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1.
Heliyon ; 10(10): e31130, 2024 May 30.
Article in English | MEDLINE | ID: mdl-38803974

ABSTRACT

The growing amount of plastic waste requires new ways of disposal or recycling. Research into the biodegradation of recalcitrant plastic polymers is gathering pace. Despite some progress, these efforts have not yet led to technologically and economically viable applications. In this study, we show that respirometric screening of environmental fungal isolates in combination with scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR) and Raman spectroscopy can be used to identify new strains with the potential for the degradation of plastic polymers. We screened 146 fungal strains, 71 isolated from car repair shops, an environment rich in long-chain hydrocarbons, and 75 isolated from hypersaline water capable of growing at high concentrations of NaCl. When grown in a minimal medium with no carbon source, some strains produced significantly more CO2 when a pure plastic polymer was added to the medium, some only at high salinity. A selection of these strains was shown by FTIR and Raman spectroscopy to alter the properties of plastic polymers: Cladosporium sp. EXF-13502 on polyamide, Rhodotorula dairenensis EXF-13500 on polypropylene, Rhodotorula sp. EXF-10630 on low-density polyethylene and Wickerhamomyces anomalus EXF-6848 on polyethylene terephthalate. Respirometry in combination with specific spectroscopic methods is an efficient method for screening microorganisms capable of at least partial plastic degradation and can be used to expand the repertoire of potential plastic degraders. This is of particular importance as our results also show that individual strains are only active against certain polymers and under certain conditions. Therefore, efficient biodegradation of plastics is likely to depend on a collection of specialized microorganisms rather than a single universal plastic degrader.

2.
J Infect Dev Ctries ; 18(4): 627-635, 2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38728650

ABSTRACT

BACKGROUND: In patients with severe neutropenia, infections can rapidly become serious and life-threatening. It is essential to understand whether pregnancy induces changes in neutrophil levels thereby posing an increased threat to the health of gravidae. METHODOLOGY: This cross-sectional study was conducted in San Health District (Mali) and involved pregnant women infected or not by malaria parasites and non-pregnant healthy volunteers. Subjects were categorized as having neutropenia, normal neutrophil levels, and neutrophilia regarding their neutrophil levels. A logistic regression analysis was performed to determine factors associated with neutrophil level variation in pregnant women. RESULTS: Whether or not the pregnant women were infected with malaria, 98 of the 202 cases (48.5%) showed neutrophilia. Surprisingly, 67 of the 71 cases of neutropenia (94.4%) observed in this study concerned healthy people who were not pregnant. The mean percentage of neutrophil levels was significantly (p < 0.001) lower (49.9%) in the first trimester compared to the second trimester of pregnancy (62.0%). A logistic regression model showed that compared to early pregnancy, the second (OR = 12.9, 95% CI 2.2-248.1, p = 0.018) and the third trimesters (OR = 13.7, 95% CI 2.3-257.5, p = 0.016) were strongly associated with the increase of neutrophil levels. CONCLUSIONS: Pregnancy can induce the production of mature neutrophils that are continually released into circulation. Neutrophil levels were lower during the first trimester of the pregnancy compared to the second and third trimesters, but not affected by the presence or absence of malaria infection.


Subject(s)
Malaria , Neutrophils , Humans , Female , Pregnancy , Mali/epidemiology , Cross-Sectional Studies , Adult , Young Adult , Malaria/blood , Neutropenia/blood , Adolescent , Pregnancy Complications, Infectious/blood , Leukocyte Count , Pregnancy Complications, Parasitic/blood , Pregnancy Complications, Parasitic/epidemiology
3.
Malar J ; 23(1): 8, 2024 Jan 04.
Article in English | MEDLINE | ID: mdl-38178145

ABSTRACT

Africa and the United States are both large, heterogeneous geographies with a diverse range of ecologies, climates and mosquito species diversity which contribute to disease transmission and nuisance biting. In the United States, mosquito control is nationally, and regionally coordinated and in so much as the Centers for Disease Control (CDC) provides guidance, the Environmental Protection Agency (EPA) provides pesticide registration, and the states provide legal authority and oversight, the implementation is usually decentralized to the state, county, or city level. Mosquito control operations are organized, in most instances, into fully independent mosquito abatement districts, public works departments, local health departments. In some cases, municipalities engage independent private contractors to undertake mosquito control within their jurisdictions. In sub-Saharan Africa (SSA), where most vector-borne disease endemic countries lie, mosquito control is organized centrally at the national level. In this model, the disease control programmes (national malaria control programmes or national malaria elimination programmes (NMCP/NMEP)) are embedded within the central governments' ministries of health (MoHs) and drive vector control policy development and implementation. Because of the high disease burden and limited resources, the primary endpoint of mosquito control in these settings is reduction of mosquito borne diseases, primarily, malaria. In the United States, however, the endpoint is mosquito control, therefore, significant (or even greater) emphasis is laid on nuisance mosquitoes as much as disease vectors. The authors detail experiences and learnings gathered by the delegation of African vector control professionals that participated in a formal exchange programme initiated by the Pan-African Mosquito Control Association (PAMCA), the University of Notre Dame, and members of the American Mosquito Control Association (AMCA), in the United States between the year 2021 and 2022. The authors highlight the key components of mosquito control operations in the United States and compare them to mosquito control programmes in SSA countries endemic for vector-borne diseases, deriving important lessons that could be useful for vector control in SSA.


Subject(s)
Malaria , Mosquito Control , Animals , United States , Malaria/epidemiology , Africa South of the Sahara , Ecology , Disease Vectors , Mosquito Vectors
4.
Trop Med Int Health ; 29(1): 33-41, 2024 01.
Article in English | MEDLINE | ID: mdl-38031206

ABSTRACT

BACKGROUND AND OBJECTIVE: Of ~5 million people living with epilepsy (PLWE) in Sub-Saharan Africa, roughly one-third experience depression and over one third experience anxiety. In Guinea, these issues may be compounded by fewer available resources, such as appropriate anti-seizure medications (ASMs). We aim to quantify seizure frequency, anxiety and depression in PLWE in Guinea, before and after a free ASM intervention and neurologist's consultation. METHODS: Guinean participants >12 years old with ≥2 unprovoked seizure were prospectively recruited. As part of a broader interview, participants reported prior 30-day seizure frequency and screened for depression (PHQ-9) (range 0-27 points) and anxiety (GAD-7) (range 0-21 points) with re-evaluation at 90 days. RESULTS: Of 148 participants enrolled (mean age = 27.3 years, range 12-72; 45% female), 62% were currently taking ASMs. For the 30 days pre-enrolment, average seizure frequency was 3.2 (95%CI 2.3, 4.2); 28% of participants were seizure-free. ASM regimens were modified for 95% of participants, mostly initiating levetiracetam (n = 115, 80% of modifications). 90-day study retention was 76% (n = 113) among whom 87% reported full adherence to the ASM. After 90 days, the average seizure frequency over the prior 30 days was 1.5 (95%CI 0.5, 2.6), significantly lower than at baseline (p = 0.002). 66% were seizure-free. At baseline, average PHQ-9 score was 21.2 (95%CI [20.2, 22.2]), indicating severe depressive symptoms. Average GAD-7 score was 16.5 [15.6, 17.4], indicating severe anxious symptoms. At 90-days, average PHQ-9 score was 17.5[16.4, 18.5] and significantly lower than baseline (p < 0.001). Average GAD-7 score was 14.4 [13.6, 15.3] and significantly lower than baseline (p = 0.002). Seizure frequency was not correlated with PHQ-9 nor GAD-7 scores at baseline but was at 90 days for both PHQ-9 (r = 0.24, p = 0.01) and GAD-7 (r = 0.22, p = 0.02) scores. The prevalence of suicidal ideation dropped from 67% to 47% of participants (p = 0.004). DISCUSSION: ASM management has dual importance for PLWE in resource-limited settings, improving both seizure control and mental health.


Subject(s)
Depression , Epilepsy , Humans , Female , Child , Adolescent , Young Adult , Adult , Middle Aged , Aged , Male , Depression/drug therapy , Depression/epidemiology , Guinea/epidemiology , Epilepsy/complications , Epilepsy/drug therapy , Epilepsy/epidemiology , Anxiety/drug therapy , Anxiety/epidemiology , Seizures/drug therapy , Seizures/epidemiology
5.
J Biol Chem ; 299(12): 105467, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37979913

ABSTRACT

In this study, we integrated machine learning (ML), structure-tissue selectivity-activity-relationship (STAR), and wet lab synthesis/testing to design a gastrointestinal (GI) locally activating JAK inhibitor for ulcerative colitis treatment. The JAK inhibitor achieves site-specific efficacy through high local GI tissue selectivity while minimizing the requirement for JAK isoform specificity to reduce systemic toxicity. We used the ML model (CoGT) to classify whether the designed compounds were inhibitors or noninhibitors. Then we used the regression ML model (MTATFP) to predict their IC50 against related JAK isoforms of predicted JAK inhibitors. The ML model predicted MMT3-72, which was retained in the GI tract, to be a weak JAK1 inhibitor, while MMT3-72-M2, which accumulated in only GI tissues, was predicted to be an inhibitor of JAK1/2 and TYK2. ML docking methods were applied to simulate their docking poses in JAK isoforms. Application of these ML models enabled us to limit our synthetic efforts to MMT3-72 and MMT3-72-M2 for subsequent wet lab testing. The kinase assay confirmed MMT3-72 weakly inhibited JAK1, and MMT3-72-M2 inhibited JAK1/2 and TYK2. We found that MMT3-72 accumulated in the GI lumen, but not in GI tissue or plasma, but released MMT3-72-M2 accumulated in colon tissue with minimal exposure in the plasma. MMT3-72 achieved superior efficacy and reduced p-STAT3 in DSS-induced colitis. Overall, the integration of ML, the structure-tissue selectivity-activity-relationship system, and wet lab synthesis/testing could minimize the effort in the optimization of a JAK inhibitor to treat colitis. This site-specific inhibitor reduces systemic toxicity by minimizing the need for JAK isoform specificity.


Subject(s)
Colitis, Ulcerative , Drug Design , Janus Kinase Inhibitors , Humans , Colitis, Ulcerative/drug therapy , Janus Kinase 1 , Janus Kinase 2 , Janus Kinase Inhibitors/pharmacology , Protein Isoforms , Machine Learning , Structure-Activity Relationship
6.
Seizure ; 111: 30-35, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37506562

ABSTRACT

BACKGROUND: This study assesses perceptions of quality of life (QOL) and overall health in people with epilepsy (PWE) in Guinea after a clinical intervention providing modified and new antiseizure medicine (ASM) regimens. METHODS: Participants 12 years and older diagnosed with active epilepsy were prospectively and consecutively enrolled at two health centers in the Republic of Guinea (one urban, one rural) in 2022. 95% of participants were prescribed new/increased ASM doses, and interviewed for QOL and overall health perceptions at enrollment and three- and six-month follow ups. Univariate and linear mixed models were used to evaluate effects on QOL and overall health over time. RESULTS: The mean QOLIE-31 score (±SD) among 148 Guinean PWE (82 male, 66 female; mean age 27.3; 137 with >1 seizure in prior year) was 51.7 ± 12.8 at enrollment, 57.6 ± 16.0 after three months (n = 116), and 52.2 ± 9.9 after six months (n = 87). Overall health scores were 53.1 ± 26.9, 72.6 ± 21.5, and 65.7 ± 20.2 respectively. After three months, PWE had improved overall health and QOLIE-31 scores (p<0.0001, p = 0.003), but these improvements persisted for overall health and not QOLIE-31 after six months (p = 0.001, p = 0.63). Seizure freedom (prior 30 days) was 26% initially, and 62 (42%) of the remaining PWE experiencing seizures achieved seizure freedom at either the first or second follow-ups. CONCLUSIONS: A noticeable discrepancy exists between Guinean PWE's self-rated perceptions of QOL and overall health. Purely clinical interventions may not be sufficient to improve QOL, especially in people that experience severe, previously-untreated epilepsy in lower income settings.

7.
MMWR Morb Mortal Wkly Rep ; 72(14): 366-371, 2023 Apr 07.
Article in English | MEDLINE | ID: mdl-37022974

ABSTRACT

Circulating vaccine-derived poliovirus (cVDPV) outbreaks* can occur when oral poliovirus vaccine (OPV, containing one or more Sabin-strain serotypes 1, 2, and 3) strains undergo prolonged circulation in under-vaccinated populations, resulting in genetically reverted neurovirulent virus (1,2). Following declaration of the eradication of wild poliovirus type 2 in 2015 and the global synchronized switch from trivalent OPV (tOPV, containing Sabin-strain types 1, 2, and 3) to bivalent OPV (bOPV, containing types 1 and 3 only) for routine immunization activities† in April 2016 (3), cVDPV type 2 (cVDPV2) outbreaks have been reported worldwide (4). During 2016-2020, immunization responses to cVDPV2 outbreaks required use of Sabin-strain monovalent OPV2, but new VDPV2 emergences could occur if campaigns did not reach a sufficiently high proportion of children. Novel oral poliovirus vaccine type 2 (nOPV2), a more genetically stable vaccine than Sabin OPV2, was developed to address the risk for reversion to neurovirulence and became available in 2021. Because of the predominant use of nOPV2 during the reporting period, supply replenishment has frequently been insufficient for prompt response campaigns (5). This report describes global cVDPV outbreaks during January 2021-December 2022 (as of February 14, 2023) and updates previous reports (4). During 2021-2022, there were 88 active cVDPV outbreaks, including 76 (86%) caused by cVDPV2. cVDPV outbreaks affected 46 countries, 17 (37%) of which reported their first post-switch cVDPV2 outbreak. The total number of paralytic cVDPV cases during 2020-2022 decreased by 36%, from 1,117 to 715; however, the proportion of all cVDPV cases that were caused by cVDPV type 1 (cVDPV1) increased from 3% in 2020 to 18% in 2022, including the occurrence of cocirculating cVDPV1 and cVDPV2 outbreaks in two countries. The increased proportion of cVDPV1 cases follows a substantial decrease in global routine immunization coverage and suspension of preventive immunization campaigns during the COVID-19 pandemic (2020-2022) (6); outbreak responses in some countries were also suboptimal. Improving routine immunization coverage, strengthening poliovirus surveillance, and conducting timely and high-quality supplementary immunization activities (SIAs) in response to cVDPV outbreaks are needed to interrupt cVDPV transmission and reach the goal of no cVDPV isolations in 2024.


Subject(s)
Disease Outbreaks , Poliomyelitis , Poliovirus Vaccine, Oral , Child , Humans , Poliomyelitis/epidemiology , Poliomyelitis/prevention & control , Poliovirus/genetics , Poliovirus Vaccine, Oral/adverse effects
8.
Cureus ; 15(2): e35515, 2023 Feb.
Article in English | MEDLINE | ID: mdl-37007400

ABSTRACT

INTRODUCTION: Chorea is an uncommon complication of stroke. The pathophysiology, the exact location of the lesions, and the evolution of this type of chorea are still poorly understood. The objective was to describe the epidemiological, clinical, and imaging profile of post-stroke chorea in a tropical environment in the context of a stroke epidemic. MATERIAL AND METHODS: We conducted a five-year retrospective observational study from 2015 to 2020 on stroke patients who presented with chorea in our department. Epidemiological, clinical, and imaging data were registered. RESULTS: Fourteen patients presented with chorea after their stroke, a frequency of 0.6%. The average age was 57.1 years with a male predominance. Hypertension was the cardiovascular risk factor in half of the patients; three patients (21.4) were diabetic. Chorea was the initial manifestation of the stroke in eight patients (57.1%). Thirteen patients (92.9%) had an ischaemic stroke and one had a cerebral haemorrhage. The middle cerebral artery (MCA) was involved in nine patients (64.3%), the anterior cerebral artery (ACA) in three patients (21.4%), and two patients (14.3%) had posterior cerebral artery (PCA) involvement. The lesions were cortical in five patients (35.7%), five other patients (35.7%) had a deep location, and four patients (28.6%) had both deep and cortical locations of their lesions. The structures affected were the lentiform nucleus (50%), the insula (35.7%), the caudate nucleus (14.3%), and the thalamus (14.3%). CONCLUSION: Post-stroke chorea is poorly studied in the tropics. In the presence of any acute abnormal movement associated with cardiovascular risk factors, post-stroke chorea should be considered. Recovery is rapid when treated early.

9.
J Glob Health ; 13: 04047, 2023 Apr 21.
Article in English | MEDLINE | ID: mdl-37083317

ABSTRACT

Background: Professional community health workers (CHWs) can help achieve universal health coverage, although evidence gaps remain on how to optimise CHW service delivery. We conducted an unblinded, parallel, cluster randomised trial in rural Mali to determine whether proactive CHW delivery reduced mortality and improved access to health care among children under five years, compared to passive delivery. Here we report the secondary access endpoints. Methods: Beginning from 26-28 February 2017, 137 village-clusters were offered care by CHWs embedded in communities who were trained, paid, supervised, and integrated into a reinforced public-sector health system that did not charge user fees. Clusters were randomised (stratified on primary health centre catchment and distance) to care during CHWs during door-to-door home visits (intervention) or based at a fixed village site (control). We measured outcomes at baseline, 12-, 24-, and 36-month time points with surveys administered to all resident women aged 15-49 years. We used logistic regression with cluster-level random effects to estimate intention-to-treat and per-protocol effects over time on prompt (24-hour) treatment within the health sector. Results: Follow-up surveys between February 2018 and April 2020 generated 20 105 child-year observations. Across arms, prompt health sector treatment more than doubled compared to baseline. At 12 months, children in intervention clusters had 22% higher odds of receiving prompt health sector treatment than those in control (cluster-specific adjusted odds ratio (aOR) = 1.22; 95% confidence interval (CI) = 1.06, 1.41, P = 0.005), or 4.7 percentage points higher (adjusted risk difference (aRD) = 0.047; 95% CI = 0.014, 0.080). We found no evidence of an effect at 24 or 36 months. Conclusions: CHW-led health system redesign likely drove the 2-fold increase in rapid child access to care. In this context, proactive home visits further improved early access during the first year but waned afterwards. Registration: ClinicalTrials.gov NCT02694055.


Subject(s)
Child Health , Community Health Services , Humans , Female , Child , Child, Preschool , Community Health Workers , Health Services Accessibility , Mali
10.
BMJ Glob Health ; 8(3)2023 03.
Article in English | MEDLINE | ID: mdl-36948531

ABSTRACT

INTRODUCTION: Though community health workers (CHWs) have improved access to antenatal care (ANC) and institutional delivery in different settings, it is unclear what package and delivery strategy maximises impact. METHODS: This study reports a secondary aim of the Proactive Community Case Management cluster randomised trial, conducted between December 2016 and April 2020 in Mali. It evaluated whether proactive home visits can improve ANC access at a population level compared with passive site-based care. 137 unique village clusters, covering the entire study area, were stratified by health catchment area and distance to the nearest primary health centre. Within each stratum, clusters were randomly assigned to intervention or control arm. CHWs in intervention clusters proactively visited all homes to provide care. In the control clusters, CHWs provided the same services at their fixed community health post to care-seeking patients. Pregnant women 15-49 years old were enrolled in a series of community-based and facility-based visits. We analysed individual-level annual survey data from baseline and 24-month and 36-month follow-up for the secondary outcomes of ANC and institutional delivery, complemented with CHW monitoring data during the trial period. We compared outcomes between: (1) the intervention and control arms, and (2) the intervention period and baseline. RESULTS: With 2576 and 2536 pregnancies from 66 and 65 clusters in the intervention and control arms, respectively, the estimated risk ratios for receiving any ANC was 1.05 (95% CI 1.02 to 1.07), four or more ANC visits was 1.25 (95% CI 1.08 to 1.43) and ANC initiated in the first trimester was 1.11 (95% CI 1.02 to 1.19), relative to the controls; no differences in institutional delivery were found. However, both arms achieved large improvements in institutional delivery, compared with baseline. Monitoring data show that 19% and 2% of registered pregnancies received at least eight ANC contacts in the intervention and control arms, respectively. Six clusters, three from each arm had to be dropped in the last 2 years of the trial. CONCLUSIONS: Proactive home visits increased ANC and the number of antenatal contacts at the clinic and community levels. ANC and institutional delivery can be increased when provided without fees from professional CHWs in upgraded primary care clinics. TRIAL REGISTRATION NUMBER: NCT02694055.


Subject(s)
Community Health Workers , Prenatal Care , Humans , Female , Pregnancy , Adolescent , Young Adult , Adult , Middle Aged , House Calls , Mali , Pregnant Women
11.
Spectrochim Acta A Mol Biomol Spectrosc ; 285: 121893, 2023 Jan 15.
Article in English | MEDLINE | ID: mdl-36137500

ABSTRACT

The transformation of sapwood (SW) into heartwood (HW) during ageing of wood tissues is the result of physiological and biochemical changes initiated in the transition zone (TZ). These changes contribute to the evolution of active (living) wood cells in SW into less/non-active (dead) wood cells in HW. Previous studies established that the biosynthesis of extractive contents is the most prominent process that occurs in the TZ. To improve our understanding of the extent and characteristics of the TZ in oak wood, the present study reports the results of color parameters (using CIELab color space) and molecular structure and composition of polysaccharide and lignin compounds (using FTIR-ATR and Py-GC-MS). For that purpose, six wood cores from individual living oak (Quercus spp.) trees were collected from two forests with similar environmental conditions, located in the Basque Country (Northern Spain). The color data indicated significant differences between SW, TZ and HW by showing that SW samples were characterized by higher hue (h°) and lower redness (a*) values than the HW, and intermediate values for the TZ. They also suggested that the variations of wood color from SW to HW occur gradually, along a wide TZ counting 4-10 measurement points in a row, depending on the tree. Furthermore, FTIR and Py-GC-MS data gave evidence of the variation trends of polysaccharide and lignin contents in the radial direction, through various FTIR ratios (1735/1325, 1590/1735, 1590/1230, and 1230/1325 cm-1) and one pyrolysis ratio (acetic acid/total polysaccharide: Ps01/Tot_Ps). The observed variations in this present study suggest that the cross-sectional transition patterns can be related to the continuous lignification process of xylem parenchyma cells, as well as the storage of polysaccharide compounds. These results contribute to our fundamental knowledge on the TZ, which may be valuable in research and industrial applications where a clear delimitation of sapwood and/or heartwood is required.


Subject(s)
Quercus , Wood , Wood/chemistry , Trees/chemistry , Trees/physiology , Lignin/analysis , Cross-Sectional Studies
12.
J Med Chem ; 65(18): 12044-12054, 2022 09 22.
Article in English | MEDLINE | ID: mdl-36070561

ABSTRACT

COVID-19 patients with severe symptoms still lack antiviral treatment options. Although remdesivir is the only FDA-approved drug for those patients, its efficacy is limited by premature hydrolysis to nucleoside (NUC), low accumulation in the disease-targeted tissue (lungs), and low antiviral potency. In this study, we synthesized a new series of remdesivir analogues by modifying the ProTide moiety. In comparison with remdesivir, the lead compound MMT5-14 showed 2- to 7-fold higher antiviral activity in four variants of SARS-CoV-2. By reducing premature hydrolysis in hamsters, MMT5-14 increased the prodrug concentration by 200- to 300-fold in the plasma and lungs but also enhanced lung accumulation of the active metabolite triphosphate nucleosides (NTP) by 5-fold. Compared to remdesivir, MMT5-14 also increased the intracellular uptake and activation in lung epithelial cells by 4- to 25-fold. These data suggest that MMT5-14 could be a potential antiviral drug to treat COVID-19 patients with severe symptoms.


Subject(s)
COVID-19 Drug Treatment , Prodrugs , Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , Alanine/pharmacology , Alanine/therapeutic use , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , Humans , Lung , Nucleosides , Prodrugs/pharmacology , Prodrugs/therapeutic use , SARS-CoV-2
13.
Acta Pharm Sin B ; 12(5): 2462-2478, 2022 May.
Article in English | MEDLINE | ID: mdl-35646532

ABSTRACT

Drug optimization, which improves drug potency/specificity by structure‒activity relationship (SAR) and drug-like properties, is rigorously performed to select drug candidates for clinical trials. However, the current drug optimization may overlook the structure‒tissue exposure/selectivity-relationship (STR) in disease-targeted tissues vs. normal tissues, which may mislead the drug candidate selection and impact the balance of clinical efficacy/toxicity. In this study, we investigated the STR in correlation with observed clinical efficacy/toxicity using seven selective estrogen receptor modulators (SERMs) that have similar structures, same molecular target, and similar/different pharmacokinetics. The results showed that drug's plasma exposure was not correlated with drug's exposures in the target tissues (tumor, fat pad, bone, uterus), while tissue exposure/selectivity of SERMs was correlated with clinical efficacy/safety. Slight structure modifications of four SERMs did not change drug's plasma exposure but altered drug's tissue exposure/selectivity. Seven SERMs with high protein binding showed higher accumulation in tumors compared to surrounding normal tissues, which is likely due to tumor EPR effect of protein-bound drugs. These suggest that STR alters drug's tissue exposure/selectivity in disease-targeted tissues vs. normal tissues impacting clinical efficacy/toxicity. Drug optimization needs to balance the SAR and STR in selecting drug candidate for clinical trial to improve success of clinical drug development.

14.
Viruses ; 14(1)2022 01 07.
Article in English | MEDLINE | ID: mdl-35062306

ABSTRACT

In Mali, a country in West Africa, cumulative confirmed COVID-19 cases and deaths among healthcare workers (HCWs) remain enigmatically low, despite a series of waves, circulation of SARS-CoV-2 variants, the country's weak healthcare system, and a general lack of adherence to public health mitigation measures. The goal of the study was to determine whether exposure is important by assessing the seroprevalence of anti-SARS-CoV-2 IgG antibodies in HCWs. The study was conducted between November 2020 and June 2021. HCWs in the major hospitals where COVID-19 cases were being cared for in the capital city, Bamako, Mali, were recruited. During the study period, vaccinations were not yet available. The ELISA of the IgG against the spike protein was optimized and quantitatively measured. A total of 240 HCWs were enrolled in the study, of which seropositivity was observed in 147 cases (61.8%). A continuous increase in the seropositivity was observed, over time, during the study period, from 50% at the beginning to 70% at the end of the study. HCWs who provided direct care to COVID-19 patients and were potentially highly exposed did not have the highest seropositivity rate. Vulnerable HCWs with comorbidities such as obesity, diabetes, and asthma had even higher seropositivity rates at 77.8%, 75.0%, and 66.7%, respectively. Overall, HCWs had high SARS-CoV-2 seroprevalence, likely reflecting a "herd" immunity level, which could be protective at some degrees. These data suggest that the low number of cases and deaths among HCWs in Mali is not due to a lack of occupational exposure to the virus but rather related to other factors that need to be investigated.


Subject(s)
COVID-19/epidemiology , Health Personnel , Occupational Exposure/analysis , Adult , Antibodies, Viral/blood , COVID-19/blood , COVID-19/diagnosis , Female , Hospitals , Humans , Immunoglobulin G/blood , Male , Mali/epidemiology , Odds Ratio , SARS-CoV-2/immunology , SARS-CoV-2/isolation & purification , Seroepidemiologic Studies
15.
Sci Rep ; 12(1): 1125, 2022 01 21.
Article in English | MEDLINE | ID: mdl-35064178

ABSTRACT

Low- to middle-income countries (LMICs) now bear most of the stroke burden. In LMICs, stroke epidemiology and health care systems are different from HICs. Therefore, a high-income country (HIC)-based predictive model may not correspond to the LMIC stroke context. Identify the impact of modifiable variables in acute stroke management in Conakry, Guinea as potential predictors of favorable stroke outcome. Data were extracted from the Conakry stroke registry that includes 1018 patients. A logistic regression model was built to predict favorable stroke outcomes, defined as mRS 0-2. Age, admission NIHSS score, mean arterial blood pressure and capillary glycemia were chosen as covariates. Delay to brain CT imaging under 24 h from symptom onset, fever, presence of sores and abnormal lung auscultation were included as factors. NIHSS score on admission, age and ischemic stroke were included in the null model as nuisance parameters to determine the contribution of modifiable variables to predict stroke favorable outcome. Lower admission NIHSS, brain CT imaging within 24 h of symptoms onset and lower mean arterial blood pressure emerged as a significant positive predictors of favorable stroke outcome with respective odd ratios (OR) of 1.35 [1.28-1.43], 2.1 [1.16-3.8] and 1.01 [1.01-1.04]. The presence of fever or sores impacted negatively stroke favorable outcomes with OR of 0.3 [0.1-0.85] and 0.25 [0.14-0.45]. The area under receiver operating characteristic curves (AUC) of the model was 0.86. This model explained 44.5% of the variability of the favorable stroke outcome with 10.2% of the variability explained by the modifiable variables when admission NIHSS, and ischemic stroke were included in the null model as nuisance parameter. In the Conakry stroke registry, using a logistic regression to predict stroke favorable outcome, five variables that led to an AUC of 0.86: admission NIHSS, early brain CT imaging, fever, sores and mean blood pressure. This paves the way for future public health interventions to test whether modulating amendable variables leads to increased favorable stroke outcomes in LMICs.


Subject(s)
Disability Evaluation , Recovery of Function , Stroke/complications , Aged , Aged, 80 and over , Brain/diagnostic imaging , Brain/physiopathology , Cohort Studies , Guinea , Humans , Male , Middle Aged , Odds Ratio , Predictive Value of Tests , ROC Curve , Registries/statistics & numerical data , Risk Assessment/methods , Risk Factors , Stroke/therapy , Tomography, X-Ray Computed , Treatment Outcome
16.
Mali Med ; 37(3): 44-49, 2022.
Article in French | MEDLINE | ID: mdl-38514950

ABSTRACT

INTRODUCTION: waste electrical and electronic equipment (WEEE), with its health and environmental issues, has become a public health problem exposing workers to toxic compounds causing respiratory problems. OBJECTIVE: To study the relationship between professional exposure to WEEE and the occurrence of respiratory problems in Bamako in 2019. MATERIAL AND METHODS: This was a 6-month cross-sectional, analytical study carried out in the city of Bamako in 2019 and involved 159 WEEE manipulators. Data were collected using a tablet (2). Univariate and multivariate analyzes were performed using SPSS version 22 with the significance level of 0.05. Odds Ratio (OR) were presented with their 95% confident interval (OR[95%CI]). RESULTS: The overall prevalence of respiratory disorders was 67.3% among WEEE handlers. It was noted that the removal of the coating of electronic wires (OR[95%CI]=25.93[2.30;291.53]), recent weight loss outside of a diet (OR[95% CI]=7,43[1.68;32.85]) and the infrequent hand washing with soap after the toilet (OR[95% CI]=11.50[2.07; 63.89]) represented a higher risk of (2) breathing problems. CONCLUSION: These results show that D3E handlers have a lot of risky behavior for respiratory problems. This study could be used to implement strategies to reduce the impact of D3E.


INTRODUCTION: les déchets d'équipements électriques et électroniques (D3E), avec leurs enjeux sanitaires et environnementaux, sont devenus un problème de santé publique exposant les travailleurs aux composés d'éléments toxiques responsables de (2ème expertise) troubles respiratoires. OBJECTIF: Etudier la relation entre l'exposition professionnelle aux D3E et la survenue des problèmes respiratoires à Bamako en 2019. MATÉRIEL ET MÉTHODES: Il s'agissait d'une étude transversale, analytique de 6 mois, menée dans la ville de Bamako en 2019 et concernait 159 manipulateurs de D3E. Les données ont été collectées sur tablette et les analyses univariées et multivariées réalisées sur SPSS version 22 au seuil de significativité de 0,05 avec présentation des Odds Ratio (OR) et leurs intervalles de confiance à 95% (OR[IC95%]). RÉSULTATS: La prévalence en général des troubles respiratoires était de 67,3% chez les manipulateurs des D3E. On notait que le retrait du revêtement des fils électroniques (OR[IC95%]=25,93[2,30;291,53]), la perte de poids récente en dehors d'un régime (OR[IC95%]=7,43[1,68;32,85]) et la rareté de lavage des mains avec du savon après les toilettes (OR[IC95%]=11,50[2,07;63,89]) représentaient un risque plus élevé de problèmes respiratoires. CONCLUSION: Ces résultats montrent que les manipulateurs de D3E ont beaucoup de comportement à risque des problèmes respiratoires. Cette étude pourrait servir à la mise en œuvre de stratégies visant à réduire l'impact des D3E.

17.
Mali Médical ; 28(3): 44-49, 30/09/2022.
Article in French | AIM (Africa) | ID: biblio-1397595

ABSTRACT

Introduction: les déchets d'équipements électriques et électroniques (D3E), avec leurs enjeux sanitaires et environnementaux, sont devenus un problème de santé publique exposant les travailleurs aux composés d'éléments toxiques responsables de (2ème expertise) troubles respiratoires. Objectif: Etudier la relation entre l'exposition professionnelle aux D3E et la survenue des problèmes respiratoires à Bamako en 2019. Matériel et Méthodes : Il s'agissait d'une étude transversale, analytique de 6 mois, menée dans la ville de Bamako en 2019 et concernait 159 manipulateurs de D3E. Les données ont été collectées sur tablette et les analyses univariées et multivariées réalisées sur SPSS version 22 au seuil de significativité de 0,05 avec présentation des Odds Ratio (OR) et leurs intervalles de confiance à 95% (OR[IC95%]). Résultats : La prévalence en général des troubles respiratoires était de 67,3% chez les manipulateurs des D3E. On notait que le retrait du revêtement des fils électroniques (OR[IC95%] =25,93[2,30;291,53]), la perte de poids récente en dehors d'un régime (OR[IC95%] =7,43[1,68;32,85]) et la rareté de lavage des mains avec du savon après les toilettes (OR[IC95%] =11,50[2,07;63,89]) représentaient un risque plus élevé de problèmes respiratoires. Conclusion :Ces résultats montrent que les manipulateurs de D3E ont beaucoup de comportement à risque des problèmes respiratoires. Cette étude pourrait servir à la mise en œuvre de stratégies visant à réduire l'impact des D3E


Introduction: waste electrical and electronic equipment (WEEE), with its health and environmental issues, has become a public health problem exposing workers to toxic compounds causing respiratory problems. Objective: To study the relationship between professional exposure to WEEE and the occurrence of respiratory problems in Bamako in 2019. Material and Methods: This was a 6-month cross-sectional, analytical study carried out in the city of Bamako in 2019 and involved 159 WEEE manipulators. Data were collected using a tablet (2). Univariate and multivariate analyzes were performed using SPSS version 22 with the significance level of 0.05. Odds Ratio (OR) were presented with their 95% confident interval (OR [95%CI]). Results: The overall prevalence of respiratory disorders was 67.3% among WEEE handlers. It was noted that the removal of the coating of electronic wires (OR [95%CI] =25.93[2.30;291.53]), recent weight loss outside of a diet (OR [95% CI] =7,43[1.68;32.85]) and the infrequent hand washing with soap after the toilet (OR [95% CI] =11.50[2.07; 63.89]) represented a higher risk of (2) breathing problems. Conclusion: These results show that D3E handlers have a lot of risky behavior for respiratory problems. This study could be used to implement strategies to reduce the impact of D3E


Subject(s)
Public Health , Occupational Exposure , Environmental Exposure , Hazardous Waste Sites , Respiratory Tract Diseases , Mali
18.
MMWR Morb Mortal Wkly Rep ; 70(49): 1691-1699, 2021 Dec 10.
Article in English | MEDLINE | ID: mdl-34882653

ABSTRACT

As of May 1, 2016, use of oral poliovirus vaccine (OPV) type 2 for routine and supplementary immunization activities ceased after a synchronized global switch from trivalent OPV (tOPV; containing Sabin strain types 1, 2, and 3) to bivalent OPV (bOPV; containing Sabin strain types 1 and 3) subsequent to the certified eradication of wild type poliovirus (WPV) type 2 in 2015 (1-3). Circulating vaccine-derived poliovirus (cVDPV) outbreaks* occur when transmission of Sabin strain poliovirus is prolonged in underimmunized populations, allowing viral genetic reversion to neurovirulence, resulting in cases of paralytic polio (1-3). Since the switch, monovalent OPV type 2 (mOPV2, containing Sabin strain type 2) has been used for response to cVDPV type 2 (cVDPV2) outbreaks; tOPV is used if cVDPV2 co-circulates with WPV type 1, and bOPV is used for cVDPV type 1 (cVDPV1) or type 3 (cVDPV3) outbreaks (1-4). In November 2020, the World Health Organization (WHO) Emergency Use Listing procedure authorized limited use of type 2 novel OPV (nOPV2), a vaccine modified to be more genetically stable than the Sabin strain, for cVDPV2 outbreak response (3,5). In October 2021, the Strategic Advisory Group of Experts on Immunization (WHO's principal advisory group) permitted wider use of nOPV2; however, current nOPV2 supply is limited (6). This report updates that of July 2019-February 2020 to describe global cVDPV outbreaks during January 2020-June 2021 (as of November 9, 2021)† (3). During this period, there were 44 cVDPV outbreaks of the three serotypes affecting 37 countries. The number of cVDPV2 cases increased from 366 in 2019 to 1,078 in 2020 (7). A goal of the Global Polio Eradication Initiative's (GPEI) 2022-2026 Strategic Plan is to better address the challenges to early CVDPV2 outbreak detection and initiate prompt and high coverage outbreak responses with available type 2 OPV to interrupt transmission by the end of 2023 (8).


Subject(s)
Disease Outbreaks/statistics & numerical data , Global Health/statistics & numerical data , Poliomyelitis/epidemiology , Poliovirus Vaccine, Oral/adverse effects , Poliovirus/isolation & purification , Humans , Poliomyelitis/etiology , Poliomyelitis/prevention & control , Poliovirus/classification , Poliovirus Vaccine, Oral/administration & dosage , Serotyping
19.
Molecules ; 26(24)2021 Dec 11.
Article in English | MEDLINE | ID: mdl-34946588

ABSTRACT

FR235222 is a natural tetra-cyclopeptide with a strong inhibition effect on histone deacetylases, effective on mammalian cells as well as on intracellular apicomplexan parasites, such as Toxoplasma gondii, in the tachyzoite and bradyzoite stages. This molecule is characterized by two parts: the zinc-binding group, responsible for the binding to the histone deacetylase, and the cyclic tetrapeptide moiety, which plays a crucial role in cell permeability. Recently, we have shown that the cyclic tetrapeptide coupled with a fluorescent diethyl-amino-coumarin was able to maintain properties of cellular penetration on human cells. Here, we show that this property can be extended to the crossing of the Toxoplasma gondii cystic cell wall and the cell membrane of the parasite in its bradyzoite form, while maintaining a high efficacy as a histone deacetylase inhibitor. The investigation by molecular modeling allows a better understanding of the penetration mechanism.


Subject(s)
Coumarins/pharmacology , Fluorescent Dyes/pharmacology , Histone Deacetylase Inhibitors/pharmacology , Histone Deacetylases/metabolism , Peptides, Cyclic/pharmacology , Coumarins/chemistry , Fluorescent Dyes/chemistry , Histone Deacetylase Inhibitors/chemistry , Models, Molecular , Peptides, Cyclic/chemistry , Toxoplasma/cytology , Toxoplasma/enzymology
20.
PLoS One ; 16(11): e0259261, 2021.
Article in English | MEDLINE | ID: mdl-34727136

ABSTRACT

Infestation by a moth woodborer species is causing mortality of Sonneratia alba Sm. mangrove by tunneling through the inner bark, cambium and conductive tissue. Infestation leads to death of some infested branches, whereas in other cases infested branches have been observed to recover from infestation. We have used Fourier transform infrared spectroscopy (FTIR) to investigate the differences in macromolecule (polysaccharide and lignin) content present in branches that died (D) of the infestation, those that recovered (R) from the infestation and control branches (C) that were not subject to any infestation. Wood samples were taken from four sampling plots (A, B, C and D) in Gazi Bay (Kenya). From each of the four plots, 15 S. alba branches were taken from five trees, from which 1 cm thick discs were cut from each of these branches to be used as samples. To identify the most characteristic FTIR bands for the three groups of samples, Principal Component Analysis (PCA) was applied on the transposed data matrix. Furthermore, canonical discriminant analysis was applied on the data considering the main FTIR band that would be identified through the PCA factors. Finally, One-way ANOVA and post hoc test were used to verify the significance of the observed trends. Branches that recovered from infestation had higher relative abundance of lignified cells. We conclude that insect-infested S. alba undergo changes related to the lignocellulosic contents. The infestation induces a decrease of the proportion of the polysaccharide content and an increase of the proportion of the lignin contents.


Subject(s)
Moths , Animals , Discriminant Analysis , Lythraceae , Wood
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