Mapping the evidence on integrated service delivery for non-communicable and infectious disease comorbidity in sub-Saharan Africa: protocol for a scoping review.

INTRODUCTION: The concurrent occurrence of infectious diseases (IDs) and non-communicable diseases (NCDs) presents complex healthcare challenges in sub-Saharan Africa (SSA), where healthcare systems often grapple with limited resources. While an integrated care approach has been advocated to address these complex challenges, there is a recognised gap in comprehensive evidence regarding the various models of integrated care, their components and the feasibility of their implementation. This scoping review aims to bridge this gap by examining the breadth and nature of evidence on integrated care models for NCDs and IDs within SSA, thereby updating the current evidence base in the domain. METHODS AND ANALYSIS: Based on the Joanna Briggs Institute (JBI) framework for scoping reviews, this study will include peer-reviewed and grey literature reporting on integrated care models for NCD-ID comorbidities in SSA. A comprehensive search of published sources in electronic databases (PubMed, Scopus, Embase, the Cochrane Library, Health System Evidence and Research4Life) and grey literature (Google Scholar, EBSCO Open Dissertations and relevant organisational websites) will be conducted to identify sources of information reported in English from 2018 onwards. The review will consider sources of evidence reporting on integrated care model for NCDs such as diabetes; chronic cardiovascular, respiratory and kidney diseases; cancers; epilepsy; and mental illness, and comorbid IDs such as HIV, tuberculosis and malaria. All sources of evidence will be considered irrespective of the study designs or methods used. The review will exclude sources that solely focus on the differentiated or patient-centred care delivery approach, and that focus on other conditions, populations or settings. The reviewers will independently screen the sources for eligibility and extract data using a JBI-adapted data tool on the Parsifal review platform. Data will be analysed using descriptive and thematic analyses and results will be presented in tables, figures, diagrams and a narrative summary. ETHICS AND DISSEMINATION: Ethical approval is not required for this review as it will synthesise published data and does not involve human participants. The final report will be submitted for publication in a peer-reviewed journal. The findings will be used to inform future research. STUDY REGISTRATION: OSF: https://doi.org/10.17605/OSF.IO/KFVEY.

Design, synthesis and mechanistic studies of novel imidazo[1,2-a]pyridines as anticancer agents.

Herein, the design, synthesis and mechanistic study of five series of imidazo[1,2-a]pyridines 8a-d, 9a-f, 11a-c, 12a-d and 14a-d as anticancer agents were discussed. The cytotoxicity of imidazo[1,2-a]pyridine derivatives was screened against NCI 60 cancer cell lines. The cytotoxicity of compounds 8b, 8c, 9e and 9f was then evaluated against leukemia K-562 cancer cell line and normal lung fibroblasts (WI38). The hydrazone derivatives 8b and 8c exhibited significant cytotoxic activities against the leukemia K-562 cancer cell line with good safety margins (IC50 = 2.91 µM, SI = 8.32 and IC50 = 1.09 µM, SI = 10.54, respectively). In addition, compounds 8b, 8c, 9e and 9f were tested for their EGFR and COX-2 inhibitory activities. The hydrazone derivatives 8b and 8c were the most active EGFR inhibitors with IC50 values of 0.123 and 0.072 µM, respectively. Compound 8c selectively inhibited COX-2 (IC50 = 1.09 µM, SI = 13.78). Moreover, the potential of compound 8c to induce apoptosis in leukemia K-562 cell line was determined. Compound 8c showed a pre-G1 apoptosis and a growth arrest of leukemia K-562 cell line at G1 phase of cell cycle. Also, compound 8c was able to induce caspase-3 overexpression (6.98 folds), if compared to control. Finally, molecular docking studies and physicochemical properties calculation of compounds 8b, 8c, 9e and 9f were carried out to explain the biological data and to predict bioavailability of the most active compounds.

Design, synthesis and molecular docking of new fused 1H-pyrroles, pyrrolo[3,2-d]pyrimidines and pyrrolo[3,2-e][1, 4]diazepine derivatives as potent EGFR/CDK2 inhibitors.

A new series of 1H-pyrrole (6a-c, 8a-c), pyrrolo[3,2-d]pyrimidines (9a-c) and pyrrolo[3,2-e][1, 4]diazepines (11a-c) were designed and synthesised. These compounds were designed to have the essential pharmacophoric features of EGFR Inhibitors, they have shown anticancer activities against HCT116, MCF-7 and Hep3B cancer cells with IC50 values ranging from 0.009 to 2.195 µM. IC50 value of doxorubicin is 0.008 µM, compounds 9a and 9c showed IC50 values of 0.011 and 0.009 µM respectively against HCT-116 cells. Compound 8b exerted broad-spectrum activity against all tested cell lines with an IC50 value less than 0.05 µM. Compound 8b was evaluated against a panel of kinases. This compound potently inhibited CDK2/Cyclin A1, DYRK3 and GSK3 alpha kinases with 10-23% compared to imatinib (1-10%). It has also arrested the cell cycle of MCF-7 cells at the S phase. Its antiproliferative activity was further augmented by molecular docking into the active sites of EGFR and CDK2 cyclin A1.

Intralesional purified protein derivative versus zinc sulfate 2% in the treatment of pediatric warts: Clinical and dermoscopic evaluation.

BACKGROUND: Warts are common in children and can be difficult to treat. Many treatments for warts are destructive and painful in contrast to intralesional immunotherapy using different types of antigens. AIM: To evaluate the efficacy, safety, and tolerability of intralesional purified protein derivative (PPD) versus intralesional zinc sulfate 2% in the treatment of pediatric warts. METHODS: This randomized clinical trial included 120 children with multiple warts divided into two equal groups. Group Ⅰ received intralesional 10 IU (0.1 ml) of PPD, group Ⅱ received intralesional zinc sulfate 2% in the largest wart every 2 weeks till improvement or for a maximum five treatment sessions. The follow-up period was 6 months after the last treatment session. RESULTS: The overall response was equal in both groups (81.7%), but the response of the injected wart was higher in the zinc sulfate group (93.4%) versus PPD group (83.3%) with no significant difference. The highest cure rates were after the 5th session in the PPD group and the 1st session in the zinc sulfate group with slightly lower numbers of sessions needed for cure in the zinc sulfate group (3 sessions) versus the PPD group (4 sessions). The zinc sulfate group showed statistically significant higher rates of complications (pain, inflammation, necrosis, and scar) than PPD group. The zinc sulfate group showed non-significant higher rates of recurrence during the follow-up period. CONCLUSION: Both intralesional PPD and zinc sulfate 2% are effective in pediatric warts with higher safety profile of PPD.

Design & synthesis of novel oxazolone & triazinone derivatives and their biological evaluation as COX-2 inhibitors.

A new series of oxazolones and triazinones were designed and synthesized and evaluated against both COX-1 and COX-2 enzymes. Full structure elucidation of the new derivatives was performed using microanalyses, IR, 1H NMR, 13C NMR and mass spectra. Most of the derivatives showed good inhibitory activity against COX-2 enzyme specifically compounds IIIc, IIIe, IVd and IVg with IC50 values 0.024, 0.019, 0.011 and 0.014µM compared to celecoxib as reference drug with IC50 value of 0.05µM. Altogether, these results indicate that these derivatives can be effective anti-inflammatory agents.

Use of the Bonfils Intubation Fiberscope in patients with limited mouth opening.

Airway management of patients with very limited mouth opening remains a challenge for the anaesthetist. We describe the use of the Bonfils Intubation Fiberscope for awake intubation in two patients with a very limited mouth opening. In the first case, a 60-year-old 80 kg female, scheduled for a right modified radical mastectomy for infiltrating ductal carcinoma (15 mm mouth opening, a short thick neck, limited neck extension, and a Mallampati class 4 airway), the Bonfils was advanced via the retromolar technique. In the second patient, a 34-year-old male, scheduled for a surgical tracheotomy for right tonsillar cancer, due to a neoplastic infiltration of the right temporomandibular joint (7 mm mouth opening and limited neck movement), the Bonfils was advanced using the midline approach. The Bonfils is a reusable, rigid, straight fiberoptic device with a curved tip, is 5 mm in diameter, and has several advantages: it is quick and easy to use, more cost effective than a flexible fiberscope, and is safe in expert hands, thanks to its smaller diameter. Our conclusion is that awake BIF intubation is a reliable, atraumatic, and well-tolerated procedure to secure a safe airway in patients with a limited mouth opening.

The impact of timing of maximal crystalloid hydration on early graft function during kidney transplantation.

BACKGROUND: Early graft function is crucial for successful kidney transplantation. Maintaining adequate hydration is complicated by rapid movement of water to the extravascular space. We designed this study to test the effect of maximal hydration during graft ischemia time on early renal function. METHODS: Forty adult patients with chronic renal failure underwent renal transplantation from related living donors. Study subjects were randomly assigned 1 of 2 regimens for intraoperative hydration. The constant infusion rate group received normal saline 0.9% at an infusion rate 10 to 12 mL . kg(-1) . h(-1) from the start of surgery until the renal vessels were unclamped after vascular anastomosis. The central venous pressure target (CVPT) group received normal saline 0.9% titrated to maintain a specific central venous pressure (CVP). The target CVP from the start of surgery until clamping of the donor renal vessels was 5 mm Hg except for the interval from clamping of the renal vessels until the end of renal vascular anastomosis, when the target CVP was 15 mm Hg. Perioperative hemodynamics, infused saline volumes, rate of infusion, onset of diuresis, graft turgidity, urine volume, and renal function during the first 5 postoperative days were recorded. RESULTS: At the end of renal ischemia time, both groups had received approximately 3 L crystalloid solution. The CVPT group achieved the highest peak of intravascular volume expansion with an average infusion rate of 48.3 mL . min(-1) during 48 +/- 12 minutes of renal ischemia. The CVPT group had better graft function, required fewer vasopressors and diuretics, and had less postoperative tissue edema than the constant infusion rate group. CONCLUSIONS: Hydration directed toward maintaining a given CVP during kidney transplantation produced a more stable hemodynamic profile and promoted diuresis. The calculated infusion rate of approximately 45 to 50 mL . min(-1), within an hour ischemia time, seems feasible to enhance early graft function. A larger trial with long-term follow-up of renal function is warranted to confirm the clinical benefit of titrating IV crystalloid administration to maintain a given CVP in this population.