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Plant secondary metabolites are important sources of biologically active compounds with wide pharmacological potentials. Among the different classes, the chalcones form integral pharmacologically active agents. Natural chalcones and bis-chalcones exhibit high antioxidant and anti-inflammatory properties in various experiments. Studies are also underway to explore more biologically active bis-chalcones by chemical synthesis of these compounds. In this study, the effects of six synthetic bis-chalcones were evaluated in intestinal epithelial cells (IEC-6); further, the anti-inflammatory potentials were studied in lipopolysaccharide-induced cytokine production in macrophages. The synthesized bis-chalcones differ from each other first of all by the nature of the aromatic cores (functional group substitution, and their position) and by the size of a central alicycle. The exposure of IEC-6 cells to peroxide radicals reduced the cell viability; however, pre-treatment with the bis-chalcones improved the cell viability in these cells. The mechanism of action was observed to be the increased levels of glutathione and antioxidant enzyme activities. Further, these bis-chalcones also inhibited the LPS-stimulation-induced inflammatory cytokine production in RAW 264.7 macrophages. Overall, the present study indicated the cytoprotective and anti-inflammatory abilities of synthetic bis-chalcones.

Plants are known to have numerous phytochemicals and other secondary metabolites with numerous pharmacological and biological properties. Among the various compounds, polyphenols, flavonoids, anthocyanins, alkaloids, and terpenoids are the predominant ones that have been explored for their biological potential. Among these, chalcones and bis-chalcones are less explored for their biological potential under in vitro experiments, cell culture models, and animal studies. In the present study, we evaluated six synthetic bis-chalcones that were different in terms of their aromatic cores, functional group substitution, and position of substitutions. The results indicated a strong antioxidant property in terms of DPPH and ABTS radical-scavenging potentials and ferric-reducing properties. In addition, compounds 1, 2, and 4 exhibited strong antibacterial activities against Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Salmonella enteritidis. The disc diffusion assay values were indicative of the antibacterial properties of these compounds. Overall, the study indicated the antioxidant and antimicrobial properties of the compounds. Our preliminary studies point to the potential of this class of compounds for further in vivo investigation.

Malaria remains a major public health challenge in Africa where annually, ~250,000 children with malaria experience a neurologic injury with subsequent neuro-disability. Evidence indicates that a higher temperature during the acute illness is a risk factor for post-infectious neurologic sequelae. As such, aggressive antipyretic therapy may be warranted among children with complicated malaria at substantial risk of brain injury. Previous clinical trials conducted primarily in children with uncomplicated malaria and using only a single antipyretic medication have shown limited benefits in terms of fever reduction; however, no studies to date have examined malaria fever management using dual therapies. In this clinical trial of aggressive antipyretic therapy, children hospitalized with central nervous system (CNS) malaria will be randomized to usual care (acetaminophen every 6 hours for a temperature ≥ 38.5°C) vs. prophylactic acetaminophen and ibuprofen every 6 hours for 72 hours. In this double-blinded, placebo controlled, two-armed clinical trial, we will enroll 284 participants from three settings at Queen Elizabeth Central Hospital in Blantyre, Malawi; at the University Teaching Hospitals Children's Hospital in Lusaka, Zambia and at Chipata Central Hospital, Chipata, Zambia. Parents or guardians must provide written informed consent. Eligible participants are 2-11 years with evidence of P. falciparum malaria infection by peripheral blood smear or rapid diagnostic test with CNS symptoms associated with malaria. Eligible children will receive treatment allocation randomization either to standard of care for fever management or to prophylactic, scheduled treatment every 6 hours for 72 hours with dual antipyretic therapies using acetaminophen and ibuprofen. Assignment to treatment groups will be with 1:1 allocation using blocked randomization. The primary outcome will be maximum temperature in the 72 hours after enrolment. Secondary outcomes include parasite clearance as determined by quantitative Histidine Rich Protein II and seizures through 72 hours after enrolment. This clinical trial seeks to challenge the practice paradigm of limited fever treatment based upon hyperpyrexia by evaluating the fever-reduction efficacy of more aggressive antipyretic using two antipyretics and prophylactic administration and will elucidate the impact of antipyretics on parasite clearance and acute symptomatic seizures. If aggressive antipyretic therapy is shown to safely reduce the maximum temperature, a clinical trial evaluating the neuroprotective effects of temperature reduction in CNS malaria is warranted.

ObjectiveEpilepsy affects approximately 50 million people globally, with approximately 80% living in low/middle-income countries (LMIC), where access to specialist care is limited. In LMIC, primary health workers provide the majority of epilepsy care, despite limited training in this field. Recognising this knowledge gap among these providers is an essential component for closing the epilepsy treatment gap in these regions.SettingIn Zambia, the vast majority of healthcare is provided by clinical officers (COs), primary health providers with 3 years post-secondary general medical education, who predominantly work in first-level health centres around the country.ParticipantsWith cooperation from the Ministry of Health, a total of 10 COs from 4 surrounding first-level health centres around the capital city of Lusaka participated, with 9 completing the entire course.InterventionCOs were trained in a 3-week structured course on paediatric seizures and epilepsy, based on adapted evidence-based guidelines.ResultsPreassessment and postassessment were conducted to assess the intervention. Following the course, there was improved overall knowledge about epilepsy (69% vs 81%, p<0.05), specifically knowledge regarding medication management and recognition of focal seizures (p<0.05), improved seizure history taking and appropriate medication titration (p<0.05). However, knowledge regarding provoked seizures, use of diagnostic studies and general aetiologies of epilepsy remained limited.ConclusionsThis pilot project demonstrated that a focused paediatric epilepsy training programme for COs can improve knowledge and confidence in management, and as such is a promising step for improving the large epilepsy treatment gap in children in Zambia. With feasibility demonstrated, future projects are needed to expand to more rural regions for more diverse and larger sample of primary health provider participants and encompass more case-based training and repetition of key concepts as well as methods to improve and assess long-term knowledge retention.

This study aims to prepare a supported catalyst based on zeolite Y doped with NaOMe (sodium methoxide) for the transesterification of waste cooking oil (WCO). The catalytic screening data showed that NaOMe/zeolite is a prominent catalyst for the transesterification of WCO prepared by a solvent-free, ball-milling process. We initially tested 5–20% of sodium methoxide loading onto zeolite Y and found that 20% is the optimum loading for the reaction. The transesterification reaction required a comparatively lower methanol-to-oil mole ratio of 16:1 with the reaction temperature as 60 °C. The ball-milled NaOMe/zeolite catalyst was characterized by BET surface area analysis, FE-SEM, TEM, FT–IR, and XRD. The BET surface analysis revealed that the surface area for zeolite Y was substantially decreased in the NaOMe/zeolite catalyst. The ball-milling process dropped the crystallinity of zeolite Y, which can be seen from the XRD and FE-SEM images of both zeolite Y and the NaOMe/zeolite catalyst. Finally, the transesterification reaction product was fully characterized by 1H-NMR and viscosity analysis for biodiesel, glycerol, and the WCO. The chemical shifts for the biodiesel and glycerol are found accordingly. This is also supported by the FT–IR characterization of biodiesel, glycerol, and WCO. It is noteworthy that a very high mass ratio of 250 g oil/g NaOMe is obtained when converting WCO to biodiesel, indicating very high catalytic activity for the aforementioned catalyst.

Objective To determine the long‐term outcomes, including mortality and recurrent seizures, among children living with HIV (CLWH) who present with new onset seizure. Methods Zambian CLWH and new onset seizure were enrolled prospectively to determine the risk of and risk factors for recurrent seizures. Demographic data, clinical profiles, index seizure etiology, and 30‐day mortality outcomes were previously reported. After discharge, children were followed quarterly to identify recurrent seizures and death. Given the high risk of early death, risk factors for recurrent seizure were evaluated using a model that adjusted for mortality. Results Among 73 children enrolled, 28 died (38%), 22 within 30‐days of the index seizure. Median follow‐up was 533 days (IQR 18–957) with 5% (4/73) lost to follow‐up. Seizure recurrence was 19% among the entire cohort. Among children surviving at least 30‐days after the index seizure, 27% had a recurrent seizure. Median time from index seizure to recurrent seizure was 161 days (IQR 86–269). Central nervous system opportunistic infection (CNS OI), as the cause for the index seizure was protective against recurrent seizures and higher functional status was a risk factor for seizure recurrence. Significance Among CLWH presenting with new onset seizure, mortality risks remain elevated beyond the acute illness period. Recurrent seizures are common and are more likely in children with higher level of functioning even after adjusting for the outcome of death. Newer antiseizure medications appropriate for co‐usage with antiretroviral therapies are needed for the care of these children. CNS OI may represent a potentially reversible provocation for the index seizure, while seizures in high functioning CLWH without a CNS OI may be the result of a prior brain injury or susceptibility to seizures unrelated to HIV and thus represent an ongoing predisposition to seizures. Plain Language Summary This study followed CLWH who experienced a new onset seizure to find out how many go on to have more seizures and identify any patient characteristics associated with having more seizures. The study found that mortality rates continue to be high beyond the acute clinical presentation with new onset seizure. Children with a CNS OI causing the new onset seizure had a lower risk of later seizures, possibly because the trigger for the seizure can be treated. In contrast, high functioning children without a CNS OI were at higher risk of future seizures.

COVID-19 has caused 4 million deaths as of 24 August 2021. A significant number of patients were admitted to undesignated ICU areas before transfer to a desig-nated ICU owing to the unavailability of ICU beds. We aim to compare the mortality and length of stay of patients in these 2 areas. We retrospectively studied all critically ill patients with COVID-19 pneumonia who were admitted to Dubai hospital between 1 January 2020 and 30 June 2020. Patients who transferred to wards other than designated ICU constitute cases, while those who were admitted directly to designated ICUs constitute controls. The demographics, clinical parameters, and treatment profile of these patients were recorded and compared. Mortality and length of stay were calculated. The sample includes 239 subjects (admitted to an undesignated ICU ward [n = 107] and directly admitted to a designated ICU ward [n = 132]). Patients admitted to an undesignated ICU had extra transfers between wards and had more days on MV (median [IQR] 18 (19) vs. 11 (14); P = 0.001), greater length of stay in the ICU (median [IQR]) 21.5 (19) vs. 15 (14); P = 0.001), and greater length of stay in hospital (median [IQR] 32 (28) vs. 21 (26); P = 0.001). Multiple logistic regression analysis showed that patients treated at an undesignated ICU have better survival (odds of death for patients cared for at an undesignated ICU was 0.347 with CI 0.178-0.676; P = 0.002). Multiple linear regression analysis also showed that patients treated at an undesignated ICU had longer stay - 4.2 days, CI 1.3-7.13, P = 0.004). Admission to an undesignated ICU impacts mortality and length of ICU and hospital stay.

Objective This study describes clinical profiles including human immunodeficiency virus (HIV) disease history and seizure etiology among children living with HIV presenting with new‐onset seizure during the era of antiretroviral therapy (ART) in Zambia. 30‐day mortality and cause of death are also reported. Methods Children living with HIV (CLWHIV) with new‐onset seizures were prospectively evaluated at one large urban teaching hospital and two non‐urban healthcare facilities. Interviews with family members, review of medical records, and where needed, verbal autopsies were undertaken. Two clinicians who were not responsible for the patients' care independently reviewed all records and assigned seizure etiology and cause of death with adjudication as needed. Results From April 2016 to June 2019, 73 children (49 urban, 24 rural) were identified. Median age was 6 years (IQR 2.2‐10.0) and 39 (53%) were male children. Seizures were focal in 36 (49%) and were often severe, with 37% presenting with multiple recurrent seizures in the 24 hours before admission or in status epilepticus. Although 36 (49%) were on ART at enrollment, only 7 of 36 (19%) were virally suppressed. Seizure etiologies were infectious in over half (54%), with HIV encephalitis, bacterial meningitis, and tuberculous meningitis being the most common. Metabolic causes (19%) included renal failure and hypoglycemia. Structural lesions identified on imaging accounted for 10% of etiologies and included stroke and non‐accidental trauma. No etiology could be identified in 12 (16%) children, most of whom died before the completion of clinical investigations. Twenty‐two (30%) children died within 30 days of the index seizure. Significance Despite widespread ART roll out in Zambia, new‐onset seizure in CLWHIV occurs in the setting of advanced, active HIV disease. Seizure severity/burden is high as is early mortality. Enhanced programs to assure early ART initiation, improve adherence, and address ART failure are needed to reduce the burden of neurological injury and premature death in CLWHIV.

Introduction. The developing world continues to face challenges in closing the large treatment gap for epilepsy, due to a high burden of disease and few experienced providers to manage the condition. Children with epilepsy are susceptible to higher rates of developmental impairments and refractory disease due to delays or absence of appropriate management as a result. We demonstrated that a structured education intervention on pediatric epilepsy can improve knowledge, confidence, and impact clinical practice of first level providers in Zambia. Methods. Three first-level facilities across Zambia were included. After initial pilot versions and revisions, the final course was implemented at each site. Pre- and post-intervention knowledge and confidence assessments were performed. Additionally, chart reviews were conducted prior to intervention and 4 months after completion of training at each site to assess change on management. Results. Twenty-three of the original 24 participants from all 3 sites completed the training; 48% clinical officers, 43% nurses, 9% other expertise. Of the 15 concepts tested by knowledge assessment, 12 showed trends in improvement, 7 of which were significant (P < .05). Chart reviews demonstrated significant improvement in documentation of seizure description (P = .008), seizure frequency (P = .00), and possible causes of seizures/epilepsy (P = .034). Discussion. Key elements of success to this program included hands on clinical skills building and case-based teaching, development of a program with direct and ongoing input from the target audience, and inclusion of assessments to monitor impact on clinical practice. Future studies looking at health outcomes are necessary to determine sustained impact.

BackgroundA large proportion of front-line paediatric healthcare in Zambia is delivered by staff with no specialist paediatric training, and training this group could significantly reduce preventable child deaths. In 2019–2020, the Tropical Health and Education Trust undertook a 6-month paediatric capacity building project in Lusaka, Zambia, funded by Health Education England.ObjectivesThe aim of the project was to improve paediatric skills of front-line healthcare workers.MethodsThree volunteers were recruited (2 paediatric registrars and 1 programme and evaluation consultant) to work with first (district) level hospitals in Lusaka. A needs analysis found that there was an under-utilisation of the structured approach to the recognition and stabilisation of unwell children on the front line.The initial suggestion of embedding the Emergency Triage and Treatment (ETAT) course was not an option due to insufficient resources and funding for a five-day course. The volunteers worked with local and international colleagues to design a one-day alternative based on local data, priorities and available resources. The Paediatric Assessment and Stabilisation (PAS) course is based on national Zambia Paediatric Association and international protocols (including ETAT, APLS and WHO).A ‘teach the teacher’ approach was used with instructors nominated from four first level hospitals and University Teaching Hospital (the local tertiary referral hospital). Two half-day sessions were held to train instructors on course teaching methods, and encourage them to be local ‘PAS Champions’ to embed their new knowledge and skills amongst their own hospital teams post-course.The pilot was funded by Lusaka Provincial Health Office, with participants recruited from the same four first level hospitals as the instructors. The course was delivered in small groups using Peyton’s four stage approach and simulation. A simulation test scenario was used at the end of the course to ensure credibility. Impact of the course was measured using a Likert scale questionnaire to assess participant confidence in managing critically ill children before and after the course.ResultsThe pilot ran four separate PAS courses. These were attended by 91 participants (including clinical officers, medical officers and nurses) of which 88 passed. Pre and post course questionnaires showed participant confidence scores increased by 19% in assessment of unwell children, and by 22% in treatment of unwell children. Free text by participants showed a positive impact on individual clinical practice. 25 instructors were trained to teach on the PAS course, as well as 2 course directors and 1 course administrator. Instructors also fed back that critically unwell children were more effectively managed within their facilities after the course. Ownership of the course was handed back to the ZPA and Ministry of Health at the end of the pilot. Unfortunately, the COVID-19 pandemic prevented any further impact analysis, and any further PAS courses were put on hold.ConclusionsAt a time where national resources are limited to fund internationally recognised paediatric courses (e.g. ETAT), it is hoped that the structured approach learned on the PAS course can benefit front line paediatric care in Zambia at present, and become an effective ‘stepping-stone’ to these courses.