The potential of single-hitched donkeys (Equus asinus) in cultivation tasks in Zimbabwe

A journal study on the use and importance of single-hitched donkeys to the draught power of Zimbabwe's rural farmers.This study was conducted at Matopos Research Station (Zimbabwe) during the 1995/96 summer cropping season to investigate the effect of soil type, animal sex and live weight of single-hitched donkeys in cultivation tasks. Twenty-four donkeys comprising males and females, equally represented in heavy (>130kg) and light (0.05) on total work done. Sex had no significant effect (P>0.05) on work output. Live weight significantly (P0.05) effect of sex and live weight on heart rate and rectal temperature changes during the post-work recovery period. Only resting time significantly (P<0.001) affected changes in the studied physiological parameters during the recovery period. The results highlighted the importance of live weight in influencing work performance draof single-hitched donkeys in cultivation tasks. Heavy donkeys of either sex are more useful than light donkeys for cultivation purposes on heavy and light soils. Live weight is more useful than other linear body measurements as a predictor of work output in cultivation tasks by single-hitched donkeys. Work-related physiological changes limit the work capacity of single working donkeys in cultivation, hence adequate rest pauses are necessar

Dual HLA B*42 and B*81-reactive T cell receptors recognize more diverse HIV-1 Gag escape variants

Closely related HLA alleles presenting similar HIV-1 epitopes can be associated with variable clinical outcome. Here the authors report their findings on CD8+ T cell responses to the HIV-1 Gag-p24 TL9 immunodominant epitope in the context of closely related protective and less protective HLA alleles, and their differential effect on viral contro

Partial compartmentalisation of HIV-1 subtype C between lymph nodes, peripheral blood mononuclear cells and plasma

HIV-1 compartmentalisation is likely to have important implications for a preventative vaccine as well as eradication strategies. We genetically characterised HIV-1 subtype C variants in lymph nodes, peripheral blood mononuclear cells and plasma of six antiretroviral (ART) naïve individuals and four individuals on ART. Full-length env (n = 171) and gag (n = 250) sequences were generated from participants using single genome amplification. Phylogenetic relatedness of sequences was assessed, and compartmentalisation was determined using both distance and tree-based methods implemented in HyPhy. Additionally, potential associations between compartmentalisation and immune escape mutations were assessed. Partial viral compartmentalisation was present in nine of the ten participants. Broadly neutralising antibody (bnAb) escape was found to be associated with partial env compartmentalisation in some individuals, while cytotoxic T lymphocyte escape mutations in Gag were limited and did not differ between compartments. Viral compartmentalisation may be an important consideration for bnAb use in viral eradication

HIV Controllers Exhibit Enhanced Frequencies of Major Histocompatibility Complex Class II Tetramer+ Gag-Specific CD4+ T Cells in Chronic Clade C HIV-1 Infection

Immune control of viral infections is heavily dependent on helper CD4(+) T cell function. However, the understanding of the contribution of HIV-specific CD4(+) T cell responses to immune protection against HIV-1, particularly in clade C infection, remains incomplete. Recently, major histocompatibility complex (MHC) class II tetramers have emerged as a powerful tool for interrogating antigen-specific CD4(+) T cells without relying on effector functions. Here, we defined the MHC class II alleles for immunodominant Gag CD4(+) T cell epitopes in clade C virus infection, constructed MHC class II tetramers, and then used these to define the magnitude, function, and relation to the viral load of HIV-specific CD4(+) T cell responses in a cohort of untreated HIV clade C-infected persons. We observed significantly higher frequencies of MHC class II tetramer-positive CD4(+) T cells in HIV controllers than progressors (P = 0.0001), and these expanded Gag-specific CD4(+) T cells in HIV controllers showed higher levels of expression of the cytolytic proteins granzymes A and B. Importantly, targeting of the immunodominant Gag41 peptide in the context of HLA class II DRB1*1101 was associated with HIV control (r = −0.5, P = 0.02). These data identify an association between HIV-specific CD4(+) T cell targeting of immunodominant Gag epitopes and immune control, particularly the contribution of a single class II MHC-peptide complex to the immune response against HIV-1 infection. Furthermore, these results highlight the advantage of the use of class II tetramers in evaluating HIV-specific CD4(+) T cell responses in natural infections. IMPORTANCE Increasing evidence suggests that virus-specific CD4(+) T cells contribute to the immune-mediated control of clade B HIV-1 infection, yet there remains a relative paucity of data regarding the role of HIV-specific CD4(+) T cells in shaping adaptive immune responses in individuals infected with clade C, which is responsible for the majority of HIV infections worldwide. Understanding the contribution of HIV-specific CD4(+) T cell responses in clade C infection is particularly important for developing vaccines that would be efficacious in sub-Saharan Africa, where clade C infection is dominant. Here, we employed MHC class II tetramers designed to immunodominant Gag epitopes and used them to characterize CD4(+) T cell responses in HIV-1 clade C infection. Our results demonstrate an association between the frequency of HIV-specific CD4(+) T cell responses targeting an immunodominant DRB1*11-Gag41 complex and HIV control, highlighting the important contribution of a single class II MHC-peptide complex to the immune response against HIV-1 infections

Establishing and Externally Validating a Hemoglobin, Albumin, Lymphocyte, and Platelet (HALP) Score-Based Nomogram for Predicting Early Recurrence in BCLC Stage 0/A Hepatocellular Carcinoma Patients After Radical Liver Resection: A Multi-Center Study

Xulin Liu,1,&ast; Zhancheng Qiu,2,&ast; Elijah Ndhlovu,1,&ast; Yunyan Wan,3 Huapeng Sun,4 Shuai Wang,5 Yugang Cao,6 Peng Zhu1 1Department of Hepatic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of China; 2Division of Liver Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan Province, People’s Republic of China; 3Department of Hepatobiliary Pancreatic Surgery, Taihe Hospital, Shiyan City, Hubei Province, People’s Republic of China; 4Department of General Surgery, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, People’s Republic of China; 5Department of Hepatobiliary Surgery, Jingzhou Central Hospital, Jingzhou, People’s Republic of China; 6Department of Hepatobiliary and Pancreatic Surgery, Huangshi Central Hospital of Edong Healthcare Group, Huangshi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Peng Zhu, Department of Hepatic Surgery, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of China, Tel +86 13907170712, Email [email protected]: Early recurrence (ER) is associated with poor prognosis in hepatocellular carcinoma (HCC). In this study, we developed and externally validated a nomogram based on the hemoglobin, albumin, lymphocytes, and platelets (HALP) score to predict ER for patients with BCLC stage 0/A HCC who underwent radical liver resection.Patients and Methods: A total of 808 BCLC stage 0/A HCC patients from six hospitals were included in this study, and they were assigned to a training cohort (n = 500) and an external validation cohort (n = 308). We used univariate and multivariate Cox regression analysis to identify the independent risk factors for disease-free survival (DFS). We also established and externally validated a nomogram based on these risk predictors. The nomogram was evaluated using the area under the receiver operating characteristic curve (AUC), the concordance index (C-index), the calibration curve, decision curve analysis (DCA), and Kaplan‒Meier analysis.Results: Multivariate COX regression showed that HBV DNA ≥ 10,000 IU/mL (P < 0.001), HALP score ≤ 38.20 (P < 0.001), tumor size (P = 0.003), clinically significant portal hypertension (P = 0.001), Edmondson-Steiner grade (III–IV) (P = 0.007), satellite nodules (P < 0.001), and MVI (P = 0.001) were independent risk factors for post-operative tumor recurrence. The AUC of our nomogram for predicting the 2-year and 5-year DFS was 0.756 and 0.750, respectively, in the training cohort and 0.764 and 0.705, respectively, in the external validation cohort. We divided the patients into low-, intermediate- and high-risk groups according to the risk score calculated by the nomogram. There were statistically significant differences in the DFS and overall survival (OS) among the three groups of patients (P < 0.001).Conclusion: We developed and externally validated a new nomogram, which is accurate and can predict ER in BCLC stage 0/A HCC patients after curative liver resection.Keywords: early recurrence, hepatocellular carcinoma, HALP score, nomogram, Barcelona Clinic of Liver Cancer staging system, disease-free surviva

CD8 lymphocytes mitigate HIV-1 persistence in lymph node follicular helper T cells during hyperacute-treated infection

HIV persistence in tissue sites despite ART is a major barrier to HIV cure. Detailed studies of HIV-infected cells and immune responses in native lymph node tissue environment is critical for gaining insight into immune mechanisms impacting HIV persistence and clearance in tissue sanctuary sites. We compared HIV persistence and HIV-specific T cell responses in lymph node biopsies obtained from 14 individuals who initiated therapy in Fiebig stages I/II, 5 persons treated in Fiebig stages III-V and 17 late treated individuals who initiated ART in Fiebig VI and beyond. Using multicolor immunofluorescence staining and in situ hybridization, we detect HIV RNA and/or protein in 12 of 14 Fiebig I/II treated persons on suppressive therapy for 1 to 55 months, and in late treated persons with persistent antigens. CXCR3(+) T follicular helper cells harbor the greatest amounts of gag mRNA transcripts. Notably, HIV-specific CD8(+) T cells responses are associated with lower HIV antigen burden, suggesting that these responses may contribute to HIV suppression in lymph nodes during therapy. These results reveal HIV persistence despite the initiation of ART in hyperacute infection and highlight the contribution of virus-specific responses to HIV suppression in tissue sanctuaries during suppressive ART

The Lived Experience Of Participants in an African RandomiseD trial (LEOPARD): protocol for an in-depth qualitative study within a multisite randomised controlled trial for HIV-associated cryptococcal meningitis.

INTRODUCTION: Individuals recruited into clinical trials for life-threatening illnesses are particularly vulnerable. This is especially true in low-income settings. The decision to enrol may be influenced by existing inequalities, poor healthcare infrastructure and fear of death. Where patients are confused or unconscious the responsibility for this decision falls to relatives. This qualitative study is nested in the ongoing AMBIsome Therapy Induction OptimisatioN (AMBITION) Trial. AMBITION is recruiting participants from five countries in sub-Saharan Africa and is trialling a novel treatment approach for HIV-associated cryptococcal meningitis, an infection known to affect brain function. We aim to learn from the experiences of participants, relatives and researchers involved in AMBITION. METHODS AND ANALYSIS: We will collect data through in-depth interviews with trial participants and the next of kin of participants who were confused at enrolment and therefore provided surrogate consent. Data will be collected in Gaborone, Botswana; Kampala, Uganda and Harare, Zimbabwe. Interviews will follow a narrative approach including participatory drawing of participation timelines. This will be supplemented by direct observation of the research process at each of the three recruiting hospitals. Interviews will also take place with researchers from the African and European institutions that form the partnership through which the trial is administered. Interviews will be transcribed verbatim, translated (if necessary) and organised thematically for narrative analysis. ETHICS AND DISSEMINATION: This study has been approved by the Health Research Development Committee, Gaborone (Reference: HPDME:13/18/1); Makerere School of Health Sciences Institutional Review Board, Kampala (Reference: 2019-061); University of Zimbabwe Joint Research Ethics Committee, Harare (Reference: 219/19), and the London School of Hygiene and Tropical Medicine (Reference: 17957). Study findings will be shared with research participants from the sites, key stakeholders at each research institution and ministries of health to help inform the development and implementation of future trials. The findings of this study will be published in journals and presented at academic meetings. TRIAL REGISTRATION: Registered at www.clinicaltrials.gov:NCT04296292

Significant improvement in quality of life following surgery for hydrocoele caused by lymphatic filariasis in Malawi: A prospective cohort study

Lymphatic filariasis (LF) is a mosquito-borne parasitic infection that causes significant disabling and disfiguring clinical manifestations. Hydrocoele (scrotal swelling) is the most common clinical condition, which affects an estimated 25 million men globally. The recommended strategy is surgical intervention, yet little is known about the impact of hydrocoele on men’s lives, and how it may change if they have access to surger