Toxoplasma-host endoplasmic reticulum interaction: How T. gondii activates unfolded protein response and modulates immune response.

Toxoplasma gondii is a neurotropic single-celled zoonotic parasite that can infect human beings and animals. Infection with T. gondii is usually asymptomatic in immune-competent individual, however, it can cause symptomatic and life-threatening conditions in immunocompromised individuals and in developing foetuses. Although the mechanisms that allow T. gondii to persist in host cells are poorly understood, studies in animal models have greatly improved our understanding of Toxoplasma-host cell interaction and how this interaction modulates parasite proliferation and development, host immune response and virulence of the parasite. T. gondii is capable of recruiting the host endoplasmic reticulum (ER), suggesting it may influence the host ER function. Herein, we provide an overview of T. gondii infection and the role of host ER during stressed conditions. Furthermore, we highlight studies that explore T. gondii's interaction with the host ER. We delve into how this interaction activates the unfolded protein response (UPR) and ER stress-mediated apoptosis. Additionally, we examine how T. gondii exploits these pathways to its advantage.

Human immunodeficiency virus care and management in incarcerated populations in Sub-Saharan Africa between 2010 and 2022: A narrative review.

BACKGROUND: Different countries in sub-Saharan Africa (SSA) have established guidelines to reduce HIV transmission and improve its management in prisons. This narrative review aimed to examine established literature on HIV care and management among incarcerated persons in SSA to identify successful interventions that could inform improved guidelines, policies, and practices related to the clinical care of this population. METHODS: We searched PubMed, Scopus, Web of Science, Embase, and TRIP Medical Databases in August 2022 for articles published between 1st January 2010 and 30th June 2022. We identified 27 eligible articles based on the Population/Concept/Context framework. RESULTS: HIV screening primarily involved mass campaigns rather than formal prison programmes, with limited implementation of universal testing and treatment. Although a few studies reported on access to antiretrovirals (ARVs), prisoners in urban areas and females had disproportionate access. Barriers identified include poor living conditions, high levels of stigma, and resource constraints. Inter-prison transfers, release from prison, and lack of established programmes hindered follow-up and linkage to care. CONCLUSIONS: The implementation of strategies such as universal testing and treatment, human resource strengthening, financing plans for testing, ARV care, and frequent assessment of risk could improve HIV care and management in prisons in SSA.

Age of first diagnosis and incidence rate of uterine fibroids in Ghana. A retrospective cohort study.

BACKGROUND: Uterine fibroids are benign tumors that grow in or on the uterus of women. Globally, they occur in more than 80% of women of African ancestry and 70% in white women. Uterine fibroid requires much attention because of its high incidence rate among women of all races and ages. This study sought to document the age of first diagnosis and incidence rates of uterine fibroids in our urban setting. METHODS: This study reviewed and analyzed the ages and year of diagnosis of all 2,469 patients with the first diagnosis of uterine fibroids from 1st January 2018 to 31st December 2021 in South-Central Ghana. The obtained data were analyzed using GNU PSPP, Python on Jupyter Notebook and Libre Office Calc with statistical significance level set at p≤0.05. RESULTS: The overall average age was 36.29±8.08 years, with age range 17-61 years and the age groups with the highest frequencies were 35-39 years (n = 642, 26.00%), 30-34 years (n = 563, 22.80%) and 40-44 years (n = 381, 15.43%). The mean ages of the patients in 2018, 2019, 2020 and 2021 were 36.70±8.00 years (95%CI = 35.97-37.43), 37.07±7.66 years (95%CI = 36.45-37.70), 35.92±7.87 years (95%CI = 35.30-36.53) and 35.78±8.54 years (95%CI = 35.19-36.38) respectively. The incidence rate (per 100,000) of uterine fibroids in 2018, 2019, 2020 and 2021 were 66.77 (95% CI = 60.63-72.90), 81.86 (95%CI = 75.19-88.58), 85.60 (95%CI = 78.85-92.35) and 92.40 (95%CI = 85.88-98.92) respectively, with 35-39 age group recording the highest in all years. CONCLUSION: The incidence rate of uterine fibroids increased as the years progressed and it is mostly high in 35-39 years age category, with a decreasing annual mean age trend indicative of early diagnosis.

Poldip2 knockdown protects against lipopolysaccharide-induced acute lung injury via Nox4/Nrf2/NF-κB signaling pathway.

Polymerase δ-interacting protein 2 (Poldip2) has been reported to mediate acute lung injury (ALI); however, the underlying mechanism is not fully explored. Male C57BL/6 mice and A549 cells were used to establish the lipopolysaccharide (LPS)-induced ALI model, then the expression of Poldip2 and its effect on oxidative stress and the resulting inflammation were detected. Adeno-associated virus serotype 6 (AAV6) mediated Poldip2 knockdown was transfected into mice via intratracheal atomization. And A549 cells stimulated with LPS was used to further confirm our hypothesis in vitro. ML385, specifically inhibited the activation of the Nrf2 signaling pathway. Our data suggested that LPS stimulation remarkably increased protein levels of Nox4 and p-P65, activities of NADPH and MPO, and generation of ROS, TNF-α, and IL-1ß while decreased protein levels of Nrf2 and HO-1 compared with those in NC shRNA + Saline group, which were obviously reversed by Poldip2 knockdown. Concomitantly, Poldip2 knockdown dramatically reduced contents of MDA and enhanced activities of SOD and GSH-Px compared to NC shRNA + LPS group. In vitro, we found that knockdown of Poldip2 significantly reversed LPS-induced increase protein levels of Nox4 and p-P65, activity of NADPH, and generation of ROS, TNF-α, and IL-1ß, and decrease protein levels of Nrf2 and HO-1, ML385 pretreatment reversed the effects of Poldip2 knockdown mentioned above. Our study indicated that Poldip2 knockdown alleviates LPS-induced ALI via inhibiting Nox4/Nrf2/NF-κB signaling pathway.

Direct enzyme-linked aptamer assay (DELAA) for diagnosis of toxoplasmosis by detection of SAG1 protein in mice and humans.

Toxoplasma gondii is a single-celled parasite commonly found in mammals and birds. Diagnosis of toxoplasmosis largely depends on measurements of the antibody and/or antigen and Toxoplasma DNAs due to the presence of tissue dwelling duplicating tachyzoites, or quiescent cysts in latent infection of the parasite. As a major surface antigen of T.gondii tachyzoites, SAG1 is a key molecule for laboratory diagnosis. However, there are no methods available yet for SAG1 detection using aptamer-based technology. Recombinant SAG1 (r-SAG1) of Toxoplasma WH3 strain (type Chinese 1) was expressed in E.coli and subjected to the synthetic oligonucleotide library for selection of nucleic acid aptamers which target the r-SAG1 antigen, with systematic evolution of ligands by exponential enrichment (SELEX) strategy. The specific aptamers were screened out and used in direct enzyme-linked aptamer assay (DELAA) for detection of native SAG1 (n-SAG1) obtained from tachyzoite lysates, mouse sera of acute infection, and human sera that had been verified for Toxoplasma DNAs by PCR amplification. As results, the soluble r-SAG1 protein was obtained from E.coli lysates by purification and identification with immunoblotting, followed by biotinylation. The selected aptamers were amplified by PCR and DNA sequencing. The results showed that the aptamer-2, with the highest affinity to n-SAG1 in the sera of animals with minimal difference in the four aptamer candidates, has a high specificity and sensitivity when used in detection of n-SAG1 in the sera of humans when compared with the commercial kit of ELISA for T.gondii circulating antigen test. We concluded that a new direct enzyme-linked aptamer assay (DELAA) was developed for the detection of the n-SAG1 protein of T. gondii. With increased sensitivity and specificity, stability, easy and cheap preparation, the aptamer-based technology is considered an efficient method for the diagnosis of active as well as reactivated toxoplasmosis.

Evaluation of the Anatomical Locations of Stroke Events From Computed Tomography Scan Examinations in a Tertiary Facility in Ghana.

Introduction Stroke events are leading causes of mortalities globally and currently increasing alarmingly in low- and middle-income nations including Ghana, thus overburdening national healthcare delivery sectors. This trend is predicted to ultimately have an impact on the socio-economic development of these countries, thus gaining the attention of policy-makers and implementers. This study was therefore conducted to evaluate the anatomical locations of stroke events from CT scan examinations and the possibly associated variables to assist in managing this non-communicable pandemic. Methods All computed tomography (CT) scans performed for stroke events at the Cape Coast Teaching Hospital from June 2016 to June 2020 were retrieved and reviewed for this study. The socio-demographics and the presence of hypertensive risk factor were also retrieved. Data were then collated, grouped, coded, inputted, and used for analysis. Chi-square test of independence was employed for assessing possible associations, and logistic regression analysis was performed to predict the anatomical locations of stroke events using sex and hypertension. Statistical significance level was specified at p ≤ 0.05. Results A total of 1,750 stroke cases were recorded during the study period, comprising 1,237 (70.7%) ischemic strokes and 513 (29.3%) hemorrhagic strokes. Majority (54.3%) of the patients were males. The average age of participants was 62.46±14.74 years. Basal ganglia (43.0%), parietal lobe (26.7%), and frontal lobe (6.9%) were the commonest anatomical locations. The elderly (≥ 60 years) were significantly affected at the basal ganglia (p=0.006), parietal lobe (p=0.005), frontal lobe (p=0.013), temporal lobe (p=0.048), and cerebellum (p=0.049). Basal ganglia lesions were significantly recorded in men, whereas lesions located at the pons were significantly seen in females. The regression model revealed that the risk of stroke at the pons increased by 2.155-folds in males (p=0.043; 95% CI=1.026-4.528). Generally, gender and hypertension were not significant predictors of stroke lesion locations. Conclusions The basal ganglia area, which falls under the middle cerebral artery territory, was the commonest anatomical location for stroke events in our setting. Knowing the anatomical locations of these stroke events has an impact on the type of interventions needed, especially at the early stages of these stroke events. CT perfusion, CT angiography, and magnetic resonance imaging (MRI) with MR angiography (MRA) when available can further assist in determining the exact cause so that urgent interventions such as endovascular treatments can be offered.

Moderating effects of plastic packaged food on association of urinary phthalate metabolites with emotional symptoms in Chinese adolescents.

Previous research reports that diet is the main source of phthalate exposure to adolescents, and phthalate is associated with adolescent mental and behavioral problems. However, no study has explored the moderating effects of eating behavior in this association. This study aimed to analyze the moderating effects of plastic packaged food consumption in the longitudinal association between phthalate metabolite concentration and emotional symptoms in adolescents. This school-based survey was carried out among adolescents in two Chinese provinces. We conducted a baseline and follow-up surveys for 893 freshmen using the purposive sampling method from December 2018 to November 2019. We used food frequency questionnaire to assess eating behavior. The Chinese version of 21-item Depression Anxiety Stress Scales was used to assess emotional symptoms, and high-performance liquid chromatography-tandem mass spectrometry was used to analyze the concentration of six urine phthalate metabolites. The results of latent moderation model indicated that plastic packaged food consumption moderated the association of low molecular weight phthalate (LMWP) with depressive symptoms (ß = 0.27, P = 0.002), anxiety symptoms (ß = 0.89, P < 0.01), and stress symptoms (ß = 0.23, P = 0.019). The moderating effects were significant at the higher scores (ß = 0.14-0.35, P < 0.05) and/or the lower scores (ß = -0.35 to -0.12, P < 0.05) of plastic packaged food consumption. The results suggest that plastic packaged food consumption to some extent moderates the longitudinal association of phthalate exposure with emotional symptoms in adolescents.

Tuberous Sclerosis: A Case Report and Review of the Literature.

Tuberous sclerosis (TS) is a rare genetic disorder of autosomal-dominant inheritance. Mutations on either of the two genes Tuberous Sclerosis Complex 1 (TSC1) or Tuberous Sclerosis Complex 2 (TSC2) play a role and result in hamartomas involving many organs, like the brain, heart, kidneys, skin, lungs, and liver. This case report is about a four-year-old boy with facial angiofibromas, hypo-pigmented skin lesions on the lower back and dorsum of the right wrist, and previous history of seizures who was referred to the radiology department of the Korle Bu Teaching Hospital for Magnetic Resonance Imaging (MRI) of the brain. The MRI of the brain revealed subependymal giant cell astrocytomas, subependymal nodules, and cortical tubers. Ultrasonography of the abdomen also showed multiple angiomyolipomas and multiple simple cysts in both kidneys. The aim of this case report is to present the imaging findings and create awareness that this rare genetic disorder does exist in Ghana and advocate for formation of support groups for parents with children with tuberous sclerosis.

The Host Autophagy During Toxoplasma Infection.

Autophagy is an important homeostatic mechanism, in which lysosomes degrade and recycle cytosolic components. As a key defense mechanism against infections, autophagy is involved in the capture and elimination of intracellular parasites. However, intracellular parasites, such as Toxoplasma gondii, have developed several evasion mechanisms to manipulate the host cell autophagy for their growth and establish a chronic infection. This review provides an insight into the autophagy mechanism used by the host cells in the control of T. gondii and the host exploitation by the parasite. First, we summarize the mechanism of autophagy, xenophagy, and LC3-associated phagocytosis. Then, we illustrate the process of autophagy proteins-mediated T. gondii clearance. Furthermore, we discuss how the parasite blocks and exploits this process for its survival.

Cytotoxic and Antioxidant Effects of Antimalarial Herbal Mixtures.

Many developing countries depend on herbal mixtures as the first line and cost-effective therapy for malaria. These mixtures with such curative tendencies may also be a source of toxicity to host cells. On the other hand, these mixtures may have anticancer potential activity characterized by cytotoxicity to cancer cells. The aim of the study was to determine the cytotoxic and antioxidant effects of five different antimalarial herbal mixtures. Five antimalarial herbal mixtures commonly used in Ghana (coded as STF, SMH, SMM, SGM, and STT) were purchased and freeze-dried. The dried samples were tested on human acute T-cell leukemia (Jurkat) and breast adenocarcinoma (MCF-7) cell lines. Cytotoxicity was assessed using the tetrazolium-based colorimetric (MTT) assay while antioxidant activity was determined using DPPH free-radical scavenging assay. Among the mixtures, SMM and SGM exhibited the strongest cytotoxicity towards Jurkat cells (IC50 values 59.17 µg/ml and 49.57 µg/ml, respectively), whereas STT showed the weakest cytotoxicity (IC50 = 244.94 µg/ml). Cytotoxic effect of SMM was also strongest towards MCF-7 cells whilst the least cytotoxic sample was SGM (IC50 > 1000 µg/ml). SMM had the highest antioxidant percentage (EC50 = 1.05 mg/ml). The increasing order of antioxidant percentage among the five herbal mixtures is SMM > SMH > STT > STF > SGM. The herbal mixtures may be potential sources of toxic agents to host cells. Therefore, further toxicity studies must be performed to safeguard health of the public. Interestingly, cytotoxicities exhibited by SMM and SGM suggest the presence of anticancer constituents in them which warrant further studies.

Incidental Finding of Dextrocardia with Situs Inversus in a 59-Year-Old Man.

Dextrocardia with situs inversus is a rare congenital anomaly, which is characterized by right-sided heart apex and inversely rotated visceral organs of the abdomen. We report an unusual case of dextrocardia with situs inversus in a 59-year-old man, referred for a pelvic ultrasound scan because of symptoms of lower urinary tract obstruction and after a fairly normal prostate specific antigen (PSA) value. A diagnosis of enlarged prostate gland with a prominent median lobe and significant residual urine volume was made, which necessitated the examination of the kidneys for hydronephrosis, resulting in the incidental finding of situs inversus. On further investigation, the diagnosis of dextrocardia with situs inversus was made. Physicians should look out for this anomaly primarily because it may be associated with other conditions like primary ciliary dyskinesia so appropriate interventions are offered to reduce morbidities and mortality.

Geographical Distribution of ß-Lactam Resistance among Klebsiella spp. from Selected Health Facilities in Ghana.

ß-Lactam-resistant Klebsiella isolates continue to cause multidrug resistance infections worldwide. This study aimed to describe the geographical distribution of extended spectrum ß-lactamase (ESBL), AmpC ß-lactamase (AmpC), and carbapenemase production among 139 Klebsiella isolates recovered from patients at major referral health facilities in Ghana. The phenotypic methods of combined disc diffusion test, modified three-dimensional test, modified Hodge test (MHT), and combined disc test were performed for each isolate to detect ESBL, AmpC, carbapenemase, and metallo-ß-lactamase (MBL) producers, respectively. Except for MBL, all other ß-lactam resistance mechanisms were highest in the healthcare facilities situated in the northern belt of Ghana. Significant regional difference of ESBL producers was observed between the northern and middle belts as well as the northern and southern belts. Genotypic detection with polymerase chain reaction (PCR) revealed the presence of bla TEM 36/139 (25.9%), bla SHV 40/139 (28.8%), bla CTX-M 37/139 (26.6%), bla OXA-48 3/139 (2.16%), and bla NDM 1/139 (0.72%) genotypes. In conclusion, there were variations in ß-lactam resistance among Klebsiella spp. from health facilities situated in the northern, middle, and southern belts of Ghana. The study provides preliminary evidence that emphasizes the need to direct more attention to antimicrobial resistance control, especially in the northern belt of Ghana. Findings from this study may be critical for creating and fine-tuning effective antimicrobial resistance control strategies and for informing accurate antibiotic prescription by practitioners.

Post Hepatitis B vaccination sero-conversion among health care workers in the Cape Coast Metropolis of Ghana.

BACKGROUND: HBV vaccine is known to offer protection against transmission of HBV infection. Health care workers are mandated to have this vaccination as part of their occupational health safety measures. Post vaccination response data for HCWs in our setting is not available. This study therefore aimed to evaluate the anti-HBs titre levels after Hepatitis B vaccination among HCWs from selected heath facilities in the Cape Coast Metropolis, Ghana. METHODS: A multicenter (3 selected sites) analytical cross-sectional study involving 711 HCWs was conducted. Five (5mls) of blood samples were collected from each study participant and the serum used for HBV immunological profile testing anti-HBs quantification by ELISA test (Fortress Diagnostics Limited, Northern Ireland, United Kingdom). Data analyses were performed using Stata version 14.0 software (STATA Corp, Texas USA). RESULTS: The median age of participants was 29 years (IQR = 26-35 years). Majority (80.9%, n = 575) took their vaccination from Government health facilities compared with 19.1% (n = 136) from private vaccination sources. A total of 7 (3 males and 4 females) were found to be HBsAg positive giving prevalence of 1%. In all, 8.2% (n = 58) of the HCWs had anti-HBs titre levels <10IU/ml giving a sero-protection rate of 91.8%. HCWs who received 3 doses of HBV vaccine were more likely to be sero-protected as compared to those who received only one dose in multivariate analysis (aOR = 3.39, 95%CI: 1.08-10.67), p<0.037). Gender, cigarette smoking and alcohol consumption were not found to be associated with sero-protection. CONCLUSION: There is a high HBV vaccine efficacy among HCWs in the Cape Coast Metropolis of Ghana with higher prevalence of anti-HBs titre level associated with full vaccine dose adherence. Post vaccination antibody titre determination could be an integral part of HBV vaccination protocol for HCWs in Ghana.

Normal Non-HDL Cholesterol, Low Total Cholesterol, and HDL Cholesterol Levels in Sickle Cell Disease Patients in the Steady State: A Case-Control Study of Tema Metropolis.

Background. Abnormal lipid homeostasis in sickle cell disease (SCD) is characterized by defects in plasma and erythrocyte lipids and may increase the risk of cardiovascular disease. This study assessed the lipid profile and non-HDL cholesterol level of SCD patients. Methods. A hospital-based cross-sectional study was conducted in 50 SCD patients, in the steady state, aged 8-28 years, attending the SCD clinic, and 50 healthy volunteers between the ages of 8-38 years. Serum lipids were determined by enzymatic methods and non-HDL cholesterol calculated by this formula: non-HDL-C = TC-HDL-C. Results. Total cholesterol (TC) (p = 0.001) and high-density lipoprotein cholesterol (HDL-C) (p < 0.0001) were significantly decreased in cases compared to controls. The levels of non-HDL-C, low-density lipoprotein cholesterol (LDL-C), and triglyceride (TG) were similar among the participants. The levels of decrease in TC and HDL were associated with whether a patient was SCD-SS or SCD-SC. Systolic blood pressure and diastolic blood pressure were each significantly associated with increased VLDL [SBP, p = 0.01, OR: 0.74 (CI: 0.6-0.93); DBP, p = 0.023, OR: 1.45 (CI: 1.05-2.0)]. Conclusion. Dyslipidemia is common among participants in this study. It was more pronounced in the SCD-SS than in SCD-SC. This dyslipidemia was associated with high VLDL as well as increased SBP and DBP.

Chronic kidney disease is common in sickle cell disease: a cross-sectional study in the Tema Metropolis, Ghana.

BACKGROUND: Renal involvement in sickle cell disease (SCD) contributes significantly to morbidity and mortality. The aim of this study was to determine the prevalence of chronic kidney disease (CKD) amongst SCD patients, and how basic clinical variables differ across haemoglobin genotypes. METHODS: A hospital-based cross-sectional study conducted from December 2013 to May 2014 at the Sickle cell clinic of the Tema General Hospital. One hundred and ninety-four (194) participants with SCD, receiving medical care at the outpatient sickle cell clinic were enrolled onto the study. A structured questionnaire was administered to obtain information on demography, clinical history, blood pressure and anthropometry. Blood and urine samples were taken for serum creatinine and proteinuria determination respectively. The estimated GFR (eGFR) was calculated using the CKD-EPI and Schwartz equations. CKD was defined according to the Kidney Disease Improving Global Outcomes (KDIGO) guidelines. Analysis was performed using GraphPad prism and P <0.05 was considered statistically significant. RESULTS: CKD was present in 39.2% of participants. Using KDIGO guidelines, 40.8% of the HbSS participants had stage 1 CKD and none had stage 2 CKD. In addition, 30.8% of the HbSC participants had stage 1 CKD and 3.8% had stage 2 CKD. There was a trend of increasing age across CKD stages and stage 2 CKD participants were oldest (P < 0.001). CONCLUSION: Results from the current study suggest that CKD is common amongst SCD patients and prevalence and intensity increases with age. Proteinuria and CKD was more common in HbSS genotype than in HbSC genotype.