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Medicinal plants are known to possess pharmacologically active compounds which have therapeutic properties and number of plants have been evaluated in disease management including venomous bites. Products of plant extracts are thus gaining importance because of their easy availability, low cost and less side effects and are evaluated for their antidote potential against Indian cobra (Naja naja) venom enzymes. In vitro enzyme inhibitions such as anti-proteolytic, anti-phospholipase, anti-hyaluronidase, anti-acetylcholine esterase and pharmacological studies (anti- hemolytic activity and anti-fibrinogenolytic activity) were evaluated for aqueous ethanolic extracts and organic extracts of Clerodendrum serratum, Azadirachta indica, Aegle marmelos, Aristolochia indica, Citrus limon, Calotropis gigantea, Cryptolepis buchanani and Butea monosperma on N. naja venom. Significant inhibitions were observed by both the extracts. However, it is interesting to note that aqueous extracts significantly inhibited phospholipase activity and organic extracts inhibited fibrinogenolytic activity of venom. The hyaluronidase activity was not observed in the venom. Indirect hemolytic assay revealed the potential of Butea monosperma extracts to completely neutralize the lysis of red blood cells (RBC) induced by cobra venom. The isolation of bioactive principles or a combination of these active principles, from the tested medicinal plants for ex vivo and in vivo anti-venom activity has to be validated by active isolated compound from extract which is responsible for neutralizing toxic snake venom enzymes. [ABSTRACT FROM AUTHOR]

Background: Accurate estimation of the burden of cancer in developing countries is a major public health concern for cancer prevention and control because of the limited coverage of population-based cancer registries (PBCRs). The cancer registration coverage status of Uganda was 11.90% and was not uniformly distributed in all regions of Uganda. This population-based survey was conducted to assess the burden of cancer in all the sub-regions of Uganda by site, sex and age group to accurately determine the cancer profile of Uganda by sub-region for a tailored intervention to mitigate cancer risk factors and burden., Methods: This study used existing administrative units of Uganda from which 55 districts emerged, forming 10 sub-regions as satellite population-based cancer registry study sites. Data on newly diagnosed cancer cases were retrospectively collected for the period 2017-2020 using a cancer notification form, entered into CanReg5 Software, exported to spreadsheets and univariate analysis was performed to determine the cancer spectrum, their proportions and crude rates by site, sex, age group and geographical location., Results: A total of 25,576 cancer cases were registered, up to 14,322 (56%) were in females and, male cancers were 11,254 (44%). The top five female cancers in all the sub-regions included cervical cancer (43%, n = 6,190), breast (22%, n = 3,200), esophagus (5.6%, n = 800), ovary (5.2%, n = 746), Kaposi Sarcoma (KS) (4.7%, n = 666) and other less common cancers (18.5%, n = 2,720). In males, the top five cancers included prostate cancer 25.1 % ( n = 2,820), esophagus 15.1% ( n = 1,704), KS 12.4% ( n = 1,395), liver 8.8% ( n = 989) and stomach 4.8% ( n = 539), with other less common male cancers accounting for 33.8% ( n = 3,807).In all the sub-regions of Uganda, cancers of the esophagus, liver and KS are common in both males and females, but the number of males with these cancers is twice that of their female counterparts. In Rwenzori, Kigezi and Bugishu sub-Regions, there seems to be an increased risk of developing other skin cancers in females, while stomach cancers have been reported in both males and females. Most of the other sub-regions register emerging cases of only ovarian cancer in females. In children, the top three cancers included lymphoma, 33.9% ( n = 653); soft tissue sarcomas, 20.8% ( n = 400); malignant bone tumors, 15.8% ( n = 305); myeloid-type leukemia, 13.8% ( n = 265); and the other less common childhood cancers combined, 15.7% ( n = 303). The proportion of childhood cancers is higher in the male child compared to the female at a ratio of 1.3:1., Conclusions: The sub-regional cancer spectrum in Uganda ranges from cervical cancer to breast, esophageal, ovarian and KS in females. Male cancers include prostate, esophageal, KS, liver and stomach cancers. Although the cancer profile is similar in most sub-regions of Uganda, except Ankole subregions with mountainous topography (Rwenzori, Kigezi, Bugisu), there has been significant variation in cancer profile, especially for males, where Non-Hodgkins Lymphomas is one of the cancers reported for Uganda by PBCRs in Gulu, and Kampala has been replaced by stomach cancers as one of the common male cancers in the sub-regions. These findings emphasize the need for the establishment and support of additional regional PBCRs and periodic population-based cancer surveys to accurately determine the burden of cancer, inform the establishment of regional cancer centers and guide national and sub-national cancer control programs in Uganda. Cancer surveillance systems using PBCRs should be part of the national cancer control program. Periodic population-based cancer surveys should also be conducted as part of Uganda's demographic and health surveys in areas without PBCRs to inform the country comprehensively and accurately on the cancer burden to design robust cancer mitigation measures., Competing Interests: The authors declare no competing interests., (© the authors; licensee ecancermedicalscience.)

Biomarkers including Forkhead/winged-helix transcription factor box P3 have been proposed in immunohistochemical techniques to diagnose cervical lesions, but can be objectively quantified and measured in blood using methods that can be standardised. In this study we quantified the serum FOXP3 concentrations and assessed their association with cervical lesions at the cervical cancer clinic of Mbarara Regional Hospital (MRRH) Southwestern Uganda. We performed secondary analysis on archived serum samples from a previous unmatched case control study in which we recruited 90 cervical cancer (CC) cases, 90 cervical intraepithelial neoplasia (CIN) cases before any form of treatment and 90 controls. Clinical and demographic data were recorded. We measured FOXP3 concentrations using quantitative ELISA. We performed descriptive statistics and logistic regression in STATA 17 and took P-values of < 0.05 as statistically significant. The mean concentration of FOXP3 was higher in serum samples from CC cases compared with CIN cases and controls, and this difference was statistically significant (P value < 0.001). More than half (52/90,58 %) of serum samples from CC cases had FOXP3 concentrations greater than 0.0545 ng/ml (P value < 0.001). Increase serum FOXP3 expression was not associated with CIN. Increase in serum FOXP3 concentrations were observed to increase the chances of CC by 2 times (OR: 2.094, P value 0.038, 95 % CI: 1.042---4.209). Serum FOXP3 is likely associated with cervical lesions especially CC in our study population. Serum FOXP3 testing may be useful in resource limited settings to aid detection of such lesions given the challenges associated with cytology and VIA. We recommend diagnostic utility studies for circulating FOXP3 as a biomarker for detection of cervical cancer., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Introduction: There is a wide range of clinical manifestations in sickle cell disease (SCD). Despite having the same condition, each person's response to disease complications differs greatly. Individuals can be categorized according to the severity of their diseases to determine which group they fall into and receive the appropriate care based on their needs. The relationship between fetal hemoglobin (HbF), lactate dehydrogenase (LDH), and disease severity in Tanzania is little understood. This investigation sought to ascertain the relationship between HbF, LDH, and disease severity in SCD patients at the Bugando Medical Center., Method: This cross-sectional study was carried out on SCD patients aged 6 months and older at the Bugando Medical Center in Mwanza, Tanzania. A total of 130 SCD patients were enrolled. The clinical history and laboratory test results for SCD patients were recorded on a specially constructed patient report form., Results: The majority of participants (56.9%) were men. For the population under study, more than half (60.8%) of participants had a moderate clinical phenotype (MCP), followed by 31.5% of asymptomatic participants and 7.7% of people with severe clinical phenotypes (SCP). Participants with SCP had substantially higher levels of LDH, with a mean level of 810.97IU/L (95% CI: 559.31-1062.64) and a p-value of 0.005. The severe clinical phenotype exhibited a significantly higher mean HbF score value of 10.09% (95% CI: 7.44-13.74%) with a p-value of 0.024 when compared to the asymptomatic and moderate clinical phenotypes., Conclusion: In SCD patients with SCP compared to ACP and MCP, the HbF levels were higher, but did not show a protective effects, and LDH can be used to predict the severity of SCD., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Kahema et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Studies suggest a need for new diagnostic approaches for cervical cancer including microRNA technology. In this review, we assessed the diagnostic accuracy of microRNAs in detecting cervical cancer and Cervical Intraepithelial Neoplasia (CIN). We performed a systematic review following the Preferred Reporting Items for Systematic Review and Meta-Analysis guideline for protocols (PRISMA-P). We searched for all articles in online databases and grey literature from 01st January 2012 to 16th August 2022. We used the quality assessment of diagnostic accuracy studies tool (QUADAS-2) to assess the risk of bias of included studies and then conducted a Random Effects Meta-analysis. We identified 297 articles and eventually extracted data from 24 studies. Serum/plasma concentration miR-205, miR-21, miR-192, and miR-9 showed highest diagnostic accuracy (AUC of 0.750, 0.689, 0.980, and 0.900, respectively) for detecting CIN from healthy controls. MicroRNA panels (miR-21, miR-125b and miR-370) and (miR-9, miR-10a, miR-20a and miR-196a and miR-16-2) had AUC values of 0.897 and 0.886 respectively for detecting CIN from healthy controls. For detection of cervical cancer from healthy controls, the most promising microRNAs were miR-21, miR-205, miR-192 and miR-9 (AUC values of 0.723, 0.960, 1.00, and 0.99 respectively). We report higher diagnostic accuracy of upregulated microRNAs, especially miR-205, miR-9, miR-192, and miR-21. This highlights their potential as stand-alone screening or diagnostic tests, either with others, in a new algorithm, or together with other biomarkers for purposes of detecting cervical lesions. Future studies could standardize quantification methods, and also study microRNAs in higher prevalence populations like in sub-Saharan Africa and South Asia. Our review protocol was registered in PROSPERO (CRD42022313275)., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.We, the authors declare that we do not have any competing interests., (© 2024 The Author(s).)

Purpose: Cervical cancer screening is vital in addressing the global burden of cervical cancer. In this study, we describe the coverage and socioeconomic inequalities in the coverage of cervical cancer screening in low- and middle-income countries (LMICs)., Methods: We analyzed data from the women's recode files of the Demographic and Health Surveys conducted in LMICs from 2010 to 2019 with variables on cervical cancer screening. We included women 21 years or older and determined the proportion of women who were screened for cervical cancer by age categories, wealth quintile, type of place of residence, level of education, and marital status. Socioeconomic inequality was measured using the concentration index (CIX) and the slope index of inequality (SII)., Results: A total of 269,506 women from 20 surveys in 16 countries were included in the survey. Generally, there was a low coverage of screening, with lower rates among women age 21-24 years, living in rural areas, in the poorest wealth quintile, with no formal education, and who have never been in union with or lived with a man. The CIX and SII values for screening for cervical cancer were positive (pro-rich) for all the countries except Tajikistan in 2012 where they were negative (pro-poor)., Conclusion: The coverage of cervical cancer screening was low in LMICs with variations by the quintile of wealth (pro-rich) and type of place of residence (pro-urban). To achieve the desired impact of cervical cancer screening services in LMICs, the coverage of cervical cancer screening programs must include women irrespective of the type of place and wealth quintiles.

Introduction: There are high incidence and mortality rates of cervical cancer among females in East Africa. This is exacerbated by limited up-to-date data on premalignant lesions and associated factors in this setting. In this study, we determined the prevalence of cervical intraepithelial lesions and associated factors among women attending the Mbarara Regional Referral Hospital cervical cancer clinic in Southwestern Uganda., Methods: In this cross-sectional study, 364 participants were recruited from among women attending the Mbarara Regional Referral Hospital cervical cancer clinic from 1 April to 30 June 2023. On consent, the study nurse collected demographic data and Pap smears, which were microscopically examined and reported by a laboratory scientist and a pathologist following the Bethesda grading system (2014). Statistical analyses were done in STATA version 17, using proportions, Chi-square, bivariate, and multivariate logistic regression analysis to determine associated factors at ⩽0.05 significance level., Results: The mean age of participants was 41.9 years. A third of all study participants (37.6%, 132/351) were contraceptive users, mostly hormonal contraceptives (87.1%, 115/132). Almost 88% (307/351) had an unknown Human Papilloma Virus status. The prevalence of cervical intraepithelial lesions among our study participants was 6.6% (23/351), of which 73.9% (17/23) were low-grade squamous intraepithelial lesions. More than half (9/17, 52.9%) of low-grade squamous intraepithelial lesions were active hormonal contraceptive users. Use of hormonal contraceptives (OR: 3.032, p : 0.0253), use of intrauterine devices (OR: 6.284, p : 0.039), and any family history of cervical cancer (OR: 4.144, p : 0.049) were significantly associated with cervical intraepithelial lesions., Conclusion: The prevalence of cervical intraepithelial lesions was 6.6%, lower than global estimates. Use of hormonal and intrauterine device contraceptives, as well as family history of cervical cancer, were significantly associated with cervical intraepithelial lesions among our study population. Prospective studies are recommended to further understand associations between different types of intrauterine devices and hormonal contraceptives, and cervical lesions., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Introduction: Tissue expression of P16ink4A is correlated with cervical lesions. In this study we determined the association between serum P16ink4A concentrations and cervical lesions among women attending the cervical cancer clinic at Mbarara Regional Hospital (MRRH) South Western Uganda., Material and Methods: We recruited 90 cervical intraepithelial neoplasia (CIN) cases, 90 cervical cancer (CC) cases before treatment and 90 controls. Clinical and demographic data were recorded. Serum P16ink4A concentrations were measured by quantitative Elisa. Cases were confirmed with cytology and/or histology. Descriptive statistics and logistic regression were done with STATA 17 and P-values of <0.05 were considered statistically significant., Results: The mean serum P16ink4A concentration among CIN cases, CC cases and controls was 1.11(+/-0.66) ng/ml, 1.45(+/-1.11) ng/ml and 1.13(+/-0.61) ng/ml respectively (p = 0.008). 50 % of CIN cases and controls as well as 60 % of CC cases had P16ink4A concentration above 0.946 ng/ml. There were increased odds of CIN for serum P16ink4A though statistically insignificant (AOR: 1.11, p-value: 0.70). There was also a statistically significant reduction in odds of CC for serum P16ink4A (AOR: 0.55, p-value: 0.01)., Conclusion: Serum P16ink4A may likely be associated with cervical lesions especially CC in our study population and this may aid detection of such lesions. Diagnostic utility studies for circulating P16ink4A in detection of cervical cancer are recommended., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)

Background: In Sub-Saharan Africa, the prevalence of dyslipidemia is on the rise, with studies showing dyslipidemia as a contributing factor to the progression of premalignant lesions to cervical cancer. In Uganda, cervical cancer and dyslipidemia are common health concerns, considering the increasing trends of dyslipidemia in the general population and inadequate information regarding dyslipidemia and cervical lesions. This study aimed to determine the prevalence of dyslipidemia and its association with precancerous and cancerous lesions of the cervix among women attending a cervical cancer clinic at the Uganda Cancer Institute., Methods: This cross-sectional study was conducted from February to April 2022 among women with premalignant and malignant lesions of the cervix. Data on social demographics and health-seeking behaviours were collected using a pretested structured questionnaire after written informed consent had been obtained. Pap smear collection preceded visual inspection with acetic acid; cervical biopsies were collected appropriately from eligible participants; and cervical lesions were classified using the Bethesda system 2014. Serum lipids, total cholesterol (T.C.), high-density lipoprotein (HDLc), low-density lipoprotein (LDLc), and triglycerides (T.G.s) were analysed using the COBAS™ 6000 Clinical Chemistry Analyser. The associations were assessed using the chi-square test, and P ≤ 0.05 was considered statistically significant., Results: The overall prevalence of dyslipidemia among women with cervical lesions was 118/159 (74%), and low HDLc was the most prevalent at 64.6% (95% CI 39.0-54.3). High T.C. (P = 0.05), high T.G.s (P = 0.011), and low HDL-c (P = 0.05) showed a significant association with precancerous lesions. High LDL-c (P = 0.019), high T.G.s (P = 0.02), and high T.G.s (P < 0.001) showed a statistically significant association with cancerous lesions., Conclusion: The prevalence of dyslipidemia was high, with high TC, T.G.s, and low HDL-c significantly associated with precancerous lesions. Also, elevated T.G.s and high LDLc were significantly associated with cancerous lesions. Women may benefit from dyslipidemia screening along with cervical cancer screening., What This Study Adds: The present study builds upon previous findings suggesting a link between dyslipidemia and cervical lesions by investigating the relationship between these two factors, specifically in women of this geographical location, where we need adequate information on these associations., (© 2024. The Author(s).)

Background: In the East African region, herbal plants are essential in the treatment and control of cancer. Given the diverse ecological and cultural makeup of the regional states, it is likely that different ethnic groups will use the same or different plants for the same or different diseases. However, since 2019, this has not been compiled into a single study., Purpose: The study aimed to compile and record the medicinal plants utilized in East Africa from April 2019 to June 2023 to treat various cancer types., Materials and Methods: The study examined 13 original studies that included ethnobotanical research conducted in East Africa. They were retrieved from several internet databases, including Google Scholar, Scopus, PubMed/Medline, Science Direct, and Research for Life. The study retrieved databases on plant families and species, plant parts used, preparation methods and routes of administration, and the country where the ethnobotanical field surveys were conducted. Graphs were produced using the GraphPad Prism 8.125 program (GraphPad Software, Inc., San Diego, CA). Tables and figures were used to present the data, which had been condensed into percentages and frequencies., Results: A total of 105 different plant species from 45 different plant families were identified, including Asteraceae (14), Euphorbiaceae (12), Musaceae (8), and Apocynaceae (7). Uganda registered the highest proportion (46% of the medicinal plants used). The most commonly mentioned medicinal plant species in cancer management was Prunus africana . Herbs (32%), trees and shrubs (28%), and leaves (45%) constituted the majority of herbal remedies. Most herbal remedies were prepared by boiling (decoction) and taken orally (57%)., Conclusion: East Africa is home to a wide variety of medicinal plant species that local populations and herbalists, or TMP, frequently use in the treatment of various types of cancer. The most frequently used families are Asteraceae and Euphorbiaceae, with the majority of species being found in Uganda. The most frequently utilized plant species is Prunus africana . Studies on the effectiveness of Prunus africana against other malignancies besides prostate cancer are required., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: There is increasing number of patients undergoing hemodialysis globally. Patients on hemodialysis experience physical and emotional stress due to the changes brought by chronic kidney disease., Aim: The study aimed at exploring the lived experiences of patients on hemodialysis treatment in Kiruddu National Referral Hospital., Methods: The study employed a phenomenological design. Data was collected using audio tape recording of the interview from 9 participants selected through purposive sampling at Kiruddu National Referral Hospital. The thematic aspects of the lived experience were uncovered using Van Manen data analysis which included three approaches: the detailed or line-by-line approach, selective or highlighting approach and holistic approach., Results: Six themes emerged during the analysis as hemodialysis prolongs survival; hemodialysis is indispensable, family financial support, physical limitations, emotional distress and adaptation., Conclusion: It was concluded from the findings that the patients undergoing haemodialysis are facing a wide range of problems such as physical and emotional problems during the course of their treatment and think that haemodialysis is the only way of survival, and these problems need to be addressed. Understanding gained in this study can help nurses to utilize this information in improving the quality of nursing care and guide patients to provide positive reinforcement for their future living., Competing Interests: The authors report no conflicts of interest in this work., (© 2023 Ogwang et al.)

Background: In Uganda, medicinal plants have been utilized to treat a variety of ailments, including cancer. However, there is little information available about the medicinal plants used to treat cancer in the Elgon subregion. As a result, the current study documented the plant species used in the management of cancer in the Elgon sub-region., Methods: Data were gathered by observation, self-administered questionnaires, interview guides, and guided field trips. Analyzing descriptive statistics and creating graphs were done using SPSS (version 21.0) and GraphPad Prism® version 9.0.0, respectively. Well-established formulae were used to calculate quantitative indices. The narratives were interpreted using major theories and hypotheses in ethnobotany., Results: A total of 50 plant species from 36 families were documented, and herbal knowledge was mainly acquired through inheritance. Fabaceae and Asteraceae comprised more plant species used in herbal preparation. Most plants were collected from forest reserves (63%); herbal therapies were made from herbs (45%); and leaves were primarily decocted (43%). The most frequently used plants were Tylosema fassoglensis, Hydnora abyssinica, Azidarachata indica, Prunus Africana, Kigelia africana, Syzygium cumini, Hydnora africana, Rhoicissus tridentata, Albizia coriaria, and Plectranthus cuanneus. All the most commonly used plants exhibited a high preference ranking (60-86%) and reliability level (74.1-93.9%). Generally, the ICF for all the cancers treated by medicinal plants was close to 1 (0.84-0.95)., Conclusions: The ten most commonly utilized plants were favored, dependable, and most important for treating all known cancers. As a result, more investigation is required to determine their phytochemistry, toxicity, and effectiveness in both in vivo and in vitro studies. This could be a cornerstone for the pharmaceutical sector to develop new anticancer medications., (© 2023. The Author(s).)

Every novel infection requires an assessment of the host response coupled with identification of unique biomarkers for predicting disease pathogenesis, treatment targets and diagnostic utility. Studies have exposed dysregulated inflammatory response induced by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as significant predictor or cause of disease severity/prognosis and death. This study evaluated inflammatory biomarkers induced by SARS-CoV-2 in plasma of patients with varying disease phenotypes and healthy controls with prognostic or therapeutic potential. We stratified SARS-CoV-2 plasma samples based on disease status (asymptomatic, mild, severe, and healthy controls), as diagnosed by RT-PCR SARS-CoV-2. We used a solid phase sandwich and competitive Enzyme-Linked Immunosorbent Assay (ELISA) to measure levels of panels of immunological (IFN-γ, TNF-α, IL-6, and IL-10) and biochemical markers (Ferritin, Procalcitonin, C-Reactive Protein, Angiotensin II, Homocysteine, and D-dimer). Biomarker levels were compared across SARS-CoV-2 disease stratification. Plasma IFN-γ, TNF-α, IL-6, and IL-10 levels were significantly (P < 0.05) elevated in the severe SARS-CoV-2 patients as compared to mild, asymptomatic, and healthy controls. Ferritin, Homocysteine, and D-dimer plasma levels were significantly elevated in severe cases over asymptomatic and healthy controls. Plasma C-reactive protein and Angiotensin II levels were significantly (P < 0.05) higher in mild than severe cases and healthy controls. Plasma Procalcitonin levels were significantly higher in asymptomatic than in mild, severe cases and healthy controls. Our study demonstrates the role of host inflammatory biomarkers in modulating the pathogenesis of COVID-19. The study proposes a number of potential biomarkers that could be explored as SARS-CoV-2 treatment targets and possible prognostic predictors for a severe outcome. The comprehensive analysis of prognostic biomarkers may contribute to the evidence-based management of COVID-19 patients., (© 2023. The Author(s).)

Background: The coronavirus 2019 (COVID-19) pandemic has caused disruptions in the delivery and utilisation of cancer services. The impact of these interruptions is disproportionately borne by low- and middle-income countries in Sub-Saharan Africa (SSA). There are speculations of increased late-stage presentation and mortality as services are returning to the pre-pandemic state. This review aims to explore the extent to which the COVID-19 pandemic impacted cancer services across SSA and to identify innovations implemented across SSA to mitigate the impacts., Methods: Using database-specific search strategies, a systematic literature search was conducted in PubMed, Ovid (MedLine), Web of Science, and African Index Medicus. Eligible studies included original research, reports, perspectives and summaries of national or regional outcomes published in the English language. The primary outcome was changes in the delivery and utilisation of cancer prevention and screening, diagnosis, treatment and follow-up services. The secondary outcome was to identify implemented innovations to mitigate the impact of the pandemic on service delivery., Results: Out of the 167 articles identified in the literature search, 46 were included in the synthesis. A majority (95.7%) of the included articles described suspension and/or delay of screening, diagnosis, and treatment services, although two studies (4.3%) described the continuation of services despite the lockdown. Care was additionally impacted by transportation limitations, shortages of staff and personal protective equipment, disruption of the medication supply chain and patients' fears and stigma associated with contracting COVID-19. A major innovation was the use of telemedicine and virtual platforms for patient consultation and follow-up during the pandemic in SSA. Furthermore, drones and mobile applications were used for sample collection, medication delivery and scheduling of treatment. In some instances, medication routes and treatment protocols were changed., Conclusions: The delivery and utilisation of cancer services decreased substantially during the pandemic. Cancer centres initiated innovative methods of care delivery, including telehealth and drone use, with long-term potential to mitigate the impact of the pandemic on service delivery. Cancer centres in SSA must explore sustainable, facility or country-specific innovations as services return to the pre-pandemic state., Registration: The review was registered in PROSPERO with registration number CRD42022351455., Competing Interests: Disclosure of interest: The authors completed the ICMJE Disclosure of Interest Form (available upon request from the corresponding author) and declare that KMB receives grants from the cancer centre at the Medical College of Wisconsin., (Copyright © 2023 by the Journal of Global Health. All rights reserved.)

The 4th Uganda Conference on Cancer and Palliative Care was held from the 14 th -15 th September 2023. It was run jointly by the Uganda Cancer Institute and the Palliative Care Association of Uganda, in collaboration with the Ministry of Health. The conference was held at the Speke Resort, Munyonyo and 450 participants came together for a face-to-face conference following the virtual one held in 2021. It was an opportunity for all those working in the fields of cancer and palliative care to come together, to share lessons and learn from each other, as well as celebrate 30 years since specialist palliative care came to Uganda. The conference was officially opened by the Commissioner for Non-Communicable Diseases on behalf of the Minister of Health, who reiterated the Government's commitment to reducing the burden of cancer and expanding the provision of palliative care within Uganda. Dr Tedros Adhanom Ghebresus, the Director General of the World Health Organization welcomed participants to the conference, and the Assistant Bishop of Kampala Diocese, the Right Reverend Hannington Mutebi shared his experience of living with cancer. The conference was organised into six tracks: Innovations and new technologies; Education, advocacy, policy and law; Health promotion, prevention and early detection; Family and community involvement and empowerment; Clinical care and symptom management; and, Psychological, social and spiritual care . The themes of paediatrics, vulnerable populations, service development and research were integrated throughout the tracks, and workshops were held that explored topics such as governance, access to essential medicines, national data reporting, research and education, and aging and ageism. Throughout the conference there was a sense of optimism, of resilience and a commitment to the ongoing development of cancer and palliative care services within the country., Competing Interests: The authors declare that they have no conflict of interest., (© the authors; licensee ecancermedicalscience.)

Objective: To compare cytogenetic abnormalities among people living with HIV (PLWH) with and without previous exposure to Mycobacterium tuberculosis (Mtb) (both latent tuberculosis infection [LTBI] and active tuberculosis [TB])., Methods: Adult PLWH (≥18 years) were randomly selected at three HIV clinics in Uganda. Previous active TB was confirmed in the clinics' TB records. LTBI was defined as a positive QuantiFERON-TB Gold Plus assay. Participants' buccal mucosal exfoliated cells were examined (per 2000 cells) using the buccal micronucleus assay for chromosomal aberrations (micronuclei and/or nuclear buds), cytokinetic defects (binucleated cells), proliferative potential (normal differentiated cells and basal cell frequency) and/or cell death (condensed chromatin, karyorrhexis, pyknotic and karyolytic cells)., Results: Among 97 PLWH, 42 (43.3%) had exposure to Mtb;16 had previous successfully treated active TB and 26 had LTBI. PLWH with exposure to Mtb had a higher median number of normal differentiated cells (1806.5 [1757.0 - 1842.0] vs. 1784.0 [1732.0 - 1843.0], p = 0.031) and fewer karyorrhectic cells (12.0 [9.0 - 29.0] vs. 18.0 [11.0 - 30.0], p = 0.048) than those without. PLWH with LTBI had fewer karyorrhectic cells than those without (11.5 [8.0 - 29.0] vs. 18.0 [11 - 30], p = 0.006)., Conclusion: We hypothesized that previous exposure to Mtb is associated with cytogenetic damage among PLWH. We found that exposure to Mtb is associated with more normal differentiated cells and less frequent karyorrhexis (a feature of apoptosis). It is unclear whether this increases the propensity for tumorigenesis., Competing Interests: Declaration of Competing Interest The authors declare no relevant conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Purpose: To better understand the barriers to accessing standard-of-care radiation therapy (RT) for breast and cervical cancer in sub-Saharan Africa and their impact on outcomes., Methods: A comprehensive literature search was completed with a medical librarian. Articles were screened by title, abstract, and full text. Included publications were analyzed for data describing barriers to RT access, available technology, and disease-related outcomes, and further grouped into subcategories and graded according to predefined criteria., Results: A total of 96 articles were included: 37 discussed breast cancer, 51 discussed cervical cancer, and eight discussed both. Financial access was affected by health care system payment models and combined burdens of treatment-related costs and lost wages. Staffing and technology shortages limit the ability to expand service locations and/or increase capacity within existing centers. Patient factors including use of traditional healers, fear of stigma, and low health literacy decrease the likelihood of early presentation and completion of therapies. Survival outcomes are worse than most high- and middle-income countries and are affected by many factors. Side effects are similar to other regions, but these findings are limited by poor documentation capabilities. Access to palliative RT is more expeditious than definitive management. RT was noted to lead to feelings of burden, lower self-esteem, and worsened quality of life., Conclusion: Sub-Saharan Africa represents a diverse region with barriers to RT that differ on the basis of funding, available technology and staff, and community populations. Although long-term solutions must focus on building capacity by increasing the number of treatment machines and providers, short-term improvements should be implemented, such as interim housing for traveling patients, increased community education to reduce late-stage diagnoses, and use of virtual visits to avoid travel.

Background: Cervical cancer remains a public health problem worldwide, especially in sub-Saharan Africa. There are challenges in timely screening and diagnosis for early detection and intervention. Therefore, studies on cervical cancer and cervical intraepithelial neoplasia suggest the need for new diagnostic approaches including microRNA technology. Plasma/serum levels of microRNAs are elevated or reduced compared to the normal state and their diagnostic accuracy for detection of cervical neoplasms has not been rigorously assessed more so in low-resource settings such as Uganda. The aim of this systematic review was therefore to assess the diagnostic accuracy of serum microRNAs in detecting cervical cancer., Methods: We will perform a systematic review following the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) statement. We will search for all articles in MEDLINE/PubMed, Web of Science, Embase, and CINAHL, as well as grey literature from 2012 to 2022. Our outcomes will be sensitivity, specificity, negative predictive values, positive predictive values or area under the curve (Nagamitsu et al, Mol Clin Oncol 5:189-94, 2016) for each microRNA or microRNA panel. We will use the quality assessment of diagnostic accuracy studies (Whiting et al, Ann Intern Med 155:529-36, 2011) tool to assess the risk of bias of included studies. Our results will be reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis for Diagnostic Test Accuracy studies (PRISMA-DTA). We will summarise studies in a flow chart and then describe them using a structured narrative synthesis. If possible, we shall use the Lehmann model bivariate approach for the meta analysis USE OF THE REVIEW RESULTS: This systematic review will provide information on the relevance of microRNAs in cervical cancer. This information will help policy makers, planners and researchers in determining which particular microRNAs could be employed to screen or diagnose cancer of the cervix., Systematic Review Registration: This protocol has been registered in PROSPERO under registration number CRD42022313275., (© 2023. The Author(s).)

Introduction: Prostate cancer screening is a valuable public health tool in the early detection of prostate cancer. In this study, we aimed to determine the socioeconomic inequalities in the coverage of prostate cancer screening in Low and Middle-Income Countries (LMICs)., Methods: This was a retrospective analysis of men's recode data files that were collected by the Demographic and Health Surveys (DHS) in LMICs (Armenia, Colombia, Honduras, Kenya, Namibia, Dominican Republic, and the Philippines). We included surveys that were conducted from 2010 to 2020 and measured the coverage of prostate cancer screening and the study population was men aged 40 years or older. Socioeconomic inequality was measured using the Concertation Index (CIX) and the Slope Index of Inequality (SII)., Results: Eight surveys from seven countries were included in the study with a total of 47,863 men. The coverage of prostate cancer screening was below 50% in all the countries with lower rates in the rural areas compared to the urban areas. The pooled estimate for the coverage of screening was 10.4% [95% CI, 7.9-12.9%). Inequalities in the coverage of prostate cancer screening between the wealth quintiles were observed in the Democratic Republic, Honduras, and Namibia. Great variation in inequalities in the coverage of prostate cancer screening between rural and urban residents was observed in Colombia and Namibia., Conclusion: The coverage of prostate cancer screening was low in LMICs with variations in the coverage by the quintile of wealth (pro-rich) and type of place of residence (pro-urban)., Policy Summary: To achieve the desired impact of prostate cancer screening services in LMICs, it is important that the coverage of screening programs targets men living in rural areas and those in low wealth quintiles., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Youth living with HIV (YLWHIV) have an increased cancer risk. Our objective is to describe the prevalence of medical record (MR) reported suspected cancers in a contemporary cohort of YLWHIV in Uganda that was assembled through MR reviews of patients 10 to 24 years old across 35 Ugandan HIV care health facilities. Clinical data were abstracted to identify suspected cancer cases and information about HIV care. Among 3728 YLWHIV, we identified eight suspected cancer cases. The most common suspected types were Kaposi sarcoma (n=4) followed by lymphoma (n=3). Challenges encountered in data abstraction were missing data for several variables and confirmatory cancer diagnostic information. In follow-up of suspected cases referred for diagnosis at the Uganda Cancer Institute (UCI), none had diagnosis records in UCI files. In addition, ∼18% of patients (n=686) were lost-to-follow-up (LTF) defined as not having returned to the clinic in ≥183 days and three patients died from presumed Kaposi sarcoma. Although our results suggest that cancer is rare in YLWHIV, the possibility that the cancer burden is higher cannot be excluded due to incomplete information in MRs and high LTF rates. Further, our study raises concern that patients referred for diagnosis are not accessing potential life-saving care.

Introduction: Programmed death 1 (PD-1)/programmed death-ligand 1 (PD-L1)-targeted immunotherapies have become a new mode of treatment for several tumours; however, there is limited evidence on the expression and prognostic value of PD-1/PD-L1 in prostate cancer, especially in African men., Methods: Plasma concentrations of PD-L1/PD-1 were assessed using enzyme-linked immunosorbent assay in patients with prostate cancer and normal healthy controls at the Uganda Cancer Institute. The associations between plasma PD-L1/PD-1 concentration levels and serum prostate-specific antigen (PSA) levels, Gleason scores, age, and body mass index (BMI) were determined., Results: We found significant differences in the median plasma concentrations of PD-L1 and PD-1 immune checkpoint molecules between prostate cancer cases and normal healthy controls of 0.285 vs 0.035 (p = 0.001) and 0.596 vs 0.355 (p = 0.017), respectively. We found no significant association between age, serum PSA levels, BMI and Gleason scores, and PD-1 among patients with prostate cancer and controls. However, elevated levels of PD-L1 were significantly associated with higher Gleason scores among patients with prostate cancer (p = 0.014)., Conclusions: Elevated PD-L1 levels were statistically significantly linked to high Gleason scores. These results may guide clinicians in assessing the prognosis of patients individually and selecting patients who will be suitable candidates for anti-PD-L1 immunotherapy., (© 2022. The Author(s).)

Background: Human herpesvirus 8 (HHV-8) causes Kaposi's sarcoma (KS). Kaposi sarcoma in HIV/AIDS patients is referred to as epidemic KS and is the most common HIV-related malignancy worldwide. The lack of a diagnostic assay to detect latent and early-stage disease has increased disease morbidity and mortality. Serum miRNAs have previously been used as potential biomarkers of normal physiology and disease. In the current study, we profiled unique serum miRNAs in patients with epidemic KS to generate baseline data to aid in developing a miRNA-based noninvasive biomarker assay for epidemic KS., Methods: This was a comparative cross-sectional study involving 27 patients with epidemic KS and 27 HIV-positive adults with no prior diagnosis or clinical manifestation of KS. DNA and RNA were isolated from blood and serum collected from study participants. Nested PCR for circulating HHV-8 DNA was performed on the isolated DNA, whereas miRNA library preparation and sequencing for circulating miRNA were performed on the RNA samples. The miRge2 pipeline and EdgeR were used to analyse the sequencing data., Results: Fifteen out of the 27 epidemic KS-positive subjects (55.6%) tested positive for HHV-8 DNA, whereas only 3 (11.1%) out of the 27 HIV-positive, KS-negative subjects tested positive for HHV-8 DNA. Additionally, we found a unique miRNA expression signature in 49 circulating miRNAs in epidemic KS subjects compared to subjects with no epidemic KS, with 41 miRNAs upregulated and 8 miRNAs downregulated. Subjects with latent KS infection had a differential upregulation of circulating miR-193a compared to HIV-positive, KS-negative subjects for whom circulating HHV-8 DNA was not detected. Further analysis of serum from epidemic KS patients revealed a miRNA signature according to KS tumor status and time since first HIV diagnosis., Conclusions: This study reveals unique circulating miRNA profiles in the serum of patients with epidemic KS versus HIV-infected subjects with no KS, as well as in subjects with latent KS. Many of the dysregulated miRNAs in epidemic KS patients were previously reported to have crucial roles in KS infection and latency, highlighting their promising roles as potential biomarkers of latent or active KS infection., Competing Interests: The authors declare that they have no competing interests., (© 2022 The Authors.)

Background: The possible clinical application of specific cytokines and chemokines contributing to tumorigenesis and the clinical outcome of several cancers has been reported. However, less invasive and easily applicable biomarkers in prostate cancer diagnosis and prognostication are still lacking. This study assessed the levels of plasma cytokines in prostate cancer patients as potential biomarkers for noninvasive early diagnosis. Methods: The plasma levels of nine cytokines, IL-6, IL-8, IL-10, IL-1β, IL-17A, IL-2, M-CSF, IL-12 and IFN-α, were detected by Luminex © liquid array-based multiplexed immunoassays in 56 prostate cancer patients on androgen deprivation therapy and radiotherapy and 27 normal healthy controls. Results: Levels of plasma proinflammatory cytokines IL-6 and IL-8 were markedly increased in prostate cancer patients compared with controls. There was, however, no significant difference in the concentrations of all cytokines in prostate cancer patients compared with controls. Increasing levels of IL-6 and IL-8 were significantly associated with high levels of plasma prostate-specific antigen (p < 0.05). Conclusion: Proinflammatory cytokines IL-6 and IL-8 are potential biomarkers for prostate cancer pathogenesis and could serve as markers of disease progression.

In Burundi most small-scale farmers still grow traditional cassava landraces that are adapted to local conditions and have been selected for consumer preferred attributes. They tend to be susceptible, in varying degrees, to devastating cassava viral diseases such as Cassava Brown Streak Disease (CBSD) and Cassava Mosaic Disease (CMD) with annual production losses of US$1 billion. For long term resistance to the disease, several breeding strategies have been proposed. A sound basis for a breeding program is to understand the genetic diversity of both landraces and elite introduced breeding cultivars. This will also assist in efforts to conserve landraces ahead of the broad distribution of improved varieties which have the possibility of replacing landraces. Our study aimed at determining the genetic diversity and relationships within and between local landraces and introduced elite germplasm using morphological and single nucleotide polymorphism (SNP) markers. A total of 118 cultivars were characterized for morphological trait variation based on leaf, stem and root traits, and genetic variation using SNP markers. Results of morphological characterization based on Ward's Method revealed three main clusters and five accessions sharing similar characteristics. Molecular characterization identified over 18,000 SNPs and six main clusters and three pairs of duplicates which should be pooled together as one cultivar to avoid redundancy. Results of population genetic analysis showed low genetic distance between populations and between local landraces and elite germplasm. Accessions that shared similar morphological traits were divergent at the molecular level indicating that clustering using morphological traits was inconsistent. Despite the variabilities found within the collection, it was observed that cassava germplasm in Burundi have a narrow genetic base., Competing Interests: The authors have declared that no competing interests exist.

While serum-circulating complement destroys invading pathogens, intracellularly active complement, termed the “complosome,” functions as a vital orchestrator of cell-metabolic events underlying T cell effector responses. Whether intracellular complement is also nonredundant for the activity of myeloid immune cells is currently unknown. Here, we show that monocytes and macrophages constitutively express complement component (C) 5 and generate autocrine C5a via formation of an intracellular C5 convertase. Cholesterol crystal sensing by macrophages induced C5aR1 signaling on mitochondrial membranes, which shifted ATP production via reverse electron chain flux toward reactive oxygen species generation and anaerobic glycolysis to favor IL-1β production, both at the transcriptional level and processing of pro–IL-1β. Consequently, atherosclerosis-prone mice lacking macrophage-specific C5ar1 had ameliorated cardiovascular disease on a high-cholesterol diet. Conversely, inflammatory gene signatures and IL-1β produced by cells in unstable atherosclerotic plaques of patients were normalized by a specific cell-permeable C5aR1 antagonist. Deficiency of the macrophage cell-autonomous C5 system also protected mice from crystal nephropathy mediated by folic acid. These data demonstrate the unexpected intracellular formation of a C5 convertase and identify C5aR1 as a direct modulator of mitochondrial function and inflammatory output from myeloid cells. Together, these findings suggest that the complosome is a contributor to the biologic processes underlying sterile inflammation and indicate that targeting this system could be beneficial in macrophage-dependent diseases, such as atherosclerosis.

The 3rd Uganda Conference on Cancer and Palliative Care was held in September 2021 with the theme: cancer and palliative care in COVID-19 and other challenging situations. It was hosted by the Uganda Cancer Institute and the Palliative Care Association of Uganda (UCI-PCAU). The conference was held virtually, with a mix of pre-recorded sessions, plenary sessions being broadcast live on television (TV) by the Uganda Broadcasting Corporation TV, live speakers at the studio and others presenting in real time via Zoom. The conference brought together >350 participants who participated on Zoom, along with those attending in person at the studio and those watching the plenary sessions on TV. At the heart of this joint UCI-PCAU conference was the commitment to not only continue but to improve the provision of cancer care and palliative care within Uganda. Key themes from the conference included: the importance of Universal Health Coverage; the impact of COVID-19 on the provision of cancer and palliative care; that both cancer care and palliative care are available in Uganda; education for all; the importance of working together to provide care and overcome challenges, e.g. through technology; the resilience shown by those working in cancer and palliative care; the grief experienced by so many people who have lost loved ones during the pandemic; the importance of good health seeking behaviour - prevention is better than cure; the challenge of funding; the need for health care equity for marginalised and vulnerable populations and finally we can't wait for the world to stop COVID-19 - COVID-19 is here to stay - we need to find solutions. The last few years have seen significant challenges due to the COVID-19 pandemic; however, despite this, cancer and palliative care service provision has continued. This conference, whilst unique and very different from previous conferences, was a great opportunity to share not only amongst each other, but also to share key messages with the public through the live broadcasting of the plenary sessions of the conference., Competing Interests: The authors declare that they have no conflicts of interest., (© the authors; licensee ecancermedicalscience.)

Haematological malignancies account for almost 10% of all cancers diagnosed in sub-Saharan Africa, although the exact incidences and treatment outcomes are difficult to discern because population-based cancer registries in the region are still underdeveloped. More research on haematological malignancies in sub-Saharan Africa is required to establish whether these cancers have a natural history similar to those diagnosed in high-income countries, about which more is known. Several factors negatively affect the outcome of haematological malignancies in sub-Saharan Africa, showcasing a need for improved understanding of the clinicobiological profile of these cancers to facilitate prevention, early detection, diagnosis, and appropriate treatment through increased capacity building, infrastructure, community awareness, coordinated resource mobilisation, and collaboration across the world. The east African governments have pooled resources for common investments to tackle non-communicable diseases, developing the East Africa's Centres of Excellence for Skills and Tertiary Education project funded by the African Development Bank, an initiative that could be replicated for the care of haematological malignancies in other countries in sub-Saharan Africa. TRANSLATION: For the French translation of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests TSU reports research support for investigator-initiated studies from Celgene, Roche, and Merck Sharp & Dohme, paid to the Fred Hutchinson Cancer Research Center and the US National Cancer Institute, outside the submitted work; and is named on US patent US-10001483-B2 as a federal employee. JMH reports salary support from Arbele ending April, 2021, outside the submitted work. All other authors declare no competing interests., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objectives: An accurate cancer diagnosis is critical to providing quality care to patients with cancer. We describe the results of a laboratory improvement process that started in 2017 to improve access to cancer diagnostics at the Uganda Cancer Institute (UCI). The overall objective of the project was to build capacity for the provision of quality and timely laboratory diagnostics to support cancer care in Uganda., Methods: A phased multistep approach was used to improve laboratory capacity, including staff training, additional staff recruitment, equipment overhaul, and optimization of the supply chain., Results: The program led to the establishment of a pathology laboratory that handled 5,700 tissue diagnoses in 2019. Immunohistochemistry services are now offered routinely. Turnaround time for histopathology has also reduced from an average of 7 to 14 days to 5.4 days. The main clinical laboratory has also increased both the test volume and the test capacity, with the additional establishment of a molecular diagnostics laboratory., Conclusions: Our project shows a pathway to the improvement of laboratory diagnostic capacity in cancer care centers in sub-Saharan Africa (SSA). Improved laboratory diagnostic capacity is critical to improving cancer care in SSA and more rational use of targeted therapies., (© American Society for Clinical Pathology, 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Cancer is one of the leading causes of death with 9.6 million deaths registered in 2018, of which 70% occur in Africa, Asia and Central and South America, the low-and middle-income countries (LMICs). The global annual expenditure on anticancer medicines increased from $96 billion in 2013 to $133 billion in 2017. This growth rate is several folds that of newly diagnosed cancer cases and therefore estimated to reach up to $200 billion by 2022. The Uganda Cancer Institute, Uganda's national referral cancer center, has increased access to cancer medicines through an efficient and cost-saving procurement system. The system has achieved cost savings of more than USD 2,000,000 on a total of 37 of 42 essential cancer medicines. This has resulted in 85.8% availability superseding the WHO's 80% target. All selected products were procured from manufacturers with stringent regulatory authority approval or a proven track record of quality products.

The complement system, well known for its central role in innate immunity, is currently emerging as an unexpected, cell-autonomous, orchestrator of normal cell physiology. Specifically, an intracellularly active complement system-the complosome-controls key pathways of normal cell metabolism during immune cell homeostasis and effector function. So far, we know little about the exact structure and localization of intracellular complement components within and among cells. A common scheme, however, is that they operate in crosstalk with other intracellular immune sensors, such as inflammasomes, and that they impact on the activity of key subcellular compartments. Among cell compartments, mitochondria appear to have built a particularly early and strong relationship with the complosome and extracellularly active complement-not surprising in view of the strong impact of the complosome on metabolism. In this review, we will hence summarize the current knowledge about the close complosome-mitochondria relationship and also discuss key questions surrounding this novel research area. LINKED ARTICLES: This article is part of a themed issue on Canonical and non-canonical functions of the complement system in health and disease. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v178.14/issuetoc., (© 2020 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Patients with coronavirus disease 2019 (COVID-19) present a wide range of acute clinical manifestations affecting the lungs, liver, kidneys and gut. Angiotensin converting enzyme (ACE) 2, the best-characterized entry receptor for the disease-causing virus SARS-CoV-2, is highly expressed in the aforementioned tissues. However, the pathways that underlie the disease are still poorly understood. Here, we unexpectedly found that the complement system was one of the intracellular pathways most highly induced by SARS-CoV-2 infection in lung epithelial cells. Infection of respiratory epithelial cells with SARS-CoV-2 generated activated complement component C3a and could be blocked by a cell-permeable inhibitor of complement factor B (CFBi), indicating the presence of an inducible cell-intrinsic C3 convertase in respiratory epithelial cells. Within cells of the bronchoalveolar lavage of patients, distinct signatures of complement activation in myeloid, lymphoid and epithelial cells tracked with disease severity. Genes induced by SARS-CoV-2 and the drugs that could normalize these genes both implicated the interferon-JAK1/2-STAT1 signaling system and NF-κB as the main drivers of their expression. Ruxolitinib, a JAK1/2 inhibitor, normalized interferon signature genes and all complement gene transcripts induced by SARS-CoV-2 in lung epithelial cell lines, but did not affect NF-κB-regulated genes. Ruxolitinib, alone or in combination with the antiviral remdesivir, inhibited C3a protein produced by infected cells. Together, we postulate that combination therapy with JAK inhibitors and drugs that normalize NF-κB-signaling could potentially have clinical application for severe COVID-19., (Copyright © 2021, American Association for the Advancement of Science.)

Background: In 2018, approximately 60,000 Ugandans were estimated to be suffering from cancer. It was also reported that only 5% of cancer patients access cancer care and 77% present with late-stage cancer coupled with low level of cancer health literacy in the population despite a wide coverage of primary healthcare facilities in Uganda. We aimed to contribute to reducing the unmet needs of cancer prevention and early detection services in Uganda through capacity building., Methods: In 2017, we conducted two national and six regional cancer control stakeholders' consultative meetings. In 2017 and 2018, we trained district primary healthcare teams on cancer prevention and early detection. We also developed cancer information materials for health workers and communities and conducted a follow-up after the training., Results: A total of 488 primary healthcare workers from 118 districts were trained. Forty-six health workers in the pilot East-central subregion were further trained in cervical, breast, and prostate cancer early detection (screening and early diagnosis) techniques. A total of 32,800 cancer information, education and communication materials; breast, cervical, prostate childhood and general cancer information booklets; health education guide, community cancer information flipcharts for village health teams and referral guidelines for suspected cancer were developed and distributed to 122 districts. Also, 16 public and private-not-for-profit regional hospitals, and one training institution received these materials. Audiovisual clips on breast, cervical, and prostate cancer were developed for mass and social media dissemination. A follow-up after six months to one year indicated that 75% of the districts had implemented at least one of the agreed actions proposed during the training., Conclusions: In Uganda, the unmet needs for cancer control services are enormous. However, building the capacity of primary healthcare workers to integrate prevention and early detection of cancer into primary health care based on low-cost options for low-income countries could contribute to reducing the unmet needs of cancer prevention and early detection in Uganda., (© 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

The Uganda Cancer Institute, the sole national comprehensive cancer center in Uganda, has a long and rich history of clinical investigation and locally relevant cancer research. Given the increasing burden of breast cancer in Uganda and elsewhere in sub-Saharan Africa (SSA) and driven by the limited availability of immunohistochemistry (IHC), we launched a clinical trial aimed at evaluating locally available diagnostics to detect the presence of hormone receptors (estrogen receptor and progesterone receptor) and human epidermal growth factor receptor 2. Preliminary data from 32 women in the diagnostic component of the study reveal high sensitivity and specificity for estrogen receptor and progesterone receptor and high specificity for human epidermal growth factor receptor 2 when comparing reverse transcriptase polymerase chain reaction with the gold standard (IHC). Innovative diagnostic and treatment strategies are required to address the burden of breast cancer that is increasing throughout SSA. Given the costs, infrastructure, and trained personnel associated with IHC, alternative testing options (including reverse transcriptase polymerase chain reaction as tested in our study) may provide an expedited and cost-effective method to determine receptor testing in breast cancer. Clinical trials conducted in the local setting are critical to determining optimal strategies for effective breast cancer management in SSA.

Background: Prostate cancer is the second most common cancer among men in Uganda, with over 2086 incident cases in 2018. This study's objective was to report the clinical characteristics and primary management of men diagnosed with prostate cancer at the Uganda Cancer Institute from 1st January 2015 to 31st December 2019., Methods: Records from all men diagnosed with Prostate cancer at the Uganda Cancer Institute from 1st January 2015 to 31st December 2019 were reviewed. Clinical characteristics and primary treatment were recorded. Risk categorization was done using the European Society for Medical Oncology prostate cancer risk group classification., Results: A total of 874 medical records for men diagnosed with prostate cancer was retrieved. The median age was 70 years (interquartile range 64-77). In this study, 501 (57.32%) patients had localized disease. Among patients with localized disease, 2 (0.23%) were classified as low-risk, 5 (0.53%) as intermediate-risk, and 494 (56.52%) as high-risk. Three hundred seventy-three (373) patients had metastatic disease at diagnosis. Among patients with distant metastases, the most common site of metastases was bone 143 (16.36%), followed by spinal cord 54 (6.18%), abdomen 22 (2.52%), and lungs 14 (1.60%). Regarding the primary treatment options majority of the patients were on chemotherapy 384(43.94%) followed by hormonal therapy 336 (38.44%) and radiotherapy 127 (14.53%)., Conclusion: The majority of the patients diagnosed with prostate cancer at the Uganda Cancer Institute presented with advanced disease. The primary treatments were mostly chemotherapy, hormonal therapy, and radiotherapy. There is a need to improve prostate cancer screening in regional health care facilities and the communities to enhance early detection and management of prostate cancer., Competing Interests: The authors have declared that no competing interests exist.

Background: During atherogenesis, cholesterol precipitates into cholesterol crystals (CC) in the vessel wall, which trigger plaque inflammation by activating the NACHT, LRR and PYD domains-containing protein 3 (NLRP3) inflammasome. We investigated the relationship between CC, complement and NLRP3 in patients with cardiovascular disease., Methods: We analysed plasma, peripheral blood mononuclear cells (PBMC) and carotid plaques from patients with advanced atherosclerosis applying ELISAs, multiplex cytokine assay, qPCR, immunohistochemistry, and gene profiling., Findings: Transcripts of interleukin (IL)-1beta(β) and NLRP3 were increased and correlated in PBMC from patients with acute coronary syndrome (ACS). Priming of these cells with complement factor 5a (C5a) and tumour necrosis factor (TNF) before incubation with CC resulted in increased IL-1β protein when compared to healthy controls. As opposed to healthy controls, systemic complement was significantly increased in patients with stable angina pectoris or ACS. In carotid plaques, complement C1q and C5b-9 complex accumulated around CC-clefts, and complement receptors C5aR1, C5aR2 and C3aR1 were higher in carotid plaques compared to control arteries. Priming human carotid plaques with C5a followed by CC incubation resulted in pronounced release of IL-1β, IL-18 and IL-1α. Additionally, mRNA profiling demonstrated that C5a and TNF priming followed by CC incubation upregulated plaque expression of NLRP3 inflammasome components., Interpretation: We demonstrate that CC are important local- and systemic complement activators, and we reveal that the interaction between CC and complement could exert its effect by activating the NLRP3 inflammasome, thus promoting the progression of atherosclerosis., (Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Communities in low-income countries are characterized by limited access to cancer prevention and early detection services, even for the commonest types of cancer. Limited resources for cancer control are one of the contributors to cancer health disparities. We explored the feasibility and benefit of conducting outreaches in partnership with local communities using the "asset-based community development (ABCD)" model., Methods: We analyzed the quarterly Uganda cancer institute (UCI) community outreach cancer health education and screening output reported secondary data without individual identifiers from July 2016 to June 2019 to compare the UCI-hospital-based and community outreach cancer awareness and screening services based on the ABCD model., Results: From July 2016 to June 2019, we worked with 107 local partners and conducted 151 outreaches. Of the total number of people who attended cancer health education sessions, 201 568 (77.9%) were reached through outreaches. Ninety-two (95%) cancer awareness TVs and radio talk-shows conducted were sponsored by local partners. Of the total people screened; 22 795 (63.0%) cervical, 22 014 (64.4%) breast, and 4904 (38.7%) prostate screening were reached through community outreach model. The screen-positive rates were higher in hospital-based screening except for Prostate screening; cervical, 8.8%, breast, 8.4%, prostate, 7.1% than in outreaches; cervical, 3.2%, breast, 2.2%, prostate, 8.2%. Of the screened positive clients who were eligible for precancer treatment like cryotherapy for treatment of precervical cancer lesions, thousands-folds monetary value and productive life saved relative to the market cost of cancer treatment and survival rate in Uganda. When the total number of clients screened for cervical, breast, and prostate cancer are subjected to the incremental cost of specific screening, a greater portion (98.7%) of the outreach cost was absorbed through community partnership., Conclusions: Outreaching and working in collaboration with communities as partners through asset-based community development model are feasible and help in cost-sharing and leverage for scarce resources to promote primary prevention and early detection of cancer. This could contribute to bridging the cancer health disparities in the target populations., (© 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Cancer incidence and mortality in sub-Saharan Africa are increasing and do account for significant premature death. The expertise of health care providers is critical to downstaging cancer at diagnosis and improving survival in low- and middle-income countries. We set out to determine the training needs of health care providers for a comprehensive oncology services package in selected hospitals in Uganda, in order to inform capacity development intervention to improve cancer outcomes in the East African region., Methods: This was a cross-sectional survey using the WHO Hennessey-Hicks questionnaire to identify the training needs of health workers involved in cancer care, across 22 hospitals in Uganda. Data were captured in real time using the Open Data Kit platform from which the data was exported to Stata version 15 for analysis using the Wilcoxon signed-rank test and Somers-Delta., Results: There were 199 respondent health professionals who were predominately female (146/199, 73.37%), with an average age of 38.97 years. There were 158/199 (79.40%) nurses, 24/199 (12.06%) medical doctors and 17/199 (8.54%) allied health professionals. Overall, the research and audit domain had the highest ranking for all the health workers (Somers-D = 0.60). The respondent's level of education had a significant effect on the observed ranking (P value = 0.03). Most of the continuing medical education (CME) topics suggested by the participants were in the clinical task-related category., Conclusion: The "research and audit" domain was identified as the priority area for training interventions to improve oncology services in Uganda. There are opportunities for addressing the identified training needs with an expanded cancer CME programme content, peer support networks and tailored training for the individual health care provider.

There is growing evidence of the microbiome's role in human health and disease since the human microbiome project. The microbiome plays a vital role in influencing cancer risk and pathogenesis. Several studies indicate microbial pathogens to account for over 15-20% of all cancers. Furthermore, the interaction of the microbiota, especially the gut microbiota in influencing response to chemotherapy, immunotherapy, and radiotherapy remains an area of active research. Certain microbial species have been linked to the improved clinical outcome when on different cancer therapies. The recent discovery of the urinary microbiome has enabled the study to understand its connection to genitourinary malignancies, especially prostate cancer. Prostate cancer is the second most common cancer in males worldwide. Therefore research into understanding the factors and mechanisms associated with prostate cancer etiology, pathogenesis, and disease progression is of utmost importance. In this review, we explore the current literature concerning the link between the gut and urinary microbiome and prostate cancer risk and pathogenesis., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s) 2020.)

Optimal treatment outcomes for breast cancer are dependent on a timely diagnosis followed by an organized, multidisciplinary approach to care. However, in many low- and middle-income countries, effective care management pathways can be difficult to follow because of financial constraints, a lack of resources, an insufficiently trained workforce, and/or poor infrastructure. On the basis of prior work by the Breast Health Global Initiative, this article proposes a phased implementation strategy for developing sustainable approaches to enhancing patient care in limited-resource settings by creating roadmaps that are individualized and adapted to the baseline environment. This strategy proposes that, after a situational analysis, implementation phases begin with bolstering palliative care capacity, especially in settings where a late-stage diagnosis is common. This is followed by strengthening the patient pathway, with consideration given to a dynamic balance between centralization of services into centers of excellence to achieve better quality and decentralization of services to increase patient access. The use of resource checklists ensures that comprehensive therapy or palliative care can be delivered safely and effectively. Episodic or continuous monitoring with established process and quality metrics facilitates ongoing assessment, which should drive continual process improvements. A series of case studies provides a snapshot of country experiences with enhancing patient care, including the implementation of national cancer control plans in Kenya, palliative care in Romania, the introduction of a 1-stop clinic for diagnosis in Brazil, the surgical management of breast cancer in India, and the establishment of a women's cancer center in Ghana., (© 2020 American Cancer Society.)