The Association Between the Genetic VDR SNP c.907+75C>T and Prostate Cancer Risk Is Modified by Tanning Potential.

BACKGROUND: Prostate cancer (PCa) is a multifactorial disease involving complex interactions between genetic and physiological/environmental factors. Vitamin D receptor (VDR) plays a role in numerous cellular pathways and it has been suggested that VDR genetic variants influence individual susceptibility to PCa. MATERIALS AND METHODS: Logistic regression analysis was used to assess the association of six VDR single nucleotide polymorphisms (SNPs) and factors such as tanning potential and UV sunlight exposure with PCa risk. RESULTS: Marginal significant interactions were found, with a 2-fold increase risk of PCa between SNP 1 (c.278-69G>A) and sunlight UV exposure [odds ratio (OR)=2.02, 95% confidence intervaI (CI)=1.036-4.36; p=0.05]; and a 4-fold increase risk of PCa between SNP 4 (c.907+75C>T) and tanning potential (OR=4.40, 95% CI=0.89-29.12; p=0.0591). In contrast, SNP 5 (rs731236, TaqI) and tanning potential interaction had a protective effect by reducing the risk of PCa by 55% (ß=-0.804; OR=0.448, 95% CI=0.197-9.42; p=0.0427). SNPs 2 (rs61614328) and 6 (rs533037428) did not show any association with PCa even in the presence of UV sunlight exposure. CONCLUSION: The protective effect of SNP 4 from PCa is lost and modified by tanning potential in African Americans. This finding needs to be verified by larger studies in different ethnic populations.

Pertussis outbreak in southern Ethiopia: challenges of detection, management, and response.

BACKGROUND: Despite the availability of effective vaccines, pertussis remains endemic with high fatality rates in low and middle-income countries (LMIC). This study aims to describe an outbreak of pertussis in a health district of Ethiopia. The study highlights the challenges faced by the health system in identifying pertussis cases and appropriately responding to the outbreak at the district level. METHODS: A descriptive cross-sectional study was conducted using data sourced from the District Public Health Emergency and Management (PHEM) surveillance service and outbreak management field reports. Stratified attack rates and fatality rates for pertussis are described. Systemic problems leading to the outbreak are explored and narrated. A modified CDC pertussis case definition was employed with a polymerase chain reaction used to confirm cases. RESULTS: From September 2018 to January 2019, 1840 suspected, probable, and confirmed pertussis cases and six deaths were identified. Pertussis cases ranged from 1 month to 51 years in age. An outbreak occurred in 14 out of the 24 villages of Dara Malo district. The overall attack rate was 1708 per 100,000 population with a fatality rate of 3.3 per 1000 pertussis cases. The highest attack rate of 12,689/100,000 was seen in infants. Among confirmed, probable and suspected pertussis cases, only 41.1% had completed the three-dose pertussis vaccine's primary schedule. The household survey revealed a population coverage of 73.4 and 40.8% for Pentavalent vaccine dose one and three respectively. Investigations suggested the existence of a poor cold chain management system in the study area. CONCLUSIONS: There is an urgent need to build capacity to strengthen routine vaccination services and improve the maintenance of the vaccine cold chain. Other LMICs are urged to take lessons learned from this outbreak to strengthen their own vaccination programs and capacitate health workers to manage local outbreaks.

Corrigendum to "Annexin 2 protein expression is associated with breast cancer subtypes in African American women" [Heliyon Volume 6, Issue 2, February 2020, e03241].

[This corrects the article DOI: 10.1016/j.heliyon.2020.e03241.].

Annexin 2 protein expression is associated with breast cancer subtypes in African American women.

BACKGROUND: A review of literature on the expression of Annexin 2 in cancer has shown that there is very limited research work on the association of this protein with breast cancer aggressiveness in African Americans. In the present study, TMA breast tissues from African American women were stained with Annexin 2 antibody to determine the association between the molecular subtypes and Annexin 2 protein expression. METHOD: An annotated case series of 135 breast cancer tissues archived from 2000 to 2010 was acquired from the Howard University Tumor Registry. The association between ANX2 expression and survival by molecular subtypes Luminal A, Luminal B, HER2, and Triple Negative (TN) was assessed using Multinomial regression, chi-square analysis, and Kaplan-Meir graphs (Stata 11). RESULTS: Our findings show a marked association between ANX2 protein expression in Luminal B and HER2 subtypes unadjusted and when adjusted for age. Borderline differences in tumor grade were found in TN only.Univariately, age (<50, 50 + years) and metastases were highly significant for overall survival, disease-free survival and recurrence-free survival. Stage, tumor size, and nodal involvement were of borderline or greater significance for overall and disease-free survival. ANX2 expression was not significant. Kaplan Meier tests of ANX2 showed significant separation of overall survival by ANX2 protein expression in all breast tumor subtypes. In multivariate analyses comparing TN to Luminal A, ANX2 was not important while controlling for age and grade. CONCLUSION: ANX2 might be a biomarker of aggressiveness and a relevant candidate biomarker in high risk African American women with Luminal B and HER2 breast cancer.

Differential expression of Annexin 2, SPINK1, and Hsp60 predict progression of prostate cancer through bifurcated WHO Gleason score categories in African American men.

BACKGROUND: Although studies have observed several markers correlate with progression of prostate cancer (PCa), no specific markers have been identified that accurately predict the progression of this disease, even in African American (AA) men who are generally at higher risk than other ethnic groups. The primary goal of this study was to explore whether three markers could predict the progression of PCa. METHOD: We investigated protein expression of Annexin 2 (ANX2), serine peptidase inhibitor, kazal type 1(SPINK1)/tumor-associated trypsin inhibitor (TATI), and heat shock protein 60 (Hsp60) in 79 archival human prostate trans-rectal ultrasound (TRUS) biopsy tissues according to a modified World Health Organization (WHO) classification: normal (WHO1a), Gleason Score (GS6 (WHO1b), GS7 subgroups (WHO2 = 3 + 4, WHO3 = 4 + 3), GS8 (WHO4), and GS9-10 (WHO5). AA men aged 41-90 diagnosed from 1990 to 2013 at Howard University were included. Automated staining assessed expression of each biomarker. Spearman correlation assessed the direction and relationship between biomarkers, WHO and modified WHO GS, age, and 5-year survival. A two-tailed t-test and ANOVA evaluated biomarkers expression in relationship to WHO normal and other GS levels, and between WHO GS levels. A logistic and linear regression analysis examined the relationship between biomarker score and WHO GS categories. Kaplan-Meier curves graphed survival. RESULTS: ANX2 expression decreased monotonically with the progression of PCa while expression of SPINK1/TATI and Hsp60 increased but had a more WHO GS-specific effect; SPINK1/TATI differed between normal and GS 2-6 and HSP60 differed between GS 7 and GS 2-6. WHO GS was found to be significantly and negatively associated with ANX2, and positively with SPINK1/TATI and Hsp60 expression. High SPINK1/TATI expression together with the low ANX2 expression at higher GS exhibited a bi-directional relationship that is associated with PCa progression and survival. CONCLUSION: Importantly, the data reveal that ANX2, and SPINK1/TAT1 highly associate with WHO GS and with the transition from one stage of PrCa to the next in AA men. Future research is needed in biracial and larger population studies to confirm this dynamic relationship between ANX2 and SPINK1 as independent predictors of PCa progression in all men.

Antimicrobial resistance in the WHO African region: current status and roadmap for action.

The high burden of communicable diseases in African countries engenders extensive antimicrobial use and subsequent resistance with substantial health, financial and societal implications. A desktop analysis to ascertain whether countries in the WHO African region have implemented the WHO Policy Package to combat antimicrobial resistance (AMR) revealed that just two countries (4.3%) have national AMR plans in place, 14.9% (7) have overarching national infection prevention and control (IPC) policies, 93.6% (44) have essential medicines lists and 91.5% (43) have national medicines policies and treatment guidelines intimating rational use. None currently have representative national surveillance systems nor do any incentivize research and development into new medicines and diagnostics. A regional situational analysis to identify scalable good practices within African, resource-constrained country contexts under the auspices of WHO-AFRO is a necessary initial step towards the development of national and regional action plans in concert with incremental progress towards achieving the objectives of the policy package and global action plan. While it is clearly the responsibility of governments to develop, resource and implement plans, regular reporting to and/or monitoring and evaluation by an overarching body such as WHO-AFRO will ensure persistent incremental progress within continuous quality and accountability improvement paradigms.

Use of footwear and foot condition among rural Ethiopian school children.

OBJECTIVE: To evaluate whether shoe-wearing affords foot protection among school children living in southern Ethiopia. METHODS: Data collectors conducted a standardized foot assessment with children in an elementary school in southern Ethiopia (N=168). RESULTS: 54% reported wearing shoes consistently in the prior three days. Children wearing closed-toed shoes showed less adherent soil and toe nail dystrophy than those wearing open-toed sandals. There were no differences by shoe type with regard to signs of foot trauma or heel fissures. CONCLUSIONS: Shoe wearing provided limited foot protection. Interventions are needed to build behavioral skills, including foot washing and wearing appropriate shoes that maximize foot protection.

Predictors of antibiotic use in African communities: evidence from medicines household surveys in five countries.

OBJECTIVES: To investigate antibiotic use in five national household surveys conducted with the WHO methodology to identify key determinants of antibiotic use in the community. METHODS: Data from The Gambia, Ghana, Kenya, Nigeria and Uganda surveys were combined. We used logistic regression models that accounted for the clustered survey design to identify the determinants of care seeking outside the home and antibiotic use for 2914 cases of recent acute illness. RESULTS: Overall, 95% of individuals with acute illness took medicines, 90% sought care outside their homes and 36% took antibiotics. In multivariate analyses, illness severity was a strong predictor of seeking care outside the home. Among those who sought outside care, the strongest predictor of antibiotic use was the presence of upper respiratory symptoms (OR: 3.02, CI: 2.36-3.86, P<0.001), followed by gastrointestinal symptoms or difficulty breathing, and antibiotics use was less likely if they had fever. The odds of receiving antibiotics were higher when visiting a public hospital or more than one healthcare facility. CONCLUSIONS: The nature and severity of symptoms and patterns of care seeking had the greatest influence on decisions to take antibiotics. Antibiotics were widely available and inappropriately used in all settings. Policies to regulate antibiotics distribution as well as interventions to educate prescribers, dispensers and consumers are needed to improve antibiotic use.

Ornithine decarboxylase activity in tissues from rats exposed to 60 Hz magnetic fields, including harmonic and transient field characteristics.

Ornithine decarboxylase (ODC) activity is used widely as a biomarker for tumor promotion in animal model systems. Several previous studies have reported increases in ODC activity in tissues of rats exposed to 60 Hz magnetic fields. The goals of this study were to confirm these findings and to determine whether ODC activity is increased in tissues of animals exposed to magnetic fields containing complex metrics. Three experiments were conducted in male F344 rats. Each study included a sham control group and a group exposed to pure continuous 60 Hz fields (0.2 mT). Additional groups included animals exposed to randomly time-varying 60 Hz fields (range of 0.02 to 0.2 mT); intermittent 60 Hz fields (2 mT) with on-off cycles ranging from 5 s to 5 min; pure continuous 180 Hz fields (2 mT); 60 Hz fields with a superimposed 3rd harmonic (total field strength, 2 mT); 60 Hz fields with superimposed third, fifth, and seventh harmonics (total field strength, 2 mT); 60 Hz fields (2 mT) with superimposed transients; and randomly time-varying 60 Hz fields (range of 0.02 to 0.2 mT) with superimposed transients. After 4 weeks of exposure (18.5 h/day), eight animals per group were euthanized within 1 h of magnetic field deactivation. Homogenates of liver, kidneys, spleen, and brain were prepared from each animal, quick-frozen, and shipped for analysis by four independent laboratories. No consistent pattern of differences in the ODC activity among experimental groups was found either within a laboratory or among laboratories. The results do not support the hypothesis that exposure to extremely low frequency magnetic fields stimulates ODC activity.

Ornithine decarboxylase activity in developing chick embryos after exposure to 60-hertz magnetic fields.

Fertilized white leghorn eggs were exposed to a 4 micro-Tesla (microT) 60 Hz horizontal magnetic field for 15, 18, 23 and 28 h. After exposure to the magnetic field, the embryos were isolated and assayed for ornithine decarboxylase (ODC) activity. ODC activity in magnetic field-exposed embryos was compared to ODC activity in sham-exposed embryos. ODC activity in magnetic field-exposed embryos was not statistically elevated above sham-exposed embryos.

Ornithine decarboxylase activity in L929 cells following exposure to 60 Hz magnetic fields.

To determine whether there is a biological basis for epidemiological studies which suggest an association between exposure to magnetic fields and cancer, we have attempted to replicate earlier findings on cellular enzymes related to cell proliferation. Here we report on an effort to replicate the doubling of ornithine decarboxylase (ODC) activity in L929 murine fibroblasts following exposure to 60 Hz magnetic fields reported by Litovitz et al. Efforts were made to reproduce the methods and exposure conditions used by the original investigators. Positive controls showed that our assay system responded to other known stimuli of ODC activity. We extended the previously reported investigations by testing a number of exposure conditions and other associated variables. Initial results suggested that cells exposed in the original investigators' laboratory demonstrated an enhanced enzyme activity, whereas cells exposed in our laboratory did not. Experiments in our laboratory using the most important elements of the original investigators' exposure system did not demonstrate any enhancement of ODC activity. Finally, a series of magnetic field exposure and sham exposure experiments conducted in the original investigators' laboratory failed to demonstrate an effect of magnetic fields on ODC activity.

Role of modulation on the effect of microwaves on ornithine decarboxylase activity in L929 cells.

The effect of 835 MHz microwaves on the activity of ornithine decarboxylase (ODC) in L929 murine cell was investigated at an SAR of approximately 2.5 W/kg. The results depended upon the type of modulation employed. AM frequencies of 16 Hz and 60 Hz produced a transient increase in ODC activity that reached a peak at 8 h of exposure and returned to control levels after 24 h of exposure. In this case, ODC was increased by a maximum of 90% relative to control levels. A 40% increase in ODC activity was also observed after 8 h of exposure with a typical signal from a TDMA digital cellular telephone operating in the middle of its transmission frequency range (approximately 840 MHz). This signal was burst modulated at 50 Hz, with approximately 30% duty cycle. By contrast, 8 h exposure with 835 MHz microwaves amplitude modulated with speech produced no significant change in ODC activity. Further investigations, with 8 h of exposure to AM microwaves, as a function of modulation frequency, revealed that the response is frequency dependent, decreasing sharply at 6 Hz an 600 Hz. Exposure with 835 MHz microwaves, frequency modulated with a 60 Hz sinusoid, yielded no significant enhancement in ODC activity for exposure times ranging between 2 and 24 h. Similarly, exposure with a typical signal from an AMPS analog cellular telephone, which uses a form of frequency modulation, produced no significant enhancement in ODC activity. Exposure with 835 MHz continuous wave microwaves produced no effects for exposure times between 2 and 24 h, except for a small but statistically significant enhancement in ODC activity after 6 h of exposure. Comparison of these results suggests that effects are much more robust when the modulation causes low-frequency periodic changes in the amplitude of the microwave carrier.

Pursuing better health care delivery at district level.

In the urban and rural districts of Tanzania's Dodoma Region a process was adopted for identifying and solving problems of health care delivery. In a single year, considerable improvements were secured in both teamwork and attitudes towards coping with managerial obstacles.

PIP: In 1990, in Tanzania, district health managers identified barriers to health care delivery in Dodoma Region. They used district action research and education to address them. The urban district health management team developed a 1-year plan of action, focusing on improving the availability of continuing education for health workers, setting up a library, formulating guidelines for good performance, and preparing a system to acknowledge and reward the best workers. The rural district health management team's 1-year action plan aimed to improve the preparation and follow-up of supervisory activities through a workshop, morning sessions, and monthly meetings with members of the district health management team. 1 year after the plan of action was implemented job satisfaction increased in the urban district; it improved significantly for perceived value of work, fringe benefits, and transport and prospects for promotion. Recognition, reward, and quality of supervision contributed greatly to the improvement in motivation. Inadequate facilities and limited items in Swahili kept health workers from using the district library more fully. The rural health management teams were significantly more satisfied with supervisory activities 1 year after implementation. A workshop helped the members work together towards common goals. 4 of the 6 heads of health units did not receive written feedback on supervision. Health unit heads made a list of recommendations to further improve health care delivery, emphasizing the need for continuing education. Health staff at periphery health units needed improved access to health education materials and to senior colleagues. Both health management teams could indeed use district action research and education without using extra resources. This process strengthened the capacities of the district health management teams and brought about positive problem-solving attitudes. Strong involvement of the central government would further increase staff motivation.

Simple nodular goiter. Treatment of 58 cases.

The treatment of 58 cases of simple nodular goiter, over a three-year period, is reported. This study was done in the Asella Regional Hospital, situated in the Arssi Region, in the central highland of Ethiopia. This is a frequent disease in this Region, and two provinces at high risk have been identified. Simple nodular goiter masked a carcinoma in 15.4% of cases. The treatment and results are discussed in details.

The management of sigmoid volvulus: report of 39 cases.

Thirty-nine cases of sigmoid volvulus treated over an 18-month period in a hospital situated in the central part of Ethiopia, where this pathology is very frequent, are reported. The authors' views on the various types of treatment are discussed in details.