Cellular and molecular biomarkers of long COVID: a scoping review.

BACKGROUND: Long-COVID (LC) encompasses diverse symptoms lasting months after the initial SARS-CoV-2 infection. Symptoms can be debilitating and affect the quality of life of individuals with LC and their families. Although the symptoms of LC are well described, the aetiology of LC remains unclear, and consequently, patients may be underdiagnosed. Identification of LC specific biomarkers is therefore paramount for the diagnosis and clinical management of the syndrome. This scoping review describes the molecular and cellular biomarkers that have been identified to date with potential use for diagnosis or prediction of LC. METHODS: This review was conducted using the Joanna Briggs Institute (JBI) Methodology for Scoping Reviews. A search was executed in the MEDLINE and EMBASE databases, as well as in the grey literature for original studies, published until October 5th, 2022, reporting biomarkers identified in participants with LC symptoms (from all ages, ethnicities, and sex), with a previous infection of SARS-CoV-2. Non-English studies, cross-sectional studies, studies without a control group, and pre-prints were excluded. Two reviewers independently evaluated the studies, extracted population data and associated biomarkers. FINDINGS: 23 cohort studies were identified, involving 2163 LC patients [median age 51.8 years, predominantly female sex (61.10%), white (75%), and non-vaccinated (99%)]. A total of 239 candidate biomarkers were identified, consisting mainly of immune cells, immunoglobulins, cytokines, and other plasma proteins. 19 of the 239 candidate biomarkers identified were evaluated by the authors, by means of receiver operating characteristic (ROC) curves. INTERPRETATION: Diverse cellular and molecular biomarkers for LC have been proposed. Validation of candidate biomarkers in independent samples should be prioritized. Modest reported performance (particularly in larger studies) suggests LC may encompass many distinct aetiologies, which should be explored e.g., by stratifying by symptom clusters and/or sex. FUNDING: Dr. Tebbutt has received funding from the Canadian Institutes of Health Research (177747) to conduct this work. The funding source was not involved in this scoping review, or in the decision to submit this manuscript for publication.

Is a higher altitude associated with shorter survival among at-risk neonates?

INTRODUCTION: We hypothesize that high altitudes could have an adverse effect on neonatal health outcomes, especially among at-risk neonates. The current study aims to assess the association between higher altitudes on survival time among at-risk neonates. METHODS: Retrospective survival analysis. Setting: Ecuadorian neonates who died at ≤28 days of life. Patients: We analyzed the nationwide dataset of neonatal deaths from the Surveillance System of Neonatal Mortality of the Ministry of Public Health of Ecuador, registered from 126 public and private health care facilities, between January 2014 to September 2017. Main outcome measures: We retrospectively reviewed 3016 patients. We performed a survival analysis by setting the survival time in days as the primary outcome and fixed and mixed-effects Cox proportional hazards models to estimate hazard ratios (HR) for each altitude stratum of each one of the health care facilities in which those neonates were attended, adjusting by individual variables (i.e., birth weight, gestational age at birth, Apgar scale at 5 minutes, and comorbidities); and contextual variables (i.e., administrative planning areas, type of health care facility, and level of care). RESULTS: Altitudes of health care facilities ranging from 80 to <2500 m, 2500 to <2750m, and ≥2750 m were associated respectively with 20% (95% CI: 1% to 44%), 32% (95% CI:<1% to 79%) and 37% (95% CI: 8% to 75%) increased HR; compared with altitudes at <80 m. CONCLUSION: Higher altitudes are independently associated with shorter survival time, as measured by days among at-risk neonates. Altitude should be considered when assessing the risk of having negative health outcomes during neonatal period.

Vaccine market and production capabilities in the Americas.

In the Americas, The United States of America, Canada, Mexico, and Brazil are the top vaccine producers and the countries with the leading infrastructure for biological manufacturing. The North American countries have the most demanding legislation regulating and controlling these pharmaceuticals' distribution and production. Some Latin American countries rank in the top 20 of worldwide vaccine manufacturers, with Cuba, Brazil, México and Colombia have a self-sufficient vaccine production of 72.7%, 54,2%; 25%; and 7.7%, respectively, of the national vaccine demand. On the other hand, the rest of Latin American countries cannot satisfy their demand for vaccines, and most of their efforts are associated with the distribution within their health systems rather than in transferring technology.Based on this literature review, the results suggest an increasing growth vaccine demand, not only for their growing populations and previously established demand but also for the recently exerted pressure due to the COVID-19 pandemic.Because the American continent has a marked inequality between the hegemonic producers of vaccines, the exporters, and those that depend heavily on importing these products, this could assert technological dependence in countries with rapid population growth and jeopardize the effectiveness of the two vaccination plans.

A report of congenital adrenal hyperplasia due to 17α-hydroxylase deficiency in two 46,XX sisters.

Congenital adrenal hyperplasia (CAH) is a group of rare orphan disorders caused by mutations in seven different enzymes that impair cortisol biosynthesis. The 17α-hydroxylase deficiency (17OHD) is one of the less common forms of CAH, corresponding to approximately 1% of the cases, with an estimated annual incidence of 1 in 50,000 newborns. Cases description - two phenotypically female Ecuadorian sisters, both with primary amenorrhea, absence of secondary sexual characteristics, and osteoporosis. High blood pressure was present in the older sister. Hypergonadotropic hypogonadism profile was observed: decreased cortisol and dehydroepiandrosterone sulfate (DHEAS), increased adrenocorticotropic hormone (ACTH) and normal levels of 17-hydroxyprogesterone, extremely high deoxycorticosterone (DOC) levels, and a tomography showed bilateral adrenal hyperplasia in both sisters. Consanguinity was evident in their ancestors. Furthermore, in the exon 7, the variant c.1216T > C, p.Trp406Arg was detected in homozygosis in the CYP17A1 gene of both sisters. We report a homozygous missense mutation in the CYP17A1 gene causing 17OHD in two sisters from Loja, Ecuador. According to the authors, this is the first time such deficiency and mutation are described in two members of the same family in Ecuador.

MicroRNAs in Breast Cancer: One More Turn in Regulation.

MicroRNAs (miRNAs) are small non-coding RNA molecules that critically regulate the expression of genes. MiRNAs are involved in physiological cellular processes; however, their deregulation has been associated with several pathologies, including cancer. In human breast cancer, differently expressed levels of miRNAs have been identified from those in normal breast tissues. Moreover, several miRNAs have been correlated with pathological phenotype, cancer subtype and therapy response in breast cancer. The resistance to therapy is increasingly a problem in patient management, and miRNAs are emerging as novel therapeutic targets and potential predictive biomarkers for treatment. This review provides an overview of the current situation of miRNAs in breast cancer, focusing on their involvement in resistance and the circulating miRNA. The mechanisms of therapeutic resistance regulated by miRNAs, such as the regulation of receptors, the modification of enzymes of drug metabolism, the inhibition of cell cycle control or pro-apoptotic proteins, the alteration of histone activity and the regulation of DNA repair machinery among others, are discussed for breast cancer clinical subtypes. Additionally, in this review, we summarize the recent knowledge that has established miRNA detection in peripheral body fluids as a suitable biomarker. We review the detection of miRNA in liquid biopsies and its implications for the diagnosis and monitoring of breast cancer. This new generation of cancer biomarkers may lead to a significant improvement in patient management.

Perspectivas actuales sobre el uso terapéutico del veneno de serpientes / Current perspectives on the therapeutic use of snake venom

Durante años los venenos de serpiente han sido empleados con ciertos fnes terapéuticos los cuales han sido relativamente poco estudiados. La mayoría de los venenos de serpientes poseen un sin número de moléculas con actividad concreta sobre proteínas y receptores específcos del cuerpo humano. Estas características convierten a los venenos en fuentes de inspiración para diseñar nuevas moléculas con actividad farmacológica, que de cierta forma contribuyen a proponer tratamientos médicos nuevos para el cáncer, la trombosis, la esclerosis múltiple, los trastornos neuromusculares o algunos trastornos cardiovasculares. En este artículo se revisa las principales proyecciones terapéuticas de los distintos venenos de serpientes que actualmente se están considerando para la industria farmacéutica como herramientas terapéuticas innovadoras para el desarrollo de nuevos fármacos

Historically, snake venoms have been used as a therapeutic option to treat several pathologies worldwide. These activities have been studied due to the presence of several proteins and molecules that have important molecular activity with human receptors. These features are currently been considered as one important source of inspiration to design new molecules with pharmacological activity, specially in diseases like cancer, thrombosis, multiple sclerosis, neuromuscular disorders and cardiovascular disorders. In this article we review the principal therapeutic projections that are currently being considered for the pharmaceutical industry as an innovative and therapeutic tool for the development of new drugs