A gastrointestinal locally activating Janus kinase inhibitor to treat ulcerative colitis.

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.

Impact of a free medication intervention on seizure recurrence and anxious and depressive symptoms in people living with epilepsy in the Republic of Guinea.

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.

Mosquito control by abatement programmes in the United States: perspectives and lessons for countries in sub-Saharan Africa.

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.

Update on Vaccine-Derived Poliovirus Outbreaks - Worldwide, January 2021-December 2022.

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.

Relationship between symptoms, barriers to care and healthcare utilisation among children under five in rural Mali.

OBJECTIVES: To identify social and structural barriers to timely utilisation of qualified providers among children under five years in a high-mortality setting, rural Mali and to analyse how utilisation varies by symptom manifestation. METHODS: Using baseline household survey data from a cluster-randomised trial, we assessed symptom patterns and healthcare trajectories of 5117 children whose mothers reported fever, diarrhoea, bloody stools, cough and/or fast breathing in the preceding two weeks. We examine associations between socio-demographic factors, symptoms and utilisation outcomes in mixed-effect logistic regressions. RESULTS: Almost half of recently ill children reported multiple symptoms (46.2%). Over half (55.9%) received any treatment, while less than one-quarter (21.7%) received care from a doctor, nurse, midwife, trained community health worker or pharmacist within 24 h of symptom onset. Distance to primary health facility, household wealth and maternal education were consistently associated with better utilisation outcomes. While children with potentially more severe symptoms such as fever and cough with fast breathing or diarrhoea with bloody stools were more likely to receive any care, they were no more likely than children with fever to receive timely care with a qualified provider. CONCLUSIONS: Even distances as short as 2-5 km significantly reduced children's likelihood of utilising healthcare relative to those within 2 km of a facility. While children with symptoms indicative of pneumonia and malaria were more likely to receive any care, suggesting mothers and caregivers recognised potentially severe illness, multiple barriers to care contributed to delays and low utilisation of qualified providers, illustrating the need for improved consideration of barriers.

Update on Vaccine-Derived Poliovirus Outbreaks - Worldwide, January 2020-June 2021.

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).

Estimating the potential impact of Attractive Targeted Sugar Baits (ATSBs) as a new vector control tool for Plasmodium falciparum malaria.

BACKGROUND: Attractive targeted sugar baits (ATSBs) are a promising new tool for malaria control as they can target outdoor-feeding mosquito populations, in contrast to current vector control tools which predominantly target indoor-feeding mosquitoes. METHODS: It was sought to estimate the potential impact of these new tools on Plasmodium falciparum malaria prevalence in African settings by combining data from a recent entomological field trial of ATSBs undertaken in Mali with mathematical models of malaria transmission. The key parameter determining impact on the mosquito population is the excess mortality due to ATSBs, which is estimated from the observed reduction in mosquito catch numbers. A mathematical model capturing the life cycle of P. falciparum malaria in mosquitoes and humans and incorporating the excess mortality was used to estimate the potential epidemiological effect of ATSBs. RESULTS: The entomological study showed a significant reduction of ~ 57% (95% CI 33-72%) in mosquito catch numbers, and a larger reduction of ~ 89% (95% CI 75-100%) in the entomological inoculation rate due to the fact that, in the presence of ATSBs, most mosquitoes do not live long enough to transmit malaria. The excess mortality due to ATSBs was estimated to be lower (mean 0.09 per mosquito per day, seasonal range 0.07-0.11 per day) than the bait feeding rate obtained from one-day staining tests (mean 0.34 per mosquito per day, seasonal range 0.28-0.38 per day). CONCLUSIONS: From epidemiological modelling, it was predicted that ATSBs could result in large reductions (> 30% annually) in prevalence and clinical incidence of malaria, even in regions with an existing high malaria burden. These results suggest that this new tool could provide a promising addition to existing vector control tools and result in significant reductions in malaria burden across a range of malaria-endemic settings.

Testing configurations of attractive toxic sugar bait (ATSB) stations in Mali, West Africa, for improving the control of malaria parasite transmission by vector mosquitoes and minimizing their effect on non-target insects.

BACKGROUND: Application methods of |Attractive Toxic Sugar Baits (ATSB) need to be improved for wide-scale use, and effects on non-target organisms (NTOs) must be assessed. The goals of this study were to determine, at the village level, the effect of different configurations of bait stations to (1) achieve < 25% Anopheles mosquito vector daily feeding rate for both males and females and (2) minimize the effect on non-target organisms. METHODS: Dye was added to Attractive Sugar Bait Stations (without toxin) to mark mosquitoes feeding on the baits, and CDC UV light traps were used to monitor for marked mosquitoes. An array of different traps were used to catch dye marked NTOs, indicating feeding on the ASB. Stations were hung on homes (1, 2, or 3 per home to optimize density) at different heights (1.0 m or 1.8 m above the ground). Eight villages were chosen as for the experiments. RESULTS: The use of one ASB station per house did not mark enough mosquitoes. Use of two and three stations per house gave feeding rates above the 25% goal. There was no statistical difference in the percentage of marked mosquitoes between two and three stations, however, the catches using two and three bait stations were both significantly higher than using one. There was no difference in An. gambiae s.l. feeding when stations were hung at 1.0 and 1.8 m. At 1.8 m stations sustained less accidental damage. ASB stations 1.8 m above ground were fed on by three of seven monitored insect orders. The monitored orders were: Hymenoptera, Lepidoptera, Coleoptera, Diptera, Hemiptera, Neuroptera and Orthoptera. Using one or two stations significantly reduced percentage of bait-fed NTOs compared to three stations which had the highest feeding rates. Percentages were as follows: 6.84 ± 2.03% Brachycera followed by wasps (Hymenoptera: Vespidae) 5.32 ± 2.27%, and Rhopalocera 2.22 ± 1.79%. Hanging the optimal number of stations per house for catching mosquitoes (two) at 1.8 m above ground, limited the groups of non-targets to Brachycera, Chironomidae, Noctuoidea, Rhopalocera, parasitic wasps and wasps (Hymenoptera). Feeding at 1.8 m only occurred when stations were damaged. CONCLUSIONS: The goal of marking quarter of the total Anopheles population per day was obtained using 2 bait stations at 1.8 m height above the ground. This configuration also had minimal effects on non-target insects.

Antiplasmodial Oleanane Triterpenoids from Terminalia albida Root Bark.

Phytochemical investigation of the n-BuOH extract of the roots of Terminalia albida Sc. Elliot (Combretaceae) led to the isolation and identification of 10 oleanane triterpenoids (1-10), among which six new compounds, i.e., albidanoside A (2), albidic acid A (4), albidinolic acid (5), albidienic acid (8), albidolic acid (9), and albidiolic acid (10), and two triterpenoid aglycones, i.e., albidic acid B (6) and albidic acid C (7), were isolated here for the first time from a natural source, along with two known compounds. The structures of these constituents were established by means of 1D and 2D NMR spectroscopy and ESI mass spectrometry. The isolated compounds were evaluated for their antiplasmodial and antimicrobial activity against the chloroquine-resistant strain Plasmodium falciparum K1, Candida albicans, and Staphylococcus aureus. Compounds 1-4, 6, 7, and 8 showed moderate antiplasmodial activity with IC50 values between 5 and 15 µM. None of the tested compounds were active against C. albicans or S. aureus. These findings emphasize the potential of T. albida as a source for discovery of new antiplasmodial compounds.

Malaria in Guinean Rural Areas: Prevalence, Management, and Ethnotherapeutic Investigations in Dionfo, Sub-Prefecture of Labe.

As part of a validation program of antimalarial traditional recipes, an ethnotherapeutic approach was applied in Dionfo, a meso-endemic Guinean rural area where conventional health facilities are insufficient. A prevalence investigation indicated a malarial burden of 4.26%. Ethnomedical and ethnobotanical surveys led to a collection of 63 plant species used against malaria from which Terminalia albida (Combretaceae) was one of the most cited. Ethnotherapeutic evaluation of a remedy based on T. albida was applied to 9 voluntary patients suffering from uncomplicated malaria. Treatment of 7 to 14 days led to an improvement of clinical symptoms and a complete parasite clearance achievement of 8/9 patients without side effects. In addition to antiplasmodial activity in vitro and in vivo previously described, this study indicates an efficacy to support the antimalarial traditional use of T. albida, which could constitute a first-aid treatment when access to other medicines is delayed in the Dionfo community. Ethnotherapeutical investigation could be a valuable approach to guide subsequent investigations on traditional remedies.

Crossing of the Cystic Barriers of Toxoplasma gondii by the Fluorescent Coumarin Tetra-Cyclopeptide.

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.

Terminalia albida treatment improves survival in experimental cerebral malaria through reactive oxygen species scavenging and anti-inflammatory properties.

BACKGROUND: The development of Plasmodium resistance to the last effective anti-malarial drugs necessitates the urgent development of new anti-malarial therapeutic strategies. To this end, plants are an important source of new molecules. The objective of this study was to evaluate the anti-malarial effects of Terminalia albida, a plant used in Guinean traditional medicine, as well as its anti-inflammatory and antioxidant properties, which may be useful in treating cases of severe malaria. METHODS: In vitro antiplasmodial activity was evaluated on a chloroquine-resistant strain of Plasmodium falciparum (K-1). In vivo efficacy of the plant extract was measured in the experimental cerebral malaria model based on Plasmodium berghei (strain ANKA) infection. Mice brains were harvested on Day 7-8 post-infection, and T cells recruitment to the brain, expression levels of pro- and anti-inflammatory markers were measured by flow cytometry, RT-qPCR and ELISA. Non-malarial in vitro models of inflammation and oxidative response were used to confirm Terminalia albida effects. Constituents of Terminalia albida extract were characterized by ultra-high performance liquid chromatography coupled with high resolution mass spectrometry. Top ranked compounds were putatively identified using plant databases and in silico fragmentation patterns. RESULTS: In vitro antiplasmodial activity of Terminalia albida was confirmed with an IC50 of 1.5 µg/mL. In vivo, Terminalia albida treatment greatly increased survival rates in P. berghei-infected mice. Treated mice were all alive until Day 12, and the survival rate was 50% on Day 20. Terminalia albida treatment also significantly decreased parasitaemia by 100% on Day 4 and 89% on Day 7 post-infection. In vivo anti-malarial activity was related to anti-inflammatory properties, as Terminalia albida treatment decreased T lymphocyte recruitment and expression of pro-inflammatory markers in brains of treated mice. These properties were confirmed in vitro in the non-malarial model. In vitro, Terminalia albida also demonstrated a remarkable dose-dependent neutralization activity of reactive oxygen species. Twelve compounds were putatively identified in Terminalia albida stem bark. Among them, several molecules already identified may be responsible for the different biological activities observed, especially tannins and triterpenoids. CONCLUSION: The traditional use of Terminalia albida in the treatment of malaria was validated through the combination of in vitro and in vivo studies.

Indoor use of attractive toxic sugar bait (ATSB) to effectively control malaria vectors in Mali, West Africa.

BACKGROUND: Attractive toxic sugar bait (ATSB) solutions containing any gut toxins can be either sprayed on plants or used in simple bait stations to attract and kill sugar-feeding female and male mosquitoes. This field study in Mali demonstrates the effect of ATSB bait stations inside houses as a vector control method that targets and kills endophilic African malaria vectors. METHODS: The studies were conducted in five villages located near the River Niger, Mali. Baseline village-wide assessments of densities for female and male Anopheles gambiae sensu lato were performed by pyrethrum spray collections (PSC) in ten houses in each of five villages. To determine the rate of mosquito feeding on bait stations, one bait station per house containing attractive sugar bait (ASB) (without toxin) plus a food dye marker, was set up in ten houses in each of the five villages. PSC collections were conducted on the following day and the percentage of female and male mosquitoes that had fed was determined by visual inspection for the dye marker. Then, a 50-day field trial was done. In an experimental village, one bait station containing ATSB (1% boric acid active ingredient) was placed per bedroom (58 bedrooms), and indoor densities of female and male An. gambiae s.l. were subsequently determined by PSC, and female mosquitoes were age graded. RESULTS: In the five villages, the percentages of An. gambiae s.l. feeding inside houses on the non-toxic bait stations ranged from 28.3 to 53.1% for females and 36.9 to 78.3% for males. Following ATSB indoor bait station presentation, there was a significant reduction, 90% in female and 93% in male populations, of An. gambiae s.l. at the experimental village. A 3.8-fold decrease in the proportion of females that had undergone four or more gonotrophic cycles was recorded at the experimental village, compared to a 1.2-fold increase at the control village. CONCLUSION: The field trial demonstrates that An. gambiae s.l. feed readily from ATSB bait stations situated indoors, leading to a substantial reduction in the proportion of older female mosquitoes. This study demonstrates that ATSB inside houses can achieve impressive malaria vector control in Africa.

A screening method for plastic-degrading fungi.

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.

Assessment of the impact of pregnancy and malaria infection on the variation of neutrophil levels in women from San, Mali.

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.

Variation of wood color and chemical composition in the stem cross-section of oak (Quercus spp.) trees, with special attention to the sapwood-heartwood transition zone.

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.

Post-stroke Chorea in the Neurology Department of Ignace Deen Hospital of Conakry, Guinea.

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.

Effect of community health worker home visits on antenatal care and institutional delivery: an analysis of secondary outcomes from a cluster randomised trial in Mali.

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.

Effects of proactive vs fixed community health care delivery on child health and access to care: a cluster randomised trial secondary endpoint analysis.

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.

Improvement in health perception but not quality of life with an antiseizure medication intervention in people with epilepsy in Guinea: A cohort study.

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.