A cross-sectional study on stool- and gastrointestinal-related outcomes of Mexican infants consuming different formulae.

BACKGROUND: Immaturities present at birth, such as in the gut microbiome and digestive, nervous, and immune system, resolve with time. Nevertheless, this may result in mild digestive symptoms early in life, particularly in formula-fed infants. Formula composition and processing may impact this discomfort. This study therefore aimed to assess stool characteristics and gastrointestinal symptoms of healthy infants fed different formulae. METHODS: A multicenter, cross-sectional, observational trial was performed in Mexico between November 2019 and January 2022, where exclusively formula-fed infants (n = 342, aged 1-4 months) were studied in four groups based on their existing formula use. Feeding was continued per practice following label instructions. For 7 days, parents/caregivers were requested to record fecal characteristics, using the Amsterdam Infant Stool Scale, and rate gastrointestinal symptoms. Stool samples were collected to determine pH, dry matter content, and fecal calprotectin levels. RESULTS: Most infants had a soft/formed stool consistency, although odds for hard stools were different between groups. Gastrointestinal symptom scores revealed significant differences for burping and diarrhea, while other symptoms did not differ between groups. No significant differences between groups were found for stool frequency, dry matter content, and fecal pH. Although calprotectin was within the expected healthy ranges, significant differences among groups were seen. Furthermore, calprotectin significantly correlated with the severity of the gastrointestinal symptoms burping, flatulence, abdominal distension, and diarrhea. CONCLUSIONS: Differences in stool characteristics and specific differences in gastrointestinal symptoms were observed between different formula brand users. This may potentially be explained by the different composition and processing of the formulae, although there are multiple factors that influence the assessed outcomes. TRIAL REGISTRATION: The study was registered in the Netherlands Trial Registry (NL7805), linked to https://trialsearch.who.int/ , on 11/06/2019.

Lymph node dendritic cells harbor inducible replication-competent HIV despite years of suppressive ART.

Although gut and lymph node (LN) memory CD4 T cells represent major HIV and simian immunodeficiency virus (SIV) tissue reservoirs, the study of the role of dendritic cells (DCs) in HIV persistence has long been limited to the blood due to difficulties to access lymphoid tissue samples. In this study, we show that LN migratory and resident DC subpopulations harbor distinct phenotypic and transcriptomic profiles. Interestingly, both LN DC subpopulations contain HIV intact provirus and inducible replication-competent HIV despite the expression of the antiviral restriction factor SAMHD1. Notably, LN DC subpopulations isolated from HIV-infected individuals treated for up to 14 years are transcriptionally silent but harbor replication-competent virus that can be induced upon TLR7/8 stimulation. Taken together, these results uncover a potential important contribution of LN DCs to HIV infection in the presence of ART.

Host Molecule Incorporation into HIV Virions, Potential Influences in HIV Pathogenesis.

During the last phase of HIV viral production, nascent HIV virions acquire a fraction of the cellular lipid membrane to create the external lipid envelope, a process by which cellular proteins present on the surface of the infected cell can be incorporated along with Env trimers. Interestingly, several studies indicated that these incorporated host molecules could conserve their biological activity and consequently contribute to HIV pathogenesis either by enhancing the infectivity of HIV virions, their tissue tropism or by affecting immune cell functions. The following review will describe the main approaches used to characterize membrane bound host molecule incorporation into HIV virions, the proposed mechanisms involved, and the role of a non-exhaustive list of incorporated molecules.

c-MAF coordinates enterocyte zonation and nutrient uptake transcriptional programs.

Small intestinal villi are structural and functional units present in higher vertebrates and uniquely adapted to nutrient absorption. Villus enterocytes are organized in transcriptional "zones" dedicated to specialized tasks such as absorption of specific nutrients. We report that the transcription factor c-MAF is expressed in differentiated lower and mid-villus enterocytes and is a target of BMP signaling. Maf inactivation perturbed the villus zonation program by increasing carbohydrate-related transcripts while suppressing transcripts linked to amino-acid and lipid absorption. The formation of cytoplasmic lipid droplets, shuttling dietary fat to chylomicrons, was impaired upon Maf loss indicating its role in dietary lipid handling. Maf inactivation under homeostatic conditions expanded tuft cells and led to compensatory gut lengthening, preventing weight loss. However, delayed Maf-/- enterocyte maturation impaired weight recovery after acute intestinal injury, resulting in reduced survival. Our results identify c-MAF as a regulator of the intestinal villus zonation program, while highlighting the importance of coordination between stem/progenitor and differentiation programs for intestinal regeneration.

Active PD-L1 incorporation within HIV virions functionally impairs T follicular helper cells.

The limited development of broadly neutralizing antibodies (BnAbs) during HIV infection is classically attributed to an inadequate B-cell help brought by functionally impaired T follicular helper (Tfh) cells. However, the determinants of Tfh-cell functional impairment and the signals contributing to this condition remain elusive. In the present study, we showed that PD-L1 is incorporated within HIV virions through an active mechanism involving p17 HIV matrix protein. We subsequently showed that in vitro produced PD-L1high but not PD-L1low HIV virions, significantly reduced Tfh-cell proliferation and IL-21 production, ultimately leading to a decreased of IgG1 secretion from GC B cells. Interestingly, Tfh-cell functions were fully restored in presence of anti-PD-L1/2 blocking mAbs treatment, demonstrating that the incorporated PD-L1 proteins were functionally active. Taken together, the present study unveils an immunovirological mechanism by which HIV specifically exploits the regulatory potential of PD-L1 to suppress the immune system during the course of HIV infection.

Evualuación del Programa Cero en un CESFAM del Sur de Chile

RESUMEN: La enfermedad de caries, constituye un importante problema de salud pública por su alta prevalencia, impacto negativo en la salud oral y sistémica en los individuos y sociedad, además por el alto costo de su tratamiento. El objetivo de este estudio fue evaluar el Programa CERO del CESFAM Dr. Alberto Reyes de la comuna de Tomé. Se realizó un estudio transversal descriptivo, la muestra correspondió al 100 % de niños ingresados al Programa Cero, adscritos del CESFAM Dr. Alberto Reyes de la comuna de Tomé el año 2018. Se revisó base de datos secundaria correspondiente a los Resúmenes Estadísticos Mensuales (REM) de atenciones y/o población en control, que se remiten al Departamento de Estadísticas e Información en Salud (DEIS) por establecimientos y/o estrategias según códigos estructurales definidos. Los resultados muestran la que el 51 % estuvo representado por hombres y el 49 % por mujeres. Las edades con mayor Ingresos, son los 6 años, con un 25 % y los niños de 4 años con proporciones que por poco alcanzan el 20 %. Las edades menormente representadas son el año de edad y los 5 años, con porcentajes inferiores al 10 %. Es necesario el abordaje de esta enfermedad con un cambio de paradigma en el manejo de la caries como un proceso de enfermedad manejando de forma más eficiente las medidas preventivas dirigidas de manera individual hacia cada paciente, proponiendo el manejo de la caries a través de la valoración del riesgo como lo hace el Programa CERO.

ABSTRACT: Dental caries constitute a significant public health problem due to its high prevalence, negative impact on individuals and society's oral and systemic health, in addition to the high cost of treatment. The aim of this study was to evaluate the CERO program of "CESFAM Dr. Alberto Reyes", from the commune of Tomé. A descriptive cross-sectional study was conducted, with a sample of 100 % of the children admitted to the CERO program, who were affiliated to the "CESFAM Dr. Alberto Reyes" from the commune of Tomé in 2018. A secondary database was reviewed corresponding to "Resúmenes Estadísticos Mensuales" (Monthly Statistical Summaries) of medical attentions and/or population under control, which is forwarded to the "Departamento de Estadísticas e Información en Salud" (Statistics and Health Information Department) by establishments and/or strategies under structural defined codes. According to results, males represent 51 %, and females 49 % of the sample. The ages with a higher number of admissions are 6 years old, representing 25 %, and 4 years old children, who almost reach 20 %. The least representing ages are 1 and 5 years old, with values lower than 10 %. It is necessary to approach this disease with a modification of the paradigm in the management of dental caries as an illness process, managing more efficiently the preventative measures aimed individually to each patient, proposing the management of dental caries through risk assessment as the CERO program does.

HIV persistence in lymph nodes.

PURPOSE OF REVIEW: HIV persists in distinct cellular and anatomical compartments in the body including blood, Central nervous system, and lymphoid tissues (spleen, lymph nodes [LNs], gut-associated lymphoid tissue) by diverse mechanisms despite antiretroviral therapy. Within LNs, human and animal studies have highlighted that a specific CD4 T cell subset - called T follicular helper cells locating in B cell follicles is enriched in cells containing replication-competent HIV as compared to extra-follicular CD4 T cells. Therefore, the objective of the present review is to focus on the potential mechanisms allowing HIV to persist within LN microenvironment. RECENT FINDINGS: The combination of factors that might be involved in the regulation of HIV persistence within LNs remain to be fully identified but may include - the level of activation, antiretroviral drug concentrations, presence of cytolytic mechanisms and/or regulatory cells, in addition to cell survival and proliferation propensity which would ultimately determine the fate of HIV-infected cells within LN tissue areas. SUMMARY: HIV persistence in blood and distinct body compartments despite long-standing and potent therapy is one of the major barriers to a cure. Given that the HIV reservoir is established early and is highly complex based on composition, viral diversity, distribution, replication competence, migration dynamics across the human body and possible compartmentalization in specific tissues, combinatorial therapeutic approaches are needed that may synergize to target multiple viral reservoirs to achieve a cure for HIV infection.

Lymph node migratory dendritic cells modulate HIV-1 transcription through PD-1 engagement.

T-follicular helper (Tfh) cells, co-expressing PD-1 and TIGIT, serve as a major cell reservoir for HIV-1 and are responsible for active and persistent HIV-1 transcription after prolonged antiretroviral therapy (ART). However, the precise mechanisms regulating HIV-1 transcription in lymph nodes (LNs) remain unclear. In the present study, we investigated the potential role of immune checkpoint (IC)/IC-Ligand (IC-L) interactions on HIV-1 transcription in LN-microenvironment. We show that PD-L1 (PD-1-ligand) and CD155 (TIGIT-ligand) are predominantly co-expressed on LN migratory (CD1chighCCR7+CD127+) dendritic cells (DCs), that locate predominantly in extra-follicular areas in ART treated individuals. We demonstrate that TCR-mediated HIV production is suppressed in vitro in the presence of recombinant PD-L1 or CD155 and, more importantly, when LN migratory DCs are co-cultured with PD-1+/Tfh cells. These results indicate that LN migratory DCs expressing IC-Ls may more efficiently restrict HIV-1 transcription in the extra-follicular areas and explain the persistence of HIV transcription in PD-1+/Tfh cells after prolonged ART within germinal centers.

Remains of Leatherback turtles, Dermochelys coriacea, at Mid-Late Holocene archaeological sites in coastal Oman: clues of past worlds.

Small, irregular isolated bones identified as remains of leatherback turtles (Dermochelys coriacea) were recovered from Mid to Late Holocene sites at Ra's al-Hamra and Ra's al-Hadd, coastal Oman. These provide the third instance of this animal being documented from any prehistoric site anywhere, and the records provide one of the oldest, if not the oldest, dates for this distinctive chelonian-even though they do not refer to fossils. Decades of research in this region has yielded vast amounts of archeological information, including abundant evidence of intense exploitation and utilization of marine turtles from about 6,500 to 4,000 BP. During part of this period, turtle remains in human burials have been extraordinary; the turtle involved, Chelonia mydas, has been abundant in the region during modern times. Yet despite intense and varied forms of prehistoric marine resource exploitation, and major, long-term archeological work, no other turtle species has been previously authenticated from these, or other coastal sites. The documentation of remains of the largest and most distinctive of living marine turtles, D. coriacea, at Ra's al-Hamra and Ra's al-Hadd, presented herein, provide detailed information that serves as the basis for future interpretations and discussions regarding incomplete, disarticulated remains from the Mid to Late Holocene, particularly in reference to taphonomic questions and diverse environmental conditions.

Transition to agriculture in South-Eastern Arabia: Insights from oral conditions.

OBJECTIVES: In Southeast (SE) Arabia, agriculture is supposed to expand around 3000 BC, but its tempo and its actual role in populations' subsistence is still debated by archaeologists. Here, we compare dental health conditions of 11 skeletal samples from coastal and inland sites, dated from the Late Neolithic (ca. 4500-3100 BC) to the Early Bronze Age (EBA), conventionally divided into Hafit (ca. 3100-2700 BC) and Umm an-Nar period (ca. 2700-2000 BC). The goal is to assess long-term trends in subsistence patterns and regional variability during the local transition to agriculture. METHODS: Seven indicators of oral health and childhood stress were analyzed, including dental wear, calculus, caries, alveolar resorption, periapical lesions, ante-mortem tooth loss (AMTL), and linear enamel hypoplasia (LEH). RESULTS: Neolithic coastal populations are globally characterized by high dental wear, high calculus frequency, high LEH frequency, and frequent periodontal disease, whereas they exhibit low abscesses and AMTL frequencies and a total absence of carious lesions. Samples from the Hafit period present high dental wear, low rates of calculus and LEH, frequent periodontal disease, combined with low abscess and AMTL frequencies and absence of caries. By contrast, samples from the Umm an-Nar period exhibit much lower dental wear, calculus and LEH rates, whereas caries, periapical lesions and AMTL frequencies increase significantly. Marked differences were observed between coastal and inland Umm an-Nar groups, the latter presenting significantly higher frequencies of caries, periapical lesions, alveolar resorption and AMTL. DISCUSSION/CONCLUSION: Oral conditions from the Neolithic coastal populations denote a diet mainly composed of unprocessed and abrasive food, with high protein and low carbohydrate intakes, and frequent stress episodes. Although Hafit populations display some changes in oral pathologies, which indicate modifications in their lifestyle and a diversification of the diet, no markers of high carbohydrate intakes were observed in our samples. The impact of agriculture on oral health appears clearly only from the Umm an-Nar period, and is more intense inland than on the coast, where marine resources are still a main component of the diet.

Early Neolithic genomes from the eastern Fertile Crescent.

We sequenced Early Neolithic genomes from the Zagros region of Iran (eastern Fertile Crescent), where some of the earliest evidence for farming is found, and identify a previously uncharacterized population that is neither ancestral to the first European farmers nor has contributed substantially to the ancestry of modern Europeans. These people are estimated to have separated from Early Neolithic farmers in Anatolia some 46,000 to 77,000 years ago and show affinities to modern-day Pakistani and Afghan populations, but particularly to Iranian Zoroastrians. We conclude that multiple, genetically differentiated hunter-gatherer populations adopted farming in southwestern Asia, that components of pre-Neolithic population structure were preserved as farming spread into neighboring regions, and that the Zagros region was the cradle of eastward expansion.

Diet and mobility in a late Neolithic population of coastal Oman inferred from radiocarbon dating and stable isotope analysis.

In Oman, the presence of highly productive marine environments, coupled with relatively limited land resources, have led to intense exploitation of coastal resources, but the question of the seasonality of occupation of coastal sites remains open. Our aim is to evaluate the contribution of marine resources to the diet of the Neolithic population of Ra's al-Hamra 5 (RH-5) to shed new light on its mobility, using stable isotopes and radiocarbon ((14)C) dating as dietary tracers. Charcoal, shell, human bone and enamel apatite from eight contemporary graves were sampled. Graves are thought to provide the best chance to obtain marine and terrestrial remains that were contemporary with the human remains in order to calculate the marine reservoir effect (MRE) for this period. Inter-individual variation in human bone apatite δ(13)C value is small, suggesting a homogenous diet. Bone apatite (14)C ages are very close to the shell ages while enamel is significantly younger and plots near the charcoal ages. Older enamel ages were obtained when a stronger acetic treatment was used, demonstrating that the young ages are due to diagenetic alteration rather than a diachronic change in diet and that only bone apatite retained in vivo dietary signals. Bone ages indicate a heavy reliance on marine resources and it is therefore unlikely that the individuals analyzed here were leaving the coast seasonally, although mobility along the coast cannot be excluded.

The microscopic (optical and SEM) examination of dental calculus deposits (DCD). Potential interest in forensic anthropology of a bio-archaeological method.

This article describes the potential interest in forensic anthropology of the microscopic analysis of dental calculus deposits (DCD), a calcified residue frequently found on the surface of teeth. Its sampling and analysis seem straightforward and relatively reproducible. Samples came from archaeological material (KHB-1 Ra's al-Khabbah and RH-5 Ra's al-Hamra, two Prehistoric graveyards located in the Sultanate of Oman, dated between the 5th and 4th millennium B.C.; Montenzio Vecchia, an Etruscan-Celtic necropolis from the north of Italy, dated between the 5th and 3rd century B.C.; body rests of Agnès Sorel, French royal mistress died in 1450 A.D.; skeleton of Pierre Hazard, French royal notary from the 15th century A.D.). Samples were studies by direct optical microscope (OM) or scanning electron microscopy (SEM). Many cytological, histological and elemental analyses were possible, producing precious data for the identification of these remains, the reconstitution of their alimentation and occupational habits, and propositions for manner of death.