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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.

There is a growing debate on the linkage between social networking platforms and mental health disorder, such as depressive behaviour or depression. However, the relationship between Instagram use and depression or depressive behaviour has not been exhaustively examined. This review aims to examine these two variables. Only peer-reviewed journal articles that are published between October 2010 and December 2018 were sought in central and journal databases. Studies were selected based on predefined criteria and assessed for risk of bias and quality of evidence using GRADE. One thousand eight hundred fifty-six studies were the outcome of the search, out of which 9 meets all eligible criteria. Of the 9 studies, three-quarter was published between 2017 and 2018, covering five continents: (North America: 3; Asia: 2; Australia: 2; South America: 1, Europe: 1). The final included studies broadly examined young Instagram users between the age of 19 and 35. The synthesis affirmed a linkage between Instagram and symptoms of depression or depressive behaviour. Variables that moderate this relationship are social comparison, self-esteem built on validation and approval of others, social media dependence, gender, negative or insufficient feedback, poor self-rated attractiveness, Instagram broadcasting and loneliness, younger users and risk of anxiety, and the number of strangers that users follow. There is a strong relationship between Instagram use and mental health disorders such as depression or depressive behaviour; however, no in-depth direct causality is proven yet. Further studies are needed to unravel the direct causality puzzles.

Nigeria between 1980 and 2018 shows a mixed relationship between education reforms and sustainable development. In 2016, over 45 percent of Nigerian graduates are unemployed and about a 39.4 percent increase in education enrolment rate had resulted in stagnated economic sustainable development in Nigeria. Following the endogenous growth theory and the environmental Kuznets hypothesis underpinnings, this study investigated the cause and effect of education reforms and sustainable development in Nigeria between 1980 and 2018. The descriptive statistics employed describe the data distribution of the included variables while the vector error correction model (VECM) econometric technique was used to determine the short-run and long-run impact of education reforms on economic, social, and environmentally sustainable development in Nigeria. The results found that qualitative education reform has a positive impact on economic and environmentally sustainable development while quantitative education has a negative impact on socially sustainable development in the long run. Further, the short-run, VECM results revealed that qualitative education reforms will speedily affect economic, social, and environmentally sustainable development than the quantitative education reforms within the period of study. The study recommends that quantity and quality education reforms should be seen as complementary and not a substitute in achieving sustainable development by the year 2030 in Nigeria.

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

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 FeSO4. Treatment with l-leucine led to depletion of oxidative-induced elevated levels of NO, MDA, and myeloperoxidase activity, with concomitant elevation of reduced glutathione and non-protein thiol levels, SOD and catalase activities. l-leucine caused a significant (p

Background: As part of our contribution to the growing pool of knowledge on the prevention and control of the COVID-19 pandemic, this study describes the demographic features of patients with COVID-19 hospitalized at Infectious Disease Center (IDC), Olodo, Ibadan, Oyo State, Nigeria.Methodology: This was a descriptive cross-sectional study of COVID-19 patients whose data were collected during admission between April 27, 2020 and June 20, 2020. SARS-CoV-2 infection was diagnosed on nasopharyngeal specimen using a real-time reverse transcription–polymerase chain reaction (rRT-PCR) assay. Data were analysed using the Statistical Package for Social Sciences (SPSS Inc., USA) version 20.0Results: Among 131 patients, 58% were between age 18 and 35 years, 48.1% were employees of private establishments, and 64.1% were males. High proportion (84.3%) of the patients spent less than 14 days on admission. As at June 20, 2020, the overall COVID-19 mortality in the IDC was 0.0%.Conclusion: This study concluded that COVID-19 was common among male Nigerians, those working in private establishments, and those aged 18-35 years. Future researches on COVID-19 in Nigeria must put gender and age into consideration. Keywords: SARS-COV2; COVID-19; age; gender; occupation French Title: Attributs démographiques des patients atteints de COVID-19dans un centre de maladies infectieuses du Nigéria Contexte: Dans le cadre de notre contribution au pool croissant de connaissances sur la prévention et le contrôle de la pandémie COVID-19, cette étude décrit les caractéristiques démographiques des patients atteints de COVID19 hospitalisés au Centre des maladies infectieuses (IDC), Olodo, Ibadan, État d'Oyo, Nigéria. Méthodologie: Il s'agissait d'une étude transversale descriptive de patients atteints de COVID-19 dont lesdonnées ont été collectées lors de l'admission entre le 27 avril 2020 et le 20 juin 2020. L'infection par le SRASCoV-2 a été diagnostiquée sur un échantillon nasopharyngé à l'aide d'une transcription inverse en temps réel–Test de réaction en chaîne par polymérase (rRT-PCR). Les données ont été analysées à l'aide du StatisticalPackage for Social Sciences (SPSS Inc., USA) version 20.0 Résultats: Parmi 131 patients, 58% avaient entre 18 et 35 ans, 48,1% étaient des employés d'établissementsprivés et 64,1% étaient des hommes. Une forte proportion (84,3%) des patients ont passé moins de 14 jours àl'admission. Au 20 juin 2020, la mortalité globale par COVID-19 dans l'IDC était de 0,0%. Conclusion: Cette étude a conclu que le COVID-19 était courant chez les hommes Nigérians, ceux travaillantdans des établissements privés et ceux âgés de 18 à 35 ans. Les futures recherches sur le COVID-19 au Nigériadoivent prendre en compte le sexe et l'âge. Mots clés: SRAS-COV2; COVID-19; âge; le sexe; occupation

The hallmarks of Alzheimer’s disease (AD) pathology include senile plaques accumulation and neurofibrillary tangles, which is thought to underlie synaptic failure. Recent evidence however supports that synaptic failure in AD may instead be instigated by enhanced N-methyl-D-aspartate (NMDA) activity, via a reciprocal relationship between soluble amyloid-β (Aβ) accumulation and increased glutamate agonist. While previous studies have shown Aβ-mediated alterations to the glutamatergic system during AD, the underlying etiology of excitotoxic glutamate-induced changes has not been explored. Here, we investigated the acute effects of stereotaxic dentate gyrus (DG) glutamate injection on behavior and molecular expression of specific proteins and neurochemicals modulating hippocampal functions. Dependence of glutamate-mediated effects on NMDA receptor (NMDAR) hyperactivation was tested using NMDARs antagonist memantine. DG of Wistar rats (12-weeks-old) were bilaterally microinjected with glutamate (500 mM) with or without daily intraperitoneal (i.p.) memantine injection (20 mg/kg) for 14 days, while controls received either intrahippocampal/i.p. PBS or i.p. memantine. Behavioral characterization in open field and Y-maze revealed that glutamate evoked anxiogenic responses and perturbed spatial memory were inhibited by memantine. In glutamate-treated rats, increased NO expression was accompanied by marked reduction in profiles of glutathione-s-transferase and glutathione peroxidase. Similarly, glutamate-mediated increase in acetylcholinesterase expression corroborated downregulation of synaptophysin and PSD-95, coupled with initiation of reactive astrogliosis (GFAP). While neurofilament immunolocalization/immunoexpression was unperturbed, we found glutamate-mediated reduction in neurogenic markers Ki67 and PCNA immunoexpression, with a decrease in NR2B protein expression, whereas mGluR1 remains unchanged. In addition, increased expression of apoptotic regulatory proteins p53 and Bax was seen in glutamate infused rats, corroborating chromatolytic degeneration of granule neurons in the DG. Interestingly, memantine abrogated most of the degenerative changes associated with glutamate excitotoxicity in this study. Taken together, our findings causally link acute glutamate dyshomeostasis in the DG with development of AD-related behavioral impairment and molecular neurodegeneration.

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.

Acetaminophen (APAP) is a commonly used over-the-counter (OTC) drug known to induce hepatotoxicity when consumed in excess. Formation of reactive oxygen species (ROS) and oxidation of cellular proteins and enzymes are directly involved in its toxic mechanisms. However, antioxidants can be helpful to inhibit or restrict the oxidative damage. Besides synthetic antioxidants, naturally-derived substances can be used to serve the purpose. In this paper, a thorough literature review revealed that APAP combined with food-derived natural antioxidants exhibit a protective effect against APAP-induced hepatotoxicity.

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 Chemotherapy is the most widely used means of controlling trypanosomosis, however, effectiveness of the drugs available is limited by a number of factors. This study investigates the oxidative stress profile of aqueous extract of the fruit pulp of Adansonia digitata on some organs in rats infected with Trypanosoma brucei brucei. Methods Thirty-five male albino rats were divided into 7 groups of 5 rats each. Groups B, C, D, E, F and G were inoculated with 0.20 ml of suspension containing 106 T. b. brucei. Group A were neither infected nor treated. Group B were infected but not treated. At onset of parasitaemia, rats in group C were treated with diminazene aceturate at 3.5 mg/kg body weight once, while rats in group D were treated with vitamin C at 200 mg/kg body weight for 3 days consecutively. Rats in groups E, F and G were treated orally for 3 days with the aqueous extract of fruit pulp of A. digitata at a dosage of 40 mg/kg, 80 mg/kg and 160 mg/kg body weight respectively. Liver and kidney tissues of the rats were collected at necropsy (10 days PI) for oxidative stress analysis. Results There was a significant (p , glutathione peroxidase and catalase among the different groups treated with aqueous extract of fruit pulp of A. digitata. Conclusion The extract of A. digitata exert protective effects against tissue peroxidation in albino rats experimentally infected with T. b. brucei.

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.

Nitric Oxide (NO) is an essential signaling molecule with diverse physiological functions in humans. The steady-state concentration and site of production of nitric oxide determine its effects in biological systems. The human cells are exposed to both beneficial and harmful effects of NO. These dual effects of NO could depend on its local concentration in the cells. Additionally, the rate of synthesis, translocation, direct interaction with other molecules, and signals contribute to the biochemical and physiological effects of NO. In this review, the biochemical and physiological role of NO, particularly in health and disease as touching on cell signaling, oxidative stress, immunity, as well as cardiovascular protection amongst others, is focused on. Therefore, this review objectively discusses the dual functionality of NO in living cells.

Background: Stenotrophomonas species are multi-resistant bacteria with ability to cause opportunistic infections. Objective: We isolated 45 Stenotrophomonas species from soil, sewage and the clinic with the aim of investigating their susceptibility to commonly used antimicrobial agents. Methodology: The identities of isolates were confirmed with 16S rRNA gene sequence and MALDI-TOF analysis. Anti-mi- crobial resistance, biofilm production and clonal diversity were also evaluated. The minimum inhibitory concentration technique as described by Clinical & Laboratory Standards Institute: CLSI Guidelines (CLSI) was employed for the evaluation of isolate susceptibility to antibiotics. Result: Forty-five Stenotrophomonas species which include 36 environmental strains and 9 clinical strains of S. maltophilia were considered in this study. 32 (88.9 %) environmental strains were identified to be S. maltophilia, 2 (5.6 %) were Stenotrophomonas nitritireducens, and 2 (5.6 %) cluster as Stenotrophomonas spp. Stenotrophomonas isolates were resistant to at least six of the antibiotics tested, including Trimethoprim/Sulfamethoxazole (SXT). Conclusion: Environmental isolates from this study were resistant to SXT which is commonly used for the treatment of S. maltophilia infections. This informs the need for good public hygiene as the environment could be a reservoir of multi-resistant bacteria. It also buttresses the importance of surveillance study in the management of bacterial resistance. Keywords: Stenotrophomonas; environmental; biochemical characterization; clonal diversity; anti-microbial susceptibility.

The Trypanosoma brucei is the causative agent of African trypanosomiasis, a disease that affects both humans and animals. Chemotherapy which forms the major means of control for the disease has several shortcomings such as limited efficacy and adverse side effects amongst others. Thus, motivating the search for better therapies. In this study, extracts of some tropical plants including the Acacia nilotica, Bombax buonopozense and Khaya senegalensis were evaluated for therapeutic and prophylactic potential in mouse model of experimental trypanosomiasis. Both diminazene aceturate and isometamidium chloride were included as reference drugs. Results showed that T. brucei caused an elevation in rat plasma indirect bilirubin and a reduction in rat plasma albumin and total protein which suggest mild hepatic dysfunction due to experimental infection. Data also revealed that the plant extracts significantly reduced the rat parasite burden both in the prophylaxis and therapeutic treatment groups when compared with the negative drug control. The infection and treatments had no adverse effect on the rat organ and body weights. The infection did not alter the activity of rat plasma ALT, AST and ALP compared with the administered extracts of A. nilotica and B. buonopozense. Further, the plant extracts ameliorated some trypanosomiasis-induced pathologies in treated rats compared with negative drug control. Taken together, findings do not only lend credence to the folkloric use of these plants for medicinal purposes but also suggest these plant extracts have potential to serve as alternative source of anti-parasitic agents particularly for the control of trypanosomiasis.

Background The antiprotozoal and antioxidant activities of Viola tricolor and Laurus nobilis have been reported recently. Thus, the existing study pursued to assess the growth inhibition effect of methanolic extract of V. tricolor (MEVT) and acetonic extract of L. nobilis (AELN) against five Babesia parasites and Theileria equi in vitro and in vivo. Results MEVT and AELN suppressed Babesia bovis, B. bigemina, B. divergens, B. caballi, and T. equi growth at half-maximal inhibitory concentration (IC50) values of 75.7 ± 2.6, 43.3 ± 1.8, 67.6 ± 2.8, 48 ± 3.8, 54 ± 2.1 μg/mL, and 86.6 ± 8.2, 33.3 ± 5.1, 62.2 ± 3.3, 34.5 ± 7.5 and 82.2 ± 9.3 μg/mL, respectively. Qualitative phytochemical estimation revealed that both extracts containing multiple bioactive constituents and significant amounts of flavonoids and phenols. The toxicity assay revealed that MEVT and AELN affected the mouse embryonic fibroblast (NIH/3 T3) and Madin–Darby bovine kidney (MDBK) cell viability with half-maximum effective concentrations (EC50) of 930 ± 29.9, 1260 ± 18.9 μg/mL, and 573.7 ± 12.4, 831 ± 19.9 μg/mL, respectively, while human foreskin fibroblasts (HFF) cell viability was not influenced even at 1500 μg/mL. The in vivo experiment revealed that the oral administration of MEVT and AELN prohibited B. microti multiplication in mice by 35.1 and 56.1%, respectively. Conclusions These analyses indicate the prospects of MEVT and AELN as good candidates for isolating new anti-protozoal compounds which could assist in the development of new drug molecules with new drug targets.

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: Natural products or naturally derived compounds are invaluable to human and animal lives either for nutritional value or for medicinal purposes. Indeed, natural products including extracts containing polychemical mixtures play a leading role in the discovery and development of drugs. However, the increasing interest in natural medicines is also attracting a growing concern about the safety of naturally derived medications. Objective: In the present study, we evaluated several naturally derived compounds for in vitro cytotoxicity in mammalian cells. Methods: A total of 54 compounds were evaluated for in vitro cytotoxic and apoptotic action in Human Fibroblast Foreskin (HFF) cells. Results: Of the 54 natural compounds screened for cellular toxicity, only nonactin and cephaeline. HBr reduced cellular viability by ≥60% with IC50 value Conclusion: Taken together, we show evidence supporting that cytotoxic and apoptotic action of nonactin and cephaeline.HBr precludes oxidative stress or ROS production.

application/pdf, Objective: To evaluate the antipiroplasmic activities of methanolic extract of Olea europaea (MOE) and acetonic extract of Acacia laeta (AAL) against Babesia and Theileria parasites in vitro and evaluate the chemotherapeutic effects of these extracts against Babesia (B.) microti in vivo. Methods: Fluorescence assay using SYBR Green 1 nucleic acid stain was used to detect inhibitory effects of the two extracts as well as the combination effects of the two extracts with diminazene aceturate and atovaquone on four Babesia species and Theileria equi in vitro while for in vivo experiments, 8-weekold female BALB/c mice were injected intraperitoneally with 1 × 107B. microti-iRBCs and treated orally at a dose of 150 mg/kg of both extracts. Results: The half maximal inhibitory concentration (IC50) values of AAL against B. bovis, B. bigemina, B. divergens, B. caballi, and Theileria equi were lower than those of MOE extracts. Toxicity assay on Madin-Darby bovine kidney, mouse embryonic fibroblast (MH/3T3), and human foreskin fibroblast cell lines showed that MOE and AAL affected only the viability of Madin-Darby bovine kidney cell line with half maximal effective concentrations (EC50) of (794.7±41.9) and (873.9±17.5) μg/mL, respectively. The oral treatments of MOE and AAL at 150 mg/kg inhibited the growth of B. microti in mice by 80.4% and 64.4%, respectively. The MOE and diminazene aceturate combination showed a higher chemotherapeutic effect than that of monotherapy. Conclusions: MOE and AAL have the potential to be an alternative remedy for treating piroplasmosis. Furthermore, the combination therapy of MOE + DA was more potent against B. microti infection in mice than their monotherapies.

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 (

In this work, we determined whether oxidative stress contributed to the activation of the kynurenine pathway by AgNPs. Male Wistar rats weighing between 130 and 146 g were randomly assigned into six groups. Animals in the negative control group were orally administered distilled water while, the other treatment groups were respectively given AgNPs (25 and 50 mg/kg bw) alone or in combination with Trolox (100 mg/kg bw). Results showed that treatments with AgNPs significantly raised protein carbonyl level in rat liver, but the co-treatment with Trolox attenuated the elevation. Conversely, AgNPs raised the level of reduced glutathione (GSH) in rat plasma and tissues compared to the negative control. Further, oral exposure to AgNPs (50 mg/kg bw) significantly elevated rat plasma and brain kynurenine levels compared to the negative control. Meantime, the co-treatment with Trolox appreciably restored kynurenine level in rat plasma, but not in the rat brain. Taken together, findings indicate that the oral administration of AgNPs alone at the doses used in this study, might not have caused oxidative stress. However, the co-treatment with Trolox appears to potentiate oxidative stress in rats following exposure to AgNPs. Furthermore, data support that the activation of the kynurenine pathway in the rat brain by AgNPs might be independent of oxidative stress. The findings are new and contribute to deepen our understanding of the cellular interaction by nanoparticles.

Summary Multifocal papillary thyroid carcinoma (PTC) is common and the number of tumor foci rarely exceeds ten. The mechanism of multifocal disease is debated, with the two main hypotheses consisting of either intrathyroidal metastatic spread from a single tumor or independent multicentric tumorigenesis from distinct progenitor cells. We report the case of a 46-year-old woman who underwent total thyroidectomy and left central neck lymph node dissection after fine-needle aspiration of bilateral thyroid nodules that yielded cytological findings consistent with PTC. Final pathology of the surgical specimen showed an isthmic dominant 1.5 cm classical PTC and over 30 foci of microcarcinoma, which displayed decreasing density with increasing distance from the central lesion. Furthermore, all malignant tumors and lymph nodes harbored the activating BRAF V600E mutation. The present case highlights various pathological features that support a mechanism of intraglandular spread, namely a strategic isthmic location of the primary tumor, radial pattern of distribution and extensive number of small malignant foci and BRAF mutational homogeneity. Learning points: Multifocal papillary thyroid carcinoma (PTC) is commonly seen in clinical practice, but the number of malignant foci is usually limited to ten or less. There is no clear consensus in the literature as to whether multifocal PTC arises from a single or multiple distinct tumor progenitor cells. Strategic location of the dominant tumor in the thyroid isthmus may favor intraglandular dissemination of malignant cells by means of the extensive lymphatic network. An important pathological finding that may be suggestive of intrathyroidal metastatic spread is a central pattern of distribution with a reduction in the density of satellite lesions with increasing distance from the dominant focus. PTCs originating from the isthmus with intraglandular metastatic dissemination behave more aggressively. As such, a more aggressive treatment course may be warranted, particularly with regard to the extent of surgery.

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: Cardiometabolic risk factors are related to the early onset of chronic health conditions. PURPOSE: To identify factors associated with perceptions about the severity of three interrelated cardiometabolic risks (i.e., high blood pressure, obesity, and cardiovascular disease) among U.S. college students. METHODS: Data were analyzed from 1,361 college students using an internet-delivered survey. Least squares regression models were fitted. Primary independent variables of interest were sex and cigarette smoking status. RESULTS: Relative to nonsmokers, smokers perceived high blood pressure (B=−0.09, P=0.001), obesity (B=−0.12, P

The devastating impacts that bio-degradable products such as plastic bags are having on human health, wildlife, and the environment is enormous, especially single-use once. Single-use plastics are non-biodegradable products and does not undergo biological decomposition nor degenerate. This review examines various government regulations targeted at changing behaviour against plastic bags consumption and their effectiveness. Following a rigorous search in 13 databases, including PubMed, Science Direct, Springer Nature, etc. only 17 peer-reviewed journal articles that are published between 2000 and 2019 and met the inclusion criteria were included in the study. Each study’s methodological quality was assessed using the GRADE system, and data were extracted using a uniquely designed form. The results revealed that regulations based solely on the thickness of plastic bags does not reduce plastic bags consumption. However, regulations focused on banning ‘single-use’ plastic bag usage, imposing higher taxes and levies on consumers, significantly reduce plastic bags consumption. Overall, the latter is considered the most effective. Also, the results show that attitude, perception and behaviour change toward bio-degradable products or climate-friendly behaviour can be significantly influenced by public policy or regulations. Although the behaviour seems short-lived in some countries, therefore further studies need to probe on why. Also, the absence of a national regulatory strategy in North America reduced the inclusion of studies from the region, hence need for more research focusing on sub-national regulations.

The scientific explorations of nanoparticles for their inherent therapeutic potencies as antimicrobial and antiviral agents due to increasing incidences of antibiotic resistance have gained more attention in recent time. This factor amongst others necessitates the search for newer and more effective antimicrobial agents. Several investigations have demonstrated the prospects of nanoparticles in the treatment of various microbial infections. The therapeutic applications of nanoparticles as either delivery agent or broad spectrum inhibition agents in viral and microbial investigations can no longer be overlooked. Their large surface area to volume ratio made them an indispensable substance as delivery agents in many respect. Various materials have been used for the synthesis of nanoparticles with unique properties channelised to meet specific therapeutic requirement. This review focuses on the antibacterial, antifungal, and antiviral potential of nanoparticles with their probable mechanism of action., Bacteria; Fungi; Virus; Nanoparticles; Anti-microbial therapy.

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.

Cancer is a major cause of mortality around the world, representing about 13% of deaths on the planet. Among the available cancer treatments, chemotherapy is most frequently utilized compared to other treatments such as surgery and radiotherapy. Many dietary antioxidants have proven to effectively prevent oxidative stress, which has been noted in many disease pathogeneses, including cancer. However, during chemotherapy or radiotherapy treatment of cancer patients, antioxidants are used as an adjuvant treatment. The use of a proof-based technique is advised in determining the supplements most suited to cancer patients. Though there are numerous opinions about the dangers and advantages of antioxidants, it is reasonable to conclude that side effects caused by antioxidants, for now, remain unclear for patients during cancer treatment, aside from smokers during radiotherapy. In this report, details of the effectiveness of antioxidants on cancer treatment aiding in the reduction of cancer therapy side effects are discussed.

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 aim of this study was to explore the inhibitory potential of apoferritin or apoferritin-capped metal nanoparticles (silver, gold and platinum) against Trypanosomabrucei arginine kinase. The arginine kinase activity was determined in the presence and absence of apoferritin or apoferritin-capped metal nanoparticles. In addition, kinetic parameters and relative inhibition of enzyme activity were estimated. Apoferritin or apoferritin-capped metal nanoparticles&rsquo, interaction with arginine kinase of T. brucei led to a &gt, 70% reduction in the enzyme activity. Further analysis to determine kinetic parameters suggests a mixed inhibition by apoferritin or apoferritin-nanoparticles, with a decrease in Vmax. Furthermore, the Km of the enzyme increased for both ATP and L-arginine substrates. Meantime, the inhibition constant (Ki) values for the apoferritin and apoferritin-nanoparticle interaction were in the submicromolar concentration ranging between 0.062 to 0.168 nM and 0.001 to 0.057 nM, respectively, for both substrates (i.e., L-arginine and ATP). Further kinetic analyses are warranted to aid the development of these nanoparticles as selective therapeutics. Also, more studies are required to elucidate the binding properties of these nanoparticles to arginine kinase of T. brucei.

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.

Summary Background Tranexamic acid reduces surgical bleeding and reduces death due to bleeding in patients with trauma. Meta-analyses of small trials show that tranexamic acid might decrease deaths from gastrointestinal bleeding. We aimed to assess the effects of tranexamic acid in patients with gastrointestinal bleeding. Methods We did an international, multicentre, randomised, placebo-controlled trial in 164 hospitals in 15 countries. Patients were enrolled if the responsible clinician was uncertain whether to use tranexamic acid, were aged above the minimum age considered an adult in their country (either aged 16 years and older or aged 18 years and older), and had significant (defined as at risk of bleeding to death) upper or lower gastrointestinal bleeding. Patients were randomly assigned by selection of a numbered treatment pack from a box containing eight packs that were identical apart from the pack number. Patients received either a loading dose of 1 g tranexamic acid, which was added to 100 mL infusion bag of 0·9% sodium chloride and infused by slow intravenous injection over 10 min, followed by a maintenance dose of 3 g tranexamic acid added to 1 L of any isotonic intravenous solution and infused at 125 mg/h for 24 h, or placebo (sodium chloride 0·9%). Patients, caregivers, and those assessing outcomes were masked to allocation. The primary outcome was death due to bleeding within 5 days of randomisation; analysis excluded patients who received neither dose of the allocated treatment and those for whom outcome data on death were unavailable. This trial was registered with Current Controlled Trials, ISRCTN11225767, and ClinicalTrials.gov, NCT01658124. Findings Between July 4, 2013, and June 21, 2019, we randomly allocated 12 009 patients to receive tranexamic acid (5994, 49·9%) or matching placebo (6015, 50·1%), of whom 11 952 (99·5%) received the first dose of the allocated treatment. Death due to bleeding within 5 days of randomisation occurred in 222 (4%) of 5956 patients in the tranexamic acid group and in 226 (4%) of 5981 patients in the placebo group (risk ratio [RR] 0·99, 95% CI 0·82–1·18). Arterial thromboembolic events (myocardial infarction or stroke) were similar in the tranexamic acid group and placebo group (42 [0·7%] of 5952 vs 46 [0·8%] of 5977; 0·92; 0·60 to 1·39). Venous thromboembolic events (deep vein thrombosis or pulmonary embolism) were higher in tranexamic acid group than in the placebo group (48 [0·8%] of 5952 vs 26 [0·4%] of 5977; RR 1·85; 95% CI 1·15 to 2·98). Interpretation We found that tranexamic acid did not reduce death from gastrointestinal bleeding. On the basis of our results, tranexamic acid should not be used for the treatment of gastrointestinal bleeding outside the context of a randomised trial. Funding UK National Institute for Health Research Health Technology Assessment Programme.

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.

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.

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 &plusmn, 0.2, 0.81 &plusmn, 0.3, 4.1 &plusmn, 0.9, 0.35 &plusmn, 0.1 and 0.68 &plusmn, 0.1 &micro, g/mL and 85.7 &plusmn, 3.1, 60 &plusmn, 8.5, 90 &plusmn, 3.7, 85.7 &plusmn, 2.1 and 78 &plusmn, 2.1 &micro, g/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 &plusmn, 24.9, 931 &plusmn, 44.9, ˃1500 &micro, g/mL and 737.7 &plusmn, 17.4, ˃1500 and ˃1500 &micro, g/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.

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.

Reproductive dysfunction is often characterized by malfunction of the reproductive tissues, which may lead to disruption of the synergistic rhythm that should bring about a progression of sexual events and the conception of new life. This may therefore result in the sexual dysfunction and infertility that can be seen in couples having prolonged biological difficulty in reproducing their offspring after having unrestricted sexual intercourse for at least twelve months. Several factors have been implicated in the cause and progression of reproductive dysfunction, including poor nutrition, drug side effects, disease states, and toxicant ingestion. A well-known food additive that has been found to be potent at initiating reproductive anomalies in males is monosodium glutamate (MSG). This regular flavor enhancer is widely used as a taste enhancer in several diets. The different mechanisms by which it may induce reproductive dysfunctions include spermatogenic alteration resulting in a low sperm count, high sperm abnormality, reduced live sperm and decreased sperm pH, oxidative damage (increased lipid peroxidation and reduced antioxidant enzyme activities), histological alteration (blood hemorrhage, distorted germ and Sertoli cells), as well as gonadotropin imbalance (reduced testosterone, luteinizing hormone, and follicle-stimulating hormone concentrations). Therefore, this review discusses various established mechanisms through which MSG may induce reproductive dysfunction and the treatment strategies to ameliorate its toxic effects.

Bacterial infections remain a serious health issue; hence there is a need for continuous search for improved antimicrobials. In addition, it is important to understand the antibacterial mechanism of prospective antimicrobials to fully harness their benefits. In this study, the antimicrobial action of silver nanoparticles was investigated. The antimicrobial potential of silver nanoparticles against different strains of bacteria was evaluated after which Escherichia coli and Staphylococcus aureus were selected as model for gram-negative and gram-positive bacteria respectively. Additionally, to determine mechanism of action, some biochemical assays including determination of kynurenine level, DNA fragmentation, lipid peroxidation and antioxidant status were carried out. Results showed that silver nanoparticles caused DNA damage and induced oxidative stress as reflected in elevated nitric oxide production and lipid peroxidation level. In contrast silver nanoparticles increased the antioxidant capacity viz-a-viz, elevated levels of total thiol, superoxide dismutase (SOD), and total antioxidant capacity (TAC) compared to untreated cells. They also initiated inconsistent alteration to the kynurenine pathway. Taken together, the findings indicate that silver nanoparticles exhibited antimicrobial action through the promotion of oxidative stress., EXCLI Journal;Vol. 19 2020

BackgroundStenotrophomonasare ubiquitous gram-negative bacteria, which can survive in a wide range of environments. They can use many substances for their growth and are known to be intrinsically resistant to many antimicrobial agents. They have been tested for biotechnological applications, bioremediation, and production of antimicrobial agents.MethodStenotrophomonas sp. Pemsol was isolated from a crude oil contaminated soil. The capability of this isolate to tolerate and degrade polycyclic aromatic hydrocarbons (PAH) such as anthraquinone, biphenyl, naphthalene, phenanthrene, phenanthridine, and xylene was evaluated in Bushnell Hass medium containing PAHs as the sole carbon sources. The metabolites formed after 30-day degradation of naphthalene by Pemsol were analyzed using Fourier Transform Infra-red Spectroscopic (FTIR), Ultra-Performance Liquid Chromatography-Mass Spectrometry (UPLC-MS) and Gas Chromatography-Mass Spectrometry (GC-MS). The genome of Pemsol was also sequenced and analyzed.ResultsAnthraquinone, biphenyl, naphthalene, phenanthrene, and phenanthridine except xylene can be used as sole carbon sources for Pemsol’s growth in Bushnell Hass medium. The degradation of naphthalene at a concentration of 1 mg/mL within 30 days was tested. A newly formed catechol peak and the disappearance of naphthalene peak detected on the UPLC-MS, and GC-MS analyses spectra respectively confirmed the complete degradation of naphthalene. Pemsol does not produce biosurfactant and neither bio-emulsify PAHs. The whole genome was sequenced and assembled into one scaffold with a length of 4,373,402 bp. A total of 145 genes involved in the degradation of PAHs were found in its genome, some of which are Pemsol-specific as compared with other 11Stenotrophomonasgenomes. Most specific genes are located on the genomic islands.Stenotrophomonassp. Pemsol’s possession of few genes that are associated with bio-emulsification gives the genetic basis for its inability to bio-emulsify PAH. A possible degradation pathway for naphthalene in Pemsol was proposed following the analysis of Pemsol’s genome. ANI and GGDH analysis indicated that Pemsol is likely a new species ofStenotrophomonas.It is the first report on a complete genome sequence analysis of a PAH-degradingStenotrophomonas.Stenotrophomonassp. Pemsol possesses features that make it a good bacterium for genetic engineering and will be an excellent tool for the remediation of crude oil or PAH-contaminated soil.

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.