Missed opportunities in the prevention and diagnosis of pediatric tuberculosis: a scoping review

Abstract Objectives: Identify potential barriers, delays, and missed opportunities in the prevention and diagnosis of childhood TB. Methods: Scoping review according to the PRISMA extension. The definitions considered for the selection followed the acronym PCC where the population (P) is children under 18years of age with TB disease, the concept (C) refers to missed opportunities for prevention and diagnosis, and context (C) is defined as a diagnosis of TB disease. The authors searched systematically in the databases; VHL/Lilacs, Medline via PubMed, Cochrane, Scopus, and Web of Science, without date or language limitation. Results: Seven studies were included. In developed countries, with low disease burden, the main shortcoming is the delay in diagnosing bacilliferous adults in contact with young children. This problem is concentrated in the portion of the population with socioeconomic vulnerability. In underdeveloped countries, with a high burden of disease, the biggest challenge is tracking children who come into contact with bacilliferous patients. Conclusions: There are still many missed opportunities in the prevention and diagnosis of childhood TB. The positive legacy of the COVID-19 pandemic should be taken advantage of and the encouragement of scientific development in the management of infectious diseases should be taken.

Guardians and Mediators of Metastasis: Exploring T Lymphocytes, Myeloid-Derived Suppressor Cells, and Tumor-Associated Macrophages in the Breast Cancer Microenvironment.

Breast cancers (BCs) are solid tumors composed of heterogeneous tissues consisting of cancer cells and an ever-changing tumor microenvironment (TME). The TME includes, among other non-cancer cell types, immune cells influencing the immune context of cancer tissues. In particular, the cross talk of immune cells and their interactions with cancer cells dramatically influence BC dissemination, immunoediting, and the outcomes of cancer therapies. Tumor-infiltrating lymphocytes (TILs), tumor-associated macrophages (TAMs), and myeloid-derived suppressor cells (MDSCs) represent prominent immune cell populations of breast TMEs, and they have important roles in cancer immunoescape and dissemination. Therefore, in this article we review the features of TILs, TAMs, and MDSCs in BCs. Moreover, we highlight the mechanisms by which these immune cells remodel the immune TME and lead to breast cancer metastasis.

Single-cell and spatiotemporal profile of ovulation in the mouse ovary.

Ovulation is a spatiotemporally coordinated process that involves several tightly controlled events, including oocyte meiotic maturation, cumulus expansion, follicle wall rupture and repair, and ovarian stroma remodeling. To date, no studies have detailed the precise window of ovulation at single-cell resolution. Here, we performed parallel single-cell RNA-seq and spatial transcriptomics on paired mouse ovaries across an ovulation time course to map the spatiotemporal profile of ovarian cell types. We show that major ovarian cell types exhibit time-dependent transcriptional states enriched for distinct functions and have specific localization profiles within the ovary. We also identified gene markers for ovulation-dependent cell states and validated these using orthogonal methods. Finally, we performed cell-cell interaction analyses to identify ligand-receptor pairs that may drive ovulation, revealing previously unappreciated interactions. Taken together, our data provides a rich and comprehensive resource of murine ovulation that can be mined for discovery by the scientific community.

Harmonization of homologous recombination deficiency testing in ovarian cancer: Results from the MITO16A/MaNGO-OV2 trial.

BACKGROUND: Homologous Recombination Deficiency (HRD) status predicts response to treatment with poly(ADP-ribose) polymerase inhibitors in Ovarian Cancer (OC) patients. The Myriad myChoiceCDx Assay is approved by Food and Drug Agency for the HRD assessment. Here we compared the HRD status obtained by three commercial panels with the results from Myriad reference test. METHODS: The HRD analysis was performed on DNA from formalin-fixed and paraffin-embedded tumor samples of 100 untreated OC patients for which Myriad assay results were available, using TruSight Oncology 500 HRD assay (Illumina), Oncomine Comprehensive Assay Plus (Thermo Fisher Scientific) and SOPHiA DDM HRD solution panel (SOPHiA Genetics). RESULTS: A good overall concordance with the reference method was demonstrated at three different levels: BRCA mutational status (from 94.4 % to 97.7 %), the genomic instability value (from 88.2 % to 95.3 %) and for the HRD status (from 90.4 % to 97.6 %). Moreover, a trend in favour of HRD positive patients for response rate, progression-free survival and overall survival similar to Myriad was observed for all three tests. DISCUSSION: Our data suggest the feasibility of commercial testing for assessing HRD status, with a good concordance with the reference method and association with clinical outcome.

Malus pumila Mill. cv Annurca apple extract might be therapeutically useful against oxidative stress and patterned hair loss.

Patterned hair loss (PHL) or androgenetic alopecia is a condition affecting about 50% of people worldwide. Several pharmacological medications have been developed over the years, but few studies have investigated their effectiveness. Therefore, new, safer and more effective strategies are required. Recent investigations showed that Annurca apple extract application could induce keratin production and promote hair growth thanks to the high amount of procyanidin B2 contained in. Hence, this study aimed to investigate the role of an Annurca apple extract in preventing PHL by testing it on human follicle dermal papilla cells (HFDPCs) for the first time. Treatment of HFDPCs with Annurca apple extract counteracted intracellular reactive oxygen species accumulation by increasing the activity of antioxidant enzymes such as superoxide dismutase 2 and catalase. Furthermore, treatment with Annurca apple extract increased ß-catenin and fibroblast growth factor 2, which are involved in hair growth stimulation. These data suggest that Annurca apple extract may be a potential therapeutically useful nutraceutical product for preventing or treating hair loss by reducing oxidative stress and inducing the expression of hair growth-related factors.

Investigation of the structure of protein-polymer conjugates in solution reveals the impact of protein deuteration and the size of the polymer on its thermal stability.

The conjugation of proteins with polymers offers immense biotechnological potential by creating novel macromolecules. This article presents experimental findings on the structural properties of maltose-binding protein (MBP) conjugated with linear biodegradable polyphosphoester polymers with different molecular weights. We studied isotopic effects on both proteins and polymers. Circular dichroism and fluorescence spectroscopy and small-angle neutron scattering reveal that the conjugation process destabilizes the protein, affecting the secondary more than the tertiary structure, even at room temperature, and that the presence of two domains in the MBP may contribute to its observed instability. Notably, unfolding temperatures differ between native MBP and the conjugates. In particular, this study sheds light on the complex interplay of factors such as the deuteration influencing protein stability and conformational changes in the conjugation processes. The perdeuteration influences the hydrogen bond network and hydrophobic interactions in the case of the MBP protein. The perdeuteration of the protein influences the hydrogen bond network and hydrophobic interactions. This is evident in the decreased thermal stability of deuterated MBP protein, in the conjugate, especially with high-molecular-mass polymers.

Case report: EBV-related eye orbits and sinuses lymphohistiocytic infiltration responsive to rituximab in a patient with X lymphoproliferative syndrome type 1.

Background and aims: X lymphoproliferative syndrome type 1 (XLP1) is a rare inborn error of immunity due to mutations of SH2D1A, encoding for slam-associated protein (SAP). The clinical phenotype includes severe mononucleosis, hemophagocytic lymphohistiocytosis (HLH), and B-cell lymphomas. Methods: We report the case of a child affected with XLP1 who presented with an incomplete HLH, triggered by Epstein-Barr virus (EBV) and treated with rituximab, involving orbits and paranasal sinuses. Results: The lesion was indistinguishable from lymphoma, complicating diagnosis and treatment. In addition, considering the high incidence of lymphoma in patients with XLP1, histology helped define its nature, driving therapeutic choices. Conclusion: We described an unusual presentation of incomplete HLH in a patient affected with XLP1: an EBV-driven infiltration of the orbits and paranasal sinuses. This led us to a challenging differential diagnosis of lymphoma-associated hemophagocytic syndrome, which can be frequently observed in patients with XLP1. Considering the extremely poor prognosis of this clinical finding, we sought for a prompt diagnosis and managed to obtain it and to immediately establish the right treatment on the basis of the pathological finding.

Missed opportunities in the prevention and diagnosis of pediatric tuberculosis: a scoping review.

OBJECTIVES: Identify potential barriers, delays, and missed opportunities in the prevention and diagnosis of childhood TB. METHODS: Scoping review according to the PRISMA extension. The definitions considered for the selection followed the acronym PCC where the population (P) is children under 18 years of age with TB disease, the concept (C) refers to missed opportunities for prevention and diagnosis, and context (C) is defined as a diagnosis of TB disease. The authors searched systematically in the databases; VHL/Lilacs, Medline via PubMed, Cochrane, Scopus, and Web of Science, without date or language limitation. RESULTS: Seven studies were included. In developed countries, with low disease burden, the main shortcoming is the delay in diagnosing bacilliferous adults in contact with young children. This problem is concentrated in the portion of the population with socioeconomic vulnerability. In underdeveloped countries, with a high burden of disease, the biggest challenge is tracking children who come into contact with bacilliferous patients. CONCLUSIONS: There are still many missed opportunities in the prevention and diagnosis of childhood TB. The positive legacy of the COVID-19 pandemic should be taken advantage of and the encouragement of scientific development in the management of infectious diseases should be taken.

Wastewater irrigation and Trichoderma colonization in tomato plants: effects on plant traits, antioxidant activity, and performance of the insect pest Macrosiphum euphorbiae.

The scarcity of freshwater for agriculture in many regions has led to the application of sewage and saline water for irrigation. Irrigation with non-conventional water sources could become a non-harmful process for plant cultivation, and the effects of their use on crops should be monitored in order to develop optimal management strategies. One possibility to overcome potential barriers is to use biostimulants such as Trichoderma spp. fungi. Tomato is a crop of great economic importance in the world. This study investigated the joint effects of Trichoderma afroharzianum T-22 on tomato plants irrigated with simulated unconventional waters. The experiment consisted of a control and three water treatments. In the control, the plants were watered with distilled water. The three water treatments were obtained by using an irrigation water added with nitrogen, a wastewater effluent, and a mixed groundwater-wastewater effluents. Potted tomato plants (variety Bobcat) were grown in a controlled growth chamber. Antioxidant activity, susceptibility to the aphids Macrosiphum euphorbiae, and tomato plant growth parameters were estimated. Trichoderma afroharzianum T-22 had a positive effect on plant growth and antioxidant defenses when plants were irrigated with distilled water. Instead, no significant morphological effects induced by T. afroharzianum T-22 on plants were observed when unconventional water was used for irrigation. However, inoculation with T. afroharzianum T-22 activated a stress response that made the colonized plants more susceptible to aphid development and increased their fecundity and longevity. Thanks to this study, it may be possible for the first time to open a new discussion on the practical possibility of using reclaimed wastewater for crop irrigation with the addition of a growth-promoting fungal symbiont.

A deep learning model to predict Ki-67 positivity in oral squamous cell carcinoma.

Anatomical pathology is undergoing its third revolution, transitioning from analogical to digital pathology and incorporating new artificial intelligence technologies into clinical practice. Aside from classification, detection, and segmentation models, predictive models are gaining traction since they can impact diagnostic processes and laboratory activity, lowering consumable usage and turnaround time. Our research aimed to create a deep-learning model to generate synthetic Ki-67 immunohistochemistry from Haematoxylin and Eosin (H&E) stained images. We used 175 oral squamous cell carcinoma (OSCC) from the University Federico II's Pathology Unit's archives to train our model to generate 4 Tissue Micro Arrays (TMAs). We sectioned one slide from each TMA, first stained with H&E and then re-stained with anti-Ki-67 immunohistochemistry (IHC). In digitised slides, cores were disarrayed, and the matching cores of the 2 stained were aligned to construct a dataset to train a Pix2Pix algorithm to convert H&E images to IHC. Pathologists could recognise the synthetic images in only half of the cases in a specially designed likelihood test. Hence, our model produced realistic synthetic images. We next used QuPath to quantify IHC positivity, achieving remarkable levels of agreement between genuine and synthetic IHC. Furthermore, a categorical analysis employing 3 Ki-67 positivity cut-offs (5%, 10%, and 15%) revealed high positive-predictive values. Our model is a promising tool for collecting Ki-67 positivity information directly on H&E slides, reducing laboratory demand and improving patient management. It is also a valuable option for smaller laboratories to easily and quickly screen bioptic samples and prioritise them in a digital pathology workflow.

Ethnobotanical inventory of medicinal plants used in the Qampaya District, Bolivia / Inventario etnobotánico de plantas medicinales usadas en el Distrito Qampaya, Bolivia

Herbal medicine therapy is traditionally practiced by indigenous healers in Bolivia for hundreds years. Due to the great geographical and ecological diversity, there are thousands of native plants, which are utilized against diverse types of diseases. Nowadays, there is a worldwide problem connected with possible loss of ethnobotany knowledge because of the lack of the interest of young people. In present study, survey focused on medicinal plants used by rural people in Qampaya District, Potosí Department, Bolivia has been done. The data were collected from 60 respondents by semi-structured interviews. The results showed that 60 plant species belonging to 30 families are known as curative plants in this area. The mostly named families were Asteraceae (14 species) followed by Lamiaceae (7 species) and Brassicaceae (4 species). Predominant health problems treated by these plants are urological problems and gastro-intestinal disorders. The most frequently used plant parts were leaves and the preparation is mostly done as infusion. Even though the knowledge of using medical plants plays important role in life of Bolivian rural people, which use plants as medicines against various types of diseases, this study showed that 25 percent of respondents didn’t know any medicinal plants. On the other hand 40 percent of asked people have known 6 or more medicinal plant species.

La terapia de la medicina herbolaria es practicada, tradicionalmente, por los curanderos indígenas en Bolivia, desde hace cientos de años. Gracias a la gran diversidad geográfica y ecológica, hay miles de plantas nativas, que se utilizan para el tratamiento de diferentes tipos de enfermedades. Hoy en día, hay un problema mundial relacionado con la posible pérdida del conocimiento etnobotánico, esto debido a la falta de interés de las nuevas generaciones. El presente estudio descriptivo, mediante una encuesta, fue enfocado a las plantas medicinales utilizadas por la población rural del Distrito Qampaya, Departamento de Potosí, Bolivia. Los datos se obtuvieron de 60 informantes mediante una encuesta semiestructurada. Los resultados mostraron que 60 especies de plantas medicinales. pertenecientes a 30 familias botánicas, son conocidas en el área de intervención. Las familias botánicas, más importantes de uso medicinal son Asteraceae (14 especies), seguido de Lamiaceae (7 especies) y Brassicaceae (4 especies). Los problemas predominantes de salud, tratados con estas especies, son los urológicos y trastornos gastrointestinales. La parte de la planta más utilizada son las hojas y la forma más común de uso es en infusión. A pesar de que el conocimiento sobre la utilización de las plantas medicinales, juega un papel importante en la vida de la población rural de Bolivia, quienes utilizan las plantas medicinales para el tratamiento de diversos tipos de enfermedades, este estudio mostró que el 25 por ciento de los encuestados no tienen conocimiento sobre la utilidad medicinal de ninguna especie vegetal. Por otro lado, el 40 por ciento de los informantes conocen 6 o más especies de plantas medicinales.