Influence of the ovine genital tract microbiota on the species artificial insemination outcome. A pilot study in commercial sheep farms

To date, there is a lack of research into the vaginal and sperm microbiome and its bearing on artificial insemination (AI) success in the ovine species. Using hypervariable regions V3–V4 of the 16S rRNA, we describe, for the first time, the combined effect of the ovine microbiome of both females (50 ewes belonging to five herds) and males (five AI rams from an AI center) on AI outcome. Differences in microbiota abundance between pregnant and non-pregnant ewes and between ewes carrying progesterone-releasing intravaginal devices (PRID) with or without antibiotic were tested at different taxonomic levels. The antibiotic treatment applied with the PRID only altered Streptobacillus genus abundance, which was significantly lower in ewes carrying PRID with antibiotic. Mageebacillus, Histophilus, Actinobacilllus and Sneathia genera were significantly less abundant in pregnant ewes. In addition, these genera were more abundant in two farms with higher AI failure. Species of these genera such as Actinobacillus seminis and Histophilus somni have been associated with reproductive disorders in the ovine species. These genera were not present in the sperm samples of AI rams, but were found in the foreskin samples of rams belonging to herd 2 (with high AI failure rate) indicating that their presence in ewes’ vagina could be due to prior transmission by natural mating with rams reared in the herd

Clinical-decision criteria to identify recurrent diabetic macular edema patients suitable for fluocinolone acetonide implant therapy (Iluvien®) and follow-up considerations/ recommendations

Current management of diabetic macular edema (DME) predominantly involves treatment with short-acting intravitreal injections of anti-vascular endothelial growth factors (anti-VEGFs) and/or corticosteroids; however, short-acting therapies (lasting between 1 and 6 months) require frequent injections to maintain efficacy, meaning a considerable treatment burden for diabetic patients with multiple comorbidities. Continuous injections needed in some cases are an economic burden for patients/healthcare system, so real-life clinical practice tends to adopt a reactive approach, ie, watch and wait for worsening symptoms, which consequently increases the risk of undertreatment and edema recurrence. On March 7th 2019, a group of experts in retinal medicine and surgery held a roundtable meeting in Madrid, Spain to discuss how to (1) optimize clinical outcomes through earlier use of fluocinolone acetonide (FAc) implant (ILUVIEN®) in patients with persistent or recurrent DME despite therapy; and, (2) to provide guidance to assist physicians in deciding which patients should be treated with ILUVIEN. In this regard, a 36-month follow-up consensus protocol is presented. In conclusion, patients that achieve a complete or partial anatomical, and preferably functional, response following one or two intravitreal dexametha-sone implants, but with recurrence of edema after 3–4 months, are deemed by the authors most likely to benefit from ILUVIEN, and the switch to FAc implant should not be delayed more than 12 months after the initiation of at least the first dexamethasone implant

Usefulness of two independent DNA and rna tissue-based multiplex assays for the routine care of advanced NSCLC patients

Personalized medicine is nowadays a paradigm in lung cancer management, offering important benefits to patients. This study aimed to test the feasibility and utility of embedding two multiplexed genomic platforms as the routine workup of advanced non-squamous non-small cell lung cancer (NSCLC) patients. Two parallel multiplexed approaches were performed based on DNA sequencing and direct digital detection of RNA with nCounter® technology to evaluate gene mutations and fusions. The results were used to guide genotype-directed therapies and patient outcomes were collected. A total of 224 advanced non-squamous NSCLC patients were prospectively included in the study. Overall, 85% of samples were successfully characterized at DNA and RNA levels and oncogenic drivers were found in 68% of patients, with KRAS, EGFR, MET∆ex14, BRAF, and ALK being the most frequent (31%, 19%, 5%, 4%, and 4%, respectively). Among all patients with complete genotyping results and follow-up data (n = 156), the median overall survival (OS) was 1.90 years (confidence interval (CI) 95% 1.69-2.10) for individuals harbouring an actionable driver treated with a matched therapy, compared with 0.59 years (CI 95% 0.39-0.79) in those not eligible for any targeted therapy and 0.61 years (CI 95% 0.12-1.10) in patients with no drivers identified (p < 0.001). Integrating DNA and RNA multiplexing technologies into the routine molecular testing of advanced NSCLC patients is feasible and useful and highlights the necessity of widespread integrating comprehensive molecular diagnosis into lung cancer care

Coagulation disorders and thromboembolic disease in COVID-19 : Review of current evidence in search of a better approach

The new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been an unprecedented global health problem, causing more than 20 million infections and more than 900,000 deaths (September 2020). The SARS-CoV-2 infection, known as COVID-19, has various clinical presentations, from asymptomatic or mild catarrhal processes to severe pneumonia that rapidly progresses to acute respiratory distress syndrome (ARDS) and multiple organ failure. In the last few months, much scientific literature has been devoted to descriptions of different aspects of the coagulation disorders and arterial and venous thrombotic complications associated with COVID-19, particularly venous thromboembolism (VTE). These studies have revealed that SARS-CoV-2 could lead to a prothrombotic state reflecting the high cumulative incidence of associated thrombotic events, particularly in patients admitted to intensive care units (ICUs). As regards the coagulopathy observed in association with SARS-CoV-2 infection, the mechanisms that activate coagulation have been hypothesized as being linked to immune responses, through the release of pro-inflammatory mediators that interact with platelets, stimulate the expression of tissue factor, induce an upregulation of plasminogen activator inhibitor-1, suppress the fibrinolytic system and lead to endothelial dysfunction, triggering thrombogenesis. D-dimer elevation has been recognized as a useful biomarker of poor prognosis, although the best cut-off point for predicting VTE in COVID-19 patients has still not been clarified. This review will try to update all the available scientific information on this important topic with enormous clinical and therapeutic implications

Glycerol Valorization towards a Benzoxazine Derivative through a Milling and Microwave Sequential Strategy

Glycerol and aminophenol intermolecular condensation has been investigated through a milling and microwave-assisted sequential strategy, towards the synthesis of a benzoxaxine derivative. Mechanochemical activation prior to the microwave-assisted process could improve the probability of contact between the reagents, and greatly favors the higher conversion of aminophenol. At the same time, following a mechanochemical–microwave sequential approach could tune the selectivity towards the formation of a benzoxazine derivative, which could find application in a wide range of biomedical areas. © 2022 by the authors. Licensee MDPI, Basel, Switzerland

Physiological concentrations of phytosterols enhance the apoptotic effects of 5-Fluorouracil in colon cancer cells

Combining natural products as co-adjuvants in 5-fluorouracil (5-FU) chemotherapy might enhance the effectiveness of 5-FU by avoiding a high dosage and/or reducing treatment times. We explored the anticancer efficacy of the phytosterols (PS) at concentrations achievable in the human colon, as well as their potential as sensitizing agents of human colon cancer cells (Caco-2 and HT-29) to 5-FU treatment. Cells proliferation, combination index, cell cycle, apoptosis, caspases activation, ROS production, and ΔΨm were determined. Co-treatment (PS+5-FU) had an antiproliferative additive effect, and moreover, in general a significantly improved efficacy was observed on cell cycle arrest at S phase, apoptosis induction and increase in caspases activation compared to 5-FU alone, while no significant effects were observed on ROS levels and ΔΨm. Our results suggest, for the first time, the ability of PS to sensitize colon cancer cells to 5-FU chemotherapy and warrant further in vivo studies to confirm our preclinical findings

Impact of SARS-CoV-2 infection on neurodegenerative and neuropsychiatric diseases: a delayed pandemic?

Introduction: SARS-CoV-2 was first detected in December 2019 in the Chinese city of Wuhan and has since spread across the world. At present, the virus has infected over 1.7 million people and caused over 100000 deaths worldwide. Research is currently focused on understanding the acute infection and developing effective treatment strategies. In view of the magnitude of the epidemic, we conducted a speculative review of possible medium- and long-term neurological consequences of SARS-CoV-2 infection, with particular emphasis on neurodegenerative and neuropsychiatric diseases of neuroinflammatory origin, based on the available evidence on neurological symptoms of acute SARS-CoV-2 infection. Development: We systematically reviewed the available evidence about the pathogenic mechanisms of SARS-CoV-2 infection, the immediate and lasting effects of the cytokine storm on the central nervous system, and the consequences of neuroinflammation for the central nervous system. Conclusion: SARS-CoV-2 is a neuroinvasive virus capable of triggering a cytokine storm, with persistent effects in specific populations. Although our hypothesis is highly speculative, the impact of SARS-CoV-2 infection on the onset and progression of neurodegenerative and neuropsychiatric diseases of neuroinflammatory origin should be regarded as the potential cause of a delayed pandemic that may have a major public health impact in the medium to long term. Cognitive and neuropsychological function should be closely monitored in COVID-19 survivors.YesIntroducción: La infección por el coronavirus SARS-CoV-2 originada en diciembre de 2019 en la región china de Wuhan ha adquirido proporciones pandémicas. A día de hoy ha ocasionado más de 1,7 millones de contagios y más de 100.000 muertes en todo el mundo. La investigación científica actual se centra en el mejor conocimiento de la infección aguda y de sus estrategias terapéuticas. Dada la magnitud de la epidemia, planteamos una revisión especulativa sobre las posibles consecuencias en patología neurológica a medio/largo plazo, con especial atención a enfermedades neurodegenerativas y neuropsiquiátricas con base neuroinflamatoria, teniendo en cuenta la evidencia directa de afectación neurológica a causa de la infección aguda. Desarrollo: Revisamos de forma sistemática lo conocido sobre los mecanismos patogénicos de la infección por SARS-CoV-2, la repercusión de la tormenta de citoquinas sobre el sistema nervioso central y su persistencia en el tiempo y las consecuencias que la neuroinflamación puede tener sobre el sistema nervioso central. Conclusiones: El SARS-CoV-2 es un virus neuroinvasivo capaz de provocar una tormenta de citoquinas que podría convertirse en persistente en población seleccionada. Aunque nuestra hipótesis tiene alto componente especulativo, la repercusión que esta situación puede tener en la puesta en marcha y progresión de enfermedades neurodegenerativas y neuropsiquiátricas con base neuroinflamatoria debe ser considerada como posible germen de una pandemia demorada que podría tener un gran impacto en salud pública a medio o largo plazo. Se hace necesario un estrecho seguimiento de la salud cognitiva y neuropsiquiátrica de los pacientes supervivientes a infección COVID-19

II Consenso Colombiano para el Manejo de la Osteoporosis Posmenopáusica

The Colombian Osteoporosis and Mineral Metabolism Association met in early 2017 to update the Colombian Consensus on Osteoporosis. This was first issued in 2005, and is seen as a necessary step in view of the underdiagnosed status of this disease, and the expected impact of population ageing. A technical team was formed with specialists with long experience across multiple disciplines, who were assigned to four working groups: definitions and epidemiology, diagnosis, pharmacological treatment, and non-pharmacological treatment. After a scientific literature review and a series of meetings, the definitions and recommendations are summarised in this article. © 2018 Asociación Colombiana de Reumatologí

II Consenso Colombiano para el Manejo de la Osteoporosis Posmenopáusica

The Colombian Osteoporosis and Mineral Metabolism Association met in early 2017 to update the Colombian Consensus on Osteoporosis. This was first issued in 2005, and is seen as a necessary step in view of the underdiagnosed status of this disease, and the expected impact of population ageing. A technical team was formed with specialists with long experience across multiple disciplines, who were assigned to four working groups: definitions and epidemiology, diagnosis, pharmacological treatment, and non-pharmacological treatment. After a scientific literature review and a series of meetings, the definitions and recommendations are summarised in this article. © 2018 Asociación Colombiana de Reumatologí