Flaviviruses affect the lives of millions of people in endemic regions and also have the potential to impact non-endemic areas. Factors such as climate change, global warming, deforestation, and increased travel and trade are linked to the spread of flaviviruses into new habitats and host species. Given the absence of specific treatments and the limited availability of vaccines, it is imperative to understand the biology of flaviviruses and develop rapid and sensitive diagnostic tests.
View Article and Find Full Text PDFThe emergence of SARS-CoV-2 in 2019 and its rapid spread throughout the world has caused the largest pandemic of our modern era. The zoonotic origin of this pathogen highlights the importance of the One Health concept and the need for a coordinated response to this kind of threats. Since its emergence, the virus has caused >7 million deaths worldwide.
View Article and Find Full Text PDFObjectives: Thymidine kinase 2 deficiency (TK2d) is a rare autosomal recessive mitochondrial disorder. It manifests as a continuous clinical spectrum, from fatal infantile mitochondrial DNA depletion syndromes to adult-onset mitochondrial myopathies characterized by ophthalmoplegia-plus phenotypes with early respiratory involvement. Treatment with pyrimidine nucleosides has recently shown striking effects on survival and motor outcomes in the more severe infantile-onset clinical forms.
View Article and Find Full Text PDFObjectives: Thymidine kinase 2 deficiency (TK2d) is a rare autosomal recessive disorder that stems from a perturbation of the mitochondrial DNA maintenance. Nucleoside treatment has recently shown promise as a disease-modifying therapy. TK2d was initially associated with rapidly progressive fatal myopathy in children featuring mitochondrial DNA depletion.
View Article and Find Full Text PDFObjective: Are circulating luteinizing hormone (LH) levels predictive of ovarian response in oocyte donors triggered with gonadotropin-releasing hormone (GnRH) agonists?
Study Design: A prospective cohort study with 224 oocyte donation cycles between 2021 and 2022 at a single center, examined the relationship between circulating luteinizing hormone (LH) levels and ovarian response. Oocyte donors underwent GnRH antagonist downregulation followed by GnRH agonist trigger. LH, estradiol, and progesterone levels were measured on day one of stimulation, trigger-day and 12 h post-trigger.
Varnimcabtagene autoleucel (var-cel) is an academic anti-CD19 chimeric antigen receptor (CAR) product used for the treatment of non-Hodgkin lymphoma (NHL) in the CART19-BE-01 trial. Here we report updated outcomes of patients with NHL treated with var-cel. B-cell recovery was compared with patients with acute lymphoblastic leukaemia (ALL).
View Article and Find Full Text PDFPurpose: Are trends in singleton donor oocyte IVF perinatal outcomes consistent over time among four international ethnically diverse infertility centers?
Methods: This retrospective cohort consisted of an infertility network of four international IVF centers across three continents. Singleton live births resulting from fresh and frozen donor oocyte embryo transfers from January 1, 2012 to December 31, 2018 were included. The main outcome measures were birth weight (BW), preterm birth (PTB), large for gestational age (LGA), small for gestational age (SGA) and gestational age (GA) at delivery.
Background: Viral rewiring of host bioenergetics and immunometabolism may provide novel targets for therapeutic interventions against viral infections. Here, we have explored the effect on bioenergetics during the infection with the mosquito-borne flavivirus West Nile virus (WNV), a medically relevant neurotropic pathogen causing outbreaks of meningitis and encephalitis worldwide.
Results: A systematic literature search and meta-analysis pointed to a misbalance of glucose homeostasis in the central nervous system of WNV patients.
Deltas and estuaries are formed through periods of marine transgression and regression, which are the continuity of a river and provide key information about its evolution. However, many of the world's deltas are increasingly exposed to the impacts of human activities. While changes affecting the subaerial parts of deltas have been intensively studied, much less is known of their subaqueous parts, the understanding of which is important in gauging overall potential delta vulnerability.
View Article and Find Full Text PDFZika virus (ZIKV) is a mosquito-borne flavivirus that was first identified in Uganda in 1947, then was essentially neglected for six decades [...
View Article and Find Full Text PDFWest Nile virus (WNV) is a neurotropic flavivirus transmitted by the bites of infected mosquitoes. Severe forms of West Nile disease (WND) can curse with meningitis, encephalitis or acute flaccid paralysis. A better understanding of the physiopathology associated with disease progression is mandatory to find biomarkers and effective therapies.
View Article and Find Full Text PDFJ Clin Med
March 2023
Primary mitochondrial myopathies (PMM) are a clinically and genetically highly heterogeneous group that, in some cases, may manifest exclusively as fatigue and exercise intolerance, with minimal or no signs on examination. On these occasions, the symptoms can be confused with the much more common chronic fatigue syndrome (CFS). Nonetheless, other possibilities must be excluded for the final diagnosis of CFS, with PMM being one of the primary differential diagnoses.
View Article and Find Full Text PDFThe flavivirus life cycle is strictly dependent on cellular lipid metabolism. Polyphenols like gallic acid and its derivatives are promising lead compounds for new therapeutic agents as they can exert multiple pharmacological activities, including the alteration of lipid metabolism. The evaluation of our collection of polyphenols against West Nile virus (WNV), a representative medically relevant flavivirus, led to the identification of ,'-(dodecane-1,12-diyl)bis(3,4,5-trihydroxybenzamide) and its 2,3,4-trihydroxybenzamide regioisomer as selective antivirals with low cytotoxicity and high antiviral activity (half-maximal effective concentrations [ECs] of 2.
View Article and Find Full Text PDFObjective: To assess the economic impact associated with overactive bladder (OAB) patients, treated with mirabegron or antimuscarinics (AM) in Spain, over a 12-month period.
Methods: A probabilistic model (second-order Monte Carlo simulation) was used in a hypothetical cohort of 1000 patients with OAB and a time horizon of 12 months. The use of resources was obtained from the retrospective observational study MIRACAT that included 3330 patients with OAB.
West Nile virus (WNV) is a re-emergent mosquito-borne RNA virus that causes major outbreaks of encephalitis around the world. However, there is no therapeutic treatment to struggle against WNV, and the current treatment relies on alleviating symptoms. Therefore, due to the threat virus poses to animal and human health, there is an urgent need to come up with fast strategies to identify and assess effective antiviral compounds.
View Article and Find Full Text PDFWe report a neonatal patient with hypertrophic cardiomyopathy (HCM), lactic acidosis and isolated complex I deficiency. Using a customized next-generation sequencing panel, we identified a novel hemizygous variant c.338G>A in the X-linked NDUFB11 gene that encodes the NADH: ubiquinone oxidoreductase subunit B11 of the mitochondrial respiratory chain (MRC) complex I (CI).
View Article and Find Full Text PDFSpike anchors are one of the most promising techniques to prevent or delay debonding in FRP reinforcement sheets. There are several parameters affecting the anchors' capacity, such as the embedment length and dowel angle. Regardless of the anchors' capacity, their contribution to the overall strength of the anchored joint is affected by a larger number of variables, including the bonded length behind the anchors, the number and arrangement of the anchors, and the contact surface between the anchor fan and the FRP sheet.
View Article and Find Full Text PDFcomprises globally emerging and re-emerging pathogens such as Zika virus (ZIKV), Dengue virus (DENV), and West Nile virus (WNV), among others. Although some vaccines are available, there is an unmet medical need as no effective antiviral treatment has been approved for flaviviral infections. The development of host-directed antivirals (HDAs) targeting host factors that are essential for viral replication cycle offers the opportunity for the development of broad-spectrum antivirals.
View Article and Find Full Text PDFLactate dehydrogenase (LDH) catalyzes the reversible conversion of L-lactate to pyruvate. LDH-A deficiency is an autosomal recessive disorder (glycogenosis type XI, OMIM#612933) caused by mutations in the LDHA gene. We present two young adult female patients presenting with intolerance to anaerobic exercise, episodes of rhabdomyolysis, and, in one of the patients, psoriasis-like dermatitis.
View Article and Find Full Text PDFThis historical cohort study evaluated clinical characteristics of progression and prognosis in adults with thymidine kinase 2 deficiency (TK2d). Records were available for 17 untreated adults with TK2d (mean age of onset, 32 years), including longitudinal data from 6 patients (mean follow-up duration, 26.5 months).
View Article and Find Full Text PDFThe quantification of mitochondrial respiratory chain (MRC) enzymatic activities is essential for diagnosis of a wide range of mitochondrial diseases, ranging from inherited defects to secondary dysfunctions. MRC lesion is frequently linked to extended cell damage through the generation of proton leak or oxidative stress, threatening organ viability and patient health. However, the intrinsic challenge of a methodological setup and the high variability in measuring MRC enzymatic activities represents a major obstacle for comparative analysis amongst institutions.
View Article and Find Full Text PDFWe reconstructed the palaeoenvironmental conditions of Cartagena Bay during the Holocene after a multidisciplinary study to identify natural variations and the anthropic processes of this coastal area. A total of 119 samples were recovered for amino acid racemization dating, 3 for radiocarbon dating (C), and four sets of 80 samples for sedimentological and palaeontological determination, mineralogical content, biomarker and trace elements quantification. Two natural scenarios were identified from the variations of n-alkane indices and palaeobiological content.
View Article and Find Full Text PDFThe Albufera de Valencia is one of the largest lagoon in the Spanish Mediterranean. Two continuous borehole cores reaching depths of 8 and 14 m in the northern part of the lagoon underwent sedimentological, micropaleontological and biological study. The organic content was also analysed, and C radiometric dating and amino acid racemization were performed.
View Article and Find Full Text PDF