Ionizing radiation protection and the linear No-threshold controversy: Extent of support or counter to the prevailing paradigm.

This study has developed a relationship that categorized radiation protection and allows for a proper, clear, and concise review of the different classifications in terms of principles of protection, dose criteria, categories, fundamental tools, exposure situations, applications and control measures. With the groundwork laid, advances of the linear no-threshold (LNT) model which has attracted attention in the field of radiobiology and epidemiology were examined in detail. Various plausible dose-response relationship scenarios were x-rayed under low-dose extrapolation. Intensive review of factors opposing the LNT model involving radiophobia (including misdiagnosis, alternative surgery/imaging, suppression of ionizing radiation (IR) research); radiobiology (including DNA damage repair, apoptosis/necrosis, senescence protection) and cost issues (including-high operating cost of LNT, incorrect prioritization, exaggeration of LNT impact, risk-to-benefit analysis) were performed. On the other hand, factors supporting the use of LNT were equally examined, they include regulatory bodies' endorsement, insufficient statistical significance, partial DNA repair, variability of irradiated bodies, different latency periods for cancer, dynamic nature of threshold and conflicting interests. After considering the gaps in the scientific investigations that either support or counter the scientific paradigm on the use of LNT model, further research and advocacy is recommended that will ultimately lead to the acceptance of an alternative paradigm by the international regulators.

Update on Targeted Therapy in Medullary Thyroid Cancer.

Medullary thyroid carcinoma (MTC) is a rare neuroendocrine tumor that accounts for 2-4% of all thyroid cancers. All inherited MTC and approximately 50% of sporadic cases are driven by mutations in the REarranged during Transfection (RET) proto-oncogene. The recent expansion of the armamentarium of RET-targeting tyrosine kinase inhibitors (TKIs) has provided effective options for systemic therapy for patients with metastatic and progressive disease. However, patients that develop resistant disease as well as those with other molecular drivers such as RAS have limited options. An improved understanding of mechanisms of resistance to TKIs as well as identification of novel therapeutic targets is needed to improve outcomes for patients with MTC.

Update on the Treatment of Medullary Thyroid Carcinoma in Patients with Multiple Endocrine Neoplasia Type 2.

Medullary Thyroid Carcinoma (MTC) is a rare neuroendocrine cancer that accounts for 1-2% of thyroid cancers in the United States (U.S.). While most cases are sporadic, 25% of MTC cases are hereditary. These hereditary cases occur in the setting of Multiple Endocrine Neoplasia Type 2A (MEN2A) or 2B (MEN2B) driven by mutations in the Rearranged during Transfection RET proto-oncogene. This article discusses hereditary MTC in the setting of MEN2 and the treatment options available for it. The first line treatment for this disease is typically a total thyroidectomy and tyrosine kinase inhibitors. Two tyrosine kinase inhibitors, vandetanib and cabozantinib, have been approved for treatment of advanced MTC, but options beyond those are limited. However, several promising treatments are being studied, which are discussed in this review.

Sociodemographic and Clinical Characteristics of Highly Active Antiretroviral Treatment-Naïve Human Immunodeficiency Virus-Seropositive Patients in Uyo, Nigeria: Are the Demographics Changing?

BACKGROUND: Human immunodeficiency virus (HIV) infection poses a great health and economic burden, especially in developing nations where a high burden of disease has been described. A previous study in Uyo shows that some characteristics associated with a higher prevalence of HIV infection include female gender, exposure to tertiary level of education, and late disease presentation. This study aimed at determining the sociodemographic and the clinical characteristics of highly active antiretroviral treatment-naïve (HAART-naïve) HIV-seropositive patients at Uyo, Nigeria. MATERIALS AND METHODS: This was a cross-sectional comparative study of 210 respondents, composed of 105 HAART-naïve HIV-seropositive patients (subjects) and an equal number of sex- and age-matched HIV-negative individuals (controls). Data were collected using pretested interviewer-administered questionnaires and hospital records. Anthropometry and blood pressure (BP) were measured for all the respondents, while clinical and immunologic staging were done for subjects. Data obtained were analyzed using SPSS v 20. P ≤ 0.05 was taken as statistically significant. RESULTS: The mean age of the respondents was 34.5 ± 9.2 years, and the male-to-female ratio was 1:2.3, with no difference between the subjects and controls (P = 0.880 for age and P = 0.943 for gender). Mean body mass index and mean diastolic BP were significantly lower in the subjects (P < 0.001 and 0.037, respectively). Female gender, secondary level of educational attainment, and unskilled employment were significantly associated with HIV infection. Majority of the respondents presented in clinical Stage 1 or 2 disease, with CD4 count >350 cells/ml. CONCLUSION: The burden of HIV infection is higher in females and in those with sociodemographic characteristics suggestive of lower socioeconomic status, however, majority of these appeared to present in early disease.

Pattern and microbiological characteristics of diabetic foot ulcers in a Nigerian tertiary hospital.

PURPOSE: To determine the pattern and bacteriological characteristics of diabetic foot ulcers in patients attending a tertiary health care facility. METHOD: 160 Patients with Diabetes Mellitus foot syndrome were recruited, out of which 52 had diabetic foot ulcers. Relevant clinical, biochemical, and microbiological evaluations were carried out on the subjects. Data analysis was done using SPSS version 20. p value was set at <0.05. RESULTS: 52 (32.5%) out of 160 subjects with Diabetes Mellitus Foot Syndrome (DMFS) had diabetic foot ulcers. Poor glycaemic control (mean HbA1c = 9.2 (2.7) %), and abuse of antibiotics (76.9%) characterized the subjects. Foot ulcers mainly involved the right lower limb and followed spontaneous blister formation (50%). Microbiological culture pattern was polymicrobial (71.2%); predominantly anaerobic organisms (53.3%). Gram positive and negative aerobic isolates yielded high sensitivity to common quinolones (76% - 87.8%). The gram positive and negative anaerobic isolates were highly sensitive to Clindamycin and Metronidazole respectively (80.2% - 97.8%). High sensitivity (>80%) yield for gram negative anaerobes was recorded for Imipinem and Ampicillin/Sulbactam. CONCLUSION: Diabetic foot ulcers (DFU) contribute about one-third of DMFS. The bacteriological isolates from these ulcers are mainly polymicrobial with high sensitivity to common antibiotics. The need for appropriate use of antibiotics should be advocated among the patients.

Prevalence of, and risk factors for erectile dysfunction in male type 2 diabetic outpatient attendees in Enugu, South East Nigeria.

Context: Erectile dysfunction (ED) is a strong predictor of poor quality of life in men with type 2 Diabetes mellitus (T2DM). Several studies evaluating ED in men with diabetes mellitus have been carried out, but few of these have been done in Nigeria. In Enugu, South East Nigeria, paucity of studies on this subject was observed. Aims: This study aims to determine the prevalence and predictors of ED in men with T2DM attending the diabetes clinics. Settings and Design: A descriptive cross-sectional study of men with T2DM in UNTH and Saint Mary's Hospital, Enugu, was carried out. The systematic sampling method was used to recruit participants. Subjects and Methods: Data collection from participants and their hospital records was done using semi-structured questionnaire. ED was assessed using the 5 items, international index of erectile function questionnaire. Statistical Analysis Used: Data analysis was done using SPSS version 20 and results presented as texts and tables. P value was set at <0.05. Results: A total of 325 participants with mean age of 57.8 ± 13.2 years were involved out of which 94.7% had ED. The proportion of participants with ED had increased with its severity. Predictors of ED included poor glycemic control, longer duration of diabetes, overweight/obesity, and older age. Poor ED health-seeking behavior and treatment were noted. Conclusions: The prevalence of ED is high. Lifestyle interventions targeted at improving glycemic control and weight loss may reduce the burden of this complication. We recommend objective ED screening using standard but brief instruments as part of routine evaluation of men with T2DM.

RésuméContexte: La dysfonction érectile (DE) est un puissant facteur prédictif de la qualité de vie médiocre chez les hommes atteints de diabète de type 2 (DT2). Plusieurs études L'évaluation de la dysfonction érectile chez les hommes atteints de diabète sucré a été réalisée, mais peu d'entre elles ont été réalisées au Nigéria. Enugu, sud-est du Nigeria, le manque d'études sur ce sujet a été observé. Objectifs: Cette étude vise à déterminer la prévalence et les prédicteurs de la dysfonction érectile chez les hommes atteints de DT2. assister aux cliniques de diabète. Paramètres et conception: Une étude transversale descriptive des hommes atteints de DT2 à l'UNTH et à l'Hôpital Saint Mary's, Enugu, a été réalisée. La méthode d'échantillonnage systématique a été utilisée pour recruter des participants. Sujets et méthodes: Collecte de données à partir de les participants et leurs dossiers d'hôpital ont été réalisés à l'aide d'un questionnaire semi-structuré. La DE a été évaluée en utilisant les 5 items, index international questionnaire sur la fonction érectile. Analyse statistique utilisée: L'analyse des données a été réalisée à l'aide de SPSS version 20 et les résultats présentés sous forme de texte et les tables. La valeur de p a été fixée à <0,05. Résultats: Au total, 325 participants âgés de 57,8 ± 13,2 ans ont été impliqués, dont 94,7% avaient ED. La proportion de participants atteints de dysfonction érectile avait augmenté avec sa gravité. Les prédicteurs de la dysfonction érectile comprenaient un contrôle glycémique médiocre, une durée plus longue du diabète, du surpoids / obésité et du troisième âge. Des comportements médiocres en matière de recherche de soins de santé et de traitement ont été notés. Conclusions: La prévalence de ED est élevé. Les interventions axées sur le mode de vie visant à améliorer le contrôle glycémique et la perte de poids peuvent réduire le fardeau de cette complication. nous recommander un dépistage objectif dans l'urgence à l'aide d'instruments standard mais brefs dans le cadre de l'évaluation de routine des hommes atteints de DT2. Mots-clés: Diabète, dysfonction érectile, Nigéria, prévalence, facteurs de risque.

Performance of waist circumference and proposed cutoff levels for defining overweight and obesity in Nigerians.

BACKGROUND: Waist circumference (WC) is a simple tool for measuring central obesity in routine clinic settings. Gender- and ethnic-specific optimal cutoff points for WC are encouraged for populations lacking such data. OBJECTIVES: To derive WC cutoff values, predictive of overweight and obesity in Nigerians and to evaluate the performance of currently recommended values. SUBJECTS AND METHODS: Apparently, healthy urban dwellers from six cities spread across Nigeria were selected for this cross-sectional study. Biophysical profiles such as blood pressure and anthropometric indices were measured according to the World Health Organization's STEPs instrument protocol. Receiver operating characteristics curve analysis was used to determine the optimal cutoff levels using the decision rule of maximum (sensitivity + specificity). The level of significance was set at P< 0.05. RESULTS: A total of 6089 subjects (3234 males and 2855 females) were recruited for the study. WC demonstrated a high area under the curve in both genders. Selected cutoff points ranged from 83 to 96 cm with high sensitivities and specificities. CONCLUSIONS: The currently recommended gender-specific WC cutoff values proved inappropriate in this study group, but WC remains a reliable tool for measuring obesity.

The metabolic syndrome in Africa: Current trends.

Metabolic syndrome is a clustering of several cardiovascular risk factors. Contrary to earlier thoughts, metabolic syndrome is no longer rare in Africa. The prevalence is increasing, and it tends to increase with age. This increase in the prevalence of metabolic syndrome in the continent is thought to be due to departure from traditional African to western lifestyles. In Africa, it is not limited to adults but is also becoming common among the young ones. Obesity and dyslipidemia seem to be the most common occurring components. While obesity appears more common in females, hypertension tends to be more predominant in males. Insulin resistance has remained the key underlying pathophysiology. Though pharmacologic agents are available to treat the different components of the syndrome, prevention is still possible by reverting back to the traditional African way of life.

Comparison of the performance of two measures of central adiposity among apparently healthy Nigerians using the receiver operating characteristic analysis.

OBJECTIVE: To compare the performance of waist circumference (WC) and waist-to-hip ratio (WHR) in predicting the presence of cardiovascular risk factors (hypertension and generalized obesity) in an apparently healthy population. MATERIALS AND METHODS: We recruited 898 apparently healthy subjects (318 males and 580 females) of the Igbo ethnic group resident in Enugu (urban), Southeast Nigeria. Data collection was done using the World Health Organization Stepwise approach to Surveillance of risk factors (STEPS) instrument. Subjects had their weight, height, waist and hip circumferences, systolic and diastolic blood pressures measured according to the guidelines in the step 2 of STEPS instrument. Generalized obesity and hypertension were defined using body mass index (BMI) and JNC 7 classifications, respectively. Quantitative and qualitative variables were analyzed using t-test and Chi-square analysis, respectively, while the performance of WC and WHR was compared using the Receiver Operating Characteristic (ROC) analysis. P value was set at <0.05. RESULTS: The mean age of the subjects was 48.7 (12.9) years. Central obesity was found in 76.9% and 66.5% of subjects using WHR and WC, respectively. WC had a significantly higher area under the curve (AUC) than WHR in all the cardiovascular risk groups, namely, generalized obesity (AUC = 0.88 vs. 0.62), hypertension alone (AUC = 0.60 vs. 0.53), and both generalized obesity and hypertension (AUC = 0.86 vs. 0.57). CONCLUSION: WC performed better than WHR in predicting the presence of cardiovascular risk factors. Being a simple index, it can easily be measured in routine clinic settings without the need for calculations or use of cumbersome techniques.

High prevalence and low awareness of hypertension in a market population in enugu, Nigeria.

Background. A community-based study put the prevalence of hypertension in Nigeria at 32.8%. Market workers in Nigeria lead sedentary life style and often depend on salt-laden fast food while at work. Method. An unselected population of market workers were screened for hypertension and its risk factors by a pretested, structured questionnaire, clinical examination, and laboratory investigation. Hypertension was defined as BP ≥ 140 and/or ≥ 90 mmHg or being on drug therapy. Results. Forty-two percent of the screened population were hypertensive. Of this number, 70.6% did not know they were hypertensive before the screening. More males than females (P = .022) were hypertensive. Prevalence of hypertension increased with age from 5.4% in the age group <20 years to 80% in the age group ≥70 years. Conclusion. The prevalence of hypertension in market workers in this study was 42%, and the majority of them were unaware of their disease.

Fine specificity of anti-MSP119 antibodies and multiplicity of Plasmodium falciparum merozoite surface protein 1 types in individuals in Nigeria with sub-microscopic infection.

BACKGROUND: The absence of antibodies specific for the 19 kDa C-terminal domain of merozoite surface protein 1 (MSP119) has been associated with high-density malaria parasitaemia in African populations. The hypothesis that a high prevalence and/or level of anti-MSP119 antibodies that may inhibit erythrocyte invasion would be present in apparently healthy individuals who harbour a sub-microscopic malaria infection was tested in this study. METHODS: Plasma samples were collected from residents in a region in Nigeria hyperendemic for malaria, who had no detectable parasitaemia by microscopy. Using a competition-based enzyme-linked-immunosorbent assay with two invasion-inhibitory monoclonal antibodies (mAbs) 12.10 and 12.8, the levels and prevalence of specific antibodies were measured. The minimum multiplicity of infection was determined using PCR. The prevalence of anaemia was also measured. RESULTS: Plasma samples from 85% of individuals contained antibodies that bound to MSP119. The inhibition of mAb 12.10 binding was strongly correlated with the prevalence (Spearman correlation test, p < 0.0001) and mean titre of anti-MSP119 antibodies (Spearman correlation test, p < 0.001) in the samples. Comparing samples from individuals with multiple infection (group M) and single infection (Group S), group M contained a higher (p = 0.04) prevalence of anti-MSP119 antibodies that competed with mAb 12.10. Using a logistic regression model, it was found that the presence of antibodies competitive with mAb 12.10 was affected negatively by anaemia (p = 0.0016) and positively by the carriage of multiple parasite genotypes (p = 0.04). CONCLUSIONS: In the search for correlates of protection against malaria, which will be essential to evaluate clinical trials of malaria vaccines based on MSP1, this study examines some potential assays and the factors that need to taken into account during their evaluation, using samples from individuals naturally exposed to malaria infection.

Cellular responses to modified Plasmodium falciparum MSP119 antigens in individuals previously exposed to natural malaria infection.

BACKGROUND: MSP1 processing-inhibitory antibodies bind to epitopes on the 19 kDa C-terminal region of the Plasmodium falciparum merozoite surface protein 1 (MSP1(19)), inhibiting erythrocyte invasion. Blocking antibodies also bind to this antigen but prevent inhibitory antibodies binding, allowing invasion to proceed. Recombinant MSP1(19) had been modified previously to allow inhibitory but not blocking antibodies to continue to bind. Immunization with these modified proteins, therefore, has the potential to induce more effective protective antibodies. However, it was unclear whether the modification of MSP1(19) would affect critical T-cell responses to epitopes in this antigen. METHODS: The cellular responses to wild-type MSP1(19) and a panel of modified MSP1(19) antigens were measured using an in-vitro assay for two groups of individuals: the first were malaria-naïve and the second had been naturally exposed to Plasmodium falciparum infection. The cellular responses to the modified proteins were examined using cells from malaria-exposed infants and adults. RESULTS: Interestingly, stimulation indices (SI) for responses induced by some of the modified proteins were at least two-fold higher than those elicited by the wild-type MSP1(19). A protein with four amino acid substitutions (Glu27-->Tyr, Leu31-->Arg, Tyr34-->Ser and Glu43-->Leu) had the highest stimulation index (SI up to 360) and induced large responses in 64% of the samples that had significant cellular responses to the modified proteins. CONCLUSION: This study suggests that specific MSP1(19) variants that have been engineered to improve their antigenicity for inhibitory antibodies, retain T-cell epitopes and the ability to induce cellular responses. These proteins are candidates for the development of MSP1-based malaria vaccines.

Cytokine profiles and antibody responses to Plasmodium falciparum malaria infection in individuals living in Ibadan, southwest Nigeria.

BACKGROUND: The ability of the host immune system to efficiently clear Plasmodium falciparum parasites during a malaria infection depends on the type of immune response mounted by the host. STUDY DESIGN: In a cross-sectional study, we investigated the cellular-and antibody responses in individuals with P. falciparum infection, in an attempt to identify immunological signs indicative of the development of natural immunity against malaria in Ibadan, Nigeria. Levels of IL-10, IL-12(p70), IFN-gamma, and IgM, IgG and IgG1-4 subclasses in the serum of 36 symptomatic children with microscopically confirmed malaria parasitaemia and 54 asymptomatic controls were analysed by ELISA. RESULTS: IFN-gamma and IL-10 were significantly higher in the symptomatic children (p=0.009, p=0.025 respectively) than in the asymptomatic controls but no differences were seen for IL-12(p70). Estimated higher ratios of IFN-gamma/IL-10 and IFN-gamma/IL-12 were also observed in the symptomatic children while the asymptomatic controls had higher IL-12/IL-10 ratio. The mean concentration levels of anti-P. falciparum IgG1, IgG2, IgG3 antibodies were statistically significantly higher in the individuals >5 years of age than <5 years while anti-P. falciparum IgG3 antibodies were notably low in <5 years category. Children <5 years had higher IgM antibodies than IgG and the expression of IgG subclasses increased with age. CONCLUSION: Taken together, malaria infection is on a delicate balance of pro- and anti-inflammatory cytokines. The higher levels of IFN-gamma seen in the symptomatic children (<6 months) may be instrumental in immune-protection against malaria by limiting parasite replication. The observed variations in immunoglobulin subclass levels were age-dependent and exposure-related.

Epidemiological factors that promote the development of severe malaria anaemia in children in Ibadan.

BACKGROUND: Effective control and management of severe malaria cases depends on a clear understanding of the local epidemiological factors and specific clinical manifestations of the disease in the different endemic regions. OBJECTIVES: To determine the prevalence of severe malaria and epidemiological factors that affect the development of malaria anaemia. METHODS: A cross-sectional survey was carried out among children below 5 years of age, at the Adeoyo State Maternity Hospital, Ibadan, Nigeria. Questionnaires and case histories were taken from patients clinically diagnosed of malaria. Thus, 372 volunteers were recruited into the study from the 3131 paediatric cases that reported over the 10-week period to the out-patient department (OPD) of the hospital. 229 (61.6%) of the recruited volunteers presented with fever (>37.5 degrees C) at consultation. These had malaria parasite and PCV tests done. RESULTS: Clinical diagnosis was confirmed microscopically in 78% (290/372) for Plasmodium infection using thick film slides. Anaemia (PCV <28%) prevalence was 28.2%. Factors that contributed to the rapid progression of uncomplicated malaria to severe status included: age of the child, level of parasitaemia, careless response and attitude of parents or guardians to fever in the children; parents' preoccupation with their jobs or other healthy children and unwillingness to use available health facilities. CONCLUSION: The study underscores the need for community involved partnership for malaria control especially through health education for the home management of malaria, especially among those experiencing some form of inequity in access to healthcare.