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Climate change studies are diverse with no single study giving a comprehensive review of climate change impacts, adaptation strategies, and policy development in West Africa. The unavailability of an all-inclusive study to serve as a guide for practitioners affects the effectiveness of climate change adaptation strategies proposed and adopted in the West African sub-region. The purpose of this study was to review the impacts of climate change risks on the crop, fishery, and livestock sectors, as well as the climate change adaptation strategies and climate-related policies aimed at helping to build resilient agricultural production systems in West Africa. The review process followed a series of rigorous stages until the final selection of 56 articles published from 2009 to 2023. Generally, the results highlighted the adverse effects of climate change risks on food security. We found a continuous decline in food crop production. Additionally, the livestock sector experienced morbidity and mortality, as well as reduction in meat and milk production. The fishery sector recorded loss of fingerlings, reduction in fish stocks, and destruction of mariculture and aquaculture. In West Africa, climate-smart agriculture technologies, physical protection of fishing, and inclusion of gender perspectives in programs appear to be the major adaptation strategies. The study therefore recommends the inclusion of ecosystem and biodiversity restoration, weather insurance, replacement of unsafe vessels, and strengthening gender equality in all climate change mitigation programs, as these will help to secure enough food for present and future generations.

Purpose Diospyros mespiliformis which is commonly known as African ebony is a valuable fruit tree species with important medicinal and nutritional values. The tree has a slow growth rate that discourages its propagation and at present attempts made towards improving its growth performance are scanty. This study, therefore, evaluates the effect of the type and quantity of animal manure on the growth performance of Diospyros mespiliformis to determine the suitable type of manure and quantity of application that will improve its growth performance.Method Poultry, cow, and goat manures were applied to Diospyros mespiliformis seedlings at 0 g (control), 15 g (10 t/ha-1), 30 g (25 t/ha-1), and 40 g (35 t/ha-1) in pots. The experiment was arranged in a 4 x 3 factorial in a completely randomized design with five (5) replicates.Results Type of manure had a significant effect on seedlings' stem height growth. The highest stem height growth of 11.64±1.54 cm was recorded by seedlings that received goat manure. The collar diameter and the number of leaves produced were not significantly affected by the type of manure. The Quantity of manure applied did not significantly affect stem height and collar diameter increment; however, it significantly affected the number of leaves produced. Application of 40 g of manures improved leaf production in Diospyros mespiliformis seedlings.Conclusion Application of animal manures improved the growth performance of Diospyros mespiliformis, however, seedlings that received goat manure had better growth performance.

Abstract Objective: To assess the potential contribution of large-scale food fortification (LSFF) towards meeting dietary micronutrient requirements in Tanzania. Design: We used household food consumption data from the National Panel Survey 2014–15 to estimate fortifiable food vehicle coverage and consumption (standardised using the adult female equivalent approach) and the prevalence at risk of inadequate apparent intake of five micronutrients included in Tanzania’s fortification legislation. We modelled four LSFF scenarios: no fortification, status quo (i.e. compliance with current fortification contents) and full fortification with and without maize flour fortification. Setting: Tanzania. Participants: A nationally representative sample of 3290 Tanzanian households. Results: The coverage of edible oils and maize and wheat flours (including products of wheat flour and oil such as bread and cakes) was high, with 91 percent, 88 percent and 53 percent of households consuming these commodities, respectively. We estimated that vitamin A-fortified oil could reduce the prevalence of inadequate apparent intake of vitamin A (retinol activity equivalent) from 92 percent without LSFF to 80 percent with LSFF at current fortification levels. Low industry LSFF compliance of flour fortification limits the contribution of other micronutrients, but a hypothetical full fortification scenario shows that LSFF of cereal flours could substantially reduce the prevalence at risk of inadequate intakes of iron, zinc, folate and vitamin B12. Conclusions: The current Tanzania LSFF programme likely contributes to reducing vitamin A inadequacy. Policies that support increased compliance could improve the supply of multiple nutrients, but the prominence of small-scale maize mills restricts this theoretical benefit.

Aims: To evaluate peppermint essential oil (PEO) inhalation's effect on young soccer athletes' motor performance. Methods: A randomized crossover design was used to test the effect of the PEO. Eleven U-17 soccer players were evaluated into two conditions (PEO and Placebo – PLA). The players were tested in squat jump and countermovement jump and inhaled PEO or PLA and 10 min later performed the physical tests again. A mixed ANOVA was performed to test the hypotheses. Results: Main effects were found for the time in jumping height in the CMJ (p = 0.037). No main and interaction effects were found in the SJ variables. Conclusion: From the results, decrease CMJ performance acutely, both conditions presented decrease in JH, but based in effect size, PLA decrease is higher (more sample size for corroborate this) possibly due to improvements in the eccentric yielding sub-phase, where mentioned phase could be reflecting neural changes (required experimental verification). The PEO could be the interest in trainers for use before of match or in the half-time for minimize the decreased of physical performance by the rest.

Abstract Ferroptosis is an iron-dependent regulated cell death that suppresses tumor growth. It is activated by extensive peroxidation of membrane phospholipids caused by oxidative stress. GPX4, an antioxidant enzyme, reduces these peroxidized membrane phospholipids thereby inhibiting ferroptosis. This enzyme has two distinct subcellular localization; the cytosol and mitochondria. Dihydroorotate dehydrogenase (DHODH) complements mitochondrial GPX4 in reducing peroxidized membrane phospholipids. It is the rate-limiting enzyme in de novo pyrimidine nucleotide biosynthesis. Its role in ferroptosis inhibition suggests that DHODH inhibitors could have two complementary mechanisms of action against tumors; inhibiting de novo pyrimidine nucleotide biosynthesis and enhancing ferroptosis. However, the link between mitochondrial function and ferroptosis, and the involvement of DHODH in the ETC suggests that its role in ferroptosis could be modulated by the Warburg effect. Therefore, we reviewed relevant literature to get an insight into the possible effect of this metabolic reprogramming on the role of DHODH in ferroptosis. Furthermore, an emerging link between DHODH and cellular GSH pool has also been highlighted. These insights could contribute to the rational design of ferroptosis-based anticancer drugs. Video Abstract

Abstract A knob bow fibula (Bügelknopffibel) of the Leutkirch type, which typologically belongs to the second half of the 4th and early 5th century CE, was excavated in 2018 in the Roman city of Augusta Raurica, present-day Kaiseraugst (AG, Switzerland). This was analyzed for the first time for its elemental composition by using the non-destructive technique of Muon Induced X-ray Emission (MIXE) in the continuous muon beam facility at the Paul Scherrer Institute (PSI). In the present work, the detection limit is 0.4 wt% with $$\sim$$ ∼ 1.5 hours of measurement time. The fibula was measured at six different positions, at a depth of 0.3–0.4 mm inside the material. The experimental results show that the fibula is made of bronze, containing the main elements copper (Cu), zinc (Zn), tin (Sn) and lead (Pb). The compositional similarities/differences between different parts of the fibula reveal that it was manufactured as two “workpieces”. One workpiece consists of the knob (13.0±0.6 wt% Pb), bow (11.9±0.4 wt% Pb) and foot (12.5 ± 0.9 wt% Pb). These show a higher Pb content, suggesting a cast bronze. The spiral (3.2 ± 0.2 wt% Pb), which is part of the other workpiece, has a comparatively lower Pb content, suggesting a forged bronze.

Background & Aims: Acute-on-chronic liver failure (ACLF) is characterised by organ failure(s), high short-term mortality, and, pathophysiologically, deranged inflammatory responses. The extracellular matrix (ECM) is critically involved in regulating the inflammatory response. This study aimed to determine alterations in biomarkers of ECM turnover in ACLF and their association with inflammation, organ failures, and mortality. Methods: We studied 283 patients with cirrhosis admitted for acute decompensation (AD) with or without ACLF, 64 patients with stable cirrhosis, and 30 healthy controls. A validation cohort (25 ACLF, 9 healthy controls) was included. Plasma PRO-C3, PRO-C4, PRO-C5, PRO-C6, and PRO-C8 (i.e. collagen type III–VI and VIII formation) and C4M and C6M (i.e. collagen type IV and VI degradation) were measured. Immunohistochemistry of PRO-C6 was performed on liver biopsies (AD [n = 7], ACLF [n = 5]). A competing-risk regression analysis was performed to explore the prognostic value of biomarkers of ECM turnover with 28- and 90-day mortality. Results: PRO-C3 and PRO-C6 were increased in ACLF compared to AD (p = 0.089 and p

Reforestation of degraded forest lands has always involved the use of multipurpose tree species. However, understanding the relations between tree growth and soil fertility attributes along slopes of degraded mine sites by reforestation is limited, especially in Ghana. Therefore, a study was carried out at a rehabilitated degraded land to determine the influence of slope on soil fertility attributes and growth performance of trees. Plots were laid in the upslope, midslope and downslope, with an adjacent undisturbed forest as a control for sampling purposes. Soil samples were collected (0–15 and 15–30 cm depth) from the various sampling locations to determine soil properties, as well as tree growth parameters (e.g., height, basal area, and biomass). Slope positions impacted on tree growth (above and below ground biomass, and basal area) and soil properties. Highest soil organic carbon (1.80%), total N (0.22%), available P (6.92 mg kg−1), exchangeable K (0.20 cmolckg−1), and NO3−-N (19.03 mg N kg−1) were observed at the midslope position, whilst the upslope recorded the least values. The results also revealed that the midslope position recorded the highest tree growth characteristics. Aboveground biomass ranged from 17.67 to 21.73 mg ha−1, indicating the trees’ potential as carbon sinks. Furthermore, principal component analysis revealed that 3 components had their eigenvalues > 1, and accounted for 79.50% of the total variance. These results clearly demonstrate that spatial variations in soil properties are influenced by slope, and gives reference for future rehabilitation processes by reforestation.

Advanced LIGO and Advanced Virgo are monitoring the sky and collecting gravitational-wave strain data with sufficient sensitivity to detect signals routinely. In this paper we describe the data recorded by these instruments during their first and second observing runs. The main data products are gravitational-wave strain time series sampled at 16384 Hz. The datasets that include this strain measurement can be freely accessed through the Gravitational Wave Open Science Center at http://gw-openscience.org, together with data-quality information essential for the analysis of LIGO and Virgo data, documentation, tutorials, and supporting software.

Soil compaction is a major problem associated with conventional agriculture characterized by usage of heavy farm machinery. However, only few studies have quantified the dynamics of soil nutrients in compacted soils under restorative interventions, particularly in sub-Saharan Africa. Field and pot experiments were therefore conducted to evaluate the extent to which soil compaction modulates NH4+ and NO3− dynamics under organic amendment in Ghana. Soils were bulked to three (1.3, 1.5, and 1.7 Mgm−3) and four (1.3, 1.5, 1.7 and 1.9 Mgm−3) density levels in field and pot experiment respectively. The treatments were laid out in a factorial experiment, replicated three times with poultry manure applied at 4 and 6 t ha−1 with a control (0 t ha−1). Mineral N generally increased from 21 to 42 days after amendment (DAA) and declined at 63 DAA in both experiments. Soil compaction decreased NO3− more than NH4+ levels, the effects being more pronounced at 21 and 63 DAA in the field experiment. Application of poultry manure (PM) at 6 t ha−1 offsetted, to a large extent, the impact of soil compaction. The 4 and 6 t ha−1 PM produced similar (p > 0.05) grain yields of 3000.00±169.04 and 3004.44±277.99 kg ha−1 in the field experiment respectively. However, grain yield decreased by 135% in compacted soil at 1.7 Mgm−3, which received no amendment, compared to same compacted soil that received 4 t ha−1 poultry manure in the field experiment. Our finding suggests that addition of 4 t ha−1 PM is required for yield improvement in compacted soils less than 1.7 Mgm−3.

The use of soils around dumpsites in rural and urban areas in Ghana is common for food production especially vegetables. However, most people use such soils without knowledge of the risk of heavy metal uptake by plants. Therefore, the evaluation of heavy metal contamination is an important component of risk assessment at waste dumpsites. Hence, this study was conducted in Sunyani municipality to determine the risk of heavy metal pollution and physicochemical properties of soils at a waste dumpsite. Fifteen (15) soil samples (5 from each zone) were collected from a depth of 0–30 cm depth within the 3 demarcated zones of the dumpsite namely; Top-site, Dump-site, and Down-site. Physicochemical properties and heavy metals (e.g. lead, zinc and cadmium) were analysed to determine their concentrations in the collected soil samples. From the result, significant differences (p down-site > top-site. The concentration of the metals ranked as Fe > Pb > As > Zn > Cd at the dumpsite. The results revealed that the soil at the dumpsite is heavily contaminated with Fe (> 30 mgkg−1) as opposed to less than 0.55 mg kg−1 for the remaining heavy metals (As, Cd, Pb and Zn). However, heavy metals contamination at the various sampling locations of the dumpsite were within the permissible limits recommended by FAO/WHO. There is the need for regular monitoring and decontamination of the dumpsite before use for agricultural activities.

High quality single crystals of NdFeAsO0.65F0.35 (the superconducting transition temperature Tc ≃ 30.6 K) were studied in zero-field (ZF) and transverse-field (TF) muon-spin rotation/relaxation (μSR) experiments. An upturn in muon-spin depolarization rate at T ≲ 3 K was observed in ZF-μSR measurements and it was associated with the onset of ordering of Nd electronic moments. Measurements of the magnetic field penetration depth (λ) were performed in the TF geometry. By applying the external magnetic field Bex parallel to the crystallographic c-axis (Bex||c) and parallel to the ab-plane (Bex||ab), the temperature dependencies of the in-plane component (λab-2) and the combination of the in-plane and the out of plane components (λab,c-2) of the superfluid density were determined, respectively. The out-of-plane superfluid density component (λc-2) was further obtained by combining the results of Bex||c and Bex||ab set of experiments. The temperature dependencies of λab-2, λab,c-2, and λc-2 were analyzed within the framework of a self-consistent two-gap model despite of using the traditional α-model. Interband coupling was taken into account, instead of assuming it to be zero as it stated in the α-model. A relatively small value of the interband coupling constant Λ12 ≃ 0.01 was obtained, thus indicating that the energy bands in NdFeAsO0.65F0.35 are only weakly coupled. In spite of their small magnitude, the coupling between the bands leads to the single value of the superconducting transition temperature Tc. The penetration depth anisotropy γλ = λc/λab was found to increase upon cooling, consistent with most of Fe-based superconductors, and their behavior is attributed to the multi-band nature of superconductivity in NdFeAsO0.65F0.35.

The toolbox for material characterization has never been richer than today. Great progress with all kinds of particles and interaction methods provide access to nearly all properties of an object under study. However, a tomographic analysis of the subsurface region remains still a challenge today. In this regard, the Muon Induced X-ray Emission (MIXE) technique has seen rebirth fueled by the availability of high intensity muon beams. We report here a study conducted at the Paul Scherrer Institute (PSI). It demonstrates that the absence of any beam time-structure leads to low pile-up events and a high signal-to-noise ratio (SNR) with less than one hour acquisition time per sample or data point. This performance creates the perspective to open this technique to a wider audience for the routine investigation of non-destructive and depth-sensitive elemental compositions, for example in rare and precious samples. Using a hetero-structured sample of known elements and thicknesses, we successfully detected the characteristic muonic X-rays, emitted during the capture of a negative muon by an atom, and the gamma-rays resulting from the nuclear capture of the muon, characterizing the capabilities of MIXE at PSI. This sample emphasizes the quality of a continuous beam, and the exceptional SNR at high rates. Such sensitivity will enable totally new statistically intense aspects in the field of MIXE, e.g., elemental 3D-tomography and chemical analysis. Therefore, we are currently advancing our proof-of-concept experiments with the goal of creating a full fledged permanently operated user station to make MIXE available to the wider scientific community as well as industry.

El autor, en el presente artículo, analiza los principales cambios normativos introducidos en el sistema de justicia peruano a partir de la aprobación de la Ley de Reforma Constitucional que crea la Junta Nacional de Justicia y su Ley Orgánica. En primer lugar, esboza los proyectos de ley presentados por el Poder Ejecutivo, con miras a reformar el sistema de justicia y el estado de la cuestión de estos. En esa línea, se analiza la Junta Nacional de Justicia (JNJ) y cómo esta ha implicado un cambio respecto a lo establecido por el otrora Consejo Nacional de la Magistratura. Al respecto, expone las funciones y composición de la Junta Nacional de Justicia, en su calidad de organismo constitucionalmente autónomo encargado de nombrar, ratificar y destituir jueces y fiscales de todos los niveles, resaltando la necesidad de garantizar procesos meritocráticos, transparentes y públicos.

Abstract Background Acute-on-chronic liver failure (ACLF) is characterized by the presence of acute decompensation (AD) of cirrhosis, organ failure, and high short-term mortality rates. Hemodynamic dysfunction and activation of endogenous vasoconstrictor systems are thought to contribute to the pathogenesis of ACLF. We explored whether copeptin, a surrogate marker of arginine vasopressin, is a potential marker of outcome in patients admitted for AD or ACLF and whether it might be of additional value to conventional prognostic scoring systems in these patients. Methods All 779 patients hospitalized for AD of cirrhosis from the CANONIC database with at least one serum sample available for copeptin measurement were included. Presence of ACLF was defined according to the CLIF-consortium organ failure (CLIF-C OF) score. Serum copeptin was measured in samples collected at days 0–2, 3–7, 8–14, 15–21, and 22–28 when available. Competing-risk regression analysis was applied to evaluate the impact of serum copeptin and laboratory and clinical data on short-term survival. Results Serum copeptin concentration was found to be significantly higher in patients with ACLF compared with those without ACLF at days 0–2 (33 (14–64) vs. 11 (4–26) pmol/L; p

Experimental studies of frustrated spin systems such as pyrochlore magnetic oxides test our understanding of quantum many-body physics. Here the authors show experimentally that Tb2Hf2O7 may be a model material for investigating how structural disorder can stabilize a quantum spin liquid phase.

Background: Patients with acutely decompensated cirrhosis (AD) may or may not develop acute-on-chronic liver failure (ACLF). ACLF is characterized by high-grade systemic inflammation, organ failures (OF) and high short-term mortality. Although patients with AD cirrhosis exhibit distinct clinical phenotypes at baseline, they have low short-term mortality, unless ACLF develops during follow-up. Because little is known about the association of profile of systemic inflammation with clinical phenotypes of patients with AD cirrhosis, we aimed to investigate a battery of markers of systemic inflammation in these patients.Methods: Upon hospital admission baseline plasma levels of 15 markers (cytokines, chemokines, and oxidized albumin) were measured in 40 healthy controls, 39 compensated cirrhosis, 342 AD cirrhosis, and 161 ACLF. According to EASL-CLIF criteria, AD cirrhosis was divided into three distinct clinical phenotypes (AD-1: Creatinine

La zarzamora (Rubus fruticosus) es una rosácea comestible cultivada en la microrregión de Coyopolan municipio de Ixhuacán de los Reyes, Veracruz, México. Esta fruta es importante en esta localidad ya que es utilizada en la elaboración de una variedad de productos artesanales, entre los que destacan el licor de zarzamora y mermelada. Algunos de estos productos además de ser un aporte económico para los habitantes, proporcionan un beneficio a la salud por sus componentes como los compuestos fenólicos que actúan como antioxidantes naturales. En este sentido el presente trabajo tuvo como objetivo elaborar una salsa como potencial alimento funcional teniendo como ingrediente principal la zarzamora y una variedad local de chile, llamado “tabaquero”; a estas salsas se les evaluó su calidad nutricional, la presencia de microorganismos a través de pruebas como coliformes totales, conteo de bacterias aerobias en placa y conteo de mohos y levaduras en alimentos, posteriormente se cuantificaronlos flavonoides, fenoles y antocianinas totales, así como también su actividad antioxidante. Como resultado se obtuvieron tres tipos de salsa, en las que se determinó que no hay presencia de microorganismos, las pruebas de calidad nutrimental indicaron que tienen buenos valores y respecto a la funcionalidad se observó que, en comparación con el fruto fresco se mantuvo la actividad antioxidante aún después del proceso. Por lo que concluimos que los productos cuentan con valores apropiados para considerarlos como potenciales alimentos funcionales.

The organizational climate survey has been an important tool in the corporate world, the way in which the institutions can assess and ascertain through the results, the degree of satisfaction of its employees and look through plan of action, achieve better results in both performance and production. Through an empirical research, exploratory qualitative research, with collection of secondary data, it was found that the implementation of the organizational climate survey, "Speak Frankly" from Itaú Unibanco, it could analyze data and make a plan of effective action aiming at continuous improvement in the organizational environment, serving as personnel management model. The results were favorable in the period from year 2012 to 2014 with an increase of the degree of satisfaction in four 4% and maintained excellent adherence to answer questions reaching 90% the number of employees.

Muon spin rotation ( μ SR) spectra recorded for manganese silicide MnSi and interpreted in terms of a quantitative analysis constrained by symmetry arguments were recently published. The magnetic structures of MnSi in zero-field at low temperature and in the conical phase near the magnetic phase transition were shown to substantially deviate from the expected helical and conical structures. Here, we present material backing the previous results obtained in zero-field. First, from simulations of the field distributions experienced by the muons as a function of relevant parameters, we confirm the uniqueness of the initial interpretation and illustrate the remarkable complementarity of neutron scattering and μ SR for the MnSi magnetic structure determination. Second, we present the result of a μ SR experiment performed on MnSi crystallites grown in a Zn-flux and compare it with the previous data recorded with a crystal obtained from Czochralski pulling. We find the magnetic structure for the two types of crystals to be identical within experimental uncertainties. We finally address the question of a possible muon-induced effect by presenting transverse field μ SR spectra recorded in a wide range of temperature and field intensity. The field distribution parameters perfectly scale with the macroscopic magnetization, ruling out a muon-induced effect.

Este artículo plantea un análisis de la figura de Francisco Franco en el marco del discurso emitido por el aparato de propaganda de la Organización Sindical Española, a través de su órgano principal, el Diario Pueblo, y de otras publicaciones sindicales durante el periodo conocido por Desarrollismo y sus antecedentes. El trabajo quiere establecer las características y evolución de una construcción propagandística de la figura mitificada de Franco ajustada a los intereses políticos del nacionalsindicalismo. Asimismo intenta situarse tanto en el contexto interno de la Organización Sindical, inmersa en un proceso de impulso, reorganización y adaptación, como en la cambiante realidad socio-económica española de los años 60.

Data analysis, presentation and distribution is of utmost importance to a genome project. A public domain software, ACeDB, has been chosen as the common basis for parasite genome databases, and a first release of TcruziDB, the Trypanosoma cruzi genome database, is available by ftp from ftp://iris.dbbm.fiocruz.br/pub/genomedb/TcruziDB as well as versions of the software for different operating systems (ftp://iris.dbbm.fiocruz.br/pub/unixsoft/). Moreover, data originated from the project are available from the WWW server at http://www.dbbm.fiocruz.br. It contains biological and parasitological data on CL Brener, its karyotype, all available T. cruzi sequences from Genbank, data on the EST-sequencing project and on available libraries, a T. cruzi codon table and a listing of activities and participating groups in the genome project, as well as meeting reports. T. cruzi discussion lists (tcruzi-l@iris.dbbm.fiocruz.br and tcgenics@iris.dbbm.fiocruz.br) are being maintained for communication and to promote collaboration in the genome project

El propòsit d’aquest article és donar consells útils, comprensibles i fàcilment aplicables sobre el procés de redacció d’una tesi doctoral d’història. Certament, no sempre un candidat a doctor té el temps necessari o les eines suficients per abordar amb confiança i possibilitats d’èxit la complexa tasca de posar sobre paper el coneixement acumulat fruit d’anys de recerca. En moltes ocasions el doctorand no té a mà els recursos per realitzar una planificació eficient de la redacció o per anticipar la possibilitat de bloquejos que poden suposar la pèrdua d’un temps preciós. És amb la intenció de cobrir una part d’aquestes necessitats que aquest article, basat en la intervenció que va fer l’autor a les Jornades Doctorials del Departament d’Història Moderna i Contemporània de la UAB el maig de 2012, vol servir d’eina o recurs per a aquells doctorands que assumeixin la importància i beneficis d’escriure bé el seu treball de recerca.

In a randomized clinical trial of early versus standard antiretroviral therapy (ART) in HIV-infected adults with a CD4 cell count between 200 and 350 cells/mm³ in Haiti, early ART decreased mortality by 75%. We assessed the cost-effectiveness of early versus standard ART in this trial.Trial data included use of ART and other medications, laboratory tests, outpatient visits, radiographic studies, procedures, and hospital services. Medication, laboratory, radiograph, labor, and overhead costs were from the study clinic, and hospital and procedure costs were from local providers. We evaluated cost per year of life saved (YLS), including patient and caregiver costs, with a median of 21 months and maximum of 36 months of follow-up, and with costs and life expectancy discounted at 3% per annum. Between 2005 and 2008, 816 participants were enrolled and followed for a median of 21 months. Mean total costs per patient during the trial were US$1,381 for early ART and US$1,033 for standard ART. After excluding research-related laboratory tests without clinical benefit, costs were US$1,158 (early ART) and US$979 (standard ART). Early ART patients had higher mean costs for ART (US$398 versus US$81) but lower costs for non-ART medications, CD4 cell counts, clinically indicated tests, and radiographs (US$275 versus US$384). The cost-effectiveness ratio after a maximum of 3 years for early versus standard ART was US$3,975/YLS (95% CI US$2,129/YLS-US$9,979/YLS) including research-related tests, and US$2,050/YLS excluding research-related tests (95% CI US$722/YLS-US$5,537/YLS).Initiating ART in HIV-infected adults with a CD4 cell count between 200 and 350 cells/mm³ in Haiti, consistent with World Health Organization advice, was cost-effective (US$/YLS

Background: Research has revealed associations between microbes of the gastrointestinal tract and stress, anxiety and depression in pregnant or postpartum women. While these studies suggest a gut-brain-behaviour axis, no studies have examined microbes of the oral cavity in relation to maternal mental health., Objective: To explore a potential oral-brain-behaviour axis related to maternal mental health., Methods: Microbes were measured in saliva obtained from 224 second-trimester (mean±SD = 17±2 weeks) women oversampled for stress. Oralome data were associated with women's recent or cumulative pregnancy stress, trait and state anxiety, depression symptoms and post-traumatic stress disorder (PTSD) symptoms. Covariates explored included age, income, alcohol and tobacco use, dental issues and physical health problems., Results: Pregnant women in the high trait anxiety or depression symptom groups had higher oral alpha diversity, indicating higher richness of species within samples. Groups with high and low PTSD symptoms differed in beta diversity, reflecting differences in community composition. Linear discriminant analysis showed differently abundant microbes in women with high stress versus low life stress, anxiety, depression, and PTSD, with the affected microbes mostly differing by symptom. Notably, members of phylum Proteobacteria were more abundant in women with high recent life stress and Spirochaetes was more abundant in women with high depression symptoms. Members of phylum Firmicutes were more abundant in the high trait anxiety and high depression groups. Genus Dialister (previously found to be lower in the gut of depressed non-pregnant people) was higher in women experiencing either high trait or state anxiety, or experiencing high depression symptoms, while genus Eikenella was elevated with high trait anxiety, depression or PTSD., Conclusions: The oral microbiome is associated with stress and mental health in pregnant women, in ways different from the gut microbiome or what has been found in non-pregnant people., Clinical Implications: Understanding oral microbiome-mental health relations may reveal future microbial targets to improve maternal psychological well-being., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. Published by BMJ.)

The stingrays of the genus Himantura imbricata are present in all of the world's oceans, but the toxicity of their venoms has not yet been thoroughly characterized. The zebrafish as a toxicology model can be used for general toxicity testing of drugs and the investigation of toxicological mechanisms. The aim of this study was to evaluate the effect of crude venom from the stingray H. imbricata on the zebrafish Danio rerio. Juvenile zebrafish were injected with different concentrations of venom from H. imbricata via subcutaneous injections. The venom's effects were established via histological examination and hemolytic activity in zebrafish. The histopathological analysis revealed significant tissue damage in the organs of the zebrafish injected with venom, including liver necrosis and kidney degeneration. A blood examination revealed echinocytes, hemolysis, and nuclear abnormalities. Bodyweight estimations and histopathological attributes of the gills, heart, muscle, liver, intestine, eye, and brain were determined. The histological staining studies of the gills, liver, and intestine were measurably higher in the venom groups compared with the other two groups. Aggregately, the result shows that zebrafish may act as a valuable biomarker for alterations impelled by H. imbricata venom. The work delivers a useful model with substantial pharmacological potential for new drugs and a better comprehension of research on stingray venom., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Silver nanoparticles (AgNPs) have gained much attention due to their unique physical, and chemical properties. Integration of phytochemicals in nanoformulation might have higher applicability in healthcare. Current work demonstrates the synthesis of green AgNPs with O. gratissimum (gr-AgNPs) O. tenuiflorum (te-AgNPs) and O. americanum (am-AgNPs) followed by an evaluation of their antimicrobial and anticancer properties. SEM analysis revealed spherical-shaped particles with average particle sizes of 69.0 ± 5 nm for te-AgNPs, 46.9 ± 9 nm for gr-AgNPs, and 58.5 ± 18.7 nm for am-AgNPs with a polydispersity index below 0.4. The synthesized am-AgNPs effectively inhibited Klebsiella pneumonia, Escherichia coli, Staphylococcus aureus, Aspergillus niger, and Candida albicans with 23 ± 1.58 mm, 20 ± 1.68 mm, 22 ± 1.80 mm, 26 ± 1.85 mm, and 22 ± 1.40 nm of zone of inhibition respectively. Synthesized AgNPs also induced apoptotic cell death in MCF-7 in concentration-dependent manner. IC 50 values for am-AgNPs, te-AgNPs, and gr-AgNPs were 14.78 ± 0.89 µg, 18.04 ± 0.63 and 15.41 ± 0.37 µg respectively which suggested that am-AgNPs were the most effective against cancer. At higher dose size (20 µg) AgNPs were equally effective to commercial standard Doxorubicin (DOX). In comparison to te-AgNPs and gr-AgNPs, am-AgNPs have higher in vitro anticancer and antimicrobial effects. The work reported Ocimum americanum for its anticancer properties with chemical profile (GCMS) and compared it with earlier reported species. The activity against microbial pathogens and selected cancer cells clearly depicted that these species have distinct variations in activity. The results have also emphasized on higher potential of biogenic silver nanoparticles in healthcare but before formulation of commercial products, detailed analysis is required with human and animal models., (© 2024. The Author(s).)

Metalloproteins play a crucial role in regulating different aspects of the immune system in humans. They have various functions in immunity, including recognizing and presenting antigens, aiding in the movement and effectiveness of immune cells, and facilitating interactions between the host and pathogens. Understanding how these proteins work can help us develop new methods to control the immune response in different diseases. Metalloproteins contain metal ions in their structure, which allows them to perform these diverse functions. They encompass a wide range of enzymes, signaling molecules, and structural proteins that utilize metal ions as cofactors for their activities. Examples of metalloproteins include superoxide dismutase, catalase, and metalloproteases, which regulate oxidative stress, inflammation, and tissue remodelling processes associated with immune activation. By studying their functions and the effects of their dysfunction, researchers can develop strategies to improve immune function and combat various diseases. This review explores the diverse functions of metalloproteins in immune processes, highlighting their significance in both health and disease., (Copyright © 2024. Published by Elsevier Inc.)

The human brain grows quickly during infancy and early childhood, but factors influencing brain maturation in this period remain poorly understood. To address this gap, we harmonized data from eight diverse cohorts, creating one of the largest pediatric neuroimaging datasets to date focused on birth to 6 years of age. We mapped the developmental trajectory of intracranial and subcortical volumes in ∼2,000 children and studied how sociodemographic factors and adverse birth outcomes influence brain structure and cognition. The amygdala was the first subcortical volume to mature, whereas the thalamus exhibited protracted development. Males had larger brain volumes than females, and children born preterm or with low birthweight showed catch-up growth with age. Socioeconomic factors exerted region- and time-specific effects. Regarding cognition, males scored lower than females; preterm birth affected all developmental areas tested, and socioeconomic factors affected visual reception and receptive language. Brain-cognition correlations revealed region-specific associations., (© 2023. The Author(s).)

Imaging genetics provides an opportunity to discern associations between genetic variants and brain imaging phenotypes. Historically, the field has focused on adults and adolescents; very few imaging genetics studies have focused on brain development in infancy and early childhood (from birth to age 6 years). This is an important knowledge gap because developmental changes in the brain during the prenatal and early postnatal period are regulated by dynamic gene expression patterns that likely play an important role in establishing an individual's risk for later psychiatric illness and neurodevelopmental disabilities. In this review, we summarize findings from imaging genetics studies spanning from early infancy to early childhood, with a focus on studies examining genetic risk for neuropsychiatric disorders. We also introduce the Organization for Imaging Genomics in Infancy (ORIGINs), a working group of the ENIGMA (Enhancing NeuroImaging Genetics through Meta-Analysis) consortium, which was established to facilitate large-scale imaging genetics studies in infancy and early childhood., (Copyright © 2023 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Sex differences in the human brain emerge as early as mid-gestation and have been linked to sex hormones, particularly testosterone. Here, we analyzed the influence of markers of early sex hormone exposure (polygenic risk score (PRS) for testosterone, salivary testosterone, number of CAG repeats, digit ratios, and PRS for estradiol) on the growth pattern of cortical surface area in a longitudinal cohort of 722 infants. We found PRS for testosterone and right-hand digit ratio to be significantly associated with surface area, but only in females. PRS for testosterone at the most stringent P value threshold was positively associated with surface area development over time. Higher right-hand digit ratio, which is indicative of low prenatal testosterone levels, was negatively related to surface area in females. The current work suggests that variation in testosterone levels during both the prenatal and postnatal period may contribute to cortical surface area development in female infants., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Nano biotechnology, when coupled with green chemistry, can revolutionize human life because of the vast opportunities and benefits it can offer to the quality of human life. Luminescent metal nanoclusters (NCs) have recently developed as a potential research area with applications in different areas like medical, imaging, sensing etc. Recently these new candidates have proved to be beneficial in the food supply chain enabling controlled release of nutrients, pesticides and as nanosensors for the detection of contaminants and play roles in healthy food storage and maintaining food quality. An assortment of nanomaterials has been employed for these applications and reviews have been published on the use of nanotechnology in agriculture. Ligand-protected metal nanoclusters are a distinctive class of small organic-inorganic nanostructures that garnered immense research interest in recent years owing to their stability at specific "magic size" compositions along with tunable properties that make them promising candidates for a wide range of nanotechnology-based applications. This review tries to consolidate the recent developments in the area of ligand-protected nanoclusters in connection with the detection of pesticides, food contaminants, heavy metal ions and plant growth monitoring for healthy agricultural practices. Its antimicrobial activity to manage the microbial contamination is highlighted. The review also throws light on the various perspectives by which food production and allied areas will be transformed in future., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Flavonoids are an important class of natural polyphenolic compounds reported to exert beneficial effects in cardiovascular and metabolic diseases, cancer, autoimmune and neurological disorders. Flavonoids possess potential antioxidant, anti-inflammatory, antiapoptotic and immuno-modulation properties. Intriguingly, the importance of flavonoids in different neurological disorders is gaining more attention due to the safety, better pharmacokinetic profile and blood-brain barrier penetration, cost-effectiveness and readiness for clinical uses/trials. Many in vitro and in vivo research studies have established the neuroprotective mechanism of flavonoids in the central nervous system (CNS) diseases. The present review summarizes the benefits of various classes of flavonoids (flavones, flavonols, flavanones, anthocyanidins, isoflavones, flavanols), chemical nature, classification, their occurrence and distribution, pharmacokinetics and bioavailability. The manuscript also presents available evidences relating to the role of flavonoids in regulating key signaling pathways such as nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway, mitogen-activated protein kinase (MAPK) pathway, Janus kinase and signal transducer and activator of transcription proteins (JAK/STAT) pathway, Toll-like receptors (TLR) pathway, nuclear factor erythroid 2-related factor 2 (Nrf2) pathway and cAMP response element-binding protein (CREB) pathway involved in neuroinflammation associated with major neurological disorders. Literature search was conducted using electronic databases like Google Scholar, Scopus, PubMed central, Springer search and Web of science. Chemical structures used in the present analysis were drawn using Chemdraw Professional 15.0 software. This collective information provides comprehensive knowledge on disease pathways and therapeutic benefits of flavonoids in neurological disorders, druggability and future scope for research., (© 2021. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Formal interventions are rationalized to be irreplaceable, especially with marginalized communities that are presumed to lack capacity. It is event centric and differ considerably from the community's experience of disaster risk and recovery within the everyday context. Thus, community engagement with multiple formal institutions that often fail to address recovery needs of the most marginalized, is inevitable. These contradictions lead to varied forms of community assertion towards addressing structural inequalities and injustices. In this paper we explore these contradictions by drawing from the work of scholars who recognize the limits of procedural justice and push for distributive justice, especially by focusing on grassroots processes using the lens of the politics of neo-liberalism and ontology of possibilities. Using a multi-sited instrumental case study approach the paper explores community's lived experiences, factors contributing to the persistence of structural inequality and injustice, and the alternate conception of justice and their assertions, in the disaster recovery context. The two case studies - Vistapit Mukti Vahini and Thayillam, inform an alternate theoretical conception of disaster recovery embedded in structural inequalities and injustices through the following three perspectives: Firstly how disaster risk and recovery emerge from historical and everyday lived reality of marginalized communities, their social relations and resulting material conditions; Secondly how challenging everyday social relations, processes and injustices is central to the community's alternate conception and assertion for disaster recovery; and finally how community assertion and recovery relies on the mobilization of vulnerability, which could mean being exposed and agentic at the same time., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Authors.)

Objective: To evaluate the relationship between air pollutant (AP) exposure and rheumatoid arthritis (RA) autoantibody status METHODS: We performed a cross sectional study utilizing enrollment data from participants in the Veterans Affairs rheumatoid arthritis registry. HLA-DRB1 shared epitope (SE), smoking, rheumatoid factor (RF), and anti-cyclic citrullinated peptide antibody (ACPA) status were collected. Mean exposure levels were obtained for AP (NO 2 , SO 2 , particulate matter [PM 2.5 , PM 10 ], and ozone) from air quality monitoring stations at patients' residential zip codes in the year prior to enrollment. Multivariable logistic and ordinary least squares regression models were used to determine independent associations of AP with RA seropositivity and autoantibody concentration., Results: The cohort included 557 veterans (90% male, 76% Caucasian), with mean age of 70 years and mean disease duration of 13 years. The majority were HLA-DRB1 SE, RF, and ACPA positive (73%, 79%, and 76%, respectively). In univariate models, PM 2.5 exposure was associated with higher ACPA concentration (p = 0.009). Similarly, in multivariable regression models, PM 2.5 exposure was independently associated with higher ACPA concentration (p = 0.037). Current smoking independently predicted RF and ACPA positivity and titers, while HLA-DRB1 SE alleles were associated with RF positivity and ACPA positivity and titers., Conclusions: In an elderly cohort of RA patients, fine particulate matter (PM 2.5 ) exposure independently predicted higher ACPA concentration. Further study of fine particulate matter in the pathogenesis of RA is warranted. Key Points • A study that integrates both genetic and environmental exposure data, relative to RA autoantibody status. • Of different air pollutants measures, exposure to fine particulate matter (PM 2.5 ) appears to be most closely linked to ACPA titers.

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder with impairments in social communication, restricted, repetitive and stereotyped behaviors. Both genetic and environmental factors are known to contribute toward pathophysiology of Autism. Environmental influences on gene expression can be mediated by methylation patterns which are established and maintained by DNA methyltransferases. Several studies in the past have investigated the role of global methylations in Autism. The present study is aimed to investigate the role of genetic variations in the DNA methyltransferase which might be critical in defining the threshold for environmental factors toward susceptibility to autism. Polymorphisms in DNA methyltransferases, DNMT1, DNMT3A, DNMT3B, and DNMT3L were screened for association with ASD in 180 autistic patients and 260 healthy controls from a south Indian population. DNMT1 rs10418707 and rs10423341, and DNMT3A rs2289195 were found to be significantly associated at genotypic and allelic level with ASD. Functional prediction indicates that these SNPs have a role in transcriptional regulation and increased expression, indicating that hypermethylation might be induced by its genotype status. The study might reflect the role of genetics variants in DNMTs in defining the threshold of environmental impact in influencing the disease or phenotype variations in ASD. © 2019 IUBMB Life, 2019., (© 2019 International Union of Biochemistry and Molecular Biology.)

Objective: To assess the potential utility of a cytokine measurement in rheumatoid arthritis (RA) patients with active joint disease but normal acute phase reactants (APR)., Methods: RA patients in a longitudinal observational registry with available cytokine array data were included. Patients were categorized based on agreement/disagreement of physical examination and APR measurements: concordant high (CH) [high tender and/or swollen joint counts (TJC + SJC > 3) and APR (ESR ≥ 28 mm/h + CRP ≥ 1.5 mg/L)]; concordant low (CL) [TJC + SJC ≤ 3 and normal APR]. Discordant (D) [TJC + SJC > 3 and normal APR] patients were stratified into low, medium, and high-disease activity (DL, DM, DH). Weighted-average and log-transformed cytokine scores were calculated based on results of a cytokine array. Chi-square tests compared categorical variables by concordance status; t tests, Wilcoxon rank-sum tests, ANOVA models, and ordinary least squares (OLS) regressions were used to compare continuous measures., Results: RA patients (n = 1467) were predominantly male (91%). Compared to CH patients (n = 174), D (n = 434) were younger, less frequently seropositive, with lower TJC, SJC, and DAS28-3v scores (p < 0.001). Cytokine scores for DL, DM, and DH groups were lower than CH patients (p < 0.001) and did not differ between DL, DM, and DH subgroups and were similar to CL (n = 356) patients. In multivariable analyses including CH and D patients, log-cytokine score was associated with higher DAS28-3v scores (p = 0.029). In multivariable analyses including CL patients, concordance status (p = 0.011) and ACPA (p = 0.013) were predictors of higher log cytokine score., Conclusion: In this study, cytokine scores did not identify active joint disease in RA patients with normal APR.

Background: In schizophrenia, genetic background may provide a substrate for intrinsic maldevelopment of the brain through environmental influences, by recruiting neurotrophic factors and cytokines, to trigger the changes that lead to impaired neuronal functions. Cytokines being the key regulators of immune/inflammatory reactions are also known to influence the dopaminergic, noradrenergic, and serotonergic neurotransmission. Therefore, functional polymorphisms in cytokine genes may result in imbalances in the pro- and anti-inflammatory cytokine production., Methods: We screened polymorphisms in pro- and anti-inflammatory cytokine genes using a case-control association study in a South Indian population. The role of allele, genotype, haplotype, and diplotypes of these cytokine genes and their epistatic interactions were assessed in contributing to the risk of developing schizophrenia. Meta-analysis for the reported associations was also monitored for global significance., Results: The pro-inflammatory cytokine gene polymorphisms in IL1Ars1800587, IL6rs1800796, TNFArs361525, and IFNGrs2069718 were associated with schizophrenia. The study also provides significant evidence for strong epistatic interactions among pro-inflammatory cytokine genes IL6 and IFNG in the development of schizophrenia. In silico analysis suggested that associated risk variants were indicative of altered transcriptional activity with higher production of IL1α, IL-6, TNF-α, and IFN-ɤ cytokines. Meta-analysis indicated heterogeneity among study population while IL1Ars1800587 was found to be globally significant., Conclusions: It is important to identify the nature of inflammatory response that can be amplified by the environment, to influence either Th1 response or Th2 response. The associated functional variants in the study are involved with increased expression resulting in higher production of the pro-inflammatory cytokines IL-1α, IL-6, TNF-α, and IFN-γ. The interaction of immunological stressors with these high producer alleles of pro-inflammatory cytokines may suggest that even a lower threshold may be sufficient to induce a resultant chronic effect on the psycho-social and environmental stressors that may result in the development and pathogenesis of schizophrenia. Understanding environmental factors that influence the expression of these pro-inflammatory cytokine genes or their interaction can possibly help in dissecting the phenotypic variation and therapeutic response to antipsychotics in schizophrenia.

Introduction: Non-diphtheritic corynebacteria are normal inhabitants of skin and mucous membrane. When isolated from clinical specimens they are often considered as contaminants. Recent reports suggest their role as emerging nosocomial pathogens., Aim: To speciate non-diphtheritic corynebacteria isolated from wound specimens, to correlate their clinical significance and to determine their invitro antimicrobial susceptibilities to 9 antimicrobial agents., Materials and Methods: Twenty five non-diphtheritic corynebacteria from skin and soft tissue infections were selected for study. Isolates were identified by battery of tests and minimum inhibitory concentration (MIC) was detected by Clinical & Laboratory Standards Institute (CLSI) described broth microdilution method. MIC was interpreted according CLSI and British Society for Antimicrobial Chemotherapy (BSAC) guidelines., Results: C. amycolatum was the predominant species (20%) followed by C. striatum (16%). Penicillin was least effective invitro followed by clindamycin and ciprofloxacin. Excellent activities were shown by vancomycin, linezolid and imipenem. Multidrug resistance was found in all the species., Conclusion: Non-diphtheritic corynebacteria are potential nosocomial pathogens among acute/chronic complicated skin and soft tissue infection. Vancomycin or linezolid can be used empirically to treat such infections until the invitro susceptibility results are available.

Introduction: Mupirocin competitively inhibits bacterial isoleucyl transfer-RNA synthetase and inhibit bacterial protein synthesis. Widespread usage and over the counter availability of the drug has resulted in resistance among Staphylococcus species., Objectives: This study aimed to determine the overall prevalence of mupirocin resistance among staphylococci. Correlate clinical significance of mupirocin resistance and its relationship to clinical use., Methods: Consecutive, nonrepetitive, clinical isolates of Staphylococcus aureus (n = 98), and coagulase-negative staphylococci (CoNS) (n = 45) from skin and soft-tissue infections between January 2014 and June 2014 were studied. Antibiotic susceptibility testing was done according to Clinical and Laboratory Standards Institute guidelines. Low- and high-level mupirocin resistance was screened by using 5 µg and 200 µg discs respectively and confirmed by agar dilution. Annual consumption of mupirocin was studied and correlated with resistance., Results: High-level mupirocin resistance was found in 8.2% S. aureus and 15.6% of CoNS, while low-level mupirocin resistance was found in 17% S. aureus and 8.9% CoNS. High-level mupirocin resistance was more common in methicillin-sensitive S. aureus isolates when compared with methicillin-resistant S. aureus isolates (P < 0.05). Mupirocin resistant S. epidermidis were associated with methicillin resistance and constitutive clindamycin resistance., Conclusion: High prevalence of mupirocin resistance was found in the present study. Increased prevalence of mupirocin resistance among community-acquired staphylococci demands the judicious use of the drug in the community.

Homocysteine (Hcy) is known to be a prognostic marker for neurological, cardiovascular and cerebrovascular diseases and several other pathophysiological conditions. A sudden surge in Hcy can increase cardiovascular events. Hemodynamic modulations are known to be associated with individual's chronotype. Therefore, precise monitoring of Hcy is crucial for evaluating its impact on risk. The aim of the present study was to investigate the rhythmicity of Hcy under controlled dietary conditions and whether this rhythmicity is under the genetic control of circadian rhythm. Five subjects were selected from 200 Malayalam speaking healthy ethnic individuals who were screened for functionally critical variants of MTHFR and hCLOCK genes. MTHFR is the rate-limiting enzyme in the methionine cycle and critical for regulating Hcy levels while hCLOCK is a critical gene responsible in regulating the day and night cycles. Rhythmicity in Hcy levels were observed in all the subjects with a consensus on a morning nadir and an evening peak. Gender specific stratification of Hcy levels were observed among similar genotypes of MTHFR and hCLOCK genes. Variations from the conventional rhythmicity of Hcy were observed among similar genotypes of MTHFR and dissimilar hCLOCK genotypes. A reduced plasma Hcy in hCLOCK rs1801260 CC genotype individuals were observed in contrast to CT genotype individuals. The study tends to suggest that Hcy and body time are genetically interdependent and throws light on some of the previously unexplained reasons for variability in Hcy levels. A population specific variation of MTHFR and hCLOCK genes also highlights ethnicity specific risk management.

Epidermal stem cells play a central role in tissue homeostasis, wound repair, tumor initiation, and gene therapy. A major impediment to the purification and molecular characterization of epidermal stem cells is the lack of a quantitative assay for cells capable of long-term repopulation in vivo, such as exists for hematopoietic cells. The tremendous strides made in the characterization and purification of hematopoietic stem cells have been critically dependent on the availability of competitive transplantation assays, because these assays permit the accurate quantitation of long-term repopulating cells in vivo. We have developed an analogous functional assay for epidermal stem cells, and have measured the frequency of functional epidermal stem cells in interfollicular epidermis. These studies indicate that cells capable of long-term reconstitution of a squamous epithelium reside in the interfollicular epidermis. We find that the frequency of these long-term repopulating cells is 1 in 35,000 total epidermal cells, or in the order of 1 in 104 basal epidermal cells, similar to that of hematopoietic stem cells in the bone marrow, and much lower than previously estimated in epidermis. Furthermore, these studies establish a novel functional assay that can be used to validate immunophenotypic markers and enrichment strategies for epidermal stem cells, and to quantify epidermal stem cells in various keratinocyte populations. Thus further studies using this type of assay for epidermis should aid in the progress of cutaneous stem cell-targeted gene therapy, and in more basic studies of epidermal stem cell regulation and differentiation.