Utility of zebrafish-based models in understanding molecular mechanisms of neurotoxicity mediated by the gut-brain axis.

The gut microbes perform several beneficial functions which impact the periphery and central nervous systems of the host. Gut microbiota dysbiosis is acknowledged as a major contributor to the development of several neuropsychiatric and neurological disorders including bipolar disorder, depression, anxiety, Parkinson's disease, Alzheimer's disease, attention deficit hyperactivity disorder, and autism spectrum disorder. Thus, elucidation of how the gut microbiota-brain axis plays a role in health and disease conditions is a potential novel approach to prevent and treat brain disorders. The zebrafish (Danio rerio) is an invaluable vertebrate model that possesses conserved brain and intestinal features with those of humans, thus making zebrafish a valued model to investigate the interplay between the gut microbiota and host health. This chapter describes current findings on the utility of zebrafish in understanding molecular mechanisms of neurotoxicity mediated via the gut microbiota-brain axis. Specifically, it highlights the utility of zebrafish as a model organism for understanding how anthropogenic chemicals, pharmaceuticals and bacteria exposure affect animals and human health via the gut-brain axis.

Angiomatosis Occurring in an Uncommon Location and Age Group: A Case Report and Literature Review.

Angiomatosis is a rare benign vascular malformation. The lesion has a highly infiltrative nature and a high recurrence rate, making it easily misdiagnosed as malignancy. Therefore, diagnosis is best made based on a combination of clinical, radiological, and histological features. This case presentation is unique because aside from the fact that the lesion is rare, it was seen in an uncommon age and location. Occurrence in such location has not been documented, making this presentation the first of its kind. A 29-year-old male presented with a swelling on the right side of the back, reportedly present for the past six years. The swelling was painless, with a history of progressive increase in size. Examination at presentation revealed a fairly round mass located on the back, 5 cm below the right scapula. He underwent a wide local surgical excision with the material sent for histopathological evaluation. Based on the morphologic features, a definitive angiomatosis diagnosis was made. Our patient had complete surgical excision with histologically confirmed free margins and no recurrence after eight months of post-operative follow-up.

Diphenyl Diselenide Through Reduction of Inflammation, Oxidative Injury and Caspase-3 Activation Abates Doxorubicin-Induced Neurotoxicity in Rats.

Neurotoxicity associated with chemotherapy is a debilitating side effect of cancer management in humans which reportedly involves inflammatory and oxidative stress responses. Diphenyl diselenide (DPDS) is an organoselenium compound which exhibits its anti-tumoral, anti-oxidant, anti-inflammatory and anti-mutagenic effects. Nevertheless, its possible effect on chemotherapy-induced neurotoxicity is not known. Using rat model, we probed the behavioral and biochemical effects accompanying administration of antineoplastic agent doxorubicin (7.5 mg/kg) and DPDS (5 and 10 mg/kg). Anxiogenic-like behavior, motor and locomotor insufficiencies associated with doxorubicin were considerably abated by both DPDS doses with concomitant enhancement in exploratory behavior as demonstrated by reduced heat maps intensity and enhanced track plot densities. Moreover, with exception of cerebral glutathione (GSH) level, superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities, biochemical data demonstrated reversal of doxorubicin-mediated decline in cerebral and cerebellar antioxidant status indices and the increase in acetylcholinesterase (AChE) activity by both doses of DPDS. Also, cerebellar and cerebral lipid peroxidation, hydrogen peroxide as well as reactive oxygen and nitrogen species levels were considerably diminished in rats administered doxorubicin and DPDS. In addition, DPDS administration abated myeloperoxidase activity, tumour necrosis factor alpha and nitric oxide levels along with caspase-3 activity in doxorubicin-administered rats. Chemoprotection of doxorubicin-associated neurotoxicity by DPDS was further validated by histomorphometry and histochemical staining. Taken together, DPDS through offsetting of oxido-inflammatory stress and caspase-3 activation elicited neuroprotection in doxorubicin-treated rats.

Exogenous taurine administration abates reproductive dysfunction in male rats exposed to silver nanoparticles.

The broad contemporary applications of silver nanoparticles (AgNPs) have been associated with various toxicities including reproductive toxicity. Taurine is well acknowledged for its potent pharmacological role in numerous disease models and chemically-mediated toxicity. We investigated the effect of taurine on AgNPs-induced reproductive toxicity in male rats. The animals were intraperitoneally injected with AgNPs (200 µg/kg) alone or co-administered with taurine at 50 and 100 mg/kg for 21 successive days. Exogenous taurine administration significantly abated AgNPs-induced oxidative injury by decreasing the levels of oxidative stress indices while boosting antioxidant enzymes activities and glutathione level in the hypothalamus, testes and epididymis of exposed animals. Taurine administration alleviated AgNPs-induced inflammatory response and caspase-3 activity, an apoptotic biomarker. Moreover, taurine significantly improved spermiogram, reproductive hormones and the marker enzymes of testicular function in AgNPs-treated animals. The ameliorative effect of taurine on pathological lesions induced by AgNPs in the exposed animals was substantiated by histopathological data. This study provides the first mechanistic evidence that taurine supplementation affords therapeutic effect against reproductive dysfunction associated with AgNPs exposure in male rats.

Data-Driven Deep Learning Neural Networks for Predicting the Number of Individuals Infected by COVID-19 Omicron Variant.

Infectious disease epidemics are challenging for medical and public health practitioners. They require prompt treatment, but it is challenging to recognize and define epidemics in real time. Knowing the prediction of an infectious disease epidemic can evaluate and prevent the disease's impact. Mathematical models of epidemics that work in real time are important tools for preventing disease, and data-driven deep learning enables practical algorithms for identifying parameters in mathematical models. In this paper, the SIR model was reduced to a logistic differential equation involving a constant parameter and a time-dependent function. The time-dependent function leads to constant, rational, and birational models. These models use several constant parameters from the available data to predict the time and number of people reported to be infected with the COVID-19 Omicron variant. Two out of these three models, rational and birational, provide accurate predictions for countries that practice strict mitigation measures, but fail to provide accurate predictions for countries that practice partial mitigation measures. Therefore, we introduce a time-series model based on neural networks to predict the time and number of people reported to be infected with the COVID-19 Omicron variant in a given country that practices both partial and strict mitigation measures. A logistics-informed neural network algorithm was also introduced. This algorithm takes as input the daily and cumulative number of people who are reported to be infected with the COVID-19 Omicron variant in the given country. The algorithm helps determine the analytical solution involving several constant parameters for each model from the available data. The accuracy of these models is demonstrated using error metrics on Omicron variant data for Portugal, Italy, and China. Our findings demonstrate that the constant model could not accurately predict the daily or cumulative infections of the COVID-19 Omicron variant in the observed country because of the long series of existing data of the epidemics. However, the rational and birational models accurately predicted cumulative infections in countries adopting strict mitigation measures, but they fell short in predicting the daily infections. Furthermore, both models performed poorly in countries with partial mitigation measures. Notably, the time-series model stood out for its versatility, effectively predicting both daily and cumulative infections in countries irrespective of the stringency of their mitigation measures.

Atrazine: cytotoxicity, oxidative stress, apoptosis, testicular effects and chemopreventive Interventions.

Atrazine (ATZ) is an environmental pollutant that interferes with several aspects of mammalian cellular processes including germ cell development, immunological, reproductive and neurological functions. At the level of human exposure, ATZ reduces sperm count and contribute to infertility in men. ATZ also induces morphological changes similar to apoptosis and initiates mitochondria-dependent cell death in several experimental models. When in vitro experimental models are exposed to ATZ, they are faced with increased levels of reactive oxygen species (ROS), cytotoxicity and decreased growth rate at dosages that may vary with cell types. This results in differing cytotoxic responses that are influenced by the nature of target cells, assay types and concentrations of ATZ. However, oxidative stress could play salient role in the observed cellular and genetic toxicity and apoptosis-like effects which could be abrogated by antioxidant vitamins and flavonoids, including vitamin E, quercetin, kolaviron, myricetin and bioactive extractives with antioxidant effects. This review focuses on the differential responses of cell types to ATZ toxicity, testicular effects of ATZ in both in vitro and in vivo models and chemopreventive strategies, so as to highlight the current state of the art on the toxicological outcomes of ATZ exposure in several experimental model systems.

Perfluorooctanoic acid induces behavioral impairment and oxidative injury in Nauphoeta cinerea nymphs.

Perfluorooctanoic acid (PFOA) is a persistent organic contaminant with potential health threats to both animals and humans. However, the impact of PFOA on insects, which play significant roles in ecosystems, is understudied. We evaluated the toxicological impact of ecologically relevant concentrations of PFOA (0, 25, 50, 100, and 200 µg L-1) on Nauphoeta cinerea nymphs following exposure for 42 consecutive days. We analyzed the behavior of the insects with automated video-tracking software and processed the head, midgut, and fat body for biochemical assays. PFOA-exposed insects exhibited significant reductions in locomotory abilities and an increase in freezing time. Furthermore, PFOA exposure reduced acetylcholinesterase activity in the insect head. PFOA exposure increased the activities of superoxide dismutase, glutathione peroxidase, and catalase in the head and midgut, but decreased them in the fat body. PFOA also significantly increased glutathione-S transferase activity, while decreasing glutathione levels in the head, midgut, and fat body. Additionally, PFOA exposure increased reactive oxygen and nitrogen species, nitric oxide, lipid peroxidation, and protein carbonyl contents in the head, midgut, and fat body of the insects. In conclusion, our findings indicate that PFOA exposure poses an ecological risk to Nauphoeta cinerea.

A Descriptive Analysis of Febrile Seizure Hospitalizations in Children with Congenital Heart Disease in the United States.

BACKGROUND: Febrile seizure (FS) is the most common convulsive disorder in children. This study analyzed the national proportion of congenital heart disease (CHD) and hospital resource utilization among children admitted for FSs in the U.S. METHODS: This is a retrospective cross-sectional analysis of pediatric patients up to six years with a primary diagnosis of FS in 2016 and 2019 using the Kids Inpatient Database (KID). The demographic, hospital, and clinical characteristics of children with and without CHD were compared using the chi-square test for categorical variables and linear regressions for continuous variables. Multivariate logistic analysis was conducted to evaluate the impact of CHD on the mean length of hospital stay. RESULTS: An estimated 10,039 children were admitted with the primary diagnosis of FS. Out of these, 117 (1.2%) had a discharge diagnosis of CHD. The mean age for children with and without CHD was 1.4 years (SD 1.60) and 1.5 years (SD 1.501), respectively. Children with CHD who required hospitalization for FS had longer mean lengths of hospital stay (2.1 days vs. 1.6 days), with an adjusted odd ratio of 0.43 (95% CI: 0.07-0.99; p-value: 0.017). Similarly, the hospital charges for children with CHD were higher than those without CHD ($30,960.28 vs. $21,005.11). CONCLUSION: Children with CHD who required inpatient admission for FSs in the U.S. were associated with increased length of hospital stay and higher resource utilization when compared with those without CHD. This highlights the need for preventive measures among this vulnerable population.

Metoprolol elicits neurobehavioral insufficiency and oxidative damage in nontarget Nauphoeta cinerea nymphs.

Metoprolol, a drug for hypertension and cardiovascular diseases, has become a contaminant of emerging concern because of its frequent detection in various environmental matrices globally. The dwindling in the biodiversity of useful insects owing to increasing presence of environmental chemicals is currently a great interest to the scientific community. In the current research, the toxicological impact of ecologically relevant concentrations of metoprolol at 0, 0.05, 0.1, 0.25, and 0.5 µg/L on Nauphoeta cinerea nymphs following exposure for 42 consecutive days was evaluated. The insects' behavior was analyzed with automated video-tracking software (ANY-maze, Stoelting Co, USA) while biochemical assays were done using the midgut, head and fat body. Metoprolol-exposed nymphs exhibited significant diminutions in the path efficiency, mobility time, distance traveled, body rotation, maximum speed and turn angle cum more episodes, and time of freezing. In addition, the heat maps and track plots confirmed the metoprolol-mediated wane in the exploratory and locomotor fitness of the insects. Compared with control, metoprolol exposure decreased acetylcholinesterase activity in insects head. Antioxidant enzymes activities and glutathione level were markedly decreased whereas indices of inflammation and oxidative injury to proteins and lipids were significantly increased in head, midgut and fat body of metoprolol-exposed insects. Taken together, metoprolol exposure induces neurobehavioral insufficiency and oxido-inflammatory injury in N. cinerea nymphs. These findings suggest the potential health effects of environmental contamination with metoprolol on ecologically and economically important nontarget insects.

Cellular and molecular mechanisms of aflatoxin B1-mediated neurotoxicity: The therapeutic role of natural bioactive compounds.

Aflatoxin B1 (AFB1), a dietary toxin from the mold Aspergillus species, is well acknowledged to elicit extra-hepatic toxicity in both animals and humans. The neurotoxicity of AFB1 has become a global public health concern. Contemporary research on how AFB1 enters the brain to elicit neuronal dysregulation leading to noxious neurological outcomes has increased greatly in recent years. The current review discusses several neurotoxic outcomes and susceptible targets of AFB1 toxicity at cellular, molecular and genetic levels. Specifically, neurotoxicity studies involving the use of brain homogenates, neuroblastoma cell line IMR-32, human brain microvascular endothelial cells, microglial cells, and astrocytes, as well as mammalian and non-mammalian models to unravel the mechanisms associated with AFB1 exposure are highlighted. Further, some naturally occurring bioactive compounds with compelling therapeutic effects on AFB1-induced neurotoxicity are reviewed. In conclusion, available data from literature highlight AFB1 as a neurotoxin and its possible pathological contribution to neurological disorders. Further mechanistic studies aimed at discovering and developing effective therapeutics for AFB1 neurotoxicity is warranted.

Amelioration of neurobehavioral, biochemical, and morphological alterations associated with silver nanoparticles exposure by taurine in rats.

The adverse effect of silver nanoparticles (AgNPs) on the nervous system is an emerging concern of public interest globally. Taurine, an essential amino acid required for neurogenesis in the nervous system, is well-documented to possess antioxidant, anti-inflammatory, and antiapoptotic activities. Yet, there is no report in the literature on the effect of taurine on neurotoxicity related to AgNPs exposure. Here, we investigated the neurobehavioral and biochemical responses associated with coexposure to AgNPs (200 µg/kg body weight) and taurine (50 and 100 mg/kg body weight) in rats. Locomotor incompetence, motor deficits, and anxiogenic-like behavior induced by AgNPs were significantly alleviated by both doses of taurine. Taurine administration enhanced exploratory behavior typified by increased track plot densities with diminished heat maps intensity in AgNPs-treated rats. Biochemical data indicated that the reduction in cerebral and cerebellar acetylcholinesterase activity, antioxidant enzyme activities, and glutathione level by AgNPs treatment were markedly upturned by both doses of taurine. The significant abatement in cerebral and cerebellar oxidative stress indices namely reactive oxygen and nitrogen species, hydrogen peroxide, and lipid peroxidation was evident in rats cotreated with AgNPs and taurine. Further, taurine administration abated nitric oxide and tumor necrosis factor-alpha levels cum myeloperoxidase and caspase-3 activities in AgNPs-treated rats. Amelioration of AgNPs-induced neurotoxicity by taurine was confirmed by histochemical staining and histomorphometry. In conclusion, taurine via attenuation of oxido-inflammatory stress and caspase-3 activation protected against neurotoxicity induced by AgNPs in rats.

Neurotoxicity of furan in juvenile Wistar rats involves behavioral defects, microgliosis, astrogliosis and oxidative stress.

Evidence suggests that furan, a widespread environmental and food contaminant, causes liver toxicity and cancer, but its implications in the brain are not well defined. We measured behavioral, glial, and biochemical responses in male juvenile rats exposed orally to 2.5, 5 and 10 mg/kg furan and vitamin E after 28 days. Furan-mediated hyperactivity peaked at 5 mg/kg and did not exacerbate at 10 mg/kg. Enhanced motor defect was also observed at 10 mg/kg. Furan-treated rats elicited inquisitive exploration but showed impaired spatial working memory. Without compromising the blood-brain barrier, furan induced glial reactivity with enhanced phagocytic activity, characterized by parenchyma-wide microglial aggregation and proliferation, which switched from hyper-ramified to rod-like morphology with increasing doses. Furan altered the glutathione-S-transferase-driven enzymatic and non-enzymatic antioxidant defence systems differentially and dose-dependently across brain regions. Redox homeostasis was most perturbed in the striatum and least disrupted in hippocampus/cerebellum. Vitamin E supplementation attenuated exploratory hyperactivity and glial reactivity but did not affect impaired working memory and oxidative imbalance. Overall, sub-chronic exposure of juvenile rats to furan triggered glial reactivity and behavioral deficits suggesting the brain's vulnerability during juvenile development to furan toxicity. It remains to be determined whether environmentally relevant furan concentrations interfere with critical brain developmental milestones.

Co-administration of thymol and sulfoxaflor impedes the expression of reproductive toxicity in male rats.

This study investigated the capability of a co-delivery system of thymol (THY) and sulfoxaflor that can serve to minimize the development of epididymal and testicular injury arise from SFX exposures alone. Forty-eight adult male rats were orally treated by gavage for 28 consecutive days. The rats were divided into six groups comprising control, THY alone (30 mg/kg), low SFX alone (79.4 mg/kg), high SFX alone (205 mg/kg) and co-exposure groups. After euthanasia, the rats epididymal and testicular damage and antioxidant status markers, myeloperoxidase (MPO) activity, levels of nitric oxide, total antioxidant capacity (TAC), total oxidative stress (TOS) and lipid peroxidation (LPO) were analyzed. Levels of tumor necrosis factor alpha (TNF-α), interleukin-1 b (IL-1ß) and caspase-3 activity were assessed using ELISA kits. The results revealed that SFX exposure caused a significant (p < 0.05) decrease in the body weight, sperm functional parameters, serum testosterone level with widespread histological abnormalities in a dose-dependent manner. Increased relative organ weights, serum levels of luteinizing hormone (LH) and follicle stimulating hormone (FSH) were observed in low SFX-treated rats. Similarly, the epididymal and testicular myeloperoxidase activity, malondialdehyde (MDA), reactive oxygen species (RONS), tumor necrosis-α, interleukin-1ß levels and caspase-3 activity were significant (p < 0.05) increased and a significant (p < 0.05) reduction in antioxidant enzyme activities and reduced glutathione (GSH) were revealed in SFX-treated rats. However, co-treatment of THY with SFX prevented SFX-induced epididymal and testicular toxicities. Thus, thymol protected against potential epididymis and testes alterations elicited by oxido-inflammatory mediators and up regulated antioxidant status.

Attenuation of doxorubicin-induced hypothalamic-pituitary-testicular axis dysfunction by diphenyl diselenide involves suppression of hormonal deficits, oxido-inflammatory stress and caspase 3 activity in rats.

BACKGROUND: Doxorubicin (DOX) is one of the popular anti-cancer drugs in the world and several literatures have implicated it in various toxicities especially cardiotoxicity and reproductive toxicity. Diphenyl diselenide (DPDS) is well acknowledged for its compelling pharmacological effects in numerous disease models and chemically-mediated toxicity. This study was carried out to investigate the effect of DPDS on DOX-induced changes in the reproductive indices of male Wistar rats. METHODS: Rats were intraperitoneally injected with 7.5 mg/kg body weight of DOX alone once followed by treatment with DPDS at 5 and 10 mg/kg for seven successive days. Excised hypothalamus, testes and epididymis were processed for biochemical and histological analyses. RESULTS: DPDS treatment significantly (p < 0.05) abated DOX-induced oxidative damage by decreasing the levels of oxidative stress indices such as hydrogen peroxide, reactive oxygen and nitrogen species, and lipid peroxidation with a respective improvement in the level of glutathione in the hypothalamic, testicular and epididymal tissues of DOX-treated rats. The activities of antioxidant enzymes such as catalase, superoxide dismutase, glutathione S-transferase and glutathione peroxidase were upregulated in the DPDS co-treated group. DPDS co-treatment alleviates the burden of DOX-induced inflammation by significant reductions in myeloperoxidase activity, levels of nitric oxide and tumor necrosis factor alpha with concomitant decline in the activity of caspase-3, an apoptotic biomarker. Consequently, significant improvement in the spermiogram, levels of reproductive hormones (follicle stimulating hormone, luteinizing hormone, prolactin, serum testosterone and intra-testicular testosterone) levels in the DPDS co-treatment group in comparison to DOX alone-treated group were observed. Histology results of the testes and epididymis showed that DPDS significantly alleviated pathological lesions induced by DOX in the animals. CONCLUSION: DPDS may modulate reproductive toxicity associated with DOX therapy in male cancer patients.

Predictive influence of personality traits on retirement anxiety among universities staff in Osun State, Nigeria.

BACKGROUND: Retirement anxiety may occur in retirement-eligible staff, and their reaction may depend on their personality traits. This study examined the predictive influence of five-factor personality traits on retirement anxiety among non-academic staff in some selected universities in Osun State, Nigeria. MATERIALS AND METHODS: The study utilized a multistage sampling technique. Two self-administered instruments, Redeemer's University Retirement Anxiety Scale and Mini-International Personality Item Pool were completed by 463 non-academic staff in five selected universities in Osun State, Nigeria. Descriptive statistics (frequency and percentages) and inferential statistics (hierarchical regression, two-sample t-test, and one-way ANOVA) were used to analyze data. RESULTS: The study found a high prevalence rate of retirement anxiety (85.1%) among university staff in Nigeria. In all, 13%, 16%, and 12.5% of the participants showed high levels of retirement anxiety dimensions (personal obligation, financial planning, and social detachment), respectively. Sociodemographic and personality traits jointly accounted for statistically significant (16%, 29%, and 22%) changes in personal obligation (R2 =0.16, P <.01), financial planning (R2 =0.29, P <.01), and social detachment (R2 =.22, P <.01), respectively. Personality traits (extraversion, agreeableness, conscientiousness, and neuroticism) and socio-demographic variables (age, educational level, job tenure, and job status) jointly contributed to the prediction of retirement anxiety dimensions (obligation concerns, financial planning, and social detachment). CONCLUSION: The findings highlighted the need for psychosocial interventions targeting the at-risk population was highlighted.

CYP24A1 and CYP3A4 Levels, Renal, Hepatic Changes, and Incidence of Oxidative Stress in Tramadol-Alcohol Concomitant Misuse.

Introduction Long-term population-based research has demonstrated a link between heavy drinking and the prevalence of kidney disorders; similarly, alcohol abuse has long been recognized as one of the main causes of liver diseases. A recent trend of concomitant use of the opioid analgesic Tramadol and alcohol among young males in sub-Saharan Africa has emerged. Aim and objectives This study's primary aim was to evaluate the incidence of concomitant use of alcohol and Tramadol among adult males, and observe the role of cytochrome p450 3A4 and CYP24A1 proteins and some oxidative stress indicators such as Malondialdehyde, lactate dehydrogenase, among study participants. The secondary aim was to evaluate the effect of alcohol and Tramadol concomitant use on Liver and kidney indices. Methods Our study population was male subjects with a history of Alcohol and Tramadol concomitant use. Liver enzymes, renal indices, oxidative stress markers, and CYP3A4 and CYP24A1 were determined from the serum of test and control participants. IBM Statistical Package for Social Sciences (SPSS) Statistics (version 21.0) was used to analyze the data obtained. Result One hundred and forty-two male subjects were included in this study. Eighty two (82) were males who admitted to abuse of Alcohol and Tramadol concomitantly for at least a year. The dose of Tramadol commonly used by Test subjects was 200 mg (43.9% of the test population), Tramadol users in the study population were largely Undergraduates (75.6% of Test participants). Gamma-glutamyl transferase and lactate dehydrogenase were significantly higher in Test subjects consuming Tramadol and alcohol combination (43.13±1.02 and 117.29±2.45, respectively) versus control (24.87±0.82; p=0.00 and 101.93±1.25; p=0.00). There was a significant decrease in serum bicarbonate levels of Test subjects (16.19±0.53) versus control (22.60±0.68; p=0.000). Cytochrome P450 24A1, was significantly lower in Test subjects (subjects consuming Tramadol and alcohol combination) (0.90±0.06; p=0.01), and significantly threefold higher in subjects with acute myeloid leukemia (AML) (5.16±0.5; p=0.00), when compared with values of non-drug/alcohol users that served as normal control (1.27±0.07). Conclusion The menace of Tramadol and alcohol concomitant abuse has taken a worrisome dimension in sub-Saharan Africa. In this study 77.4% of participants reported euphoria as reason for combining Alcohol and Tramadol, 6.5% claimed it was for faster pain relief and enhanced sexual performance or prolong penile erection was the response of 58.1% of the test participants. Findings of reduced CYP3A4 with Alcohol and Tramadol concomitant use could be associated with delayed drug inactivation and increased drug euphoric action.

Immunohistochemical Profiling of HER-2/neu, Steroid Hormone Receptors and KI-67 Biomarkers in A Cohort of Nigerian Women with Breast Cancer.

Background: Progressive improvement in the accuracy of profiling of hormone receptors in breast cancer provides the basis for targeted endocrine therapy, a major pillar of multimodal breast cancer treatment. However, the disparity in findings from comparatively smaller sample-sized studies in West Africa has led to somewhat conflicting conclusions and recommendations. Objectives: This study investigates the immunohistochemical (IHC) profile of breast cancer specimens for estrogen receptor (ER), progesterone receptor (PR), human epidermal receptor-2 (HER2)/neu, and Ki-67 in a tertiary hospital in Ibadan, Nigeria over 12 years. Materials and Methods: We reviewed 998 IHC reports, documented clinicopathologic parameters, computed patterns of biomarkers, and stratified them based on the American Society of Clinical Oncology/College of American Pathologists recommendations. Descriptive analysis including frequency, mean, and median were generated from the data extracted. Results: Out of the 998 cases, 975 (97.7%) were females and 23 (2.3%) were males. The mean age was 48.84 ± 11.99 years. Open biopsies were the most common types of specimens (320, 41.6%): lumpectomy and incisional biopsy of ulcerated, fungating or unresectable tumours. In those cases, 246 (32.0%) were samples of breast-conserving or ablative surgical extirpation (mastectomy/wide local excision/quadrantectomy), and 203 (26.4%) were obtained by core needle biopsies. Invasive ductal carcinoma was the most common histopathological type (673, 94.5%). The majority of graded tumours were intermediate grade (444, 53.5%). Four hundred and sixty-nine (48.4%) were ER positive, 414 (42.8%) were PR positive, and 180 (19.4%) were HER2/neu positive. Three hundred and thirty-four (34.0%) were triple-negative. Eighty-nine cases had Ki-67 staining done, and of these 61 (68.5%) had positive nuclear staining. Conclusion: Steroid hormone receptors and HER-2/neu proportions in our cohort are likely to be more representative than the widely varied figures hitherto reported in the sub-region. We advocate routine IHC analysis of breast cancer samples as a guide to personalized endocrine therapy.

Development and validation of the Redeemer's University Suicidality Scale.

Background: The need for a culturally suitable scale for suicidality within the multilingual Nigerian society necessitated this research interest. Aim: The study is a development and validation of the Redeemer's University Suicidality Scale (RUSS). Setting: South western Nigeria. Methods: This comprised of initial generation of items; face and content validity, item refinement and administration of RUSS to 150 university undergraduates, using exploratory factor analysis at the first, second and third stages. In the fourth stage, 184 undergraduates responded to the 20-item RUSS, Suicide Ideation Scale (SIS) and General Health Questionnaire (GHQ-12). Data gathered at this stage were analysed for congruent validity, reliability and norms. Results: The principal component analysis extracted four components from items whose eigenvalues exceeded one. Twenty-one of the 25 items loaded best in the first, two in the second and one on the third component(s). Only items in the first component were retained. Item-total correlation further showed that the values of one item in the first component fell below the very good discrimination and was deleted from the scale. The RUSS has a Cronbach's alpha of 0.93. Congruence validity coefficient of r = 0.881 (p < 0.001) and r = 0.605 (p < 0.001) was observed between RUSS and SIS and between RUSS and GHQ-12, respectively. Conclusion: The RUSS is gender-sensitive, has acceptable psychometric properties and is recommended as a diagnostic tool for assessing suicidal behaviour in adolescents and adults. Contribution: This article contributes to the development of a culture sensitive measure for suicidality.

Persistent oxidative injury and neurobehavioral impairment in adult male and female Nauphoeta cinerea exposed to perfluorooctanoic acid.

This study aimed to elucidate if the toxicity of perfluorooctanoic acid (PFOA), an emerging persistent organic contaminant, is reversible or not in adult male and female Nauphoeta cinerea. Both sexes of Nauphoeta cinerea were separately exposed to 0, 1 and 5 mg/L PFOA in drinking water for 21 consecutive days. PFOA-exposed Nauphoeta cinerea exhibited significant deficits in the locomotor and exploratory capabilities with concomitant increase in anxiogenic behaviors which persisted after cessation of PFOA exposure. Moreover, PFOA-induced decrease in acetylcholinesterase activity persisted after cessation of PFOA exposure in both insects' sexes. Catalase and superoxide dismutase activities were increased in the midgut but restored to control following cessation of PFOA exposure. The increased reactive oxygen and nitrogen species, nitric oxide and hydrogen peroxide levels persisted in the head whereas they were abated in the midgut after cessation of PFOA exposure. However, PFOA-induced persistent increase in lipid peroxidation and protein carbonyl levels in the head and midgut of insects. Collectively, PFOA exposure elicited persistent neurobehavioral and oxidative injury similarly in both sexes of adult Nauphoeta cinerea during this investigation.