Phosphorylated histone variant γH2Av is associated with chromatin insulators in Drosophila.

Chromatin insulators are responsible for orchestrating long-range interactions between enhancers and promoters throughout the genome and align with the boundaries of Topologically Associating Domains (TADs). Here, we demonstrate an association between gypsy insulator proteins and the phosphorylated histone variant H2Av (γH2Av), normally a marker of DNA double strand breaks. Gypsy insulator components colocalize with γH2Av throughout the genome, in polytene chromosomes and in diploid cells in which Chromatin IP data shows it is enriched at TAD boundaries. Mutation of insulator components su(Hw) and Cp190 results in a significant reduction in γH2Av levels in chromatin and phosphatase inhibition strengthens the association between insulator components and γH2Av and rescues γH2Av localization in insulator mutants. We also show that γH2Av, but not H2Av, is a component of insulator bodies, which are protein condensates that form during osmotic stress. Phosphatase activity is required for insulator body dissolution after stress recovery. Together, our results implicate the H2A variant with a novel mechanism of insulator function and boundary formation.

<i>Drosophila</i> insulator proteins exhibit in vivo liquid-liquid phase separation properties.

Mounting evidence implicates liquid-liquid phase separation (LLPS), the condensation of biomolecules into liquid-like droplets in the formation and dissolution of membraneless intracellular organelles (MLOs). Cells use MLOs or condensates for various biological processes, including emergency signaling and spatiotemporal control over steady-state biochemical reactions and heterochromatin formation. Insulator proteins are architectural elements involved in establishing independent domains of transcriptional activity within eukaryotic genomes. In <i>Drosophila</i>, insulator proteins form nuclear foci known as insulator bodies in response to osmotic stress. However, the mechanism through which insulator proteins assemble into bodies is yet to be investigated. Here, we identify signatures of LLPS by insulator bodies, including high disorder tendency in insulator proteins, scaffold-client-dependent assembly, extensive fusion behavior, sphericity, and sensitivity to 1,6-hexanediol. We also show that the cohesin subunit Rad21 is a component of insulator bodies, adding to the known insulator protein constituents and γH2Av. Our data suggest a concerted role of cohesin and insulator proteins in insulator body formation and under physiological conditions. We propose a mechanism whereby these architectural proteins modulate 3D genome organization through LLPS.

Factors associated with acute kidney injury recovery in a tertiary hospital in Ghana: a prospective study.

INTRODUCTION: Acute kidney injury (AKI) is a challenging problem in developing countries due to late presentation of its victims to health care facilities. Data on the pattern of AKI, its outcome and factors associated with its recovery is scanty in developing countries therefore impeding AKI management. Aim: to study AKI recovery rate and its associated factors. METHODS: An observational study conducted from September 2013 to June 2014 at Korle-Bu Teaching Hospital (KBTH). Participants were adults, admitted with AKI at KBTH. Kidney Disease: Improving Global Outcomes (KDIGO) criteria was used to diagnose and stage AKI. RESULTS: Mean age (SD) of the participants was 41.9 (± 19.2) years. About a third of the patients (34.6%) were less than 29 years with 30-39 years and 40-60 years constituting 23.0% and 23.6% respectively. Females were in the majority (56.0%). AKI stages I, II and III accounted for 11.0%, 6.8% and 70.7% respectively. Majority, 82.2% of the patients recovered their kidney function. Stage III AKI was significantly associated with decreasing odds of recovery [OR = 0.4, 95%CI = 0.4-2.6, p = 0.002]. In addition, normal blood sodium was associated with recovery from AKI [OR, 95%CI = 2.3, (1.1-5.3), p = 0.043]. Almost half (45.5%) presented with fever whereas 32.5% and 22.5% presented with peripheral oedema and pulmonary oedema respectively. CONCLUSION: The study demonstrated high kidney function recovery following AKI. Dominant clinical features were fever, peripheral and pulmonary oedema. Advanced stage was associated with poor recovery whereas normal serum sodium level improves kidney function recovery.

Colorectal cancer survival rates in Ghana: A retrospective hospital-based study.

BACKGROUND: Colorectal cancer (CRC) is one of the commonest cancers associated with diverse prognosis times in different parts of the world. Despite medical interventions, the overall clinical outcomes and survival remains very poor for most patients in developing countries. This study therefore investigated the survival rate of colorectal cancer and its prognostic factors among patients at Komfo Anokye Teaching Hospital, Ghana. METHODOLOGY: In this retrospective cohort study, a total of 221 patients diagnosed with CRC from 2009 to 2015 at the Surgical and Oncological units of Komfo Anokye Teaching Hospital (KATH), Kumasi, Ghana were employed. The survival graphs were obtained using the Kaplan-Meier method and compared by the Log-rank test. Cox regression analysis was used to assess prognostic factors. All analyses were performed by SPSS version 22. RESULTS: The median survival time was 15 months 95% CI (11.79-18.21). The overall survival rate for CRC over the 5 years period was 16.0%. The survival rates at the 1st, 2nd, 3rd, 4th and 5th years were 64% 95% CI (56.2-71.1), 40% 95% CI (32.2-50.1), 21% 95% CI (11.4-30.6) 16% 95% CI (8.9-26.9) and 16% 95% CI (7.3-24.9). There was a significant difference in the survival rate of colorectal cancer according to the different stages (p = 0.0001). Family history [HR = (3.44), p = 0.029)], Chemotherapy [HR = (0.23), p = <0.0001)], BMI [HR = (1.78), p = 0.017)] and both chemo/radiotherapy (HR = (3.63), p = 0.042)] were the significant social and clinical factors influencing the overall survival. Pathological factors such as TNM tumour stage (p = 0.012), depth of tumour invasion (p = 0.036), lymph node metastasis (p = 0.0001), and distance metastasis (p = 0.001) were significantly associated with overall survival. CONCLUSION: The study has clearly demonstrated that survival rate for CRC patients at KATH, Ghana is very low in a 5 years period. This is influenced by significant number of clinical and pathological prognostic factors. Identification of prognostic factors would be a primary basis for early prediction and treatment of patients with colorectal cancer.

Comparative Assessment of Knowledge, Attitudes, and Practice of Breast Self-Examination among Female Secondary and Tertiary School Students in Ghana.

BACKGROUND: Breast cancer remains a serious public health problem globally. It is particularly increasing among adolescents and premenopausal women. Breast self-examination (BSE) is the most effective and feasible means of detecting breast cancer early in developing countries. This study aimed at evaluating and comparing knowledge of BSE among secondary and tertiary school students and at revealing their attitudes and practices about BSE. METHOD: This cross-sectional study was conducted among 1036 female secondary and tertiary school students of Kwame Nkrumah University of Science and Technology and Technology Senior High School. Data was obtained using a pretested questionnaire to access sociodemography, knowledge, attitudes, and practice of BSE among the students. RESULT: Most students were within the age of 15-24 years; 90.9% were aware of BSE. A high level of knowledge on BSE was found in 54.5% of the students. Knowledge was significantly higher in tertiary than secondary school students (p=0.002). 24.1% of the students thought BSE could be performed anytime; however only 8.1% of the students performed BSE monthly as recommended, whilst 41.8% had never practiced. Of these, more secondary students had never practiced BSE as compared to the tertiary students. 22.3% indicated they would wait for a change in a detected breast lump before seeking medical attention. 96.3% of the participants agree BSE is a good practice which must be encouraged. CONCLUSION: Teaching of BSE should be intensified beginning at the high school level, emphasizing practice and its benefits for early detection of breast cancer.

Evaluation of Individual and Combined Markers of Urine Dipstick Parameters and Total Lymphocyte Count as a Substitute for CD4 Count in Low-Resource Communities in Ghana.

We evaluated the individual and combined levels of urine dipstick and total lymphocyte count (TLC) as surrogate markers for CD4 count in a low-resource community in Ghana. This cross-sectional study recruited 200 HIV-infected patients from the Saint Francis Xavier Hospital, Assin Fosu, Ghana. Complete blood count, CD4 count, and urine dipstick analysis were measured for participants. The threshold values were determined as <350 cells/µl for CD4, <1200 cells/µl for TLC, and ≥+ on urine dipstick analysis. The mean age of participants was 43.09 years. Proteinuria ≥ + [aOR = 4.30 (3.0-18.5)], leukocyturia ≥ + [aOR = 2.91 (1.33-12.5)], hematuria ≥ + [aOR = 2.30 (1.08-9.64)], and TLC < 1200 cells/µl [aOR = 3.26 (3.94-15.29)] were significantly associated with increased risk of CD4 count < 350 cells/µl. Using the individual markers, the best substitute marker for predicting CD4 count < 350 cells/µl was proteinuria at a cutoff point ≥ 2++, AUC of 0.973, sensitivity of 97.6%, specificity of 100.0%, PPV of 100.0%, and NPV of 89.1%. A combination of ≤ 1200 TLC + ≥ 2++ (leukocyturia + proteinuria + hematuria) yielded an AUC of 0.980, sensitivity (72.8%), specificity (100.0%), PPV (100.0%), and NPV (97.9%). Proteinuria could serve as a noninvasive screening tool, but the combination of proteinuria, leukocyturia, hematuria, and TLC serves as a better substitute marker for CD4 count in monitoring the disease progression among HIV patients in low-resource communities.

Predictors of Noncompliance to Antihypertensive Therapy among Hypertensive Patients Ghana: Application of Health Belief Model.

This study determined noncompliance to antihypertensive therapy (AHT) and its associated factors in a Ghanaian population by using the health belief model (HBM). This descriptive cross-sectional study conducted at Kintampo Municipality in Ghana recruited a total of 678 hypertensive patients. The questionnaire constituted information regarding sociodemographics, a five-Likert type HBM questionnaire, and lifestyle-related factors. The rate of noncompliance to AHT in this study was 58.6%. The mean age (SD) of the participants was 43.5 (±5.2) years and median duration of hypertension was 2 years. Overall, the five HBM constructs explained 31.7% of the variance in noncompliance to AHT with a prediction accuracy of 77.5%, after adjusting for age, gender, and duration of condition. Higher levels of perceived benefits of using medicine [aOR=0.55(0.36-0.82),p=0.0001] and cue to actions [aOR=0.59(0.38-0.90),p=0.0008] were significantly associated with reduced noncompliance while perceived susceptibility [aOR=3.05(2.20-6.25), p<0.0001], perceived barrier [aOR=2.14(1.56-2.92), p<0.0001], and perceived severity [aOR=4.20(2.93-6.00),p<0.0001] were significantly associated with increased noncompliance to AHT. Participant who had completed tertiary education [aOR=0.27(0.17-0.43), p<0.0001] and had regular source of income [aOR=0.52(0.38-0.71), p<0.0001] were less likely to be noncompliant. However, being a government employee [aOR=4.16(1.93-8.96), p=0.0002)] was significantly associated increased noncompliance to AHT. Noncompliance to AHT was considerably high and HBM is generally reliable in assessing treatment noncompliance in the Ghanaian hypertensive patients. The significant predictors of noncompliance to AHT were higher level of perceived barriers, susceptibility, and severity. Intervention programmes could be guided by the association of risk factors, HBM constructs with noncompliance to AHT in clinical practice.

Patterns and presentations of colorectal cancer at Komfo-Anokye teaching hospital Kumasi, Ghana.

INTRODUCTION: Colorectal cancer is a major cause of morbidity and mortality globally and its incidence is increasing in developing countries. This study determined the incidence, clinical features and the histopathological patterns of colorectal cancer at Komfo Anokye Teaching Hospital (KATH), Kumasi, Ghana. METHODS: A retrospective review of all colorectal cancer cases over a six year period from (2009-2015) presented to the Surgical and Oncological Department of KATH. Patients' records were retrieved and information on their demographics, clinical and pathological presentations recorded. RESULTS: In all, 221 cases of colorectal cancer were identified over the study period. The mean age was 54 ± 16.8 and ranged from 16 to 90 years. Sixteen (7.24%) had family history of cancer and the prevalence of comorbidities was (24.89%). The commonest clinical symptoms presented were weight loss (44.80%), bleeding per rectum (39.82%) and abdominal pain (38.91%) Majority of the patients presented with rectal cancers (48.87%). Microscopically, adenocarcinoma (68.33%) was the most common histopathological type. According to Tumour Node Metastasis (TNM) staging of cancer, majority of the patients 89(40.27%) were identified as being in late stage (TNM Stage III). The overall crude annual incidence was 4.62 per 100000 populations. The age specific standardized incidence rate was 7.93 per 100,000 population. CONCLUSION: This study has clearly showed a high incidence in colorectal cancer at KATH, with similar trends in clinico-pathological patterns comparable to that of most African countries. These include predominance of rectal cancers, high incidence among younger people and delayed presentation of the disease at advanced stage.

Knowledge of bloodless medicine among nurses at the Medical/Surgical Directorate of Komfo Anokye Teaching Hospital, Ghana; a descriptive cross sectional study.

OBJECTIVE: This study assessed the knowledge of bloodless medicine (BM) among nurses at the medical and surgical directorate of Komfo Anokye Teaching Hospital. A paper questionnaire was administered to 322 nurses to obtain information on socio-demographic characteristics and knowledge of BM. RESULTS: More than half (52.1%) of the nurses were aware of BM. The major source of information on BM was from the internet. Out of the study population, 90.1% knew iron therapy as BM strategy. The largest proportions of the participants (51.2%) had witnessed BM treatment at the medical and surgical directorate with the Tot'hema (44.6%) being the major used drug. Flu-like symptoms (37.0%) and organ damage (50.0%) were the commonly known side effects of BM respectively. Most of the participants (97.5%) knew that doctors request for blood transfusion. The major known reason for demand of BM was religious beliefs (53.7%). Higher percentages (71.9%) of the participants were not aware of bloodless surgery although the few who were aware, had heard of this through an internet search. Participants were generally aware of BM but less knowledgeable of specific components of BM. There is the need for prompt hospital and public health education through workshops and in-service training.