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Pleiotropy is a widespread phenomenon that may increase insight into the etiology of biological and disease traits. Since genome-wide association studies frequently provide information on a single trait only, only univariate pleiotropy detection methods are applicable, with yet unknown comparative performance. Here, we compared five such methods with respect to their ability to detect pleiotropy, including meta-analysis, ASSET, conditional false discovery rate (cFDR), cross-phenotype Bayes (CPBayes), and pleiotropic analysis under the composite null hypothesis (PLACO), by performing extended computer simulations that varied the underlying etiological model for pleiotropy for a pair of traits, including the number of causal variants, degree of traits' overlap, effect sizes as well as trait prevalence, and varying sample sizes. Our results indicate that ASSET provides the best trade-off between power and protection against false positives. We then applied ASSET to a previously published International League Against Epilepsy (ILAE) consortium data set on complex epilepsies, comprising genetic generalized epilepsy and focal epilepsy cases and corresponding controls. We identified a novel candidate locus at 17q21.32 and confirmed locus 2q24.3, previously identified to act pleiotropically on both epilepsy subtypes by a mega-analysis. Functional annotation, tissue-specific expression, and regulatory function analysis as well as Bayesian colocalization analysis corroborated this result, rendering 17q21.32 a worthwhile candidate for follow-up studies on pleiotropy in epilepsies.

Reactive species, such as those of oxygen, nitrogen, and sulfur, are considered part of normal cellular metabolism and play significant roles that can impact several signaling processes in ways that lead to either cellular sustenance, protection, or damage. Cellular redox processes involve a balance in the production of reactive species (RS) and their removal because redox imbalance may facilitate oxidative damage. Physiologically, redox homeostasis is essential for the maintenance of many cellular processes. RS may serve as signaling molecules or cause oxidative cellular damage depending on the delicate equilibrium between RS production and their efficient removal through the use of enzymatic or nonenzymatic cellular mechanisms. Moreover, accumulating evidence suggests that redox imbalance plays a significant role in the progression of several neurodegenerative diseases. For example, studies have shown that redox imbalance in the brain mediates neurodegeneration and alters normal cytoprotective responses to stress. Therefore, this review describes redox homeostasis in neurodegenerative diseases with a focus on Alzheimer’s and Parkinson’s disease. A clearer understanding of the redox-regulated processes in neurodegenerative disorders may afford opportunities for newer therapeutic strategies.

The people living in Onne are highly vulnerable to PAH exposure due to constant exposure to black soot through oral, dermal, and inhalation routes. This work aims to determine the PAHs profile of selected soils in Onne, to determine the health risks associated with PAHs exposure through the soil, and to determine the impact of reduced industrial and other activities on the PAHs profile and associated public health risks. This study evaluated 16 priority polycyclic aromatic hydrocarbon (PAHs) pollutants in soil samples from the four (4) major clans in Onne using a gas chromatography flame ionization detector (GC-FID) during and after the COVID-19 lockdown. The results showed a differential presence of PAHs during and after the lockdown. Of the 16 priority PAHs, 10 and 8 PAHs were respectively detected during and after the COVID-19 lockdown. High molecular weight PAHs such as benzo(k)fluoranthene and benzo(a)anthracene were major contributors during the lockdown, while low molecular weight PAHs such as naphthalene, acenaphthylene, and fluorene were present at higher levels after the lockdown. An assessment of health risk by incremental lifetime cancer risks revealed that the entire population of Onne might be at risk of cancer development across periods, though a higher risk was presented during the lockdown. In addition, children under the age of 18 may be at greater risk. To the best of our knowledge, there is no previous report on the impact of the COVID-19 lockdown on soil PAH profile and health risks, with particular attention to the Onne industrial host community. Earlier work considered the ecological risks of heavy metals on dumpsites in Onne. Taken together, the PAH-contaminated soil in Onne poses an immediate health concern. Therefore, reduced anthropological activities, as evident during the COVID-19 lockdown, may play a role in exposure and cancer risk reduction. While there may not be another lockdown due to the challenging impacts associated with a physical lockdown, firmly controlled economic activity can be a solution if embraced by stakeholders. The COVID-19-lockdown was encumbered with restricted movements and security checks, which limited the number of samples collected. However, the Local Government Council (Department of the Environment) granted permission for the researchers to work with a minimal threat to their lives.

BACKGROUND Few Nigerian studies have examined BMI in people with schizophrenia. The aims of the present study were to assess the prevalence and distribution of obesity in Nigerians with schizophrenia and to examine the clinical correlates of BMI and obesity. METHODS A total of 207 people with schizophrenia met the inclusion criteria and were evaluated for BMI.The Positive and Negative Syndrome Scale (PANSS), Hamilton Depression Rating Scale (HDRS), Social and Occupational Functioning Assessment Scale (SOFAS) were rated for all participants. Anthropometric measures such as weight and height were taken using a standard protocol. RESULTS The prevalence of obesity was 12.6%. The non-obese participants were made up of underweight 24 (11.7%), normal weight 118 (57%) and overweight 38 (18.4%). Compared to non-obese participants, obese participants were older, more educated, more likely to be employed, had higher incomes, lower PANSS score (negative subscale), had fewer female participants, and better social and occupational functioning (p

Objectives This study aims to identify older adult malnutrition in Texas, examine county-level characteristics associated with crude malnutrition death rates, and describe assets and opportunities available to address and improve malnutrition among the older population. Design Secondary data analysis using the Centers for Disease Control and Prevention’s WONDER online database, the U.S. Census 2014–2018 American Community Survey, and the U.S. Department of Agriculture’s Food Access Research Atlas data. Setting All 254 counties in the state of Texas. Participants Individuals aged 65 years and older. Measurement The dependent variable was the proportion of county-level malnutrition crude death rates. Independent variables included Health Provider Shortage Area designations, rurality, poverty status, food access, age, race, ethnicity, and education. Results The overall malnutrition crude death rate in Texas was 65.6 deaths per 100,000 older Texans, ranging from 0 to 414.46 deaths per 100,000 depending on the county. Higher malnutrition crude death rates were associated with non-metropolitan counties (P=0.018), lower education (P=0.047), greater household poverty (P=0.010), and low food access (P

Cryptosporidium and Toxoplasma are parasites that have caused problems worldwide. Cryptosporidium causes severe watery diarrhoea and may be fatal in immunocompromised patients and in infants. Nitazoxanide is the only agent currently approved by the FDA, but its efficacy is limited. Toxoplasmosis is also a problem in the immunocompromised, as currently available treatment options have limited efficacy and patient tolerance can be poor. In the present investigation, we screened libraries of epigenetic compounds to identify those that inhibited C. parvum growth. Nullscript was identified as a compound with an inhibitory effect on C. parvum and T. gondii growth, and was less toxic to host cells. Nullscript was also able to significantly decrease oocyst excretion in C. parvum-infected SCID mice., Graphical abstract Image 1, Highlights • A library of epigenetic compounds was used to screen for compounds effective against Cryptosporiium parvum. • Nullscript has been shown to be effective in inhibiting the growth of C. parvum and T. gondii. • Nullscript significantly decreased oocyst excretion in C. parvum-infected SCID mice.

The epidemiology of cancer-associated thrombosis (CAT) among uninsured and vulnerable populations in the US is not well-characterized. We performed a retrospective cohort study for patients with newly diagnosed cancer from 2011 to 2020 at Harris Health System, which cares for uninsured residents in the Houston metropolitan area. Patient demographics, NCI comorbidity index, area of deprivation index (ADI), cancer histology, staging, and systemic therapy data were extracted. CAT included overall venous thromboembolism (VTE) or pulmonary embolism +/- lower extremity deep vein thrombosis (PE/LE-DVT) within 1 year of diagnosis. We used multivariable Fine-Gray models to assess the associations with CAT accounting for death as a competing risk. Among 15 342 patients, 74% were uninsured and 84% lived in socioeconomically disadvantaged neighborhoods. There were 16% Non-Hispanic White (NHW), 28% Non-Hispanic Black (NHB), 50% Hispanic (27% Mexican), and 6% Asian/Pacific Islanders (API). The 1-year CAT incidence rate was 14.6%. Overall VTE was lower for Hispanics versus NHW (SHR 0.87 [0.76-0.99]) and API versus NHW (SHR 0.58 [0.44-0.77]). PE/LE-DVT was higher for NHB versus NHW (SHR 1.18 [1.01-1.39]). CAT was also associated with chemotherapy-based regimens (+/- immunotherapy), age, obesity, cancer type/staging, VTE history, and recent hospitalization. NCI comorbidity and ADI scores were associated with mortality but not CAT. In a large cohort of underserved patients with cancer, we identified an elevated incidence of CAT with known and novel risk predictors. Hispanics had lower adjusted rates of CAT and mortality. Our findings highlight the need to investigate and incorporate vulnerable populations in clinical trials.

Hurricane Harvey was associated with flood-related damage to chemical plants and oil refineries, and the flooding of hazardous waste sites, including 13 Superfund sites. As clean-up efforts began, concerns were raised regarding the human health impact of possible increased chemical exposure resulting from the hurricane and subsequent flooding. Personal sampling devices in the form of silicone wristbands were deployed to a longitudinal panel of individuals (n = 99) within 45 days of the hurricane and again one year later in the Houston metropolitan area. Using gas chromatography–mass spectroscopy, each wristband was screened for 1500 chemicals and analyzed for 63 polycyclic aromatic hydrocarbons (PAHs). Chemical exposure levels found on the wristbands were generally higher post-Hurricane Harvey. In the 1500 screen, 188 chemicals were detected, 29 were detected in at least 30% of the study population, and of those, 79% (n = 23) were found in significantly higher concentrations (p < 0.05) post-Hurricane Harvey. Similarly, in PAH analysis, 51 chemicals were detected, 31 were detected in at least 30% of the study population, and 39% (n = 12) were found at statistically higher concentrations (p < 0.05) post-Hurricane Harvey. This study indicates that there were increased levels of chemical exposure after Hurricane Harvey in the Houston metropolitan area.

The testis is an immune-privileged organ susceptible to oxidative stress and inflammation, two major factors implicated in male infertility. A reduction in the concentration and activities of testicular function biomarkers has been shown to correlate with impaired hypothalamic-pituitary-testicular axis and oxidative stress. However, the use of natural products to ameliorate these oxidative stress-induced changes may be essential to improving male reproductive function. Quercetin possesses several pharmacological activities that may help to combat cellular reproduction-related assaults, such as altered sperm function and reproductive hormone dysfunction, and dysregulated testicular apoptosis, oxidative stress, and inflammation. Studies have shown that quercetin ameliorates testicular toxicity, largely by inhibiting the generation of reactive oxygen species, with the aid of the two antioxidant pharmacophores present in its ring structure. The radical-scavenging property of quercetin may alter signal transduction of oxidative stress-induced apoptosis, prevent inflammation, and increase sperm quality in relation to the hormonal concentration. In this review, the therapeutic potential of quercetin in mediating male reproductive health is discussed.

Background Antepartum depression is the most common mental health disorder in pregnancy and it is also a risk factor for adverse perinatal outcomes. Low and middle income countries like Nigeria bear a higher burden of antepartum depression compared with high income countries. Prioritizing mental health issues among pregnant women is crucial to achieving the Sustainable Development Goals. We determined the prevalence, associated factors and perinatal outcomes of antepartum depression among pregnant women in Ibadan, Nigeria. Methods A prospective cohort study was conducted among 1745 pregnant women enrolled early in pregnancy (≤ 20 weeks) at four comprehensive obstetric facilities within Ibadan metropolis. Antepartum depression was ascertained during the third trimester using the Edinburg Postpartum Depression Scale ≥ 12. The primary exposure was antepartum depression and the outcome variables were the perinatal outcomes. The associated factors assessed included sociodemographic, obstetric, psychological, and lifestyle characteristics. Bi-variate logistic and Poisson regression analyses were used to assess the factors and relative risk for perinatal outcomes of antepartum depression. Results The prevalence of antepartum depression was 14.1%. The significant factors associated with APD after adjusting for confounders were: high income (≥ 20, 000) which was protective (AOR) = 0.59; 95% CI: (0.40 – 0.88); p-value: 0.010] and perceived stress increased the odds of APD in a monotonic fashion: moderate stress [AOR = 2.39; 95% CI: (1.01 – 5.7); p-value: 0.047], high stress [AOR = 6.43; 95% CI: (2.28 – 18.2); p-value: p-value = 0.007]. Depression did not increase the risk of having low birth weight babies (p = 0.513), macrosomia (p = 0.894), birth asphyxia (p = 0.317), and caesarean section (p = 0.298). Conclusions APD was prevalent among our study population. The significant factors identified in this study can be targeted to reduce the occurrence of APD among pregnant women in Nigeria through appropriate social and public health interventions which include APD screening, counselling, and the provision of emotional support for pregnant women during antenatal care.

Testicular dysfunction, a major contributory factor to infertility, has received a lot of attention over the recent years. Several studies have linked abnormal sperm function and morphology with an enhanced generation of reactive oxygen species (ROS) and oxidative stress. The nuclear factor erythroid-derived 2 (Nrf2) is a transcriptional response to cellular stresses (intrinsic or extrinsic) that regulates the oxidative status, mitochondrial dysfunction, inflammation, and proteostasis. In this review, the therapeutic role of Nrf2 was explored. To do so, scientific data were retrieved from databases such as Elsevier, Wiley, Web of Science, Springer, PubMed, Taylor and Francis, and Google Scholar using search terms such as "Nrf2" and "testis," "sperm," "testicular function," and "testosterone." It has been noted that Nrf2 influences the physiology and pathology of testicular dysfunction, especially in the spermatogenic process, by regulating cellular resistance to oxidative stress, inflammation, and environmental toxicants. However, numerous compounds serve as activators and inhibitors of testicular Nrf2. Nrf2 activators might play a therapeutic role in the prevention and treatment of testicular dysfunction, while molecules that inhibit Nrf2 might induce dysfunction in testis components. Nrf2 activators protect cells against oxidative damage and activate Nrf2/KEAP1 signaling which promotes its movement to the nucleus, and increased Nrf2 function and expression, along with their downstream antioxidant gene. Nrf2 inhibitors facilitate oxidative stress via interfering with the Nrf2 signal pathway. The Nrf2 activation could serve as a promising therapeutic target for testicular dysfunction. This review explored the effect of Nrf2 on testicular function while highlighting potential activators and inhibitors of Nrf2.

BACKGROUND: Women who attend sexual health clinics are at high risk for sexually transmitted infections and unintended pregnancy. Long-acting reversible contraceptives (LARC) are very effective contraceptive methods, but the provision of LARC in such clinics is not well described in the literature. METHODS: We conducted a retrospective chart review of women who presented to Denver Sexual Health Clinic for any reason and received family planning services between April 1, 2016, and October 31, 2018. We assessed demographic and clinical factors associated with contraceptive method received and conducted a subanalysis of those with intrauterine device (IUD) insertions on the same-day versus delayed insertion. Among those who received an IUD, we assessed rates of pelvic inflammatory disease (PID) 30 days after insertion. RESULTS: Of the 5064 women who received family planning services in our clinic, 1167 (23%) were using a LARC method at the time of their visit. Of the 3897 who were not using a LARC, fewer women, 12.6%, chose LARC (IUD and progestin implant), compared with 33.3% who chose new short-acting reversible contraceptives. Further analysis of the 270 IUD initiators revealed 202 (74.8%) received the IUD on the same day, whereas 68 (25.2%) had delayed IUD insertion. There were 9 incident cases of gonorrhea or chlamydia in those who received same-day IUD and 1 incident case among those who had delayed IUD insertion. There were no cases of PID at 30 days after insertion in either group. CONCLUSIONS: Study findings support IUD provision in a sexual health clinic on the day of initial visit without increased risk of PID.

PURPOSE: Area deprivation index (ADI), a measure of neighborhood socioeconomic disadvantage, has been linked to metabolic outcomes in the general population, but has received limited attention in survivors of childhood acute lymphoblastic leukemia (ALL), a population with high rates of overweight and obesity. METHODS: We retrospectively reviewed heights and weights of ≥5 year survivors of pediatric ALL (diagnosed 1990–2013). Residential addresses were geocoded using ArcGIS to assign quartiles of ADI, a composite of 17 measures of poverty, housing, employment, and education, with higher quartiles reflecting greater deprivation. Odds ratios (OR) and 95% confidence intervals (CI) for the association between ADI quartiles and overweight/obesity or obesity alone were calculated with logistic regression. RESULTS: On average, participants (n=454, 50.4% male, 45.2% Hispanic) were age 5.5 years at diagnosis and 17.4 years at follow-up. At follow-up, 26.4% were overweight and 24.4% obese. Compared to the lowest ADI quartile, survivors in the highest quartile were more likely to be overweight/obese at follow up (OR = 2.33, 95% CI: 1.23–4.44) after adjusting for race/ethnicity, sex, age at diagnosis, and age at follow-up. The highest ADI quartile remained significantly associated with obesity (OR = 5.28, 95% CI: 1.79–15.54) after accounting for weight status at diagnosis. CONCLUSIONS: This study provides novel insights into possible social determinants of health inequalities among survivors of childhood ALL by reporting a significant association between neighborhood deprivation and overweight/obesity. IMPLICATIONS FOR CANCER SURVIVORS: Survivors of childhood ALL residing in neighborhood with greater socioeconomic disadvantage may be at increased risk of overweight and obesity and candidates for targeted interventions.

Background Our previous reports demonstrated the prospects of a new series of imidazoles as a source of alternative anti-parasite treatments, thus warranting further studies that include toxicity profiling. Objective In this study, we evaluated three imidazoles: bis-imidazole (compound 1), phenyl-substituted 1H-imidazole (compound 2), and thiopene-imidazole (compound 3) for cellular toxicity and possible mechanisms. Methods The three (3) compounds were assessed for in vitro cytotoxic action. Additionally, we probed likely mechanistic actions of these imidazoles. Findings showed dose-dependent cellular toxicity by these imidazoles. Results In the presence of antioxidant (Trolox), cytotoxicity was improved for compounds 2 and 3 but not for compound 1. Meantime, compound 7 promoted reactive oxygen species (ROS) production, which was abated in the presence of a standard antioxidant (Trolox). Additionally, the three (3) imidazoles impaired mitochondrial membrane potential (MMP). While MMP was not restored after treatment removal, the addition of antioxidant (Trolox) improved MMP for compounds 2 and 3 treatment. Additionally, compound 1 elevated expression of hypoxia-inducing factor 1-alpha (HIF-1α). This may not be unconnected with the capacity of compound 1 to cause oxidative stress. Conclusion We show evidence that supports the cytotoxic action of imidazoles involves likely impairment to redox balance and mitochondrial membrane potential. The findings help our understanding of the mechanistic action of these imidazoles in living cells, and altogether may boost their prospects as new and alternative anti-protozoans.

Toxoplasma gondii can infect virtually all warm-blooded animals, including humans. It can differentiate between rapidly replicating tachyzoites that cause acute infection and slowly growing bradyzoites in tissue cysts. Treatment options for toxoplasmosis are challenging because current therapies cannot eradicate the latent T. gondii infection that is mainly caused by the bradyzoite forms. Accordingly, recurrence of infection is a problem for immunocompromised patients and congenitally infected patients. Protein kinases have been widely studied in eukaryotic cells, and while little is known about signaling in Toxoplasma infection, it is likely that protein kinases play a key role in parasite proliferation, differentiation, and probably invasion. To identify optimized new kinase inhibitors for drug development against T. gondii, we screened a library of kinase inhibitor compounds for anti-Toxoplasma activity and host cell cytotoxicity. Pyrimethamine served as a positive control and 0.5% DMSO was used as a negative control. Among the 80 compounds screened, 6 compounds demonstrated ≥ 80% parasite growth inhibition at concentrations at which 5 compounds did not suppress host cell viability, while 3 kinase inhibitors (Bay 11-7082, Tyrphostin AG 1295 and PD-98059) had suppressive effects individually on parasite growth and host cell invasion, but did not strongly induce bradyzoite formation. Electronic supplementary material The online version of this article (10.1007/s00436-020-06673-9) contains supplementary material, which is available to authorized users.

BackgroundThe aim of the current study was to explore the effect of gender, age at onset, and duration on the long-term course of schizophrenia.MethodsTwenty-nine centers from 25 countries representing all continents participated in the study that included 2358 patients aged 37.21 ± 11.87 years with a DSM-IV or DSM-5 diagnosis of schizophrenia; the Positive and Negative Syndrome Scale as well as relevant clinicodemographic data were gathered. Analysis of variance and analysis of covariance were used, and the methodology corrected for the presence of potentially confounding effects.ResultsThere was a 3-year later age at onset for females (P P P P = .001). No significant effects were found concerning duration of illness.DiscussionOur results confirmed a later onset and a possibly more benign course and outcome in females. Age at onset manifested a single peak in both genders, and surprisingly, earlier onset was related to a slower progression of the illness. No effect of duration has been detected. These results are partially in accord with the literature, but they also differ as a consequence of the different starting point of our methodology (a novel staging model), which in our opinion precluded the impact of confounding effects. Future research should focus on the therapeutic policy and implications of these results in more representative samples.

Background: Racial/ethnic minorities are more likely than non-Hispanic whites (NHW) to be diagnosed with advanced stage hepatocellular carcinoma (HCC). We examined the role of neighborhood disadvantage as a mediator of the association between race/ethnicity and HCC stage at diagnosis. Methods: We used data from HCC cases diagnosed in Texas from 2007 to 2015. HCC cases were classified as local versus regional/advanced stage. A mediation model approach was used to estimate the average direct effect, average mediated (indirect) effect, total effect, and proportion mediated by the Area Deprivation Index (ADI), a composite measure of disadvantage. Results: 7,622 had local while 6303 had regional/advanced HCC. 46.1% of cases were NHW, 15.0% non-Hispanic Black (NHB), and 38.9% Hispanic. NHBs were less likely than NHWs to be diagnosed with local stage HCC [total effect RR, 0.921; 95% confidence interval (95% CI), 0.898–0.947]; however, only 2.26% of this effect was mediated through ADI. Conversely, Hispanics were more likely than NHWs to be diagnosed with local stage HCC (total effect RR, 1.019; 95% CI, 1.001–1.037) and ADI mediated 12.56% of the effect of race/ethnicity on HCC stage. ADI was not associated with HCC stage and therefore was not a mediator of the association with HCC stage when we compared Hispanics with NHBs. Conclusions: Neighborhood socioeconomic disadvantage may explain/mediate some of the association between race/ethnicity and HCC stage; however, the mediating effect was not uniform across populations. Impact: For NHBs, other individual and neighborhood level factors, not reflected in the ADI, contribute to their lower likelihood of being diagnosed with local HCC. See related commentary by Lazo et al., p. 1254

Vascularization is fundamental to the growth and spread of tumor cells to distant sites. As a consequence, angiogenesis, the sprouting of new blood vessels from existing ones, is a characteristic trait of cancer. In 1971, Judah Folkman postulated that tumour growth is angiogenesis dependent and that by cutting off blood supply, a neoplastic lesion could be potentially starved into remission. Decades of research have been devoted to understanding the role that vascular endothelial growth factor (VEGF) plays in tumor angiogenesis, and it has been identified as a significant pro-angiogenic factor that is frequently overexpressed within a tumor mass. Today, anti-VEGF drugs such as Sunitinib, Sorafenib, Axitinib, Tanibirumab, and Ramucirumab have been approved for the treatment of advanced and metastatic cancers. However, anti-angiogenic therapy has turned out to be more complex than originally thought. The failure of this therapeutic option calls for a reevaluation of VEGF as the major target in anti-angiogenic cancer therapy. The call for reassessment is based on two rationales: first, tumour blood vessels are abnormal, disorganized, and leaky; this not only prevents optimal drug delivery but it also promotes hypoxia and metastasis; secondly, tumour growth or regrowth might be blood vessel dependent and not angiogenesis dependent as tumour cells can acquire blood vessels via non-angiogenic mechanisms. Therefore, a critical assessment of VEGF, VEGFRs, and their inhibitors could glean newer options such as repurposing anti-VEGF drugs as vascular normalizing agents to enhance drug delivery of immune checkpoint inhibitors.

Dear EditorThe COVID-19 pandemic had a significant impact on the delivery of medical education across the UK, with the majority of face-to-face teaching cancelled during the first wave, and medical...

The COVID-19 pandemic during lockdown has highlighted the importance of identifying individuals most at risk of infection with SARS-CoV-2, underscoring the need to assess factors contributing to susceptibility to disease. With the rapidly evolving nature of the pandemic and its new variants, there is an inadequate understanding on whether there are certain factors such as a specific symptom or collection of symptoms that combined with life-style behaviors may be useful to predict susceptibility. The study aims to explore such factors from pre-vaccination data to guide public health response to potential new waves.An anonymous electronic survey was distributed through social media during the lockdown period in the United States from April to June 2020. Respondents were questioned regarding COVID testing, presenting symptoms, demographic information, comorbidities, and confirmation of COVID-19 test results. Stepwise logistic regression was used to identify predictors for COVID-19 perceived susceptibility. Selected classifiers were assessed for prediction performance using area under receiver operating characteristic (AUROC) curve analysis.A total of 130 participants deemed as susceptible because they self-reported their perception of having COVID-19 (but without the evidence of positive test) were compared with 130 individuals with documented negative test results. Participants had a mean age of 45 years, and 165 (63%) were female. Final multivariable model showed significant associations with perceived susceptibility for the following variables: fever (OR:33.5; 95%CI: 3.9,85.9), body ache (OR:3.0; 95%CI:1.1,6.4), contact history (OR:2.7; 95%CI:1.1,6.4), age 50 (OR:2.7; 95%CI:1.1, 6.6) and smoking (OR:3.3; 95%CI: 1.2,9.1) after adjusting for other symptoms and presence of comorbid conditions. The AUROC ranged from poor to fair (0.65-0.76) for cluster of symptoms but improved to a good model (AUROC = 0.803) after inclusion of sociodemographic and lifestyle behaviors e.g., age and smoking tobacco.Fever and body aches suggest association with perceived COVID-19 susceptibility in the presence of demographic and lifestyle behaviors. Using other constitutional and respiratory symptoms with fever and body aches, the parsimonious classifier correctly predicts 80.3% of COVID-19 perceived susceptibility. A larger cohort of respondents will be needed to study and refine classifier performance in future lockdowns and with expected surge of new variants of COVID-19 pandemic.

Background: Specific phobia (SP) is a relatively common disorder associated with high levels of psychiatric comorbidity. Because of its early onset, SP may be a useful early marker of internalizing psychopathology, especially if generalized to multiple situations. This study aimed to evaluate the association of childhood generalized SP with comorbid internalizing disorders. Methods: We conducted retrospective analyses of the cross-sectional population-based World Mental Health Surveys using the Composite International Diagnostic Interview. Outcomes were lifetime prevalence, age of onset, and persistence of internalizing disorders; past-month disability; lifetime suicidality; and 12-month serious mental illness. Logistic and linear regressions were used to assess the association of these outcomes with the number of subtypes of childhood-onset (

Background and PurposeVirus mitigation strategies such as adhering to stay-at-home orders, practicing social distancing, and engaging in personal protective behaviors are central to slowing the spread of COVID-19. This population-based cohort study sought to identify sociodemographic characteristics and Health Belief Model factors that are associated with nonadherence to COVID-19 mitigation strategies with the goal of informing public health messaging campaigns.MethodsAn online population-based survey was distributed via social media over an 8-week period from April 13, 2020, to June 8, 2020.ResultsData were derived from 2,222 adults (57% female; 40% racial/ethnic minorities). Univariate analyses revealed that men, younger aged (18–30 years) and unmarried adults, and noncollege educated individuals had lower levels of perceived threat, control, and knowledge about COVID-19 (p ≤ .001). Multivariable linear regression models further revealed that male gender was significantly associated with reporting lower levels of adherence to COVID-19 mitigation strategies (p < .001), and that higher levels of perceived threat, perceived control, and knowledge about how to keep oneself and others safe from COVID-19 were significantly associated with reporting higher levels of adherence to COVID-19 mitigation strategies (p < .01).ConclusionsFindings suggest that public health appeals that target men, emphasize individual risk, and provide clear, consistent guidance on what individuals can do to decrease their risk for COVID-19 may be effective in motivating increased mitigation adherence.

Owing to the urgent need for therapeutic interventions against the SARS-coronavirus 2 (SARS-CoV-2) pandemic, we employed an in silico approach to evaluate the SARS-CoV-2 inhibitory potential of newly synthesized imidazoles. The inhibitory potentials of the compounds against SARS-CoV-2 drug targets - main protease (Mpro), spike protein (Spro) and RNA-dependent RNA polymerase (RdRp) were investigated through molecular docking analysis. The binding free energy of the protein-ligand complexes were estimated, pharmacophore models were generated and the absorption, distribution, metabolism, excretion and toxicity (ADMET) properties of the compounds were determined. The compounds displayed various levels of binding affinities for the SARS-CoV-2 drug targets. Bisimidazole C2 scored highest against all the targets, with its aromatic rings including the two imidazole groups contributing to the binding. Among the phenyl-substituted 1H-imidazoles, C9 scored highest against all targets. C11 scored highest against Spro and C12 against Mpro and RdRp among the thiophene-imidazoles. The compounds interacted with HIS 41 - CYS 145 and GLU 288 - ASP 289 - GLU 290 of Mpro, ASN 501 of Spro receptor binding motif and some active site amino acids of RdRp. These novel imidazole compounds could be further developed as drug candidates against SARS-CoV-2 following lead optimization and experimental studies.

This study examined individual-level determinants of self-reported changes in healthy (diet and physical activity) and addictive (alcohol use, smoking, and vaping) lifestyle behaviors during the initial COVID-19 lockdown period in the USA. A national online survey was administered between May and June 2020 that targeted a representative U.S. sample and yielded data from 1276 respondents, including 58% male and 50% racial/ethnic minorities. We used univariate and multivariable linear regression models to examine the associations of sociodemographic, mental health, and behavioral determinants with self-reported changes in lifestyle behaviors. Some study participants reported increases in healthy lifestyle behaviors since the pandemic (i.e., 36% increased healthy eating behaviors, and 33% increased physical activity). However, they also reported increases in addictive lifestyle behaviors including alcohol use (40%), tobacco use (41%), and vaping (46%). With regard to individual-level determinants, individuals who reported adhering to social distancing guidelines were also more likely to report increases in healthy lifestyle behaviors (β = 0.12, 95% CI 0.04 to 0.21). Conversely, women (β = −0.37, 95% CI −0.62 to −0.12), and unemployed individuals (β = −0.33, 95% CI −0.64 to −0.02) were less likely to report increases in healthy lifestyle behaviors. In addition, individuals reporting anxiety were more likely to report increases in addictive behaviors (β = 0.26, 95% CI 0.09 to 0.43). Taken together, these findings suggest that women and unemployed individuals may benefit from interventions targeting diet and physical activity, and that individuals reporting anxiety may benefit from interventions targeting smoking and alcohol cessation to address lifestyle changes during the pandemic.

Background: Although there is evidence of socioeconomic disparities in survival of children diagnosed with central nervous system (CNS) tumors, the impact of neighborhood socioeconomic deprivation on the survival of these malignancies has not been adequately studied. We investigated the association between area deprivation index (ADI), a measure of neighborhood socioeconomic disadvantage, and pediatric CNS tumor survival. Methods: Demographic and clinical characteristics, geocoded addresses at diagnosis, and vital status of pediatric CNS tumor cases (n = 5,477) for the period 1995 to 2017 were obtained from the Texas Cancer Registry. ADI scores were computed for census tracts in Texas using the U.S. Census Bureau 2010 geography. Tracts were classified into quartiles as least, third-most, second-most, and most disadvantaged. Children were mapped to quartiles based on residency at diagnosis. The adjusted hazard ratio (HR) and 95% confidence interval (CI) were calculated. Results: The results showed a significantly increased HR for death among children in the most (HR, 1.29; 95% CI, 1.09–1.51), second-most (HR, 1.18; 95% CI, 1.01–1.38), and third-most disadvantaged census tracts (HR, 1.18; 95% CI, 1.02–1.37) compared with children in the least disadvantaged tracts. Conclusions: Children living in the most disadvantaged neighborhoods experienced a significantly higher risk of mortality, indicating the important role of socioeconomic disparities in the survival of pediatric CNS tumors. Impact: The demographic and socioeconomic disparities identified by this study should be considered when planning treatment strategies for these susceptible groups and thus, lead to a better outcome in socioeconomically disadvantaged children diagnosed with CNS tumors.

Studies which have explored the effect of spirituality on suicidality among patients with schizophrenia have been characterized by inconsistent results. The aim of this study was to examine the relationship between spirituality and suicidality among stable patients with schizophrenia in Nigeria. The Daily Spiritual Experience Scale was applied to measure spirituality. There was found a significant relationship between spirituality and having had suicidal thoughts in a lifetime. Spirituality was negatively correlated with the severity of negative symptoms, total positive and negative syndrome scale score (PANSS), the severity of depression, and positively correlated with functioning.

Neurodegenerative diseases (NDs) like Alzheimer’s disease, multiple sclerosis, amyotrophic lateral sclerosis, Parkinson’s disease, and Huntington’s disease predominantly pose a significant socioeconomic burden. Characterized by progressive neural dysfunction coupled with motor or intellectual impairment, the pathogenesis of ND may result from contributions of certain environmental and molecular factors. One such condition is hypoxia, characterized by reduced organ/tissue exposure to oxygen. Reduced oxygen supply often occurs during the pathogenesis of ND and the aging process. Despite the well-established relationship between these two conditions (i.e., hypoxia and ND), the underlying molecular events or mechanisms connecting hypoxia to ND remain ill-defined. However, the relatedness may stem from the protective or deleterious effects of the transcription factor, hypoxia-inducible factor 1-alpha (HIF-1α). The upregulation of HIF-1α occurs in the pathogenesis of most NDs. The dual function of HIF-1α in acting as a “killer factor” or a “protective factor” depends on the prevailing local cellular condition. The kynurenine pathway is a metabolic pathway involved in the oxidative breakdown of tryptophan. It is essential in neurotransmission and immune function and, like hypoxia, associated with ND. Thus, a good understanding of factors, including hypoxia (i.e., the biochemical implication of HIF-1α) and kynurenine pathway activation in NDs, focusing on Alzheimer’s disease could prove beneficial to new therapeutic approaches for this disease, thus the aim of this review.

Central to developing effective control measures for the COVID-19 pandemic is understanding the epidemiology of transmission in the community. Geospatial analysis of neighborhood-level data could provide insight into drivers of infection. In the current analysis of Harris County, Texas, we used custom interpolation tools in GIS to disaggregate COVID-19 incidence estimates from the zip code to census tract estimates—a better representation of neighborhood-level estimates. We assessed the associations between 29 neighborhood-level characteristics and COVID-19 incidence using a series of aspatial and spatial models. The variables that maintained significant and positive associations with COVID-19 incidence in our final aspatial model and later represented in a geographically weighted regression model were the percentage of the Black/African American population, percentage of the foreign-born population, area derivation index (ADI), percentage of households with no vehicle, and percentage of people over 65 years old inside each census tract. Conversely, we observed negative and significant association with the percentage employed in education. Notably, the spatial models indicated that the impact of ADI was homogeneous across the study area, but other risk factors varied by neighborhood. The current findings could enhance decision making by local public health officials in responding to the COVID-19 pandemic. By understanding factors that drive community transmission, we can better target disease control measures.

Clinical and genetic factors have been reported as influencing the development of sickle cell nephropathy (SCN). However, such data remain limited in the paediatric population. In this cross-sectional study, we enrolled 361 sickle cell disease children from the Democratic Republic of Congo. Participants were genotyped for the beta (β)-globin gene, apolipoprotein L1 (APOL1) risk variants, and haem oxygenase-1 (HMOX1) GT-dinucleotide repeats. As markers of kidney damage, albuminuria, hyperfiltration and decreased estimated glomerular filtration with creatinine (eGFRcr) were measured. An association of independent clinical and genetic factors with these markers of kidney damage were assessed via regression analysis. Genetic sequencing confirmed sickle cell anaemia in 326 participants. Albuminuria, hyperfiltration and decreased eGFRcr were present in 65 (20%), 52 (16%) and 18 (5·5%) patients, respectively. Regression analysis revealed frequent blood transfusions, indirect bilirubin and male gender as clinical predictors of SCN. APOL1 high-risk genotype (G1/G1, G2/G2 and G1/G2) was significantly associated with albuminuria (P = 0·04) and hyperfiltration (P = 0·001). HMOX1 GT-dinucleotide long repeats were significantly associated with lower eGFRcr. The study revealed a high burden of kidney damage among Congolese children and provided evidence of the possible role of APOL1 and HMOX1 in making children more susceptible to kidney complications.

BACKGROUND We assessed whether self-descriptions, self-perceptions, perceived substance use of friends, and actual substance use were associated with high school girls' frequency of making social comparisons to peers. METHODS We analyzed data from the Adolescent Health Risk Behavior Survey data for 357 high school girls using multinomial logistic regression. RESULTS Compared to those who "never/rarely" made social comparisons, participants who self-described as fearing something constantly (p = .014) and forced to imitate the people they like (p = .009) were more likely to "usually" compare themselves to peers. Participants who described themselves as feeling forced to imitate the people they like (p = .022), were not the person they would like to be (p = .005), and did not remain calm under pressure (p = .010), were more likely to "often/always" make social comparisons. Participants who perceived themselves as unattractive (p = .034) and self-centered (p = .016) were more likely to "often/always" make social comparisons. Participants who perceived a larger proportion of friends use illicit drugs were less likely to "usually" make social comparisons (p = .027). Participants who perceived a larger proportion of friends drink alcohol were more likely to "often/always" make social comparisons (p = .018). CONCLUSIONS Girls who perceive and describe themselves more negatively are at increased odds of making social comparisons to peers.

Diabetes mellitus (DM) and coronavirus disease 2019 (COVID-19) are public health issues worldwide, and their comorbidities trigger the progress to severe disease and even death in such patients. Globally, DM has affected an estimated 9.3% adults, and as of April 18, 2021, the World Health Organization (WHO) has confirmed 141,727,940 COVID-19 confirmed cases. The virus is spread via droplets, aerosols, and direct touch with others. Numerous predictive factors have been linked to COVID-19 severity, including impaired immune response and increased inflammatory response, among others. Angiotensin receptor blockers and angiotensin converting enzyme 2 have also been identified as playing a boosting role in both susceptibility and severity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Specifically, in DM patients, both their control and management during this pandemic is herculean as the restriction periods have markedly hampered the maintenance of means to control glycemia, hypertension, and neuroendocrine and kidney diseases. In addition, as a result of the underlyin cardio-metabolic and immunological disorders, DM patients are at a higher risk of developing the severe form of COVID-19 despite other comorbidities, such as hypertension, also potentially boosting the development of higher COVID-19 severity. However, even in non-DM patients, SARS-CoV-2 may also cause transient hyperglycemia through induction of insulin resistance and/or pancreatic β-cell injury. Therefore, a strict glucose monitoring of DM patients with COVID-19 is mandatory to prevent life-threatening complications.

Workplace violence (WPV) has been extensively studied in hospitals, yet little is known about WPV in outpatient physician clinics. These settings and work tasks may present different risk factors for WPV compared to hospitals, including the handling/exchange of cash, and being remotely located without security presence. We conducted a systematic literature review to describe what is currently known about WPV in outpatient physician clinics. Six literature databases were searched and reference lists from included articles published from 2000–2019. Thirteen quantitative and five qualitative manuscripts were included which all focused on patient/family-perpetrated violence in outpatient physician clinics. No studies examined other violence types (e.g., worker-on-worker; burglary). The overall prevalence of Type II violence ranged from 9.5% to 74.6%, with the most common form being verbal abuse (42.1–94.3%), followed by threat of assault (14.0–57.4%), bullying (2.5–5.7%), physical assault, (0.5–15.9%) and sexual harassment/assault (0.2–9.3%). Worker consequences included reduced work performance, anger, and depression. Most workers did not receive training on how to manage a violent patient. More work is needed to examine the prevalence and risk factors of WPV in outpatient physician clinics for purposes of informing prevention efforts in these settings.

The antioxidant and anti-proinflammatory activities of L-leucine were investigated on oxidative testicular injury, ex vivo. In vitro analysis revealed L-leucine to be a potent scavenger of free radicals, while inhibiting acetylcholinesterase activity. Oxidative injury was induced in testicular tissues using FeSO

Highlights • Online platforms are now an effective tool for marketing and policy development. • Consumers’ emotions and opinions are important for interventions to be effective. • Clarity about DRS including its operations is required to enhance participation. • A UK-wide scheme with similar operations and structure should be introduced. • DRS may not contribute to sustainability rather it might increase pollution., Packaging waste production, especially single-use containers, is exerting detrimental effects on terrestrial and aquatic ecosystems, including human health. To internalise the externalities associated with single-use containers, different instruments, including a deposit refund scheme (DRS), have been operationalised in many countries. Therefore, DRS is introduced in Scotland to reduce plastic litters by increasing recycling rates and incentivising pro-environmental behavioural change. This study addresses the complexity of single-use plastic containers by analysing consumers’ perceptions regarding the introduction of DRS in Scotland. Using 940 comments from the BBC “Have Your Say” messageboard, this study adopts sentiment analysis to understand consumers’ opinions about the introduction and implementation of DRS in Scotland. Findings suggest that a UK-wide scheme that is similar in terms of operations and structure is required for DRS to be successful. While consumers’ knowledge and opinions about DRS are mixed, the efficacy of DRS including its relevance is questioned and raises doubts about its contribution to sustainability. The findings imply the need for UK countries to negotiate and collaborate on appropriate and attractive interventions in addressing post-consumer single-use plastic containers. The implications of the findings for policy and practice, especially in improving the operations of DRS are further discussed.

This survey study assessed public concerns about symptoms of coronavirus disease 2019 and individual actions in response to the pandemic.

Background Few studies have evaluated social determinants of outcomes disparities for children with acute lymphoblastic leukemia (ALL). We investigated the association of area deprivation index (ADI), a measure of neighborhood socioeconomic disadvantage, with overall survival (OS) among children and adolescents with ALL. Procedure We obtained demographic and clinical data, geocoded addresses at diagnosis, and vital status on all Texas children diagnosed with ALL from 1995 to 2011 (N = 4104). Using the US Census Bureau 2010 geography, we computed ADI scores for all census tracts in Texas and grouped the tracts into quartiles: least, third-most, second-most, and most disadvantaged. We mapped children to ADI quartiles based on residence at diagnosis, and estimated OS using Cox regression adjusting for sex, race/ethnicity, age, and metropolitan/nonmetropolitan residence. Results Five-year OS ranged from 89% (95% confidence interval [CI] 87-91%) for children in the least disadvantaged tracts to 79% (95% CI 76-81%) for children in the most disadvantaged tracts (P = 4E-7). An elevated hazard ratio (HR) for death was observed for children in the most disadvantaged tracts (HR 1.57, 95% CI 1.23-2.00), and trends toward increased mortality were observed in the third-most and second-most disadvantaged tracts (HR 1.23, 95% CI 0.97-1.57 and HR 1.27, 95% CI 0.99-1.62, respectively). In stratified analyses, area disadvantage was more strongly associated with OS in males than females. Conclusions Neighborhood socioeconomic disadvantage is associated with inferior OS in this analysis of over 4100 children with ALL, highlighting the substantial contributions of social-environmental factors to childhood cancer survival. This association was stronger in males than females.

The rapid growth of the global aging population has raised attention to the health and healthcare needs of older adults. The purpose of this mini-review is to: (1) elucidate the complex factors affecting the relationship between chronological age, socio-economic status (SES), access to care, and healthy aging using a SES-focused framework; (2) present examples of interventions from across the globe; and (3) offer recommendations for research-guided action to remediate the trend of older age being associated with lower SES, lack of access to care, and poorer health outcomes. Evidence supports a relationship between SES and healthcare access as well as healthcare access and health outcomes for older adults. Because financial resources are proportional to health status, efforts are needed to support older adults and the burdened healthcare system with financial resources. This can be most effective with grassroots approaches and interventions to improve SES among older adults and through data-driven policy and systems change.

BackgroundIn August 2017, Hurricane Harvey caused unprecedented flooding across the greater Houston area. Given the potential for widespread flood-related exposures, including mold and sewage, and the emotional and mental toll caused by the flooding, we sought to evaluate the short- and long-term impact of flood-related exposures on the health of Houstonians. Our objectives were to assess the association of flood-related exposures with allergic symptoms and stress among Houston-area residents at two time points: within approximately 30 days (T1) and 12 months (T2) after Hurricane Harvey’s landfall.MethodsThe Houston Hurricane Harvey Health (Houston-3H) Study enrolled a total of 347 unique participants from four sites across Harris County at two times: within approximately 1-month of Harvey (T1,n = 206) and approximately 12-months after Harvey (T2,n = 266), including 125 individuals who participated at both time points. Using a self-administered questionnaire, participants reported details on demographics, flood-related exposures, and health outcomes, including allergic symptoms and stress.ResultsThe majority of participants reported hurricane-related flooding in their homes at T1 (79.1%) and T2 (87.2%) and experienced at least one allergic symptom after the hurricane (79.4% at T1 and 68.4% at T2). In general, flood-exposed individuals were at increased risk of upper respiratory tract allergic symptoms, reported at both the T1 and T2 time points, with exposures to dirty water and mold associated with increased risk of multiple allergic symptoms. The mean stress score of study participants at T1 was 8.0 ± 2.1 and at T2, 5.1 ± 3.2, on a 0–10 scale. Participants who experienced specific flood-related exposures reported higher stress scores when compared with their counterparts, especially 1 year after Harvey. Also, a supplementary paired-samples analysis showed that reports of wheezing, shortness of breath, and skin rash did not change between T1 and T2, though other conditions were less commonly reported at T2.ConclusionThese initial Houston-3H findings demonstrate that flooding experiences that occurred as a consequence of Hurricane Harvey had lasting impacts on the health of Houstonians up to 1 year after the hurricane.

Neurocognitive impairments (NCI) are common in patients with bipolar I disorder. However, reports about the affected domains, outcomes and magnitude have been inconsistent. The aim of this study was to compare the magnitude (severity) and specificity (domains), of (NCI) in euthymic Bipolar I Disorder (BD) patients with a demographically and educationally matched sample of patients with schizophrenia in remission (SC) and healthy controls (HC).The Screen for Cognitive Impairment in Psychiatry (SCIP) was applied in this cross-sectional study, to all consecutive and consenting euthymic outpatients with bipolar I disorder (BD) (n = 76), remitted patients with schizophrenia (n = 130) and age and gender-matched healthy controls (HC) (n = 100). The cognitive tests done included Verbal List Learning-Immediate (VLT-I), Working Memory Test (WMT), Verbal Fluency Test (VFT), Verbal Learning Test-Delayed (VLT-D) and Processing Speed Test (PST). Within the bipolar group, the association between NCI and functioning was assessed.There was a significant difference in the proportions of participants that had cognitive impairment from the 3 groups (37% (HC) vs. 71.1% (BD) vs. 91.5%(SC) (p=0.001). The BD group in comparison to the HCs did worse on all domains of the SCIP except WMT and PST. The BD group was not significantly different from the SC group in all neuropsychological domains of the SCIP except WMT. BD group significantly functions better than the SC group. The severity of depressive symptomatology and VLT-I were independent predictors of functioning in the BD group.Cognitive impairment affects almost all the neurocognitive domains of the BD group. The difference in NCI between euthymic BD patients and SC in remission are quantitative rather than qualitative.

Neisseria gonorrhoeae (gonococcus) is a Gram-negative bacterium that causes gonorrhoea—a sexually transmitted disease. This gonococcus has progressively developed resistance to most of the available antimicrobials. Only a few countries around the world have been able to run extensive surveillance programmes on gonococcal infection and antimicrobial resistance, raising a global concern. Thus, this review focuses on the mechanisms of resistance to recommended antimicrobials in the past and present time. The approaches by the scientific community in the development of novel technologies such as whole-genome sequencing to predict antimicrobial resistance, track gonococcal transmission, as well as, introduce new therapeutics like Solithromycin, Zoliflodacin, and Gepotidacin were also discussed.

BackgroundThe aim of the current study was to explore the changing interrelationships among clinical variables through the stages of schizophrenia in order to assemble a comprehensive and meaningful disease model.MethodsTwenty-nine centers from 25 countries participated and included 2358 patients aged 37.21 ± 11.87 years with schizophrenia. Multiple linear regression analysis and visual inspection of plots were performed.ResultsThe results suggest that with progression stages, there are changing correlations among Positive and Negative Syndrome Scale factors at each stage and each factor correlates with all the others in that particular stage, in which this factor is dominant. This internal structure further supports the validity of an already proposed four stages model, with positive symptoms dominating the first stage, excitement/hostility the second, depression the third, and neurocognitive decline the last stage.ConclusionsThe current study investigated the mental organization and functioning in patients with schizophrenia in relation to different stages of illness progression. It revealed two distinct “cores” of schizophrenia, the “Positive” and the “Negative,” while neurocognitive decline escalates during the later stages. Future research should focus on the therapeutic implications of such a model. Stopping the progress of the illness could demand to stop the succession of stages. This could be achieved not only by both halting the triggering effect of positive and negative symptoms, but also by stopping the sensitization effect on the neural pathways responsible for the development of hostility, excitement, anxiety, and depression as well as the deleterious effect on neural networks responsible for neurocognition.

Trichuriasis and ascariasis are neglected tropical diseases caused by the gastrointestinal dwelling nematodes Trichuris trichiura (a whipworm) and Ascaris lumbricoides (a roundworm), respectively. Both parasites are staggeringly prevalent, particularly in tropical and subtropical areas, and are associated with substantial morbidity. Infection is initiated by ingestion of infective eggs, which hatch in the intestine. Thereafter, T. trichiura larvae moult within intestinal epithelial cells, with adult worms embedded in a partially intracellular niche in the large intestine, whereas A. lumbricoides larvae penetrate the gut mucosa and migrate through the liver and lungs before returning to the lumen of the small intestine, where adult worms dwell. Both species elicit type 2 anti-parasite immunity. Diagnosis is typically based on clinical presentation (gastrointestinal symptoms and inflammation) and the detection of eggs or parasite DNA in the faeces. Prevention and treatment strategies rely on periodic mass drug administration (generally with albendazole or mebendazole) to at-risk populations and improvements in water, sanitation and hygiene. The effectiveness of drug treatment is very high for A. lumbricoides infections, whereas cure rates for T. trichiura infections are low. Novel anthelminthic drugs are needed, together with vaccine development and tools for diagnosis and assessment of parasite control in the field.

Persons of African ancestry are thought to carry a higher risk for extrapyramidal syndromes (EPS) in schizophrenia.We investigated the phenomenon of spontaneous and treatment-emergent EPS in a sample comprising Xhosa (South Africa) and Yoruba (Nigeria) Africans with first-episode schizophrenia and first exposure to antipsychotics.The Extrapyramidal Symptom Rating Scale (ESRS) and a variety of validated tools were used for the assessment of participants before, and two-weekly after treatment with low dose flupenthixol decanoate. Participants were followed up for 12 months. Association of EPS with clinical characteristics was investigated using Pearson's correlation and linear regression analyses.Of 88 participants at baseline, 16 (18.1%) had at least one definite EPS prior to antipsychotic exposure and 34 (38.6%) had treatment-emergent EPS. While spontaneous Parkinsonism was associated with negative symptoms (These findings support the hypothesis suggesting that spontaneously occurring Parkinsonism in schizophrenia may be the motor spectrum of negative symptomatology. Future studies of this relationship may lead to early identification of patients who may be more sensitive to EPS.

Background The plenteous resistance to and undesirable consequences of the existing antipiroplasmic therapies have emphasized the urgent need for new chemotherapeutics and drug targets for both prophylaxis and chemotherapy. Hydroxyurea (HYD) is an antineoplastic agent with antitrypanosomal activity. Eflornithine (α-difluoro-methyl ornithine, DFMO) is the best choice therapy for the treatment of late-stage Gambian human African trypanosomiasis. Methods In this study, the inhibitory and combination efficacy of HYD and DFMO with existing babesicidal drugs (diminazene aceturate (DA), atovaquone (ATV), and clofazimine (CLF)) deoxyribonucleotide in vitro against the multiplication of Babesia and Theileria. As well as, their chemotherapeutic effects were assessed on B. microti strain that infects rodents. The Cell Counting Kits-8 (CCK-8) test was used to examine their cytotoxicity on human foreskin fibroblast (HFF), mouse embryonic fibroblast (NIH/3T3), and Madin–Darby bovine kidney (MDBK) cells. Findings HYD and DFMO suppressed the multiplication of all tested species (B. bigemina, B. bovis, B. caballi, B. divergens, and T. equi) in a dose-related manner. HFF, NIH/3T3, or MDBK cell viability was not influenced by DFMO at 1000 μM, while HYD affected the MDBK cell viability at EC50 value of 887.5±14.4 μM. The in vitro combination treatments of DFMO and HYD with CLF, DA, and ATV exhibited synergistic and additive efficacy toward all tested species. The in vivo experiment revealed that HYD and DFMO oral administration at 100 and 50 mg/kg inhibited B. microti multiplication in mice by 60.1% and 78.2%, respectively. HYD-DA and DFMO-DA combined treatments showed higher chemotherapeutic efficacy than their monotherapies. Conclusion These results indicate the prospects of HYD and DFMO as drug candidates for piroplasmosis treatment, when combined mainly with DA, ATV, and CLF. Therefore, further studies are needed to combine HYD or DFMO with either ATV or CLF and examine their impact on B. microti infection in mice.

AimsIn low- and middle-income countries (LMIC) in general and sub-Sahara African (SSA) countries in particular, there is both a large treatment gap for mental disorders and a relative paucity of empirical evidence about how to fill this gap. This is more so for severe mental disorders, such as psychosis, which impose an additional vulnerability for human rights abuse on its sufferers. A major factor for the lack of evidence is the few numbers of active mental health (MH) researchers on the continent and the distance between the little evidence generated and the policy-making process.MethodsThe Partnership for Mental Health Development in Africa (PaM-D) aimed to bring together diverse MH stakeholders in SSA, working collaboratively with colleagues from the global north, to create an infrastructure to develop MH research capacity in SSA, advance global MH science by conducting innovative public health-relevant MH research in the region and work to link research to policy development. Participating SSA countries were Ghana, Kenya, Liberia, Nigeria and South Africa. The research component of PaM-D focused on the development and assessment of a collaborative shared care (CSC) program between traditional and faith healers (T&FHs) and biomedical providers for the treatment of psychotic disorders, as a way of improving the outcome of persons suffering from these conditions. The capacity building component aimed to develop research capacity and appreciation of the value of research in a broad range of stakeholders through bespoke workshops and fellowships targeting specific skill-sets as well as mentoring for early career researchers.ResultsIn the research component of PaM-D, a series of formative studies were implemented to inform the development of an intervention package consisting of the essential features of a CSC for psychosis implemented by primary care providers and T&FHs. A cluster randomised controlled trial was next designed to test the effectiveness of this package on the outcome of psychosis. In the capacity-building component, 35 early and mid-career researchers participated in the training workshops and several established mentor-mentee relationships with senior PaM-D members. At the end of the funding period, 60 papers have been published and 21 successful grant applications made.ConclusionThe success of PaM-D in energising young researchers and implementing a cutting-edge research program attests to the importance of partnership among researchers in the global south working with those from the north in developing MH research and service in LMIC.

Berberis vulgaris (B. vulgaris) and Rhus coriaria (R. coriaria) have been documented to have various pharmacologic activities. The current study assessed the in vitro as well as in vivo inhibitory efficacy of a methanolic extract of B. vulgaris (MEBV) and an acetone extract of R. coriaria (AERC) on six species of piroplasm parasites. The drug-exposure viability assay was tested on three different cell lines, namely mouse embryonic fibroblast (NIH/3T3), Madin-Darby bovine kidney (MDBK) and human foreskin fibroblast (HFF) cells. Qualitative phytochemical estimation revealed that both extracts containing alkaloid, tannin, saponins and terpenoids and significant amounts of flavonoids and polyphenols. The GC-MS analysis of MEBV and AERC revealed the existence of 27 and 20 phytochemical compounds, respectively. MEBV and AERC restricted the multiplication of Babesia (B.) bovis, B. bigemina, B. divergens, B. caballi, and Theileria (T.) equi at the half-maximal inhibitory concentration (IC50) of 0.84 ± 0.2, 0.81 ± 0.3, 4.1 ± 0.9, 0.35 ± 0.1 and 0.68 ± 0.1 µg/mL and 85.7 ± 3.1, 60 ± 8.5, 90 ± 3.7, 85.7 ± 2.1 and 78 ± 2.1 µg/mL, respectively. In the cytotoxicity assay, MEBV and AERC inhibited MDBK, NIH/3T3 and HFF cells with half-maximal effective concentrations (EC50) of 695.7 ± 24.9, 931 ± 44.9, >1500 µg/mL and 737.7 ± 17.4, >1500 and >1500 µg/mL, respectively. The experiments in mice showed that MEBV and AERC prohibited B. microti multiplication at 150 mg/kg by 66.7% and 70%, respectively. These results indicate the prospects of these extracts as drug candidates for piroplasmosis treatment following additional studies in some clinical cases.

Toxoplasma gondii causes toxoplasmosis, a common infection against which better drugs are needed. Recently, we showed that inorganic nanoparticles have anti-Toxoplasma activity. Here, we sought to enhance the anti-parasitic efficacy and host biocompatibility of these nanoparticles by modifying their surface with amino acids. The amino acids used were selected based on the nutritional requirements of Toxoplasma gondii. Amino acid-capped nanoparticles (amino-NPs) were synthesized, purified, and then screened for anti-Toxoplasma activity in in vitro infection models. The amino-NPs showed enhanced anti-parasitic selectivity as well as improved host biocompatibility. Oxidative stress, modulation of host HIF-1α, and activation of the kynurenine pathway contributed to the anti-parasitic action of the amino-NPs. Our findings provide additional support for the potential use of nanoparticles as innovative anti-parasitic agents. Findings glean additional perspective that highlight prospects of nanoparticles not only as innovative source of anti-parasitic agents but also provide evidence for probable biological mechanism.

KEY POINTS Congenital diaphragmatic hernia (CDH), which occurs in about 1 in 3300 live births, is a congenital defect in the diaphragm that allows herniation of abdominal viscera into the thorax.[1][1] The resulting abnormal lung development leads to pulmonary hypoplasia and pulmonary hypertension

Toxoplasma gondii is the etiological agent of toxoplasmosis, a common parasitic disease that affects nearly one-third of the human population. The primary infection can be asymptomatic in healthy individuals but may prove fatal in immunocompromised individuals. Available treatment options for toxoplasmosis patients are limited, underscoring the urgent need to identify and develop new therapies. Non-biased screening of libraries of chemical compounds including the repurposing of well-characterized compounds is emerging as viable approach to achieving this goal. In the present investigation, we screened libraries of natural product and FDA-approved compounds to identify those that inhibited T. gondii growth. We identified 32 new compounds that potently inhibit T. gondii growth. Our findings are new and promising, and further strengthen the prospects of drug repurposing as well as the screening of a wide range of chemical compounds as a viable source of alternative anti-parasitic therapeutic agents.