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1.
Epilepsia Open ; 9(2): 750-757, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38366961

RESUMO

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.


Assuntos
Epilepsia Generalizada , Infecções por HIV , Criança , Humanos , Anticonvulsivantes/uso terapêutico , Estudos de Coortes , Convulsões/tratamento farmacológico , Epilepsia Generalizada/tratamento farmacológico , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Dano Encefálico Crônico/induzido quimicamente , Dano Encefálico Crônico/complicações , Dano Encefálico Crônico/tratamento farmacológico
2.
J Acquir Immune Defic Syndr ; 95(3): 291-296, 2024 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-38032746

RESUMO

BACKGROUND: Seizures are relatively common among children with HIV in low- and middle-income countries and are associated with significant morbidity and mortality. Early treatment with antiretroviral therapy (ART) may reduce this risk by decreasing rates of central nervous system infections and HIV encephalopathy. METHODS: We conducted a prospective, unmatched case-control study. We enrolled children with new-onset seizure from University Teaching Hospital in Lusaka, Zambia and 2 regional hospitals in rural Zambia. Controls were children with HIV and no history of seizures. Recruitment took place from 2016 to 2019. Early treatment was defined as initiation of ART before 12 months of age, at a CD4 percentage >15% in children aged 12-60 months or a CD4 count >350 cells/mm 3 for children aged 60 months or older. Logistic regression models were used to evaluate the association between potential risk factors and seizures. RESULTS: We identified 73 children with new-onset seizure and compared them with 254 control children with HIV but no seizures. Early treatment with ART was associated with a significant reduction in the odds of seizures [odds ratio (OR) 0.04, 95% confidence interval: 0.02 to 0.09; P < 0.001]. Having an undetectable viral load at the time of enrollment was strongly protective against seizures (OR 0.03, P < 0.001), whereas history of World Health Organization Stage 4 disease (OR 2.2, P = 0.05) or CD4 count <200 cells/mm 3 (OR 3.6, P < 0.001) increased risk of seizures. CONCLUSIONS: Early initiation of ART and successful viral suppression would likely reduce much of the excess seizure burden in children with HIV.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , Criança , Humanos , Lactente , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Zâmbia/epidemiologia , Estudos de Casos e Controles , Fatores de Risco , Convulsões/tratamento farmacológico , Convulsões/prevenção & controle , Convulsões/complicações , Contagem de Linfócito CD4 , Fármacos Anti-HIV/uso terapêutico
3.
Int J Crit Illn Inj Sci ; 13(3): 85-91, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38023571

RESUMO

Background: The optimal timing of intubation has been debated among healthcare professionals, current studies do not show any differences between early and late intubation. most studies failed to show any significant difference in clinical outcomes between early or late intubation. Methods: The study was conducted as a retrospective review of subjects with confirmed coronavirus disease 2019 admitted to the Dubai Hospital intensive care unit (ICU). Study variables included time to intubation, duration of supplemental oxygen requirement >15 L/min, and cumulative duration of tachypnea and tachycardia while on the aforementioned oxygen requirement on this oxygen usage level. Each time duration was assessed for correlation with clinical variables including mortality and length of stay in ICU and hospital. Results: Subjects who require endotracheal intubation within 4 h after the start of oxygen >15 L/min have lower survival (P = 0.03). Subjects who have tachypnea on the aforementioned oxygen requirement for 6-19.5 h (P = 0.01) before they require intubation have better survival. No duration of tachycardia has any significant effect on survival. Only the duration of invasive mechanical ventilation (MV) correlated with the hospital length of stay. Conclusions: Subjects who require endotracheal intubation within 4 h after the start of oxygen >15 L/min have lower survival. The optimal time for intubation is after tachypnea of 6 h but before 19.5 h. No duration of tachycardia has any significant effect on survival. Only the duration of invasive MV correlated with the hospital length of stay.

4.
Molecules ; 28(17)2023 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-37687181

RESUMO

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.


Assuntos
Antioxidantes , Chalconas , Antioxidantes/farmacologia , Chalconas/farmacologia , Lipopolissacarídeos/farmacologia , Morte Celular , Peróxidos , Citocinas
5.
Chem Commun (Camb) ; 59(34): 5090-5093, 2023 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-37039018

RESUMO

Herein, we report the synthesis and self-assembly of a new class of amphiphilic azo dyes derived from a plant-based phenol, cardanol. Analysis of the self-assembly of these new azo derivatives was intriguing, and they exhibit some unique nanostructures, such as bicelles and microgel-like structures, and smectic-type thermotropic mesophases.

6.
Am J Trop Med Hyg ; 108(5): 1052-1062, 2023 05 03.
Artigo em Inglês | MEDLINE | ID: mdl-36972691

RESUMO

Lumbar puncture (LP) and cerebrospinal fluid (CSF) diagnostics are critical for evaluating central nervous system infections but are often not conducted, resulting in the "Tap Gap." To investigate patient, provider, and health systems factors contributing to the Tap Gap in Zambia, we conducted focus group discussions with adult caregivers of hospitalized inpatients and in-depth interviews with nurses, clinicians, pharmacy workers, and laboratory staff. Transcripts were independently thematically categorized by two investigators using inductive coding. We identified seven patient-related factors: 1) alternative understandings of CSF; 2) alternative information about LPs, including misinformation; 3) mistrust of doctors; 4) consent delays; 5) fear of blame; 6) peer pressure against consent; and 7) association between LP and stigmatized conditions. Four clinician-related factors were identified: 1) limited LP knowledge and expertise, 2) time constraints, 3) delays in LP requests by clinicians, and 4) fear of blame for bad outcomes. Finally, five health systems-related factors were identified: 1) supply shortages, 2) constrained access to neuroimaging, 3) laboratory factors, 4) availability of antimicrobial medications, and 5) cost barriers. Efforts to improve LP uptake must incorporate interventions to increase patient/proxy willingness to consent and improve clinician LP competencies while addressing both upstream and downstream health system factors. Key upstream factors include inconsistently available consumables for performing LPs and lack of neuroimaging. Critical downstream factors include laboratory services that offer poor availability, reliability, and/or timeliness of CSF diagnostics and the reality that medications needed to treat diagnosed infections are often unavailable unless the family has resources to purchase privately.


Assuntos
Lipopolissacarídeos , Punção Espinal , Adulto , Humanos , Zâmbia , Reprodutibilidade dos Testes , Pacientes Internados
7.
Molecules ; 27(23)2022 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-36500302

RESUMO

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.


Assuntos
Anti-Infecciosos , Chalconas , Animais , Antioxidantes/farmacologia , Antioxidantes/química , Testes de Sensibilidade Microbiana , Chalconas/farmacologia , Antocianinas , Extratos Vegetais/química , Anti-Infecciosos/farmacologia , Antibacterianos/farmacologia , Antibacterianos/química , Escherichia coli
8.
PLoS One ; 17(10): e0268414, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36206262

RESUMO

BACKGROUND: 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. METHODS: 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. DISCUSSION: 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.


Assuntos
Antipiréticos , Malária Falciparum , Fármacos Neuroprotetores , Parasitos , Acetaminofen/uso terapêutico , Animais , Antipiréticos/uso terapêutico , Sistema Nervoso Central , Criança , Febre/tratamento farmacológico , Febre/prevenção & controle , Histidina , Humanos , Ibuprofeno/uso terapêutico , Malária Falciparum/complicações , Malária Falciparum/tratamento farmacológico , Fármacos Neuroprotetores/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Convulsões/tratamento farmacológico , Resultado do Tratamento , Zâmbia
9.
Epilepsia Open ; 7(2): 315-324, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35305291

RESUMO

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.


Assuntos
Complexo AIDS Demência , Infecções por HIV , Complexo AIDS Demência/complicações , Criança , Pré-Escolar , Feminino , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Humanos , Masculino , População Rural , Convulsões/tratamento farmacológico , Convulsões/etiologia , Zâmbia
10.
Anaesthesiol Intensive Ther ; 54(5): 378-386, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36734448

RESUMO

INTRODUCTION: 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. MATERIAL AND METHODS: 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. RESULTS: 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). CONCLUSIONS: Admission to an undesignated ICU impacts mortality and length of ICU and hospital stay.


Assuntos
COVID-19 , Síndrome do Desconforto Respiratório , Humanos , Tempo de Internação , COVID-19/terapia , Estudos Retrospectivos , Estado Terminal/terapia , Unidades de Terapia Intensiva , Mortalidade Hospitalar
11.
Curr Org Synth ; 19(3): 463-475, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34620065

RESUMO

AIMS: In this paper, we report on the synthesis and liquid crystalline properties of some low molecular weight bis-chalcone compounds derived from acetone, cyclopentanone and cyclohexanone mesogenic cores. BACKGROUND: Structurally bis-chalcones belong to a broader family of chalcone compounds. Chalcone is a compound that consists of two aromatic rings linked by an unsaturated α, ß-ketone. OBJECTIVE: Liquid crystalline chalcones are prepared by aliphatic chain substituents on two aromatic rings. Chalcones are well studied for their mesomorphic properties. Compared to a large number of chalcone based LCs reported, only a few articles have been published on the mesomorphic properties of bis-chalcone compounds. The target compounds of the present study varied not only in their central core but also in number and position of terminal aliphatic chain substitution-a key structural unit in deciding the liquid crystalline properties of a compound. METHODS: All target compounds were synthesized in good yield by base catalyzed Claisen-Schmidt condensation reaction. Molecular structures were confirmed by FT-IR, 1H NMR, 13C NMR, and mass spectroscopic methods. Liquid crystalline property of these compounds was evaluated using polarizing optical microscopy and differential scanning calorimetry. RESULTS: Although none of the acetone based compounds exhibited mesomorphism, cyclopentanone and cyclohexanone based compounds with octyloxy chain at para position on either side of the dibenzylidine ring stabilized liquid crystalline smectic (SmA and SmC) and nematic (N) phases. The observed structure-liquid crystalline property relationship was explained by structural analysis of molecules using DFT calculations. Considering the inherent photoluminescence nature of the chalcone moiety, a preliminary study was carried out on a selected compound to reveal its fluorescence property. CONCLUSION: Our study brings about an important structure-liquid crystalline property relationship in a relatively unexplored class of bis-chalcone liquid crystals.


Assuntos
Chalcona , Chalconas , Acetona , Chalcona/química , Cicloexanonas , Peso Molecular , Espectroscopia de Infravermelho com Transformada de Fourier
12.
J Acquir Immune Defic Syndr ; 89(1): 56-63, 2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34878435

RESUMO

BACKGROUND: Multiple previous studies have identified a detrimental effect of pediatric HIV on cognitive function. Socioeconomic status (SES) is one of the strongest predictors of cognitive performance and may affect the relationship between HIV and cognition. METHODS: As part of the ongoing HIV-Associated Neurocognitive Disorders in Zambia (HANDZ) study, a prospective cohort study, we recruited 208 participants with HIV and 208 HIV-exposed uninfected controls, all aged 8-17 years. A standardized questionnaire was administered to assess SES, and all participants had comprehensive neuropsychological testing. An NPZ8 score was derived as a summary measure of cognitive function. Logistic regression and linear regression were used to model the relationship between SES and cognitive function, and mediation analysis was used to identify specific pathways by which SES may affect cognition. RESULTS: Children with HIV performed significantly worse on a composite measure of cognitive function (NPZ8 score -0.19 vs. 0.22, P < 0.001) and were more likely to have cognitive impairment (33% vs. 19%, P = 0.001). Higher SES was associated with reduced risk of cognitive impairment (odds ratio 0.8, 95% confidence interval: 0.75-0.92, P < 0.001) in both groups, with similar effects in children with HIV and HIV-exposed uninfected groups. SES was more strongly correlated with NPZ8 score in children with HIV than in uninfected controls (Pearson's R 0.39 vs. 0.28), but predicted NPZ8 in both groups. Mediation analysis suggested that the effect of SES on cognition was most strongly mediated through malnutrition. CONCLUSIONS: Cognitive function is strongly correlated with SES in children with HIV, suggesting a synergistic effect of HIV and poverty on cognitive function.


Assuntos
Infecções por HIV , Adolescente , Criança , Cognição , Infecções por HIV/psicologia , Humanos , Transtornos Neurocognitivos/complicações , Transtornos Neurocognitivos/epidemiologia , Estudos Prospectivos , Classe Social , Zâmbia/epidemiologia
13.
J Cancer Res Ther ; 18(3): 681-690, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34708812

RESUMO

Objective: To evaluate the antiproliferative and apoptosis inducing activity of different sydnones on cancer cell lines and their interaction with cancer proteins by molecular docking studies. Material and Methods: Antiproliferative activity was carried out by MTT assay and apoptosis inducing activity was performed by DAPI and Annexin V and propidium iodide staining. Molecular docking studies were performed using AutoDock Tools 1.5.6. Pharmacokinetics properties like ADME and toxicity were analysed by pkCSM web server. Result: In this study, four new sydnone compounds 3-(4-nonylbiphenyl-4'-yl) sydnone (MC-182), 3-(4-propylbiphenyl-4'-yl) sydnone (MC-454), 3-(4-hexylbiphenyl-4'-yl) sydnone (MC-433), and 3-(4-methylbiphenyl-4'-yl) sydnone (MC-431) were screened for antiproliferative and apoptotic effect against BT-474 (human breast cancer), HeLa (human cervical cancer) and Jurkat (human myeloid leukemia) Mostly, all the sydnone compounds exhibited decent antiproliferative effectiveness, but compound MC-431, MC-433, and MC-454 showed more antiproliferative activity (IC50 1.71, 10.09 and 2.87 µM against BT-474, Hela and Jurkat cell line, respectively). The changes of morphological characteristics of cancer cells determined by staining techniques indicate the apoptotic cell death. The molecular docking and interaction studies were carried out between sydnones with cancer proteins (epidermal growth factor domain receptor tyrosine kinase [EGF-TK], tumor necrosis factor-alpha [TNF-α] and Caspase3. Among all four sydnone molecules, two compounds MC-454 and MC-431 showed good binding energy with targeted proteins. Drug-like property was predicted by ADME toxicity study. Conclusion: The results indicate sydnone compounds were found to exhibit anticancer activity by inducing apoptosis. The molecular docking study of sydnones with cancer proteins showed a decent interaction affinity. The results of absorption, distribution, metabolism, excretion and toxicity studies by the Insilco approach also proved that MC-454 sydnone showed better In-Vivo administration. Thus, the current research work indicates that these sydnone compounds would be prospective in developing anticancer medicines.


Assuntos
Antineoplásicos , Sidnonas , Antineoplásicos/química , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Ensaios de Seleção de Medicamentos Antitumorais , Receptores ErbB/metabolismo , Humanos , Simulação de Acoplamento Molecular , Estrutura Molecular , Estudos Prospectivos , Sidnonas/farmacologia
14.
Am J Trop Med Hyg ; 105(5): 1429-1433, 2021 08 09.
Artigo em Inglês | MEDLINE | ID: mdl-34370711

RESUMO

In much of sub-Saharan Africa, lumbar punctures (LPs) are performed less frequently than indicated. This is often attributed to patient/family refusal; however, other factors have not been systematically evaluated. We investigated predictors of LP performance for a prospective cohort of people with HIV and new-onset seizures at three hospitals in Zambia. We enrolled 257 participants, including 184 (72%) adults and 144 (56%) urban participants. LPs were performed for 65% of adults and 33% of children, and for 69% of urban and 38% of rural participants. In multivariate logistic regression analyses, LP completion was significantly less likely at one rural site and among children compared to adults. The worst WHO HIV disease stage was associated with increased odds of undergoing LP. Low LP completion rates in Zambia are multifactorial and related to health system and provider factors and patient/family preferences. Further research is necessary to understand this complex problem and develop interventions to improve LP uptake.


Assuntos
Infecções por HIV/diagnóstico , População Rural/estatística & dados numéricos , Convulsões/diagnóstico , Punção Espinal/estatística & dados numéricos , População Urbana/estatística & dados numéricos , Adolescente , Adulto , Fatores Etários , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estudos Prospectivos , Adulto Jovem , Zâmbia
15.
J Pediatric Infect Dis Soc ; 10(12): 1071-1079, 2021 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-34437702

RESUMO

BACKGROUND: Place-based inequalities, such as exposure to violence and access to nutritious food and clean water, may contribute to human immunodeficiency virus (HIV)-associated cognitive impairment. In this study, we investigated neighborhood effects on cognition in children and adolescents with HIV in Lusaka, Zambia. METHODS: We conducted a prospective cohort study of 208 children with perinatally acquired HIV (ages 8-17) and 208 HIV-exposed uninfected controls. Participants underwent neuropsychological testing and interviews assessing socioeconomic status. Geographic regions with clusters of participants with HIV and cognitive impairment were identified using quantitative geographic information systems (QGIS) and SaTScan. Associations between location of residence and cognitive function were evaluated in bivariable and multivariable regression models. Mediation analysis was performed to assess direct and indirect effects of location of the residence on cognitive impairment. RESULTS: Residence in Chawama, one of the poorest neighborhoods in Lusaka, was significantly associated with cognitive impairment in participants with HIV (odds ratio 2.9; P = .005) and remained significant in a multivariable regression model controlling for potential confounders. Mediation analysis found that 46% of the cognitive effects of residence in Chawama were explained by higher rates of malnutrition, lower school attendance, and poorer self-reported health. CONCLUSIONS: Place-based socioeconomic inequality contributes to cognitive impairment in Zambian children and adolescents with HIV. Neighborhood effects may be mediated by concentrated poverty, malnutrition, limited access to education and health care, and other yet unknown environmental factors that may be potentially modifiable.


Assuntos
Disfunção Cognitiva , Infecções por HIV , Adolescente , Criança , Disfunção Cognitiva/epidemiologia , Sistemas de Informação Geográfica , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Humanos , Estudos Prospectivos , Fatores Socioeconômicos , Zâmbia/epidemiologia
16.
Glob Pediatr Health ; 7: 2333794X20968718, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33225022

RESUMO

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.

17.
Pediatr Neurol ; 102: 36-43, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31492585

RESUMO

BACKGROUND: Neurocysticercosis is the most common parasitic infection of the brain and a leading cause of epilepsy in resource-limited settings. Although neurocysticercosis and human immunodeficiency virus coinfections have commonly been reported, there are few data on how they interact. As part of an observational study of human immunodeficiency virus and cognition in Lusaka, Zambia, we identified a cluster of subjects with neurocysticercosis. We hypothesized that the neighborhood of residence may be an important factor driving clustering of neurocysticercosis and used a geographic information systems approach to investigate this association. METHODS: A total of 34 subjects with human immunodeficiency virus and 13 subjects without human immunodeficiency virus (aged eight to 17 years) enrolled in the HIV-Associated Neurocognitive Disorders in Zambia study, had magnetic resonance imaging of the brain performed, and were evaluated for neurocysticercosis. Quantitative geographic information systems was utilized to investigate the relationship between neighborhood of residence, HIV, and neurocysticercosis. RESULTS: Three of 34 subjects with human immunodeficiency virus (8.82%) and one of 13 controls were found to have neurocysticercosis. Geographic cluster analysis demonstrated that all subjects with neurocysticercosis were clustered in two adjacent neighborhoods (Chawama and Kanyama) with lower rates of piped water (Chawama: 22.8%, Kanyama: 26.7%) and flush toilets (Chawama: 14.0%, Kanyama: 14.0%) than the surrounding neighborhoods. CONCLUSION: We describe a cluster of patients with both neurocysticercosis and human immunodeficiency virus in Lusaka. Cases of neurocysticercosis clustered in neighborhoods with low rates of piped water and limited access to flush toilets. Geographic information systems may be a useful approach for studying the relationship between human immunodeficiency virus and neurocysticercosis. Larger studies are necessary to further investigate this association.


Assuntos
Sistemas de Informação Geográfica , Infecções por HIV/epidemiologia , Neurocisticercose/epidemiologia , Adolescente , Criança , Comorbidade , Feminino , Infecções por HIV/diagnóstico por imagem , Humanos , Estudos Longitudinais , Imageamento por Ressonância Magnética , Masculino , Neurocisticercose/diagnóstico por imagem , Zâmbia/epidemiologia
18.
BMJ Open ; 9(7): e029322, 2019 07 24.
Artigo em Inglês | MEDLINE | ID: mdl-31345977

RESUMO

OBJECTIVE: Epilepsy 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. SETTING: In 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. PARTICIPANTS: With 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. INTERVENTION: COs were trained in a 3-week structured course on paediatric seizures and epilepsy, based on adapted evidence-based guidelines. RESULTS: Preassessment 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. CONCLUSIONS: This 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.


Assuntos
Epilepsia/terapia , Pessoal de Saúde/educação , Adulto , Criança , Feminino , Humanos , Masculino , Projetos Piloto , Atenção Primária à Saúde , Zâmbia
19.
ACS Appl Mater Interfaces ; 9(45): 39569-39575, 2017 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-29067801

RESUMO

We report a robust soft photonic crystal system, fabricated using blue phase (BP) liquid crystal, which can efficiently filter the visible light. The BP gel system is obtained without surface treatment or polymerization, and thus is facile and cost effective to fabricate. Perfect monodomain with vivid color is achieved with a low electric field, which can be further tuned to reflect a second color. Most importantly, apart from the field-induced color switching, a dark/transparent state is also achieved due to complete unwinding of the BP helical structure. A potential application as a tunable color-reflecting mirror, which can be switched between "reflecting" and "transparent" states, is proposed.

20.
Afr J Emerg Med ; 7(Suppl): S3-S9, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-30505668

RESUMO

INTRODUCTION: We sought to review recent evidence-based guidelines and where applicable, primary data to extrapolate insights into the appropriate management of acute seizures in children in resource-limited settings. METHODS: PubMed and Google scholar searches were conducted with attention to publications from the last three to five years, including a focused search for acute seizure management guidelines relevant to resource limited settings. Since all guidelines to date, except the World Health Organization's, assume ready access to invasive ventilation and advanced diagnostic testing, guidelines and primary data were used to propose management appropriate for resource-limited settings where respiratory suppression from treatment presents a major challenge in management. RESULTS: Acute seizures are among the commonest medical emergencies encountered in the African settings. Seizure management must occur simultaneously with the diagnostic assessment, which should include addressing life threatening causes (e.g. hypoglycaemia, malaria) and with attention given to the most likely aetiology in a particular region or setting. For ongoing seizures, initial treatment with benzodiazepines is indicated. There is evidence of efficacy for several agents and delivery modes. Longer-acting antiepileptic drugs (AEDs) should be on hand if acute seizures fail to respond to two doses of benzodiazepines. There is little direct evidence comparing the relative efficacy of different long-acting AEDs for acute seizure management in African children. Findings suggest that generalising data from Western settings, where different aetiologies and risk factors for seizures prevail, may be inappropriate. DISCUSSION: Though treatment options and diagnostics may be dictated by available medications and capacity, it is possible for virtually any healthcare setting to develop a relevant and feasible local guideline for seizure management. Clear specifications on when to refer to a higher level of care should be part of the care plan.

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