Tecnologias em saúde da hanseníase no âmbito da Atenção Primária à Saúde: revisão de escopo / Leprosy health technologies in Primary Health Care: a scoping review / Tecnologías en salud de la lepra en el ámbito de la Atención Primaria a la Salud: revisión del alcance

Objetivo: mapear as tecnologias em saúde para manejo no cuidado à pessoa com hanseníase na Atenção Primária à Saúde. Método: revisão de escopo baseada na metodologia do JBI, em seis bases de dados, seguindo a checklist Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews. Foram incluídos estudos publicados em qualquer idioma, com diferentes abordagens metodológicas. Resultados: os 14 estudos incluídos na revisão mostram que a aplicabilidade de tecnologias para o manejo do cuidado a pessoa com hanseníase na Atenção Primária à Saúde, possibilitam a confirmação de diagnóstico, acompanhamento, monitoramento e prevenção de incapacidades. Conclusão: nota-se que tecnologia em saúde se apresentam como ferramentas que auxiliam no processo de cuidado na assistência a pessoas com hanseníase, a fim de permitir aos profissionais de saúde conhecimento sobre a doença, proporcionando qualidade na sua prática de saúde.

Objective: to map health technologies for managing the care of people with leprosy in Primary Health Care. Method: scoping review based on the JBI methodology in six databases, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews checklist. Studies published in any language were included, with different methodological approaches. Results: the 14 studies included in the review show that the applicability of technologies for the management of care for people with leprosy in Primary Health Care makes it possible to confirm diagnosis, follow-up, monitoring, and prevention of disabilities. Conclusion: it has been noted that health technologies are tools that help in the process of caring for people with leprosy, to provide health professionals with knowledge about the disease, improving quality of health practice.

Objetivo: mapear las tecnologías en salud para el manejo en el cuidado a la persona con lepra en la Atención Primaria a la Salud. Método: revisión del alcance basada en la metodología del JBI, en seis bases de datos, siguiendo la checklist Preferred Reporting Items for Systematic Reviews and Meta-Analysis extension for Scoping Reviews. Se han incluido estudios publicados en cualquier idioma, con diferentes enfoques metodológicos. Resultados: los 14 estudios incluidos en la revisión muestran que la aplicabilidad de tecnologías para el manejo del cuidado a la persona con lepra en la Atención Primaria a la Salud posibilita la confirmación de diagnóstico, seguimiento, monitoreo y prevención de incapacidades. Conclusión: se percibe que las tecnologías en salud se presentan como herramientas que ayudan en el proceso de cuidado en la asistencia a personas con lepra, con fines de permitir a los profesionales de salud el acceso al conocimiento sobre la enfermedad, proporcionando calidad en su práctica de salud.

Analysis of neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios as inflammatory biomarkers in chronic kidney disease: impact of parathyroidectomy / Análise das relações neutrófilo/linfócito e plaqueta/linfócito como marcadores inflamatórios na doença renal crônica: impacto da paratireoidectomia

Abstract Introduction: Secondary hyperparathyroidism (SHPT) is one of the causes for inflammation in CKD. We assessed the impact of parathyroidectomy (PTX) on neutrophil-to-lymphocyte (N/L) and platelet-to-lymphocyte (P/L) ratios in SHPT patients. Methods: A total of 118 patients [hemodialysis (HD, n = 81), and transplant recipients (TX, n = 37)] undergoing PTX between 2015 and 2021 were analyzed. Results: There was a significant reduction in calcium and PTH levels in both groups, in addition to an increase in vitamin D. In the HD group, PTX did not alter N/L and P/L ratios. In the TX group, there was a reduction in N/L and P/L ratios followed by a significant increase in total lymphocyte count. Conclusion: N/L and P/L ratios are not reliable biomarkers of inflammation in SHPT patients undergoing PTX. Uremia, which induces a state of chronic inflammation in dialysis patients, and the use of immunosuppression in kidney transplant recipients are some of the confounding factors that prevent the use of this tool in clinical practice.

Resumo Introdução: O hiperparatireoidismo secundário (HPTS) é uma das causas de inflamação na DRC. Avaliamos o impacto da paratireoidectomia (PTX) nas relações neutrófilo/linfócito (N/L) e plaqueta/linfócito (P/L) em pacientes com HPTS. Métodos: Foram analisados 118 pacientes [hemodiálise (HD, n = 81) e transplantados (TX, n = 37)] submetidos à PTX entre 2015 e 2021. Resultados: Houve redução significativa de cálcio e PTH nos dois grupos, além de elevação de vitamina D. No grupo HD, a PTX não mudou as relações N/L e P/L. Já no grupo TX, houve redução nas relações N/L e P/L acompanhadas de elevação significativa do número de linfócitos totais. Conclusão: As relações N/L e P/L não são marcadores fidedignos de inflamação em pacientes com HPTS submetidos à PTX. A uremia, que induz um estado de inflamação crônica em pacientes dialíticos, e o uso de imunossupressão em pacientes transplantados renais são alguns dos fatores de confusão que impedem o uso dessa ferramenta na prática clínica.

Radio-miRs: a comprehensive view of radioresistance-related microRNAs.

Radiotherapy is a key treatment option for a wide variety of human tumors, employed either alone or alongside with other therapeutic interventions. Radiotherapy uses high-energy particles to destroy tumor cells, blocking their ability to divide and proliferate. The effectiveness of radiotherapy is due to genetic and epigenetic factors that determine how tumor cells respond to ionizing radiation. These factors contribute to the establishment of resistance to radiotherapy, which increases the risk of poor clinical prognosis of patients. Although the mechanisms by which tumor cells induce radioresistance are unclear, evidence points out several contributing factors including the overexpression of DNA repair systems, increased levels of reactive oxygen species, alterations in the tumor microenvironment, and enrichment of cancer stem cell populations. In this context, dysregulation of microRNAs or miRNAs, critical regulators of gene expression, may influence how tumors respond to radiation. There is increasing evidence that miRNAs may act as sensitizers or enhancers of radioresistance, regulating key processes such as the DNA damage response and the cell death signaling pathway. Furthermore, expression and activity of miRNAs have shown informative value in overcoming radiotherapy and long-term radiotoxicity, revealing their potential as biomarkers. In this review, we will discuss the molecular mechanisms associated with the response to radiotherapy and highlight the central role of miRNAs in regulating the molecular mechanisms responsible for cellular radioresistance. We will also review radio-miRs, radiotherapy-related miRNAs, either as sensitizers or enhancers of radioresistance that hold promise as biomarkers or pharmacological targets to sensitize radioresistant cells.

Risk factors of death or chronic renal replacement therapy requirements in patients with thrombotic microangiopathies without ADAMTS-13 deficiency.

Thrombotic microangiopathy (TMA), characterized by microangiopathic hemolytic anemia, thrombocytopenia, and multisystem organ dysfunction, is a life-threatening disease. Patients with TMA who do not exhibit a severe ADAMTS-13 deficiency (defined as a disintegrin-like and metalloprotease with thrombospondin type 1 motif no. 13 activity ≥10%: TMA-13n) continue to experience elevated mortality rates. This study explores the prognostic indicators for augmented mortality risk or necessitating chronic renal replacement therapy (composite outcome: CO) in TMA-13n patients. We included 42 TMA-13n patients from January 2008 to May 2018. Median age of 41 years and 60% were female. At presentation, 62% required dialysis, and 57% warranted intensive care unit admission. CO was observed in 45% of patients, including a 9-patient mortality subset. Multivariate logistic regression revealed three independent prognostic factors for CO: early administration of eculizumab (median time from hospitalization to eculizumab initiation: 5 days, range 0-19 days; odds ratio [OR], 0.14; 95% confidence interval [CI], 0.02-0.94), presence of neuroradiological lesions (OR, 6.67; 95% CI, 1.12-39.80), and a PLASMIC score ≤4 (OR, 7.39; 95% CI, 1.18-46.11). In conclusion, TMA-13n patients exhibit a heightened risk of CO in the presence of low PLASMIC scores and neuroradiological lesions, while early eculizumab therapy was the only protective factor.

State of art of micronuclei assay in exfoliative cytology as a clinical biomarker of genetic damage in oral carcinogenesis: A systematic review and meta-analysis.

Oral squamous cell carcinoma (OSCC) is the most common oral malignancy, often preceded by oral potentially malignant disorders (OPMDs). Currently, no clinical biomarker exists to predict malignancy, necessitating OPMD follow-up. Habits and environmental factors, such as smoking, and alcohol consumption, influence OSCC onset. Increased micronuclei (MNs) formation has been observed in the development of OSCC. Non-invasive diagnostic tests like exfoliative cytology offer painless and regular monitoring options. This study evaluates the impact of tobacco, alcohol, and pesticide exposure on MNs occurrence in exfoliative cytology-collected oral mucosal cells, assessing their potential as non-invasive biomarker for OSCC development prediction and monitoring in high-risk patients. Despite results from this meta-analysis supporting the existence of a stepwise increase from controls to patients with OPMD to OSCC, the translation of these findings into clinical practice is limited due to intra- and inter-individual heterogeneity, as well as methodological variability in MNs quantification. Various factors contribute to this heterogeneity, including demographic variables, methodological variability of different laboratories, staining techniques, sample collection location, and patient characteristics. All these points were discussed to provide further insights and improve standardization for future studies.

Unveiling myocardial microstructure shifts: exploring the impact of diabetes in stable CAD patients through CMR T1 mapping.

BACKGROUND: This study investigates myocardial structural changes in stable coronary artery disease (CAD) patients with type 2 diabetes (T2D) using cardiac magnetic resonance (CMR) strain and T1 mapping. METHODS: A total of 155 stable CAD patients underwent CMR examination, including left ventricular (LV) morphology and function assessment, late gadolinium enhancement (LGE), and feature tracking (CMR-FT) for LV global longitudinal, circumferential, and radial strain. T1 mapping with extracellular volume (ECV) evaluation was also performed. RESULTS: Among the enrolled patients, 67 had T2D. Diabetic patients exhibited impaired LV strain and higher ECV compared to non-diabetics. Multivariate analysis identified T2D as an independent predictor of increased ECV and decreased strain. CONCLUSIONS: CMR-based strain and T1 mapping highlighted impaired myocardial contractility, elevated ECV, and potential interstitial fibrosis in diabetic patients with stable CAD. This suggests a significant impact of diabetes on myocardial health beyond CAD, emphasizing the importance of a comprehensive assessment in these individuals. TRIAL REGISTRATION: http://www.controlled-trials.com/ISRCTN09454308.

Performance of the Brazilian Fracture Assessment Risk Tool (FRAX) model and the age-dependent intervention thresholds according to National Osteoporosis Guideline Group (NOGG) guidelines on fracture prediction in community-dwelling older adults: the São Paulo Ageing and Health (SPAH) Study.

The SPAH study is a population-based prospective cohort of Brazilian community-dwelling elderlies with higher fracture risk than observed in the studies used to construct the Brazilian FRAX model. In this study, the FRAX tool was a good fracture predictor within this high-risk elderly cohort, especially when calculated without bone density. PURPOSE: To determine the performances of FRAX and age-dependent intervention thresholds according to National Osteoporosis Guideline Group (NOGG) guidelines with and without bone mineral density (BMD) regarding fracture prediction in community-dwelling elderly Brazilians. METHODS: Seven hundred and five older adults (447 women; 258 men) were followed for 4.3 ± 0.8 years. FRAX risk for hip and major osteoporotic fractures with and without BMD was calculated at baseline. The bivariate analysis investigated the associations between the absolute probability of fracture (FRAX), as well as the age-dependent intervention thresholds (NOGG), and the incidence of vertebral fracture (VF), non-vertebral fracture (NVF), and major osteoporotic fractures (MOF), segregated by sex. Age-adjusted Poisson's multiple regression and ROC curves were constructed to determine FRAX and NOGG's accuracies as fracture predictors. RESULTS: Fractures occurred in 22% of women and 15% of men. FRAX with and without BMD was higher in women with all types of fractures (p < 0.001). Only NOGG risk classification without BMD was associated with NVF (p = 0.047) and MOF (p = 0.024). FRAX was associated with NVF in the multiple regression, regardless of BMD. ROC curves of FRAX with and without BMD had AUCs of 0.74, 0.64, and 0.61 for NVF, VF, and MOF, respectively. The most accurate risk cutoffs for FRAX were 8% for MOF and 3% for hip fractures. No statistically significant associations were found in men. CONCLUSION: FRAX predicted NVF more accurately than VF or MOF in elderlies, regardless of BMD. These results reiterate that FRAX may be used without BMD, even considering that Brazilian elderlies have known higher fracture risk.

In-party love spreads more efficiently than out-party hate in online communities.

In this article, we present the findings of a comprehensive longitudinal social network analysis conducted on Twitter across four consecutive election campaigns in Spain, spanning from 2015 to 2019. Our focus is on the discernible trend of increasing partisan and ideological homogeneity within interpersonal exchanges on this social media platform, alongside high levels of networking efficiency measured through average retweeting. This diachronic study allows us to observe how dynamics of party competition might contribute to perpetuating and strengthening network ideological and partisan homophily, creating 'epistemic bubbles' in Twitter, yet showing a greater resistance to transforming them into 'partisan echo-chambers.' Specifically, our analysis reveals that the rise of a new radical right-wing party (RRP), Vox, has heightened ideological homogeneity among users across the entire ideological spectrum. However, this process has not been uniform. While users aligned with mainstream political parties consistently share content that reinforces in-party affinity, resulting in highly efficient 'epistemic bubbles,' the emergence of the RRP has given rise to a distinct group of users associated with the most extreme partisan positions, characterized by a notable proportion of out-partisan hostility content, which has fostered the creation of low-efficient 'partisan echo-chambers.'

Total Gestational Weight Gain Is Explained by Leptin and Body Fat, Regardless of Pre-Pregnancy Body Mass Index and Other Adipokines, in Mexican Adolescents.

Pre-pregnancy body mass index (pBMI) is a predictor of gestational weight gain (GWG). However, other factors, such as adipokines and inflammation markers, may also be associated with GWG. The aim of the study was to determine the association of leptin, adiponectin, irisin, and C-reactive protein, with GWG in adolescents. A longitudinal study was conducted from 2018 to 2023 in adolescents with a clinically healthy pregnancy. The assessments included sociodemographic and clinical data, pBMI, percent of body fat, serum concentrations of leptin, adiponectin, irisin, and high-sensitivity C-reactive protein (hsCRP), and total GWG adequacy. Cox regression models were performed, the outcome variables were inadequate and excessive GWG. In 198 participants, being overweight/obesity was marginally associated with a protective effect against inadequate GWG (HR = 0.44, 95%CI = 0.18-1.06), regardless of maternal characteristics and adipokines. Leptin (HR = 1.014, 95%CI = 1.008-1.021), and body fat percent (HR = 1.11, 95%CI = 1.05-1.17) were associated with a higher risk of excessive GWG, independent of other maternal variables such as pBMI, while adiponectin was associated with a lower risk. These findings suggest that, in Mexican adolescents, adipose tissue and its adipokines during pregnancy may play a more significant role in the final GWG than body weight.

The Postbiotic Properties of Butyrate in the Modulation of the Gut Microbiota: The Potential of Its Combination with Polyphenols and Dietary Fibers.

The gut microbiota is a diverse bacterial community consisting of approximately 2000 species, predominantly from five phyla: Firmicutes, Bacteroidetes, Actinobacteria, Proteobacteria, and Verrucomicrobia. The microbiota's bacterial species create distinct compounds that impact the host's health, including well-known short-chain fatty acids. These are produced through the breakdown of dietary fibers and fermentation of undigested carbohydrates by the intestinal microbiota. The main short-chain fatty acids consist of acetate, propionate, and butyrate. The concentration of butyrate in mammalian intestines varies depending on the diet. Its main functions are use as an energy source, cell differentiation, reduction in the inflammatory process in the intestine, and defense against oxidative stress. It also plays an epigenetic role in histone deacetylases, thus helping to reduce the risk of colon cancer. Finally, butyrate affects the gut-brain axis by crossing the brain-blood barrier, making it crucial to determine the right concentrations for both local and peripheral effects. In recent years, there has been a significant amount of attention given to the role of dietary polyphenols and fibers in promoting human health. Polyphenols and dietary fibers both play crucial roles in protecting human health and can produce butyrate through gut microbiota fermentation. This paper aims to summarize information on the key summits related to the negative correlation between intestinal microbiota diversity and chronic diseases to guide future research on determining the specific activity of butyrate from polyphenols and dietary fibers that can carry out these vital functions.

The Role of OCT in Follow-Up of Fungal Keratitis Caused by Beauveria bassiana in Contact Lens Wearer.

A 25-year-old Caucasic female was referred to our clinic after suffering from infectious keratitis in the right eye for a month. The patient was a contact lens user and had no history of ocular trauma. Furthermore, the patient did not report any relevant antecedent. The main complaint was intense photophobia and pain. Infectious keratitis remains one of the main complications of contact lens wear and can become a therapeutic challenge in some patients. Although the most frequent causal agent is bacterial, other causes such as herpes virus, Acanthamoeba or fungi should be considered when antimicrobial therapy does not work as expected clinically. Fungal keratitis normally appears on previously damaged corneas, but it can also develop in contact lens wearers. Beauveria bassiana is an unusual pathogen which has been diagnosed more frequently lately per the clinical reports in the last 30 years, so it can be included in the diagnostic scheme when a fungal keratitis is suspected. In clinical management, AS-OCT may be a functional tool to assess the evolution and monitor the response to microbial agents and surgery. Although more studies are needed, some characteristic features have been described and can help to diagnose a fungal keratitis against other infections. AS-OCT can also play an important role in monitoring the corneal scarring after the keratitis episode, and it may be useful to plan post-infection therapy for visual rehabilitation.

Somatic Mutations in KEAP1-NRF2 Complex in Breast Cancer.

Breast cancer remains the leading cause of cancer deaths for women. Long-term estrogen exposure is considered carcinogenic due to semiquinone production and to compromised detoxification. Metabolic regulator polymorphisms, such as KEAP1 (rs1048290) and NRF2 (rs35652124, rs6721961, rs6706649), can be valuable in understanding the individual cytoprotection profile. Thus, we aim to genotype these polymorphisms in blood, tumours and surrounding tissue, to identify somatic mutations and correlate it to prognoses. A total of 23 controls and 69 women with histological confirmed breast cancer were recruited, and DNA from blood/surrounding/tumour tissue was genotyped. Genotyping and clinicopathological data were correlated. We verified that rs35652124 presents different genotype distribution between the blood/surrounding tissue (p-value = 0.023) and tumour/surrounding tissues (p-value = 0.041). Apart from rs35652124 and considering the histological grade, the other four polymorphisms have different distributions among different tissues. There is a tendency towards the loss of heterozygosity in the surrounding tissue when compared to blood and tumour tissues, and higher genotype variability in histologic grade 2. These somatic mutations and different distribution patterns may indicate a heterogeneous and active microenvironment, influencing breast cancer outcome. Additionally, it would be pertinent to evaluate the predictive value of the histologic grade 2 considering somatic mutation profiles and distributions.

Marked increase in cryptosporidiosis cases, Spain, 2023.

BackgroundBy mid-September 2023, several event notifications related to cryptosporidiosis had been identified from different regions in Spain. Therefore, a request for urgent notification of cryptosporidiosis cases to the National Surveillance Network was launched.AimWe aimed at assessing the extent of the increase in cases, the epidemiological characteristics and the transmission modes and compared to previous years.MethodsWe analysed data on case notifications, outbreak reports and genotypes focusing on June-October 2023 and compared the results to 2016-2022.ResultsIn 2023, 4,061 cryptosporidiosis cases were notified in Spain, which is an increase compared to 2016-2022. The cumulative incidence was 8.3 cases per 100,000 inhabitants in 2023, sixfold higher than the median of 1.4 cases per 100,000 inhabitants 2016-2022. Almost 80% of the cases were notified between June and October. The largest outbreaks were related to contaminated drinking water or swimming pools. Cryptosporidium hominis was the most common species in the characterised samples (115/122), and the C. hominis IfA12G1R5 subtype, previously unusual in Spain, was detected from 76 (62.3%) of the 122 characterised samples.ConclusionsA substantial increase in cryptosporidiosis cases was observed in 2023. Strengthening surveillance of Cryptosporidium is essential for prevention of cases, to better understand trends and subtypes circulating and the impact of adverse meteorological events.

Conservation of cis-Regulatory Syntax Underlying Deuterostome Gastrulation.

Throughout embryonic development, the shaping of the functional and morphological characteristics of embryos is orchestrated by an intricate interaction between transcription factors and cis-regulatory elements. In this study, we conducted a comprehensive analysis of deuterostome cis-regulatory landscapes during gastrulation, focusing on four paradigmatic species: the echinoderm Strongylocentrotus purpuratus, the cephalochordate Branchiostoma lanceolatum, the urochordate Ciona intestinalis, and the vertebrate Danio rerio. Our approach involved comparative computational analysis of ATAC-seq datasets to explore the genome-wide blueprint of conserved transcription factor binding motifs underlying gastrulation. We identified a core set of conserved DNA binding motifs associated with 62 known transcription factors, indicating the remarkable conservation of the gastrulation regulatory landscape across deuterostomes. Our findings offer valuable insights into the evolutionary molecular dynamics of embryonic development, shedding light on conserved regulatory subprograms and providing a comprehensive perspective on the conservation and divergence of gene regulation underlying the gastrulation process.

Postnatal zinc deficiency due to giardiasis disrupts hippocampal and cerebellar development.

BACKGROUND: Giardiasis and zinc deficiency have been identified as serious health problems worldwide. Although Zn depletion is known to occur in giardiasis, no work has investigated whether changes occur in brain structures. METHODS: Three groups of gerbils were used: control (1), orogastrically inoculated on day 3 after birth with trophozoites of two isolates of Giardia intestinalis (HGINV/WB) group (2 and 3). Estimates were made at five ages covering: establishment of infection, Giardia population growth, natural parasite clearance and a post-infection age. QuantiChrome zinc assay kit, cresyl violet staining and TUNEL technique were used. RESULTS: A significant decrease (p<0.01) in tissue zinc was observed and persisted after infection. Cytoarchitectural changes were observed in 75% of gerbils in the HGINV or WB groups. Ectopic pyramidal neurons were found in the cornus ammonis (CA1-CA3). At 60 and 90 days of age loss of lamination was clearly visible in CA1. In the dentate gyrus (DG), thinning of the dorsal lamina and abnormal thickening of the ventral lamina were observed from 30 days of age. In the cerebellum, we found an increase (p<0.01) in the thickness of the external granular layer (EGL) at 14 days of age that persisted until day 21 (C 3 ± 0.3 µm; HGINV 37 ± 5 µm; WB 28 ± 3 µm); Purkinje cell population estimation showed a significant decrease; a large number of apoptotic somas were observed scattered in the molecular layer; in 60 and 90 days old gerbils we found granular cell heterotopia and Purkinje cell ectopia. The pattern of apoptosis was different in the cerebellum and hippocampus of parasitized gerbils. CONCLUSION: The morphological changes found suggest that neuronal migration is affected by zinc depletion caused by giardiasis in early postnatal life; for the first time, the link between giardiasis-zinc depletion and damaged brain structures is shown. This damage may explain the psychomotor/cognitive delay associated with giardiasis. These findings are alarming. Alterations in zinc metabolism and signalling are known to be involved in many brain disorders, including autism.

Halophilic archaea as tools for bioremediation technologies.

Haloarchaea are extremophilic microorganisms belonging to the Archaea domain that require high salt concentrations to be alive, thus inhabiting ecosystems like salty ponds, salty marshes, or extremely salty lagoons. They are more abundantly and widely distributed worldwide than initially expected. Most of them are grouped into two families: Halobacteriaceae and Haloferacaceae. The extreme conditions under which haloarchaea survive contribute to their metabolic and molecular adaptations, thus making them good candidates for the design of bioremediation strategies to treat brines, salty water, and saline soils contaminated with toxic compounds such as nitrate, nitrite, oxychlorates such as perchlorate and chlorate, heavy metals, hydrocarbons, and aromatic compounds. New advances in understanding haloarchaea physiology, metabolism, biochemistry, and molecular biology suggest that biochemical pathways related to nitrogen and carbon, metals, hydrocarbons, or aromatic compounds can be used for bioremediation proposals. This review analyses the novelty of the most recent results showing the capability of some haloarchaeal species to assimilate, modify, or degrade toxic compounds for most living beings. Several examples of the role of these microorganisms in the treatment of polluted brine or salty soils are also discussed in connection with circular economy-based processes. KEY POINTS: • Haloarchaea are extremophilic microorganisms showing genuine metabolism • Haloarchaea can metabolise compounds that are highly toxic to most living beings • These metabolic capabilities are useful for designing soil and water bioremediation strategies.

Quantitative flow ratio for the functional assessment of extracranial internal carotid artery stenosis.

BACKGROUND: In asymptomatic patients presenting with significant internal carotid artery (ICA) stenoses undergoing endovascular revascularization, a selective angiography before stenting (CAS) is required. Sometimes, angiographic findings could be discordant from non-invasive assessment and a tool able to evaluate functional relevance of the stenosis could be of value. We sought to evaluate the usefulness of quantitative flow ratio (QFR) as angiography-based tool for functional assessment of ICA stenoses. METHODS: We prospectively enrolled 50 asymptomatic patients undergoing CAS. Peak systolic velocity (PSV, cm/s) assessed at color Doppler echocardiography was used to identify significant stenoses (PSV >125 cm/s). At angiography, assessment of ICA stenosis was obtained visually (%DSVISUAL) and according NASCET criteria (%DSNASCET). Stenoses were considered significant if >60%. After exclusion of 20 vessels, QFR, area stenosis (AS, %) and minimal lumen area (MLA, mm2) were obtained in the remaining 80 vessels. RESULTS: At linear regression analysis, QFR significantly correlated with PSV (r2=0.52, P<0.001) as well as with %DSNASCET (r2=0.68, P<0.001) and %DSVISUAL (r2=0.71, P<0.001). Using PSV as reference, QFR showed good accuracy to predict functionally significant stenosis (AUC=0.98, P<0.001) with a cut-off value of 0.93. As compared with %DSNASCET and %DSVISUAL, QFR showed a significantly higher accuracy (61% vs. 73% vs. 94%, respectively; P<0.05), sensitivity (43% vs. 61% vs. 93%, respectively; P<0.05) and negative predictive value (46% vs. 51% vs. 85%, respectively; P<0.05) for detecting hemodynamically significant ICA stenoses. CONCLUSIONS: This study suggest the potential benefit of adopting QFR for functional assessment of extracranial ICA stenoses. These data should be validated in larger studies.

Mediterranean ketogenic diet accounts for reduced pain frequency and intensity in patients with chronic migraine: A pilot study.

BACKGROUND: An increasing amount of evidence suggests that migraine is a response to cerebral energy deficiencies or oxidative stress levels that exceed antioxidant capacity. Current pharmacological options are inadequate in treating patients with chronic migraine, and a growing interest focuses on nutritional approaches as non-pharmacological treatments. The ketogenic diet, mimicking fasting that leads to an elevation of ketone bodies, is a therapeutic intervention targeting cerebral metabolism that has recently shown great promise in the prevention of migraines. Moreover, Mediterranean elements like vegetables, nuts, herbs, spices, and olive oil that are sources of anti-inflammatory elements (omega-3 fatty acids, polyphenols, vitamins, essential minerals, and probiotics) may create a positive brain environment by reducing imbalance in the gut microbiome. METHODS: On the basis of these indications, a combined Mediterranean-ketogenic diet was administered to chronic migraine patients for 4 (T1) and 8 weeks (T2), and anthropometric estimations were collected at T1 and T2 while biochemical parameters at only T2. RESULTS: A significant reduction (p < 0.01) in migraine frequency and intensity was detected as early as 4 weeks of dietary intervention, which was associated with a reduced fat mass (p < 0.001) as well as Homa index (p < 0.05) and insulin levels (p < 0.01) after 8 weeks. CONCLUSION: Overall, Mediterranean-ketogenic diet may be considered an effective non-pharmacological intervention for migraine, with positive outcomes on body composition.

An updated patent review of TRPA1 antagonists (2020 - present).

INTRODUCTION: TRPA1 is a nonselective calcium channel, a member of the transient receptor potential (TRP) superfamily, also referred to as the 'irritant' receptor, being activated by pungent and noxious exogenous chemicals as well as by endogenous algogenic stimuli, to elicit pain, itching, and inflammatory conditions. For this reason, it is considered an attractive therapeutic target to treat a wide range of diseases including acute and chronic pain, itching, and inflammatory airway diseases. AREAS COVERED: The present review covers patents on TRPA1 antagonists disclosed from 2020 to present, falling in the following main classes: i) novel therapeutic applications for known or already disclosed antagonists, ii) identification and characterization of TRPA1 antagonists from natural sources, and iii) synthesis and evaluation of novel compounds. EXPERT OPINION: Despite the limited number of TRPA1 antagonists in clinical trials, there is an ever-growing interest on this receptor-channel as therapeutic target, mainly due to the relevant outcomes from basic research, which unveiled novel physio-pathological mechanisms where TRPA1 is believed to play a pivotal role, for example the Alzheimer's disease or ocular diseases, expanding the panel of potential therapeutic applications for TRPA1 modulators.