory and dermal illnesses among drinking water recipients were obtained from an administrative record database. A two-stage model was used to analyze time-series data for an association between cyanobacterial blooms and the occurrence of illnesses. At the first stage, predictive autoregressive generalized additive models for Poisson-distributed outcomes were fitted to daily illness count data and daily predictive variables. At the second stage, residuals from the first stage models were regressed against lagged categorized cyanobacteria concentration estimates., Results: The highest cyanobacteria concentration (above the 75th percentile) was associated with an additional 4.3 cases of respiratory illness (95% confidence interval: 0.7, 8.0, p = 0.02, n = 268) compared to cyanobacteria concentrations below the 50th percentile in a two-day lag. There were no significant associations between satellite derived cyanobacterial concentrations and lagged data on GI or dermal illnesses., Conclusion: The study demonstrated a significant positive association between satellite-derived cyanobacteria concentrations in source water and respiratory illness occurring 2 days later. Future studies will require direct measures of cyanotoxins and health effects associated with exposure to cyanobacteria-impacted drinking water sources., (© 2021. The Author(s).)

Background: Exposure to the bioaccumulative pesticide dichlorodiphenyltrichloroethane (DDT) and its metabolite dichlorodiphenyldichloroethylene (DDE) has been associated with increased risk of insulin resistance and obesity in humans and experimental animals. These effects appear to be mediated by reduced brown adipose tissue (BAT) thermogenesis, which is regulated by the sympathetic nervous system. Although the neurotoxicity of DDT is well-established, whether DDT alters sympathetic innervation of BAT is unknown. We hypothesized that perinatal exposure to DDT or DDE promotes thermogenic dysfunction by interfering with sympathetic regulation of BAT thermogenesis., Methods: Pregnant C57BL/6 J mice were administered environmentally relevant concentrations of DDTs (p,p'-DDT and o,p'-DDT) or DDE (p,p'-DDE), 1.7 mg/kg and 1.31 mg/kg, respectively, from gestational day 11.5 to postnatal day 5 by oral gavage, and longitudinal body temperature was recorded in male and female offspring. At 4 months of age, metabolic parameters were measured in female offspring via indirect calorimetry with or without the β3 adrenergic receptor agonist, CL 316,243. Immunohistochemical and neurochemical analyses of sympathetic neurons innervating BAT were evaluated., Results: We observed persistent thermogenic impairment in adult female, but not male, mice perinatally exposed to DDTs or p,p'-DDE. Perinatal DDTs exposure significantly impaired metabolism in adult female mice, an effect rescued by treatment with CL 316,243 immediately prior to calorimetry experiments. Neither DDTs nor p,p'-DDE significantly altered BAT morphology or the concentrations of norepinephrine and its metabolite DHPG in the BAT of DDTs-exposed mice. However, quantitative immunohistochemistry revealed a 20% decrease in sympathetic axons innervating BAT in adult female mice perinatally exposed to DDTs, but not p,p'-DDE, and 48 and 43% fewer synapses in stellate ganglia of mice exposed to either DDTs or p,p'-DDE, respectively, compared to control., Conclusions: These data demonstrate that perinatal exposure to DDTs or p,p'-DDE impairs thermogenesis by interfering with patterns of connectivity in sympathetic circuits that regulate BAT.

Background: Toxoplasma gondii is a protozoan parasite that infects cats as definitive hosts and other warm-blooded animals including humans as intermediate hosts. It forms infectious cysts in the brain, muscle and other tissues establishing life-long latent infection. Approximately 10% of the US population is infected. While latent infections are largely asymptomatic, they are associated with neurological deficits and elevated risks of neuropsychiatric diseases., Methods: This cross-sectional epidemiological study investigated associations of T. gondii infections with biomarkers of inflammation and vascular injury: soluble intercellular adhesion molecule 1 (ICAM-1), soluble vascular cell adhesion molecule 1 (VCAM-1), C-reactive protein (CRP), and serum amyloid A (SAA). Serum samples from 694 adults in the Raleigh-Durham-Chapel Hill, North Carolina metropolitan area were tested for IgG antibody response to T. gondii, and for the above biomarkers using commercially available assays., Results: T. gondii seroprevalence rate in this sample was 9.7%. Seropositivity was significantly associated with 11% (95% confidence limits 4, 20%) greater median levels of VCAM-1 (p = 0.003), and marginally significantly with 9% (1, 17%), and 36% (1, 83%) greater median levels of ICAM-1, and CRP, respectively (p = 0.04 for each) after adjusting for sociodemographic and behavioral covariates, while the 23% (- 7, 64%) adjusted effect on SAA was not statistically significant (p = 0.15)., Conclusions: Latent infections with T. gondii are associated with elevated biomarkers of chronic inflammation and vascular injury that are also known to be affected by ambient air pollution.

Background: Across taxa, animals with depleted intestinal microbiomes show disrupted behavioral phenotypes. Axenic (i.e., microbe-free) mice, zebrafish, and fruit flies exhibit increased locomotor behavior, or hyperactivity. The mechanism through which bacteria interact with host cells to trigger normal neurobehavioral development in larval zebrafish is not well understood. Here, we monoassociated zebrafish with either one of six different zebrafish-associated bacteria, mixtures of these host-associates, or with an environmental bacterial isolate., Results: As predicted, the axenic cohort was hyperactive. Monoassociation with three different host-associated bacterial species, as well as with the mixtures, resulted in control-like locomotor behavior. Monoassociation with one host-associate and the environmental isolate resulted in the hyperactive phenotype characteristic of axenic larvae, while monoassociation with two other host-associated bacteria partially blocked this phenotype. Furthermore, we found an inverse relationship between the total concentration of bacteria per larvae and locomotor behavior. Lastly, in the axenic and associated cohorts, but not in the larvae with complex communities, we detected unexpected bacteria, some of which may be present as facultative predators., Conclusions: These data support a growing body of evidence that individual species of bacteria can have different effects on host behavior, potentially related to their success at intestinal colonization. Specific to the zebrafish model, our results suggest that differences in the composition of microbes in fish facilities could affect the results of behavioral assays within pharmacological and toxicological studies.

Background: Citizens affected by substance use disorders are high-risk populations for both SARS-CoV-2 infection and COVID-19-related mortality. Relevant vulnerabilities to COVID-19 in people who suffer substance use disorders are described in previous communications. The COVID-19 pandemic offers a unique opportunity to reshape and update addiction treatment networks., Main Body: Renewed treatment systems should be based on these seven pillars: (1) telemedicine and digital solutions, (2) hospitalization at home, (3) consultation-liaison psychiatric and addiction services, (4) harm-reduction facilities, (5) person-centered care, (6) promote paid work to improve quality of life in people with substance use disorders, and (7) integrated addiction care. The three "best buys" of the World Health Organization (reduce availability, increase prices, and a ban on advertising) are still valid. Additionally, new strategies must be implemented to systematically deal with (a) fake news concerning legal and illegal drugs and (b) controversial scientific information., Conclusion: The heroin pandemic four decades ago was the last time that addiction treatment systems were updated in many western countries. A revised and modernized addiction treatment network must include improved access to care, facilitated where appropriate by technology; more integrated care with addiction specialists supporting non-specialists; and reducing the stigma experienced by people with SUDs.

Background: Francisella tularensis is a fastidious, Gram-negative coccobacillus and is the causative agent of tularemia. To assess viability yet overcome lengthy incubation periods, a culture-based PCR method was used to detect early growth of the lowest possible number of F. tularensis cells. This method utilized a previously developed enhanced F. tularensis growth medium and is based on the change in PCR cycle threshold at the start and end of each incubation., Results: To test method robustness, a virulent Type A1 (Schu4) and B (IN99) strain and the avirulent Live Vaccine Strain (LVS) were incubated with inactivated target cells, humic acid, drinking and well water, and test dust at targeted starting concentrations of 1, 10, and 100 CFU mL - 1 (low, mid, and high, respectively). After 48 h, LVS growth was detected at all targeted concentrations in the presence of 10 6 inactivated LVS cells; while Schu4 and IN99 growth was detected in the presence of 10 4 Schu4 or IN99 inactivated cells at the mid and high targets. Early detection of F. tularensis growth was strain and concentration dependent in the presence of fast-growing well water and test dust organisms. In contrast, growth was detected at each targeted concentration by 24 h in humic acid and drinking water for all strains., Conclusions: Results indicated that the culture-based PCR assay is quick, sensitive, and specific while still utilizing growth as a measure of pathogen viability. This method can circumvent lengthy incubations required for Francisella identification, especially when swift answers are needed during epidemiological investigations, remediation efforts, and decontamination verification.

Background: Anemia in cardiac surgery patients has been associated with poor outcomes. Transfusion of red blood cells during surgery is common practice for perioperative anemia, but may come with risks. Little is known about the association between intra-operative transfusion and mortality in patients undergoing cardiac surgery., Methods: Single centre historical cohort study in 2933 adult patients undergoing coronary surgery with or without aortic valve replacement from June 2011 until September 2014. To estimate the odds ratio for mortality in patients receiving intra-operative transfusion, a propensity score based logistic regression analysis was performed., Results: Intra-operative transfusion was associated with a more than three-fold increased risk of 30-day mortality. Patients in the highest quartile of probability of transfusion were older (age 75 vs 66; P <  0.001), had a higher EuroSCORE (6 vs 3; P <  0.001), had lower preoperative hemoglobin levels (7.6 vs 8.9 mmol/l; P < 0.001), had combined surgery more often (CABG + AVR in 33.4% of cases vs 6.6% (P < 0.001) and a longer duration of surgery (224 vs 188 min; P < 0.001). The association between intra-operative transfusion and mortality persisted after adjustment for these risk factors (adjusted OR 2.6; P = 0.007)., Conclusions: Intra-operative transfusion of red blood cells was found to be associated with increased mortality in adults undergoing coronary surgery. Preoperative patient optimization may improve perioperative outcomes by reducing the likelihood of requiring transfusion and thus its associated risk.

Background: Consumers' conviction of the benefits of probiotics is influenced by their existing beliefs and by the information they receive from healthcare professionals. The attitude of healthcare professionals towards commercially available probiotics will, therefore, determine how trustworthy and beneficial these products are perceived by consumers. Furthermore, due to European Union legislation, companies are prohibited from displaying information on product packaging; therefore, consumers are dependent primarily on healthcare professionals for correct information and guidance on the use of these products. The aim of this pilot study was to explore the understanding and use of probiotics in clinical practice by professionals who are involved in child healthcare in different European countries and to assess how much they value the scientific evidence behind these products., Methods: The study was performed using a cross-sectional, descriptive, 30-question online questionnaire circulated among healthcare professionals belonging to three professional categories that are typically involved in childhood probiotic prescription: paediatricians, dieticians and general practitioners. The questionnaire was developed using web-based standard guidelines, and the questions were modelled on those used in previously published probiotics studies., Results: Overall, 27,287 healthcare professionals belonging to three major European scientific societies were contacted by the organizations participating in the study. In total, 1360 valid questionnaires were recorded, and the results were statistically analysed., Conclusions: The results emphasize the importance for healthcare professionals to be properly educated and updated on probiotics. An improved knowledge about probiotics led to increased prescriptive confidence. To disseminate accurate information on probiotics, healthcare professionals look for appropriate and scientifically validated educational platforms to acquire information, explore concerns and barriers and look for positive approaches towards recommending probiotics.

Background: Push-pull strategies have been proposed as options to complement primary malaria prevention tools, indoor residual spraying (IRS) and long-lasting insecticide-treated nets (LLINs), by targeting particularly early-night biting and outdoor-biting mosquitoes. This study evaluated different configurations of a push-pull system consisting of spatial repellents [transfluthrin-treated eave ribbons (0.25 g/m 2 ai)] and odour-baited traps (CO 2 -baited BG-Malaria traps), against indoor-biting and outdoor-biting malaria vectors inside large semi-field systems., Methods: Two experimental huts were used to evaluate protective efficacy of the spatial repellents (push-only), traps (pull-only) or their combinations (push-pull), relative to controls. Adult volunteers sat outdoors (1830 h-2200 h) catching mosquitoes attempting to bite them (outdoor-biting risk), and then went indoors (2200 h-0630 h) to sleep under bed nets beside which CDC-light traps caught host-seeking mosquitoes (indoor-biting risk). Number of traps and their distance from huts were varied to optimize protection, and 500 laboratory-reared Anopheles arabiensis released nightly inside the semi-field chambers over 122 experimentation nights., Results: Push-pull offered higher protection than traps alone against indoor-biting (83.4% vs. 35.0%) and outdoor-biting (79% vs. 31%), but its advantage over repellents alone was non-existent against indoor-biting (83.4% vs. 81%) and modest for outdoor-biting (79% vs. 63%). Using two traps (1 per hut) offered higher protection than either one trap (0.5 per hut) or four traps (2 per hut). Compared to original distance (5 m from huts), efficacy of push-pull against indoor-biting peaked when traps were 15 m away, while efficacy against outdoor-biting peaked when traps were 30 m away., Conclusion: The best configuration of push-pull comprised transfluthrin-treated eave ribbons plus two traps, each at least 15 m from huts. Efficacy of push-pull was mainly due to the spatial repellent component. Adding odour-baited traps slightly improved personal protection indoors, but excessive trap densities increased exposure near users outdoors. Given the marginal efficacy gains over spatial repellents alone and complexity of push-pull, it may be prudent to promote just spatial repellents alongside existing interventions, e.g. LLINs or non-pyrethroid IRS. However, since both transfluthrin and traps also kill mosquitoes, and because transfluthrin can inhibit blood-feeding, field studies should be done to assess potential community-level benefits that push-pull or its components may offer to users and non-users.

Background: Health related quality of life (HRQL) is an important patient related outcome measure after cardiac surgery. Preoperative determinants for postoperative HRQL have not yet been identified, but could aid in preoperative decision making. The aim of this article is to identify associations between preoperative determinants and change in HRQL 1 year after coronary artery bypass grafting (CABG)., Methods: Single centre retrospective cohort study in 658 patients. Change in HRQL was defined as a decrease or increase of ≥5 points on the physical or mental domain of the Short Form 12 (SF-12) questionnaire. Patients were stratified in three groups according to worse, unchanged, or better HRQL. Multinomial logistic regression analysis was used to investigate the association between preoperative risk factors and postoperative change in HRQL., Results: Physical HRQL improved in 22.8% of patients, did not change in 61.2% of patients and worsened in 16.0% of patients. Comorbidities associated with change in physical HRQL were a history of stroke, atrial fibrillation, vascular disease or pulmonary disease. Most important risk factor for change in physical HRQL was preoperative HRQL. Higher preoperative SF-12 score decreased the odds for worse physical HRQL and increased the odds for better physical HRQL. Mental HRQL improved in 49.8% of patients, remained unchanged in 34.5% of patients and worsened in 15.7% of patients. Preoperative HRQL was an important risk factor for a change in mental HRQL. Higher preoperative physical HRQL increased the odds for improved mental HRQL. Lower preoperative mental HRQL increased the odds for better mental HRQL., Conclusions: One year after CABG the majority of patients experiences equal or improved HRQL compared to before surgery. Most important preoperative risk factor for change in HRQL is preoperative HRQL.

Background: Quantitative structure-activity relationship (QSAR) models are important tools used in discovering new drug candidates and identifying potentially harmful environmental chemicals. These models often face two fundamental challenges: limited amount of available biological activity data and noise or uncertainty in the activity data themselves. To address these challenges, we introduce and explore a QSAR model based on custom distance metrics in the structure-activity space., Methods: The model is built on top of the k-nearest neighbor model, incorporating non-linearity not only in the chemical structure space, but also in the biological activity space. The model is tuned and evaluated using activity data for human estrogen receptor from the US EPA ToxCast and Tox21 databases., Results: The model closely trails the CERAPP consensus model (built on top of 48 individual human estrogen receptor activity models) in agonist activity predictions and consistently outperforms the CERAPP consensus model in antagonist activity predictions., Discussion: We suggest that incorporating non-linear distance metrics may significantly improve QSAR model performance when the available biological activity data are limited.

Background: Toxoplasma gondii infection can be acquired through ingestion of infectious tissue cysts in undercooked meat or environmental oocysts excreted by cats. This cross-sectional study assessed environmental risk factors for T. gondii infections and an association between latent infections and a measure of physiologic dysregulation known as allostatic load., Methods: Serum samples from 206 adults in the Durham-Chapel Hill, North Carolina area were tested for immunoglobulin (IgG) responses to T. gondii using commercial ELISA kits. Allostatic load was estimated as a sum of 15 serum biomarkers of metabolic, neuroendocrine and immune functions dichotomized at distribution-based cutoffs. Vegetated land cover within 500 m of residences was estimated using 1 m resolution data from US EPA's EnviroAtlas., Results: Handling soil with bare hands at least weekly and currently owning a cat were associated with 5.3 (95% confidence limits 1.4; 20.7) and 10.0 (2.0; 50.6) adjusted odds ratios (aOR) of T. gondii seropositivity, respectively. There was also a significant positive interaction effect of handling soil and owning cats on seropositivity. An interquartile range increase in weighted mean vegetated land cover within 500 m of residence was associated with 3.7 (1.5; 9.1) aOR of T. gondii seropositivity. Greater age and consumption of undercooked pork were other significant predictors of seropositivity. In turn, T. gondii seropositivity was associated with 61% (13%; 130%) greater adjusted mean allostatic load compared to seronegative individuals. In contrast, greater vegetated land cover around residence was associated with significantly reduced allostatic load in both seronegative (p < 0.0001) and seropositive (p = 0.004) individuals., Conclusions: Residents of greener areas may be at a higher risk of acquiring T. gondii infections through inadvertent ingestion of soil contaminated with cat feces. T. gondii infections may partially offset health benefits of exposure to the natural living environment.

Background: Controlled blood-feeding is essential for maintaining laboratory colonies of disease-transmitting mosquitoes and investigating pathogen transmission. We evaluated a low-cost artificial feeding (AF) method, as an alternative to direct human feeding (DHF), commonly used in mosquito laboratories., Methods: We applied thinly-stretched pieces of polytetrafluoroethylene (PTFE) membranes cut from locally available seal tape (i.e. plumbers tape, commonly used for sealing pipe threads in gasworks or waterworks). Approximately 4 ml of bovine blood was placed on the bottom surfaces of inverted Styrofoam cups and then the PTFE membranes were thinly stretched over the surfaces. The cups were filled with boiled water to keep the blood warm (~37 °C), and held over netting cages containing 3-4 day-old inseminated adults of female Aedes aegypti, Anopheles gambiae (s.s.) or Anopheles arabiensis. Blood-feeding success, fecundity and survival of mosquitoes maintained by this system were compared against DHF., Results: Aedes aegypti achieved 100% feeding success on both AF and DHF, and also similar fecundity rates (13.1 ± 1.7 and 12.8 ± 1.0 eggs/mosquito respectively; P > 0.05). An. arabiensis had slightly lower feeding success on AF (85.83 ± 16.28%) than DHF (98.83 ± 2.29%) though these were not statistically different (P > 0.05), and also comparable fecundity between AF (8.82 ± 7.02) and DHF (8.02 ± 5.81). Similarly, for An. gambiae (s.s.), we observed a marginal difference in feeding success between AF (86.00 ± 10.86%) and DHF (98.92 ± 2.65%), but similar fecundity by either method. Compared to DHF, mosquitoes fed using AF survived a similar number of days [Hazard Ratios (HR) for Ae. aegypti = 0.99 (0.75-1.34), P > 0.05; An. arabiensis = 0.96 (0.75-1.22), P > 0.05; and An. gambiae (s.s.) = 1.03 (0.79-1.35), P > 0.05]., Conclusions: Mosquitoes fed via this simple AF method had similar feeding success, fecundity and longevity. The method could potentially be used for laboratory colonization of mosquitoes, where DHF is unfeasible. If improved (e.g. minimizing temperature fluctuations), the approach could possibly also support studies where vectors are artificially infected with blood-borne pathogens.

Background: The genetic etiology of human lipid quantitative traits is not fully elucidated, and interactions between variants may play a role. We performed a gene-centric interaction study for four different lipid traits: low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC), and triglycerides (TG)., Results: Our analysis consisted of a discovery phase using a merged dataset of five different cohorts ( n  = 12,853 to n  = 16,849 depending on lipid phenotype) and a replication phase with ten independent cohorts totaling up to 36,938 additional samples. Filters are often applied before interaction testing to correct for the burden of testing all pairwise interactions. We used two different filters: 1. A filter that tested only single nucleotide polymorphisms (SNPs) with a main effect of p  < 0.001 in a previous association study. 2. A filter that only tested interactions identified by Biofilter 2.0. Pairwise models that reached an interaction significance level of p  < 0.001 in the discovery dataset were tested for replication. We identified thirteen SNP-SNP models that were significant in more than one replication cohort after accounting for multiple testing., Conclusions: These results may reveal novel insights into the genetic etiology of lipid levels. Furthermore, we developed a pipeline to perform a computationally efficient interaction analysis with multi-cohort replication.

Background: The wellbeing and livelihood of farmers in impoverished regions of the world is intrinsically linked to the health and welfare of their livestock; hence improved animal health is a pragmatic component of poverty alleviation. Prerequisite knowledge and understanding of the animal health challenges facing cattle keepers in Malawi is constrained by the lack of veterinary infrastructure, which inevitably accompanies under-resourced rural development in a poor country., Methods: We collaborated with public and private paraveterinary services to locate 62 village Zebu calves and 60 dairy co-operative calves dispersed over a wide geographical area. All calves were visited twice about 2 to 3 weeks apart, when they were clinically examined and faecal samples were collected. The calves were treated with 7.5 mg/kg of a locally-available albendazole drench on the first visit, and pre- and post- treatment trichostrongyle and Toxocara faecal egg counts were performed using a modified McMaster method., Results: Our clinical findings point towards a generally poor level of animal health, implying a role of ticks and tick-transmitted diseases in village calves and need for improvement in neonatal calf husbandry in the dairy co-operative holdings. High faecal trichostrongyle egg counts were not intuitive, based on our interpretation of the animal management information that was provided. This shows the need for better understanding of nematode parasite epidemiology within the context of local husbandry and environmental conditions. The albendazole anthelmintic was effective against Toxocara , while efficacy against trichostrongyle nematodes was poor in both village and dairy co-operative calves, demonstrating the need for further research to inform sustainable drug use., Conclusions: Here we describe the potential value of faecal nematode egg counting as a platform for communicating with and gaining access to cattle keepers and their animals, respectively, in southern Malawi, with the aim of providing informative background knowledge and understanding that may aid in the establishment of effective veterinary services in an under-resourced community.

Quantitative structure activity relationships (QSARs) are theoretical models that relate a quantitative measure of chemical structure to a physical property or a biological effect. QSAR predictions can be used for chemical risk assessment for protection of human and environmental health, which makes them interesting to regulators, especially in the absence of experimental data. For compatibility with regulatory use, QSAR models should be transparent, reproducible and optimized to minimize the number of false negatives. In silico QSAR tools are gaining wide acceptance as a faster alternative to otherwise time-consuming clinical and animal testing methods. However, different QSAR tools often make conflicting predictions for a given chemical and may also vary in their predictive performance across different chemical datasets. In a regulatory context, conflicting predictions raise interpretation, validation and adequacy concerns. To address these concerns, ensemble learning techniques in the machine learning paradigm can be used to integrate predictions from multiple tools. By leveraging various underlying QSAR algorithms and training datasets, the resulting consensus prediction should yield better overall predictive ability. We present a novel ensemble QSAR model using Bayesian classification. The model allows for varying a cut-off parameter that allows for a selection in the desirable trade-off between model sensitivity and specificity. The predictive performance of the ensemble model is compared with four in silico tools (Toxtree, Lazar, OECD Toolbox, and Danish QSAR) to predict carcinogenicity for a dataset of air toxins (332 chemicals) and a subset of the gold carcinogenic potency database (480 chemicals). Leave-one-out cross validation results show that the ensemble model achieves the best trade-off between sensitivity and specificity (accuracy: 83.8 % and 80.4 %, and balanced accuracy: 80.6 % and 80.8 %) and highest inter-rater agreement [kappa ( κ ): 0.63 and 0.62] for both the datasets. The ROC curves demonstrate the utility of the cut-off feature in the predictive ability of the ensemble model. This feature provides an additional control to the regulators in grading a chemical based on the severity of the toxic endpoint under study.

Background: Serious concern has been raised about the sustainability of public health care systems of European Nations and ultimately about the health of European citizens, as a result of the economic crisis that has distressed Europe since 2008. The severe economic crisis of the Euro zone, which is still afflicting Europe in 2016, has in fact threatened to equally impact public health services of nations presenting either a weak or a strong domestic growth., Comments: On behalf of the European Paediatric Association, the Union of National European Societies and Associations, the authors of the Commentary debates the relationship between the effects of economic instability and health, through the report on an article recently published in the Italian Journal of Pediatrics, which emphasized the importance of integrating existing public health care services, otherwise independently provided by public hospitals, and Primary Care Paediatric networks. The interconnections between the effects of economic instability and health are briefly commented, following the observation that these two factors are not yet fully understood, and that the definition of proper solutions to be applied in circumstances, where health is negatively impacted by periods of economic distress, is still open for discussion. Furthermore it is noted that the pressure to "deliver more for less" often seems to be the driving force forging the political strategic decisions in the area of pediatric healthcare, rather than social, cultural, and economic sensitivity and competences. Thus, the delivery of appropriate pediatric healthcare seems not to be related exclusively to motivations aimed to the benefit of children, but more often to other intervening factors, including economic, and political rationales., Conclusions: The conclusions emphasize that local European experiences suggest that positive and cost effective healthcare programs are possible, and they could serve as a model in the development of effective cross-border regional program, not weakening the quality of services provided to children.

Background: Cardiovascular health effects of fine particulate matter (PM2.5) exposure from wildfire smoke are neither definitive nor consistent with PM2.5 from other air pollution sources. Non-comparability among wildfire health studies limits research conclusions., Methods: We examined cardiovascular and respiratory health outcomes related to peat wildfire smoke exposure in a population where strong associations were previously reported for the 2008 Evans Road peat wildfire. We conducted a population-based epidemiologic investigation of associations between daily county-level modeled wildfire PM2.5 and cardiopulmonary emergency department (ED) visits during the 2011 Pains Bay wildfire in eastern North Carolina. We estimated changes in the relative risk cumulative over 0-2 lagged days of wildfire PM2.5 exposure using a quasi-Poisson regression model adjusted for weather, weekends, and poverty., Results: Relative risk associated with a 10 μg/m(3) increase in 24-h PM2.5 was significantly elevated in adults for respiratory/other chest symptoms 1.06 (1.00-1.13), upper respiratory infections 1.13 (1.05-1.22), hypertension 1.05 (1.00-1.09) and 'all-cause' cardiac outcomes 1.06 (1.00-1.13) and in youth for respiratory/other chest symptoms 1.18 (1.06-1.33), upper respiratory infections 1.14 (1.04-1.24) and 'all-cause' respiratory conditions 1.09 (1.01-1.17)., Conclusions: Our results replicate evidence for increased risk of cardiovascular outcomes from wildfire PM2.5 and suggest that cardiovascular health should be considered when evaluating the public health burden of wildfire smoke.

Background: Previous human exposure studies of traffic-related air pollutants have demonstrated adverse health effects in human populations by comparing areas of high and low traffic, but few studies have utilized microenvironmental monitoring of pollutants at multiple traffic locations while looking at a vast array of health endpoints in the same population. We evaluated inflammatory markers, heart rate variability (HRV), blood pressure, exhaled nitric oxide, and lung function in healthy participants after exposures to varying mixtures of traffic pollutants., Methods: A repeated-measures, crossover study design was used in which 23 healthy, non-smoking adults had clinical cardiopulmonary and systemic inflammatory measurements taken prior to, immediately after, and 24 hours after intermittent walking for two hours in the summer months along three diverse roadways having unique emission characteristics. Measurements of PM2.5, PM10, black carbon (BC), elemental carbon (EC), and organic carbon (OC) were collected. Mixed effect models were used to assess changes in health effects associated with these specific pollutant classes., Results: Minimal associations were observed with lung function measurements and the pollutants measured. Small decreases in BP measurements and rMSSD, and increases in IL-1β and the low frequency to high frequency ratio measured in HRV, were observed with increasing concentrations of PM2.5 EC., Conclusions: Small, acute changes in cardiovascular and inflammation-related effects of microenvironmental exposures to traffic-related air pollution were observed in a group of healthy young adults. The associations were most profound with the diesel-source EC.

Background: The potential for seasonal differences in the physicochemical characteristics of ambient particulate matter (PM) to modify interactive effects with gaseous pollutants has not been thoroughly examined. The purpose of this study was to compare cardiac responses in conscious hypertensive rats co-exposed to concentrated ambient particulates (CAPs) and ozone (O3) in Durham, NC during the summer and winter, and to analyze responses based on particle mass and chemistry., Methods: Rats were exposed once for 4 hrs by whole-body inhalation to fine CAPs alone (target concentration: 150 μg/m3), O3 (0.2 ppm) alone, CAPs plus O3, or filtered air during summer 2011 and winter 2012. Telemetered electrocardiographic (ECG) data from implanted biosensors were analyzed for heart rate (HR), ECG parameters, heart rate variability (HRV), and spontaneous arrhythmia. The sensitivity to triggering of arrhythmia was measured in a separate cohort one day after exposure using intravenously administered aconitine. PM elemental composition and organic and elemental carbon fractions were analyzed by high-resolution inductively coupled plasma-mass spectrometry and thermo-optical pyrolytic vaporization, respectively. Particulate sources were inferred from elemental analysis using a chemical mass balance model., Results: Seasonal differences in CAPs composition were most evident in particle mass concentrations (summer, 171 μg/m3; winter, 85 μg/m3), size (summer, 324 nm; winter, 125 nm), organic:elemental carbon ratios (summer, 16.6; winter, 9.7), and sulfate levels (summer, 49.1 μg/m3; winter, 16.8 μg/m3). Enrichment of metals in winter PM resulted in equivalent summer and winter metal exposure concentrations. Source apportionment analysis showed enrichment for anthropogenic and marine salt sources during winter exposures compared to summer exposures, although only 4% of the total PM mass was attributed to marine salt sources. Single pollutant cardiovascular effects with CAPs and O3 were present during both summer and winter exposures, with evidence for unique effects of co-exposures and associated changes in autonomic tone., Conclusions: These findings provide evidence for a pronounced effect of season on PM mass, size, composition, and contributing sources, and exposure-induced cardiovascular responses. Although there was inconsistency in biological responses, some cardiovascular responses were evident only in the co-exposure group during both seasons despite variability in PM physicochemical composition. These findings suggest that a single ambient PM metric alone is not sufficient to predict potential for interactive health effects with other air pollutants.

Background: Cooking over open fires using solid fuels is both common practice throughout much of the world and widely recognized to contribute to human health, environmental, and social problems. The public health burden of household air pollution includes an estimated four million premature deaths each year. To be effective and generate useful insight into potential solutions, cookstove intervention studies must select cooking technologies that are appropriate for local socioeconomic conditions and cooking culture, and include interdisciplinary measurement strategies along a continuum of outcomes., Methods/design: REACCTING (Research on Emissions, Air quality, Climate, and Cooking Technologies in Northern Ghana) is an ongoing interdisciplinary randomized cookstove intervention study in the Kassena-Nankana District of Northern Ghana. The study tests two types of biomass burning stoves that have the potential to meet local cooking needs and represent different "rungs" in the cookstove technology ladder: a locally-made low-tech rocket stove and the imported, highly efficient Philips gasifier stove. Intervention households were randomized into four different groups, three of which received different combinations of two improved stoves, while the fourth group serves as a control for the duration of the study. Diverse measurements assess different points along the causal chain linking the intervention to final outcomes of interest. We assess stove use and cooking behavior, cooking emissions, household air pollution and personal exposure, health burden, and local to regional air quality. Integrated analysis and modeling will tackle a range of interdisciplinary science questions, including examining ambient exposures among the regional population, assessing how those exposures might change with different technologies and behaviors, and estimating the comparative impact of local behavior and technological changes versus regional climate variability and change on local air quality and health outcomes., Discussion: REACCTING is well-poised to generate useful data on the impact of a cookstove intervention on a wide range of outcomes. By comparing different technologies side by side and employing an interdisciplinary approach to study this issue from multiple perspectives, this study may help to inform future efforts to improve health and quality of life for populations currently relying on open fires for their cooking needs.

The potential effects of combinations of dilute whole diesel exhaust (DE) and ozone (O₃), each a common component of ambient airborne pollutant mixtures, on lung function were examined. Healthy young human volunteers were exposed for 2 hr to pollutants while exercising (~50 L/min) intermittently on two consecutive days. Day 1 exposures were either to filtered air, DE (300 μg/m³), O₃ (0.300 ppm), or the combination of both pollutants. On Day 2 all exposures were to O₃ (0.300 ppm), and Day 3 served as a followup observation day. Lung function was assessed by spirometry just prior to, immediately after, and up to 4 hr post-exposure on each exposure day. Functional pulmonary responses to the pollutants were also characterized based on stratification by glutathione S-transferase mu 1 (GSTM1) genotype. On Day 1, exposure to air or DE did not change FEV1 or FVC in the subject population (n = 15). The co-exposure to O₃ and DE decreased FEV1 (17.6%) to a greater extent than O₃ alone (9.9%). To test for synergistic exposure effects, i.e., in a greater than additive fashion, FEV1 changes post individual O₃ and DE exposures were summed together and compared to the combined DE and O₃ exposure; the p value was 0.057. On Day 2, subjects who received DE exposure on Day 1 had a larger FEV1 decrement (14.7%) immediately after the O₃ exposure than the individuals' matched response following a Day 1 air exposure (10.9%). GSTM1 genotype did not affect the magnitude of lung function changes in a significant fashion. These data suggest that altered respiratory responses to the combination of O₃ and DE exposure can be observed showing a greater than additive manner. In addition, O₃-induced lung function decrements are greater with a prior exposure to DE compared to a prior exposure to filtered air. Based on the joint occurrence of these pollutants in the ambient environment, the potential exists for interactions in more than an additive fashion affecting lung physiological processes.

Background: Determining the fate of inhaled contaminants in the human respiratory system has challenged scientists for years. Human and animal studies have provided some data, but there is a paucity of data for toxic contaminants and sensitive populations (such as children, elderly, diseased)., Methods: Three-dimensional modeling programs and publicly available human physiology data have been used to develop a comprehensive model of the human respiratory system., Results: The in silico human respiratory system model, which includes the extrathoracic region (nasal, oral, pharyngeal, and laryngeal passages), the upper airways (trachea and main bronchi), the tracheobronchial tree, and branching networks through alveolar region, allows for virtually any variation of airway geometries and disease states. The model allows for parameterization of variables that define the subject's airways by integrating morphological changes created by disease, age, etc. with a dynamic morphology., Conclusions: The model can be used for studies of sensitive populations and the homeland security community, in cases where inhalation studies on humans cannot be conducted with toxic contaminants of interest.

Introduction: The potential of alcohol withdrawal to cause acute coronary events is an area that needs the urgent attention of clinicians and researchers., Case Presentation: We report the case of a 52-year-old heavy-alcohol-using Sri Lankan man who developed electocardiogram changes suggestive of an acute coronary event during alcohol withdrawal. Despite the patient being asymptomatic, subsequent echocardiogram showed evidence of ischemic myocardial dysfunction. We review the literature on precipitation of myocardial ischemia during alcohol withdrawal and propose possible mechanisms., Conclusions: Alcohol withdrawal is a commonly observed phenomenon in hospitals. However, the number of cases reported in the literature of acute coronary events occurring during withdrawal is few. Many cases of acute ischemia or sudden cardiac deaths may be attributed to other well known complications of delirium tremens. This is an area needing the urgent attention of clinicians and epidemiologists.

Background: Asthma and allergy represent complex phenotypes, which disproportionately burden ethnic minorities in the United States. Strong evidence for genomic factors predisposing subjects to asthma/allergy is available. However, methods to utilize this information to identify high risk groups are variable and replication of genetic associations in African Americans is warranted., Methods: We evaluated 41 single nucleotide polymorphisms (SNP) and a deletion corresponding to 11 genes demonstrating association with asthma in the literature, for association with asthma, atopy, testing positive for food allergens, eosinophilia, and total serum IgE among 141 African American children living in Detroit, Michigan. Independent SNP and haplotype associations were investigated for association with each trait, and subsequently assessed in concert using a genetic risk score (GRS)., Results: Statistically significant associations with asthma were observed for SNPs in GSTM1, MS4A2, and GSTP1 genes, after correction for multiple testing. Chromosome 11 haplotype CTACGAGGCC (corresponding to MS4A2 rs574700, rs1441586, rs556917, rs502581, rs502419 and GSTP1 rs6591256, rs17593068, rs1695, rs1871042, rs947895) was associated with a nearly five-fold increase in the odds of asthma (Odds Ratio (OR) = 4.8, p = 0.007). The GRS was significantly associated with a higher odds of asthma (OR = 1.61, 95% Confidence Interval = 1.21, 2.13; p = 0.001)., Conclusions: Variation in genes associated with asthma in predominantly non-African ethnic groups contributed to increased odds of asthma in this African American study population. Evaluating all significant variants in concert helped to identify the highest risk subset of this group.

Background: The nuclear receptor peroxisome proliferator-activated receptor alpha (PPARalpha) regulates responses to chemical or physical stress in part by altering expression of genes involved in proteome maintenance. Many of these genes are also transcriptionally regulated by heat shock (HS) through activation by HS factor-1 (HSF1). We hypothesized that there are interactions on a genetic level between PPARalpha and the HS response mediated by HSF1., Results: Wild-type and PPARalpha-null mice were exposed to HS, the PPARalpha agonist WY-14,643 (WY), or both; gene and protein expression was examined in the livers of the mice 4 or 24 hrs after HS. Gene expression profiling identified a number of Hsp family members that were altered similarly in both mouse strains. However, most of the targets of HS did not overlap between strains. A subset of genes was shown by microarray and RT-PCR to be regulated by HS in a PPARalpha-dependent manner. HS also down-regulated a large set of mitochondrial genes specifically in PPARalpha-null mice that are known targets of PPARgamma co-activator-1 (PGC-1) family members. Pretreatment of PPARalpha-null mice with WY increased expression of PGC-1beta and target genes and prevented the down-regulation of the mitochondrial genes by HS. A comparison of HS genes regulated in our dataset with those identified in wild-type and HSF1-null mouse embryonic fibroblasts indicated that although many HS genes are regulated independently of both PPARalpha and HSF1, a number require both factors for HS responsiveness., Conclusions: These findings demonstrate that the PPARalpha genotype has a dramatic effect on the transcriptional targets of HS and support an expanded role for PPARalpha in the regulation of proteome maintenance genes after exposure to diverse forms of environmental stress including HS.

Background: Exposure to particulate matter is a risk factor for cardiopulmonary disease but the underlying molecular mechanisms remain poorly understood. In the present study we sought to investigate the cardiopulmonary responses on spontaneously hypertensive rats (SHRs) following inhalation of UfCPs (24 h, 172 mug.m-3), to assess whether compromised animals (SHR) exhibit a different response pattern compared to the previously studied healthy rats (WKY)., Methods: Cardiophysiological response in SHRs was analyzed using radiotelemetry. Blood pressure (BP) and its biomarkers plasma renin-angiotensin system were also assessed. Lung and cardiac mRNA expressions for markers of oxidative stress (hemeoxygenase-1), blood coagulation (tissue factor, plasminogen activator inhibitor-1), and endothelial function (endothelin-1, and endothelin receptors A and B) were analyzed following UfCPs exposure in SHRs. UfCPs-mediated inflammatory responses were assessed from broncho-alveolar-lavage fluid (BALF)., Results: Increased BP and heart rate (HR) by about 5% with a lag of 1-3 days were detected in UfCPs exposed SHRs. Inflammatory markers of BALF, lung (pulmonary) and blood (systemic) were not affected. However, mRNA expression of hemeoxygenase-1, endothelin-1, endothelin receptors A and B, tissue factor, and plasminogen activator inhibitor showed a significant induction (~2.5-fold; p < 0.05) with endothelin 1 being the maximally induced factor (6-fold; p < 0.05) on the third recovery day in the lungs of UfCPs exposed SHRs; while all of these factors - except hemeoxygenase-1 - were not affected in cardiac tissues. Strikingly, the UfCPs-mediated altered BP is paralleled by the induction of renin-angiotensin system in plasma., Conclusion: Our finding shows that UfCPs exposure at levels which does not induce detectable pulmonary neutrophilic inflammation, triggers distinct effects in the lung and also at the systemic level in compromised SHRs. These effects are characterized by increased activity of plasma renin-angiotensin system and circulating white blood cells together with moderate increases in the BP, HR and decreases in heart rate variability. This systemic effect is associated with pulmonary, but not cardiac, mRNA induction of biomarkers reflective of oxidative stress; activation of vasoconstriction, stimulation of blood coagulation factors, and inhibition of fibrinolysis. Thus, UfCPs may cause cardiovascular and pulmonary impairment, in the absence of detectable pulmonary inflammation, in individuals suffering from preexisting cardiovascular diseases.

Background: The clinical efficacy of camptothecin (CPT), a drug specifically targeting topoisomerase I (TopoI), is under evaluation for the treatment of malignant gliomas. Due to the high unresponsiveness of these tumours to chemotherapy, it would be very important to study the signalling network that drives camptothecin outcome in this type of cancer cells. To address this issue, we had previously compared the expression profile of human U87-MG glioblastoma cells with that of a CPT-resistant counterpart, giving evidence that the development of a robust inflammatory response was the main transcriptional effect associated with CPT resistance. Here we report time-related changes and cell line specific patterns of gene expression after CPT treatment by using two p53 wild-type glioblastoma cell lines, U87-MG and DBTRG-05, with different sensitivities to TopoI inhibition., Results: First, we demonstrated that CPT treatment brings the two cell lines to completely different outcomes: accelerated senescence in U87-MG and apoptosis in DBTRG-05 cells. Then, to understand the different susceptibility to CPT, we used oligo-microarray to identify the genes whose expression was regulated during a time-course treatment, ranging from 2 h to 72 h. The statistical analysis of microarray data by MAANOVA (MicroArray ANalysis Of VAriance) showed much less modulated genes in apoptotic DBTRG-05 cells (155) with respect to the senescent U87-MG cells (3168), where the number of down-regulated genes largely exceeded that of the up-regulated ones (80% vs. 20%). Despite this great difference, the two data-sets showed a large overlapping (60% circa) mainly due to the expression of early stress responsive genes. The use of High-Throughput GoMINER and EASE tools, for functional analysis of significantly enriched GO terms, highlighted common cellular processes and showed that U87-MG and DBTRG-05 cells shared many GO terms, which are related to the down-regulation of cell cycle and mitosis and to the up-regulation of cell growth inhibition and DNA damage.Furthermore, the down-regulation of MYC and DP1 genes, which act as key transcription factors in cell growth control, together with the inhibition of BUB1, BUB3 and MAD2 mRNAs, which are known to be involved in the spindle checkpoint pathway, were specifically associated with the execution of senescence in U87-MG cells and addressed as critical factors that could drive the choice between different CPT-inducible effectors programs. In U87-MG cells we also found inflammation response and IL1-beta induction, as late transcriptional effects of Topo I treatment but these changes were only partially involved in the senescence development, as shown by IL1-beta gene silencing., Conclusion: By comparing the transcription profile of two glioblastoma cell lines treated with camptothecin, we were able to identify the common cellular pathways activated upon Topo I inhibition. Moreover, our results helped in identifying some key genes whose expression seemed to be associated with the execution of senescence or apoptosis in U87-MG and DBTRG-05 cells, respectively.