Endemic Burkitt lymphoma (eBL) is primarily found in children in equatorial regions and represents the first historical example of a virus-associated human malignancy. Although Epstein-Barr virus ...(EBV) infection and MYC translocations are hallmarks of the disease, it is unclear whether other factors may contribute to its development. We performed RNA-Seq on 20 eBL cases from Uganda and showed that the mutational and viral landscape of eBL is more complex than previously reported. First, we found the presence of other herpesviridae family members in 8 cases (40%), in particular human herpesvirus 5 and human herpesvirus 8 and confirmed their presence by immunohistochemistry in the adjacent non-neoplastic tissue. Second, we identified a distinct latency program in EBV involving lytic genes in association with TCF3 activity. Third, by comparing the eBL mutational landscape with published data on sporadic Burkitt lymphoma (sBL), we detected lower frequencies of mutations in MYC, ID3, TCF3 and TP53, and a higher frequency of mutation in ARID1A in eBL samples. Recurrent mutations in two genes not previously associated with eBL were identified in 20% of tumors: RHOA and cyclin F (CCNF). We also observed that polyviral samples showed lower numbers of somatic mutations in common altered genes in comparison to sBL specimens, suggesting dual mechanisms of transformation, mutation versus virus driven in sBL and eBL respectively.
Background:
Healthcare workers responding to the Corona Virus Pandemic (COVID-19) are at risk of mental illness. Data is scanty on the burden of mental disorders among Kenyan healthcare workers ...responding to the pandemic that can inform mental health and psychosocial support. The purpose of this study was to establish the frequency and associated factors of worry, generalized anxiety disorder, depression, posttraumatic stress disorder and poor quality of sleep among Kenyan health care workers at the beginning of COVID-19 pandemic.
Methods:
We conducted an online survey among 1,259 health care workers in Kenya. A researcher developed social demographic questionnaire and several standardized tools were used for data collection. Standardized tools were programmed into Redcap, (Research Electronic Data Capture) and data analysis was performed using R Core Team. In all analysis a
p
-value < 0.05 was considered significant.
Results:
66% of the participants reported experiencing worry related to COVID-19. 32.1% had depression, 36% had generalized anxiety, 24.2% had insomnia and 64.7% scored positively for probable Post Traumatic Stress Disorder (PTSD). Depression was higher among females compared to men (36.5 vs. 26.9%,
p
= 0.003), workers <35 years old compared to older ones (38.1 vs. 26.4%,
p
< 0.001), and those who were not married compared to those who were married (40.6 vs. 27.6%,
p
< 0.001). Generalized anxiety was commoner among workers aged <35 years (43.5 vs. 29.3%,
p
< 0.001), females (41.7 vs. 29.2%,
p
< 0.001), those who mere not married compared to the married (45.2 vs. 31.2%,
p
< 0.001) and those with <10 years working experience (41.6 to 20.5%,
p
< 0.001). Younger health care professional had a higher proportion of insomnia compared to the older ones (30.3 vs. 18.6%,
p
< 0.001). Insomnia was higher among those with <10 years' experience compared to those with more than 20 years' experience(27.3 vs. 17.6%,
p
= 0.043)
Conclusion:
Many Kenyan healthcare workers in the early phase of COVID-19 pandemic suffered from various common mental disorders with young, female professionals who are not married bearing the bigger burden. This data is useful in informing interventions to promote mental and psychosocial wellbeing among Kenyan healthcare workers responding to the pandemic.
Abstract
Background
Cervical cancer screening is slowly transitioning from Pappanicolaou cytologic screening to primary Visual Inspection with Acetic Acid (VIA) or HPV testing as an effort to enhance ...early detection and treatment. However, an effective triage tests needed to decide who among the VIA or HPV positive women should receive further diagnostic evaluation to avoid unnecessary colposcopy referrals is still lacking. Evidence from experimental studies have shown potential usefulness of Squamous Cell Carcinoma Antigen (SCC Ag), Macrophage Colony Stimulating Factor (M-CSF), Vascular Endothelial Growth Factor (VEGF), MicroRNA, p16INKa / ki-67, HPV E6/E7/mRNA, and DNA methylation biomarkers in detecting premalignant cervical neoplasia. Given the variation in performance, and scanty review studies in this field, this systematic review described the diagnostic performance of some selected assays to detect high-grade cervical intraepithelial neoplasia (CIN2+) with histology as gold standard.
Methods
We systematically searched articles published in English between 2012 and 2020 using key words from PubMed/Medline and SCOPUS with two reviewers assessing study eligibility, and risk of bias. We performed a descriptive presentation of the performance of each of the selected assays for the detection of CIN2 + .
Results
Out of 298 citations retrieved, 58 articles were included. Participants with cervical histology yielded CIN2+ proportion range of 13.7–88.4%. The diagnostic performance of the assays to detect CIN2+ was; 1) SCC-Ag: range sensitivity of 78.6–81.2%, specificity 74–100%. 2) M-CSF: sensitivity of 68–87.7%, specificity 64.7–94% 3) VEGF: sensitivity of 56–83.5%, specificity 74.6–96%. 4) MicroRNA: sensitivity of 52.9–67.3%, specificity 76.4–94.4%. 5) p16INKa / ki-67: sensitivity of 50–100%, specificity 39–90.4%. 6) HPV E6/E7/mRNA: sensitivity of 65–100%, specificity 42.7–90.2%, and 7) DNA methylation: sensitivity of 59.7–92.9%, specificity 67–98%.
Conclusion
Overall, the reported test performance and the receiving operating characteristics curves implies that implementation of p16ink4a/ki-67 assay as a triage for HPV positive women to be used at one visit with subsequent cryotherapy treatment is feasible. For the rest of assays, more robust clinical translation studies with larger consecutive cohorts of women participants is recommended.
Healthcare workers play a key role in responding to pandemics like the on-going COVID-19 one. Harmful alcohol use among them could result in inefficiencies in health service delivery. This is ...particularly concerning in sub-Saharan Africa where the health workforce is already constrained. The aim of this study is to document the burden and correlates of harmful alcohol use among healthcare workers at the beginning of the COVID-19 pandemic in Kenya with the aim of informing policy and practice.
This study was a cross-sectional analysis of data obtained from a parent online survey that investigated the burden and factors associated with mental disorders among healthcare workers during the COVID-19 pandemic in Kenya. We analyzed data obtained from a sub-population of 887 participants who completed the Alcohol Use Disorder Identification Test questionnaire. We used descriptive statistics to summarize the socio-demographic characteristics of the participants and multivariate analysis to determine the factors associated with harmful alcohol use.
Three hundred and eighty nine (43.9%) participants reported harmful alcohol use. The factors significantly associated with increased odds of endorsing harmful alcohol use were: being male (AOR = 1.56; 95% CI = 1.14, 2.14;
= 0.006), being unmarried (AOR = 2.06; 95% CI = 1.48, 2.89;
< 0.001), having 11-20 years of experience as compared to having 20+ years of experience (AOR = 1.91; 95% CI = 1.18, 3.12;
= 0.009), and being a specialist (AOR = 2.78; CI = 1.64, 4.78;
= < 0.001) or doctor (AOR = 2.82; 95% CI = 1.74, 4.63;
< 0.001) as compared to being a nurse.
A high proportion of healthcare workers reported harmful alcohol use at the beginning of the COVID-19 pandemic in Kenya. Males, the unmarried, those with 11-20 years of experience in the health field, doctors and specialists, were more likely to report harmful alcohol use. These findings highlight the need to institute interventions for harmful alcohol use targeting these groups of healthcare workers in Kenya during the COVID-19 pandemic in order to optimize functioning of the available workforce.
Over the past few years, a number of studies have revealed that a significant number of men with prostate cancer had genetic defects in the DNA damage repair gene response and mismatch repair genes. ...Certain of these modifications, notably gene alterations known as homologous recombination (HRR) genes;
PALB2
,
CHEK2 BRCA1
,
BRCA2
,
ATM
, and genes for DNA mismatch repair (MMR);
MLH1
,
MSH2
,
MSH6
, and
PMS2
are connected to a higher risk of prostate cancer and more severe types of the disease. The DNA damage repair (DDR) is essential for constructing and diversifying the antigen receptor genes required for T and B cell development. But this DDR imbalance results in stress on DNA replication and transcription, accumulation of mutations, and even cell death, which compromises tissue homeostasis. Due to these impacts of DDR anomalies, tumor immunity may be impacted, which may encourage the growth of tumors, the release of inflammatory cytokines, and aberrant immune reactions. In a similar vein, people who have altered MMR gene may benefit greatly from immunotherapy. Therefore, for these treatments, mutational genetic testing is indicated. Mismatch repair gene (MMR) defects are also more prevalent than previously thought, especially in patients with metastatic disease, high Gleason scores, and diverse histologies. This review summarizes the current information on the mutation spectrum and clinical significance of DDR mechanisms, such as HRR and MMR abnormalities in prostate cancer, and explains how patient management is evolving as a result of this understanding.
Breast cancer incidence and mortality vary significantly among different nations and racial groups. African nations have the highest breast cancer mortality rates in the world, even though the ...incidence rates are below those of many nations. Differences in disease progression suggest that aggressive breast tumors may harbor a unique molecular signature to promote disease progression. However, few studies have investigated the pathology and clinical markers expressed in breast tissue from regional African patient populations.
We collected 68 malignant and 89 non-cancerous samples from Kenyan breast tissue. To characterize the tumors from these patients, we constructed tissue microarrays (TMAs) from these tissues. Sections from these TMAs were stained and analyzed using immunohistochemistry to detect clinical breast cancer markers, including estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor 2 receptor (HER2) status, Ki67, and immune cell markers.
Thirty-three percent of the tumors were triple negative (ER-, PR-, HER2-), 59% were ER+, and almost all tumors analyzed were HER2-. Seven percent of the breast cancer patients were male, and 30% were <40 years old at diagnosis. Cancer tissue had increased immune cell infiltration with recruitment of CD163+ (M2 macrophage), CD25+ (regulatory T lymphocyte), and CD4+ (T helper) cells compared to non-cancer tissue.
We identified clinical biomarkers that may assist in identifying therapy strategies for breast cancer patients in western Kenya. Estrogen receptor status in particular should lead initial treatment strategies in these breast cancer patients. Increased CD25 expression suggests a need for additional treatment strategies designed to overcome immune suppression by CD25+ cells in order to promote the antitumor activity of CD8+ cytotoxic T cells.
Purpose of Review. The aim of this review is to provide a case driven presentation of the presenting features and diagnostic criteria particularly focusing on the management of FPIES. It also ...summarises the natural history and resolution of cow’s milk induced FPIES. Data Sources. OvidSP Database was used to search for literature using the keywords food protein-induced enterocolitis and FPIES. Recent Findings. The diagnosis of FPIES is often delayed following two or more presentations. Symptoms in the acute form include profuse vomiting usually 2–6 hours following ingestion of food. Vomiting may or may not be accompanied by diarrhoea. Management involves removing the causal food protein from diet. There is some concomitance in cow’s milk and soya induced FPIES. Hence extensively hydrolysed formula is the milk of choice unless breast-feeding is carried out in which case that should be continued. Summary. FPIES is a complex form of non-IgE mediated food allergy. More awareness and knowledge of the condition are required to prevent misdiagnosis. Early diagnosis and removal of the culprit food protein improve the outcome. Good nutritional advice and clear management plans are important. More multicentre studies are required to reevaluate and produce consistent oral food challenge criteria and guidelines.
Chronic inflammation has been associated with dysglycemia among people living with HIV (PLHIV). There is however, limited data regarding this phenomenon in sub-Sahara Africa (SSA). Therefore we ...assessed the levels of C-reactive protein (CRP) and Interleukin 6 (IL-6) on a cohort of PLHIV and its associations with dysglycemia in Tanzania.
We conducted a cross-sectional study at the Infectious Disease Clinic (IDC) in Tanzania from March to May 2018. Purposive sampling was used to identify participants who had an undetectable viral load, were on 1st line anti-retroviral therapy (ART) and had an overnight fast. The WHO stepwise approach for non-communicable disease (NCD) surveillance was used to collect data. Fasting blood glucose and blood glucose after 75 g oral glucose load was measured, and Enzyme-linked immunosorbent assay (ELISA) was used to test for inflammatory markers (IL-6 and CRP). Associations were explored using the Chi square test and binary logistic regression was performed to estimate the odds ratios. A p-value less than 0.05 was considered statistically significant.
A total of 240 participants were enrolled. Forty two percent were overweight/obese (> 25 kg/m
), 89% had a high waist to height ratio. The median ART duration was 8(5-10) years. The prevalence of dysglycemia among our cohort of PLHIV was 32%. High CRP was associated with a 2.05 increased odds of having dysglycemia OR 2.05 (1.15-3.65) (p = 0.01). Taking stavudine was associated with a 1.99 odds of having dysglycemia OR 1.99 (1.04-3.82) (p = 0.03).We did not find a significant association between IL-6 and dysglycemia.
High CRP and taking stavudine were significantly associated with dysglycemia among PLHIV with undetectable viral load.
Burkitt's lymphoma (BL) is a common aggressive non-Hodgkin's lymphoma in East and Central Africa among children. Persistent infections with Epstein Barr virus or Plasmodium falciparum are associated ...with immune hyperstimulation. It is hypothesised that inadvertent cytokine responses to infections indirectly or directly influence B cell neoplastic transformation through c-myelocytomatosis (c-myc) gene translocation. We sought to describe cytokines in children and adolescents with BL. Participants were recruited from western Kenya with parental consent, diagnosis confirmed using histology and consensus panel of immunohistochemistry antibodies. T helper1/2/17A and transforming growth factor-β1 (TGF-β1) cytokines were estimated using cytometric bead array in plasma. Complete blood counts (CBC) were determined by Beckman Coulter
.
Out of 104 enrolled participants, 32% were confirmed BL and 68% grouped as non-BL. Mean (pg/ml) levels of cytokines in BL and non-BL were: interleukin (IL)-6 100.3 and 39.4 p = 0.152; IL-10 11.5 and 12.5 p = 0.363; IL-17A 17.8 and 64.9 p = 0.094 respectively. Expressions of interferon-γ, IL-2 and tumour necrosis factor-α were low and TGF-β1 undetectable in both groups. Mean CBC differed between the two groups before and after chemotherapy, WBC being significantly so. Interleukin-6, IL-17A and IL-10 responses to infections in the study area may be associated with pathogenesis and be potential therapeutic targets.
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