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1.
BMJ Paediatr Open ; 8(1)2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38844382

RESUMO

BACKGROUND: Neural tube defects are a significant cause of morbidity and mortality that can occur in the early pregnancy periods. Though the burden is high, it gains only limited attention. In Ethiopia, the estimated number of neural tube defect cases was significantly higher. So, identifying factors contributing to it would be significant for planning risk reduction and preventive strategies. Therefore, identifying the possible determinants was aimed at this study. METHODS: A hospital-based, unmatched case-control study was conducted on 104 cases and 208 controls selected from neonatal intensive care units of teaching hospitals in Gedeo Zone and Sidama Region, southern Ethiopia from December 2021 to November 2022. All neural tube defect cases were included consecutively and controls were selected by using a simple random sampling method. Data were collected using interviewer-administered semistructured questionnaires. Data analysis was done by using SPSS V.25. Binary logistic regression was used, and variables with a p value less than 0.25 in bivariate analysis were entered into the multivariable logistic regression model. An adjusted OR with a 95% CI was estimated, and finally, variables that show a level of p value less than 0.05 in multivariable analysis were declared statistically significant. RESULT: After controlling confounders, factors such as unplanned pregnancy 2.20 (95% CI 1.20 to 4.041), history of abortions 2.09 (95% CI 1.19 to 3.67), khat chewing 6.67 (95% CI 2.95 to 15.06), antipyretic and analgesic medications 2.87 (95% CI 1.47 to 5.56) and, being a female neonate 2.11 (95% CI 1.21 to 3.67) were significantly associated with a neural tube defect. CONCLUSION: This study has identified some determinants of neural tube defects. Hence, the behavioural, medical and obstetrical conditions of mothers need serious evaluation in the prepregnancy period. So, improving preconception counselling and prenatal care practices would have a significant role in reducing the risk of neural tube defects.


Assuntos
Hospitais de Ensino , Unidades de Terapia Intensiva Neonatal , Defeitos do Tubo Neural , Humanos , Etiópia/epidemiologia , Feminino , Estudos de Casos e Controles , Recém-Nascido , Unidades de Terapia Intensiva Neonatal/estatística & dados numéricos , Masculino , Gravidez , Defeitos do Tubo Neural/epidemiologia , Defeitos do Tubo Neural/prevenção & controle , Adulto , Fatores de Risco , Adulto Jovem
2.
BMC Prim Care ; 25(1): 8, 2024 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-38166736

RESUMO

BACKGROUND: Antibiotic resistance is growing globally. The practice of health professionals when prescribing antibiotics in primary health care settings significantly impacts antibiotic resistance. Antibiotic prescription is a complex process influenced by various internal and external factors. This systematic review aims to summarize the available evidence regarding factors contributing to the variation in antibiotic prescribing among physicians in primary healthcare settings. METHODS: This systematic review was conducted based on PRISMA guidelines. We included qualitative, quantitative and mixed methods studies that examined factors influencing prescription practice and variability among primary healthcare physicians. We excluded editorials, opinions, systematic reviews and studies published in languages other than English. We searched studies from electronic databases: PubMed, ProQuest Health and Medicine, Web Science, and Scopus. The quality of the included studies was appraised using the Mixed Methods Appraisal Tool (Version 2018). Narrative synthesis was employed to synthesize the result and incorporate quantitative studies. RESULTS: Of the 1816 identified studies, 49 studies spanning 2000-2023 were eligible for review. The factors influencing antibiotic prescription practice and variability were grouped into physician-related, patient-related, and healthcare system-related factors. Clinical guidelines, previous patient experience, physician experience, colleagues' prescribing practice, pharmaceutical pressure, time pressure, and financial considerations were found to be influencing factors of antibiotic prescribing practice. In addition, individual practice patterns, practice volume, and relationship with patients were also other factors for the variability of antibiotic prescription, especially for intra-physician prescription variability. CONCLUSION: Antibiotic prescription practice in primary health care is a complex practice, influenced by a combination of different factors and this may account for the variation. To address the factors that influence the variability of antibiotic prescription (intra- and inter-physician), interventions should aim to reduce diagnostic uncertainty and provide continuous medical education and training to promote patient-centred care.


Assuntos
Antibacterianos , Médicos , Humanos , Resistência Microbiana a Medicamentos , Assistência Centrada no Paciente , Prescrições
3.
Cell Rep Med ; 4(11): 101292, 2023 11 21.
Artigo em Inglês | MEDLINE | ID: mdl-37992687

RESUMO

Glucagon-like peptide-1 (GLP-1) is an incretin hormone and neurotransmitter secreted from intestinal L cells in response to nutrients to stimulate insulin and block glucagon secretion in a glucose-dependent manner. Long-acting GLP-1 receptor agonists (GLP-1 RAs) have become central to treating type 2 diabetes (T2D); however, these therapies are burdensome, as they must be taken daily or weekly. Technological innovations that enable less frequent administrations would reduce patient burden and increase patient compliance. Herein, we leverage an injectable hydrogel depot technology to develop a GLP-1 RA drug product capable of months-long GLP-1 RA delivery. Using a rat model of T2D, we confirm that one injection of hydrogel-based therapy sustains exposure of GLP-1 RA over 42 days, corresponding to a once-every-4-months therapy in humans. Hydrogel therapy maintains management of blood glucose and weight comparable to daily injections of a leading GLP-1 RA drug. This long-acting GLP-1 RA treatment is a promising therapy for more effective T2D management.


Assuntos
Diabetes Mellitus Tipo 2 , Humanos , Animais , Ratos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Hidrogéis/uso terapêutico , Biomimética , Peptídeo 1 Semelhante ao Glucagon
4.
bioRxiv ; 2023 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-36778223

RESUMO

Glucagon-like peptide-1 (GLP-1) is an incretin hormone and neurotransmitter secreted from intestinal L-cells in response to nutrients to stimulate insulin and block glucagon secretion in a glucose-dependent manner. GLP-1 in itself is rapidly degraded, but long-acting GLP-1 receptor agonists (GLP-1 RAs) have become central in the treatment of T2D because of the beneficial effects extending also beyond glucose control. Currently, these therapeutics must be injected either daily or weekly or taken daily orally, leaving room for technological innovations that enable less frequent administrations, which will reduce patient burden and increase patient compliance. An ideal GLP-1 RA drug product would provide continuous therapy for upwards of four months from a single administration to match the cadence with which T2D patients typically visit their physician. In this work, we leveraged an injectable hydrogel depot technology to develop a long-acting GLP-1 RA drug product. By modulating the hydrogel properties to tune GLP-1 RA retention within the hydrogel depot, we engineered formulations capable of months-long GLP-1 RA delivery. Using a rat model of T2D, we confirmed that a single injection of hydrogel-based therapies exhibits sustained exposure of GLP-1 RA over 42 days, corresponding to a once-every four month therapy in humans. Moreover, these hydrogel therapies maintained optimal management of blood glucose and weight comparable to daily injections of a leading GLP-1 RA drug molecule. The pharmacokinetics and pharmacodynamics of these hydrogel-based long-acting GLP-1 RA treatments are promising for development of novel therapies reducing treatment burden for more effective management of T2D. Progress and Potential: While insufficient access to quality healthcare is problematic for consistent management of Type II diabetes (T2D), poor adherence to burdensome treatment regimens is one of the greatest challenges for disease management. Glucagon-like peptide 1 (GLP1) drugs have become central to the treatment of T2D due to their many beneficial effects beyond improving glucose control. Unfortunately, while optimization of GLP1 drugs has reduced treatment frequency from daily to weekly, significant patient burden still leads to poor patience compliance. In this work we developed an injectable hydrogel technology to enable GLP1 drugs only requiring administration once every four months. We showed in a rat model of T2D that one injection of a hydrogel-based therapy improves management of blood glucose and weight when compared with daily injections of the leading drug used clinically. These hydrogel-based GLP1 treatments are promising for reducing treatment burden and more effectively managing T2D. Future Impact: A GLP-1-based drug product providing four months of continuous therapy per administration could be transformational for the management of Type II diabetes (T2D). One of the most challenging aspects of diabetes management with GLP-1 mimics is maintenance of consistent levels of the drugs in the body, which is complicated by poor patient compliance on account of the high frequency of dosing required for current treatments. By leveraging a unique sustained release hydrogel depot technology we develop a months-long GLP-1 drug product candidate that has the potential to reduce patient burden and improving diabetes management. Overall, the hydrogel technology we describe here can dramatically reduce the frequency of therapeutic interventions, significantly increasing patient quality of life and reducing complications of diabetes management.Our next steps will focus on optimization of the drug formulations in a swine model of T2D, which is the most advanced and translationally-relevant animal model for these types of therapeutics. The long-term vision for this work is to translate lead candidate drug products towards clinical evaluation, which will also require comprehensive safety evaluation in multiple species and manufacturing our these materials according to Good Manufacturing Practices. The months-long-acting GLP-1 drug product that will come from this work has the potential to afford thus far unrealized therapeutic impact for the hundreds of millions of people with diabetes worldwide.

5.
Biomater Sci ; 11(6): 2065-2079, 2023 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-36723072

RESUMO

Prolonged maintenance of therapeutically-relevant levels of broadly neutralizing antibodies (bnAbs) is necessary to enable passive immunization against infectious disease. Unfortunately, protection only lasts for as long as these bnAbs remain present at a sufficiently high concentration in the body. Poor pharmacokinetics and burdensome administration are two challenges that need to be addressed in order to make pre- and post-exposure prophylaxis with bnAbs feasible and effective. In this work, we develop a supramolecular hydrogel as an injectable, subcutaneous depot to encapsulate and deliver antibody drug cargo. This polymer-nanoparticle (PNP) hydrogel exhibits shear-thinning and self-healing properties that are required for an injectable drug delivery vehicle. In vitro drug release assays and diffusion measurements indicate that the PNP hydrogels prevent burst release and slow the release of encapsulated antibodies. Delivery of bnAbs against SARS-CoV-2 from PNP hydrogels is compared to standard routes of administration in a preclinical mouse model. We develop a multi-compartment model to understand the ability of these subcutaneous depot materials to modulate the pharmacokinetics of released antibodies; the model is extrapolated to explore the requirements needed for novel materials to successfully deliver relevant antibody therapeutics with different pharmacokinetic characteristics.


Assuntos
COVID-19 , Hidrogéis , Camundongos , Animais , Hidrogéis/farmacocinética , SARS-CoV-2 , Anticorpos Amplamente Neutralizantes , Sistemas de Liberação de Medicamentos , Polímeros , Anticorpos
6.
Adv Ther (Weinh) ; 6(1)2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36684707

RESUMO

Monoclonal antibodies are a staple in modern pharmacotherapy. Unfortunately, these biopharmaceuticals are limited by their tendency to aggregate in formulation, resulting in poor stability and often requiring low concentration drug formulations. Moreover, existing excipients designed to stabilize these formulations are often limited by their toxicity and tendency to form particles such as micelles. Here, we demonstrate the ability of a simple "drop-in", amphiphilic copolymer excipient to enhance the stability of high concentration formulations of clinically-relevant monoclonal antibodies without altering their pharmacokinetics or injectability. Through interfacial rheology and surface tension measurements, we demonstrate that the copolymer excipient competitively adsorbs to formulation interfaces. Further, through determination of monomeric composition and retained bioactivity through stressed aging, we show that this excipient confers a significant stability benefit to high concentration antibody formulations. Finally, we demonstrate that the excipient behaves as an inactive ingredient, having no significant impact on the pharmacokinetic profile of a clinically relevant antibody in mice. This amphiphilic copolymer excipient demonstrates promise as a simple formulation additive to create stable, high concentration antibody formulations, thereby enabling improved treatment options such as a route-of-administration switch from low concentration intravenous (IV) to high concentration subcutaneous (SC) delivery while reducing dependence on the cold chain.

7.
Parasite Epidemiol Control ; 20: e00283, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36704118

RESUMO

Despite a significant reduction in the burden of malaria in children under five years-old, the efficient implementation of seasonal malaria chemoprevention (SMC) at large scale remains a major concern in areas with long malaria transmission. Low coverage rate in the unattainable areas during the rainy season, a shift in the risk of malaria to older children and the rebound in malaria incidence after stopping drug administration are mainly reported in these areas. These gaps represent a major challenge in the efficient implementation of SMC measures. An open randomized study was conducted to assess the effect of a fifth additional round to current regime of SMC in older children living in Dangassa, a rural malaria endemic area. Poisson regression Model was used to estimate the reduction in malaria incidence in the intervention group compared to the control group including age groups (5-9 and 10-14 years) and the use of long-lasting insecticidal nets (LLINs; Yes or No) with a threshold at 5%. Overall, a downward trend in participation rate was observed from August (94.3%) to November (87.2%). In November (round 4), the risk of malaria incidence was similar in both groups (IRR = 0.66, 95%CI [0.35-1.22]). In December (round 5), a decrease of 51% in malaria incidence was observed in intervention group compared to control group adjusted for age groups and the use of LLINs (IRR = 0.49, 95%CI [0.26-0.94]), of which 17% of reduction is attributable to the 5th round in the intervention group. An additional fifth round of SMC resulted in a significant reduction of malaria incidence in the intervention group. The number of SMC rounds could be adapted to the local condition of malaria transmission.

8.
Womens Health (Lond) ; 18: 17455057221133685, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36300294

RESUMO

BACKGROUND: In Ethiopia, the number of homeless girls and women is increasing, and the government has yet to devise a strategy to address the issue of teenage homelessness. They are influenced by numerous dimensions of health, including physical health, mental health, and social isolation. At all stages of homelessness, the stakeholders and homeless people must work together to address the issue. As a result, this study will be helpful to generate relevant data that may guide policymakers in designing solutions for this underserved group of people. OBJECTIVES: To explore coping mechanisms and suggestions to stakeholders among women experiencing homelessness in Dire Dawa city, eastern Ethiopia, 2021. DESIGN: A community-based phenomenological qualitative study was conducted at Dire Dawa city. METHODS: Data were collected from women experiencing homelessness and key informants through focus group discussion and in-depth interviews using a semi-structured tool. A total of 31 women experiencing homelessness (13 in-depth interviews and 3 focus group discussion with 6 participants in each) and 2 key informants participated in this study. Data were analyzed thematically using computer-assisted qualitative data analysis software Atlas.ti 7. The thematic analysis follows six steps: familiarization, coding, generating themes, reviewing themes, naming themes, and writing up. RESULTS: Two major themes were driven: coping mechanisms and suggestions to stakeholders. There are three subthemes under the coping mechanism (begging, survival sex, and child prostitution) while there are a total of seven subthemes under suggestions to stakeholders (integration and collaboration, special attention to children, family education, shelter and job, schooling, sexual education, and addiction rehabilitation). CONCLUSION: Child prostitution and survival sex are a very common coping mechanism which is practiced by women experiencing homelessness. Changing society's mindset and paying special attention to children is critical. Furthermore, the government and various stakeholders should work together to develop a rehabilitation program for street children who have been exposed to substance use.


Assuntos
Pessoas Mal Alojadas , Adolescente , Criança , Feminino , Humanos , Pessoas Mal Alojadas/psicologia , Adaptação Psicológica , Pesquisa Qualitativa , Grupos Focais , Escolaridade
9.
Earth Surf Process Landf ; 47(5): 1252-1270, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35873354

RESUMO

The meandering of alluvial rivers may be forced by normal faulting due to tectonically altered topographic gradients of the river valley and channel at and near the fault zone. Normal faulting can affect river meandering by either instantaneous (e.g. surface-rupturing earthquakes) or gradual displacement. To enhance our understanding of river channel response to tectonic faulting at the fault zone scale we used the physics-based, two-dimensional morphodynamic model Nays2D to simulate the responses of a laboratory-scale alluvial river with vegetated floodplain to various faulting and offset scenarios. The results of a model with normal fault downstepping in the downstream direction show that channel sinuosity and bend radius increase up to a maximum as a result of the faulting-enhanced valley gradient. Hereafter, a chute cutoff reduces channel sinuosity to a new dynamic equilibrium value that is generally higher than the pre-faulting sinuosity. A scenario where a normal fault downsteps in the upstream direction leads to reduced morphological change upstream of the fault due to a backwater effect induced by the faulting. The position within a meander bend at which faulting occurs has a profound influence on the evolution of sinuosity; fault locations that enhance flow velocities over the point bar during floods result in a faster sinuosity increase and subsequent chute cutoff than locations that enhance flow velocity directed towards the floodplain. This upward causation from the bend scale to the reach and floodplain scale arises from the complex interactions between meandering and floodplain and the nonlinearities of the sediment transport and chute cutoff processes. Our model results provide a guideline to include process-based reasoning in the interpretation of geomorphological and sedimentological observations of fluvial response to faulting. The combination of these approaches leads to better predictions of possible effects of faulting on alluvial river meandering.

10.
bioRxiv ; 2022 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-35665002

RESUMO

Prolonged maintenance of therapeutically-relevant levels of broadly neutralizing antibodies (bnAbs) is necessary to enable passive immunization against infectious disease. Unfortunately, protection only lasts for as long as these bnAbs remain present at a sufficiently high concentration in the body. Poor pharmacokinetics and burdensome administration are two challenges that need to be addressed in order to make pre- and post-exposure prophylaxis with bnAbs feasible and effective. In this work, we develop a supramolecular hydrogel as an injectable, subcutaneous depot to encapsulate and deliver antibody drug cargo. This polymer-nanoparticle (PNP) hydrogel exhibits shear-thinning and self-healing properties that are required for an injectable drug delivery vehicle. In vitro drug release assays and diffusion measurements indicate that the PNP hydrogels prevent burst release and slow the release of encapsulated antibodies. Delivery of bnAbs against SARS-CoV-2 from PNP hydrogels is compared to standard routes of administration in a preclinical mouse model. We develop a multi-compartment model to understand the ability of these subcutaneous depot materials to modulate the pharmacokinetics of released antibodies; the model is extrapolated to explore the requirements needed for novel materials to successfully deliver relevant antibody therapeutics with different pharmacokinetic characteristics.

11.
Preprint em Inglês | bioRxiv | ID: ppbiorxiv-493347

RESUMO

Prolonged maintenance of therapeutically-relevant levels of broadly neutralizing antibodies (bnAbs) is necessary to enable passive immunization against infectious disease. Unfortunately, protection only lasts for as long as these bnAbs remain present at a sufficiently high concentration in the body. Poor pharmacokinetics and burdensome administration are two challenges that need to be addressed in order to make pre- and post-exposure prophylaxis with bnAbs feasible and effective. In this work, we develop a supramolecular hydrogel as an injectable, subcutaneous depot to encapsulate and deliver antibody drug cargo. This polymer-nanoparticle (PNP) hydrogel exhibits shear-thinning and self-healing properties that are required for an injectable drug delivery vehicle. In vitro drug release assays and diffusion measurements indicate that the PNP hydrogels prevent burst release and slow the release of encapsulated antibodies. Delivery of bnAbs against SARS-CoV-2 from PNP hydrogels is compared to standard routes of administration in a preclinical mouse model. We develop a multi-compartment model to understand the ability of these subcutaneous depot materials to modulate the pharmacokinetics of released antibodies; the model is extrapolated to explore the requirements needed for novel materials to successfully deliver relevant antibody therapeutics with different pharmacokinetic characteristics.

12.
Environ Monit Assess ; 194(1): 37, 2021 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-34935078

RESUMO

Surface water is subject to strong anthropogenic pressures caused by the development and extension of agricultural activities and also by industrial and domestic activities. As a result, rational and sustainable management of water resources is necessary in order to protect them. The objective of this work is the use of geographic information system GIS and the application of the weighted index of the water quality evaluation system SEQ-Eau for the overall assessment of the physicochemical quality of surface waters of the Moulouya River. First, a cartographic representation of the study area was produced with the development of quality maps for the various alterations relating to acidification, temperature, mineralization, phosphorus materials, and organic and oxidizable materials. The overall quality map is generated from the lowest index of all the alterations considered. The results generally show surface water of excellent quality in the Upper Moulouya and of average to poor quality in the Middle and Lower Moulouya. The alteration of water, linked mainly to mineralization and phosphorus nutrients, organic and oxidizable matter, reveals a domestic type pollution in relation to urban wastewater and agricultural discharges in addition to the impact of the geological substratum of the watershed. The seasonal impact is influenced by the increase in the degree of deterioration of water quality due to the increase in the concentration of pollutants and the decrease in precipitation during the summer season.


Assuntos
Rios , Poluentes Químicos da Água , Efeitos Antropogênicos , Monitoramento Ambiental , Marrocos , Poluentes Químicos da Água/análise , Qualidade da Água
13.
Insects ; 12(8)2021 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-34442258

RESUMO

Mosquitoes-borne diseases are major public health issues particularly in Africa. Vector control interventions and human-made environmental/climatic changes significantly affect the distribution and abundance of vector species. We carried out an entomological survey targeting host-seeking mosquitos in two different ecological contexts-coastal and inland-in Senegal, by CDC-light and BG-sentinel traps. Results show high predominance of Culex quinquefasciatus (90%) and of Anopheles arabiensis within malaria vectors (46%), with mean numbers of females/trap/nights =8 and <1, respectively, reinforcing previous evidence of changes in species composition and abundance, highlighting thus increasing risk of transmission of filariasis and emerging arboviruses in the Senegambia region. From the methodological perspective, results show a higher specificity of BG traps for Cx. quinquefasciatus and of CDC traps for An. gambiae s.l. and highlight that, despite both traps target the host-seeking fraction of the population, they provide different patterns of species abundance, temporal dynamics and host-seeking activity, leading to possible misinterpretation of the species bionomics. This draws attention to the need of taking into account trapping performance, in order to provide realistic quantification of the number of mosquitoes per units of space and time, the crucial parameter for evaluating vector-human contact, and estimating risk of pathogen transmission.

14.
Thromb Haemost ; 121(8): 992-1007, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34169495

RESUMO

BACKGROUND: One year after the declaration of the coronavirus disease 2019 (COVID-19) pandemic by the World Health Organization (WHO) and despite the implementation of mandatory physical barriers and social distancing, humanity remains challenged by a long-lasting and devastating public health crisis. MANAGEMENT: Non-pharmacological interventions (NPIs) are efficient mitigation strategies. The success of these NPIs is dependent on the approval and commitment of the population. The launch of a mass vaccination program in many countries in late December 2020 with mRNA vaccines, adenovirus-based vaccines, and inactivated virus vaccines has generated hope for the end of the pandemic. CURRENT ISSUES: The continuous appearance of new pathogenic viral strains and the ability of vaccines to prevent infection and transmission raise important concerns as we try to achieve community immunity against severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) and its variants. The need of a second and even third generation of vaccines has already been acknowledged by the WHO and governments. PERSPECTIVES: There is a critical and urgent need for a balanced and integrated strategy for the management of the COVID-19 outbreaks organized on three axes: (1) Prevention of the SARS-CoV-2 infection, (2) Detection and early diagnosis of patients at risk of disease worsening, and (3) Anticipation of medical care (PDA). CONCLUSION: The "PDA strategy" integrated into state policy for the support and expansion of health systems and introduction of digital organizations (i.e., telemedicine, e-Health, artificial intelligence, and machine-learning technology) is of major importance for the preservation of citizens' health and life world-wide.


Assuntos
COVID-19/epidemiologia , COVID-19/prevenção & controle , Saúde Pública , COVID-19/diagnóstico , Teste para COVID-19/métodos , Vacinas contra COVID-19/uso terapêutico , Gerenciamento Clínico , Humanos , Programas de Imunização/métodos , Pandemias/prevenção & controle , Saúde Pública/métodos , Medição de Risco , SARS-CoV-2/isolamento & purificação
16.
Clin Transl Sci ; 14(4): 1292-1302, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33503331

RESUMO

The frequencies of genetic variants in the CYP3A4 and CYP3A5 genes differ greatly across global populations, leading to profound differences in the metabolic activity of these enzymes and resulting drug metabolism rates, with important consequences for therapeutic safety and efficacy. Yet, the impact of genetic variants on enzyme activity are incompletely described, particularly in American Indian and Alaska Native (AIAN) populations. To characterize genetic variation in CYP3A4 and CYP3A5 and its effect on enzyme activity, we partnered with AIAN people living in two regions of Alaska: Yup'ik Alaska Native people living in the Yukon-Kuskokwim Delta region of rural southwest Alaska and AIAN people receiving care at the Southcentral Foundation in Anchorage, Alaska. We identified low frequencies of novel and known variation in CYP3A4 and CYP3A5, including low frequencies of the CYP3A4*1G and CYP3A5*1 variants, and linkage disequilibrium patterns that differed from those we previously identified in an American Indian population in western Montana. We also identified increased activity of the CYP3A4*1G allele in vitro and in vivo. We demonstrated that the CYP3A4*1G allele confers increased protein content in human lymphoblastoid cells and both increased protein content and increased activity in human liver microsomes. We confirmed enhanced CYP3A4-mediated 4ß-vitamin D hydroxylation activity in Yup'ik people with the CYP3A4*1G allele. AIAN people in Alaska and Montana who carry the CYP3A4*1G allele-coupled with low frequency of the functional CYP3A5*1 variant-may metabolize CYP3A substrates more rapidly than people with the reference CYP3A4 allele.


Assuntos
/genética , Citocromo P-450 CYP3A/metabolismo , Indígenas Norte-Americanos/genética , Xenobióticos/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , Linhagem Celular Tumoral , Criança , Pré-Escolar , Citocromo P-450 CYP3A/genética , Ensaios Enzimáticos , Feminino , Humanos , Lactente , Recém-Nascido , Desequilíbrio de Ligação , Masculino , Microssomos Hepáticos , Pessoa de Meia-Idade , Testes Farmacogenômicos , Variantes Farmacogenômicos , Polimorfismo de Nucleotídeo Único , Adulto Jovem
18.
Clin Shoulder Elb ; 23(3): 131-135, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33330247

RESUMO

BACKGROUND: Resection of the radial head is a surgical indication for comminuted radial head fracture in which internal fixation is inaccessible. Some complications from the surgery can alter the function of the patient's elbow. The objective of this study was to assess functional outcome of the elbow after resection of the radial head. METHODS: A retrospective longitudinal study was performed with patients who underwent radial head resection between 2008 and 2018. Elbow function was assessed by the Mayo Elbow Performance Index (MEPI) for 11 patients comprising three women and eight men. The mean follow-up was 47.6 months. The mean age was 41±10.3 years. RESULTS: Nine patients had a stable and painless elbow. The mean extension-flexion arc was 97.73°±16.03°. The mean values of pronation and supination were 76.8° and 74.5°, respectively. The mean MEPI score was 83.2 points, and restoration of overall function was achieved in 81% of the cases. Poor function was noted in one in 10 that presented with a terrible triad. CONCLUSIONS: Resection of the radial head restored elbow functionality at a rate of 81%, which was a good outcome for patients.

19.
PLoS One ; 15(10): e0232993, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33052917

RESUMO

In pre-colonial and colonial times Côte d'Ivoire probably hosted one of the largest elephant populations in West Africa, resulting in the country's name Côte d'Ivoire (in English Ivory Coast) by French settlers. Numbers declined and by the early 90s it was estimated that the total number of both savannah and forest elephants had reached 63 to 360 elephants in the entire country. Here we present updated information on the distribution and conservation status of forest elephant in Côte d'Ivoire based on multiple sources-dung counts on line transects, records of human-elephant conflict, media reports, sign and interview surveys-obtained during the period 2011-2017. We used Pearson correlation to determine the correlation between the presence of forest elephant and site variables (size of the forest, percentage of area converted into plantation, size of the forest left, size of human population inside the PA, poaching index, distance to the nearest road, population density in the Department, level of protection of the PA). To examine the effect of ecological traits on elephant extirpation, we used Principal Components Analysis (PCA) to check for multicollinearity among variables. Based on dung count elephant presence was confirmed in only 4 of the 25 protected areas surveyed. PAs with higher level of protection have higher probability to be home of elephant population. The viability of these populations is uncertain, since they have a small size and are isolated. Aggressive conservation actions including law enforcement for the protection of their remaining habitat and ranger patrolling are needed to protect the remaining forest elephant populations.


Assuntos
Conservação dos Recursos Naturais/métodos , Elefantes/crescimento & desenvolvimento , Animais , Côte d'Ivoire , Extinção Biológica , Humanos , Densidade Demográfica , Análise de Componente Principal , Inquéritos e Questionários
20.
PLoS One ; 15(4): e0232291, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32343755

RESUMO

Cervical cancer is the leading cause of female cancer deaths in Sénégal which is ranked 17th in incidence globally, however, the screening rate there is very low. Nuanced gendered perceptions and health behaviors of both women and men play a significant role in women's health. Our study analyzed gender differences on perceptions of gender roles, discrimination, cancer attitudes, cancer stigma, and influences in healthcare decision making within our study population to inform ongoing cervical cancer prevention work in the rural region of Kédougou, Sénégal. We conducted a cross-sectional survey of 158 participants, 101 women and 57 men (ages 30-59) across nine non-probability-sampled communities from October 2018 through February 2019. Bivariate analysis was conducted to assess gender differences across all variables. We also conducted analyses to determine whether there were significant differences in beliefs and attitudes, by screening behavior and by education. We found significant gender differences regarding the perception of a woman's role (P < 0.001) and a man's role (P = 0.007) as well as in the everyday discrimination questions of "decreased respect by spouse" (P < 0.001). Regarding cancer stigma, among women, 18.00% disagreed and 10.00% strongly disagreed while among men, 3.6% disagreed and 1.8% strongly disagreed that "If I had cancer, I would want my family to know that I have it." When making decisions about one's healthcare, women are more likely than men to trust social contacts such as their spouse (46.5% vs 5.3%, p < 0.001) while men are more likely than women to trust health service personnel such as a nurse (50.9% vs 18.8%, p < 0.001). Furthermore, men and women were both more likely to state that men have the final decision regarding the healthcare decisions of women (p < 0.001). Our data reveal structural disadvantages for women within our study population as well as gender differences in the adapted everyday discrimination scale and cancer stigma scale. Higher rates of both personal and perceived cancer stigma among women has profound implications for how population and community level communication strategies for cancer prevention and control should be designed. Efforts to advance the goal of the elimination of cervical cancer should, in the short-term, seek to gain a more profound understanding of the ways that gender, language, and other social determinants impact negative social influences and other barriers addressable through interventions. Social and behavior change communication may be one approach that can focus both on education while seeking to leverage the social influences that exist in achieving immediate and long-term goals.


Assuntos
Atitude Frente a Saúde , Discriminação Social , Estigma Social , Neoplasias do Colo do Útero/psicologia , Adulto , Estudos Transversais , Tomada de Decisões , Escolaridade , Feminino , Identidade de Gênero , Humanos , Masculino , Programas de Rastreamento/psicologia , Pessoa de Meia-Idade , Saúde da População Rural , População Rural , Senegal/epidemiologia , Inquéritos e Questionários , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/epidemiologia , Saúde da Mulher
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