Preclinical Evidence Supporting Early Initiation of Citalopram Treatment in Machado-Joseph Disease.

Spinocerebellar ataxias are dominantly inherited neurodegenerative disorders with no disease-modifying treatment. We previously identified the selective serotonin reuptake inhibitor citalopram as a safe and effective drug to be repurposed for Machado-Joseph disease. Pre-symptomatic treatment of transgenic (CMVMJD135) mice strikingly ameliorated mutant ataxin-3 (ATXN3) pathogenesis.

Efficacy of essential oils from plants cultivated in the Amazonian Biome against gastrointestinal nematodes in sheep.

The excessive use of anthelmintics to control nematodes has resulted in anthelminthic resistance. Essential oils (EOs) are a rich source of bioactive molecules that can be assessed for their ability to control resistant parasite populations. The aims of this study were to screen EOs from 10 plant species in vitro for anthelmintic activity against , evaluate the cytotoxicity of those EOs in a human immortalized keratinocyte cell line (HaCaT), and test the most promising EO candidate in vivo in Santa Inês sheep.

Altered neural signatures of interoception in multiple sclerosis.

Multiple sclerosis (MS) patients present several alterations related to sensing of bodily signals. However, no specific neurocognitive impairment has yet been proposed as a core deficit underlying such symptoms. We aimed to determine whether MS patients present changes in interoception-that is, the monitoring of autonomic bodily information-a process that might be related to various bodily dysfunctions.

Using microalgae in the circular economy to valorise anaerobic digestate: challenges and opportunities.

Managing organic waste streams is a major challenge for the agricultural industry. Anaerobic digestion (AD) of organicwastes is a preferred option in the waste management hierarchy, as this processcangenerate renewableenergy, reduce emissions from wastestorage, andproduce fertiliser material.However, Nitrate Vulnerable Zone legislation and seasonal restrictions can limit the use of digestate on agricultural land.

Intracytoplasmic sperm injection for male infertility and consequences for offspring.

Intracytoplasmic sperm injection (ICSI) has become the most commonly used method of fertilization in assisted reproductive technology. The primary reasons for its popularity stem from its effectiveness, the standardization of the procedure, which means that it can easily be incorporated into the routine practice of fertility centres worldwide, and the fact that it can be used to treat virtually all forms of infertility. ICSI is the clear method of choice for overcoming untreatable severe male factor infertility, but its (over)use in other male and non-male factor infertility scenarios is not evidence-based.

Estimation of age-dependent decrease in blastocyst euploidy by next generation sequencing: development of a novel prediction model.

Background: We developed a model to estimate the female age-dependent decrease in blastocyst euploidy and the impact of blastocyst cohort size on the likelihood of having at least one euploid blastocyst for transfer.

Methods: Retrospective analysis of 1296 trophectoderm biopsies by next-generation sequencing analysis from 436 infertile couples undergoing intracytoplasmic sperm injection and preimplantation genetic testing for aneuploidy. A logistic regression model was fit to the data.

Impact of Body Mass Index on female fertility and ART outcomes.

As the global mean Body Mass Index (BMI) is on the rise, the importance of understanding exactly how female fertility is impacted by once outlier BMI values, becomes ever more important. Studies have implicated abnormal BMI on the female reproductive system by contributing to anovulation, irregular menses, adverse oocyte quality, endometrial alterations, and hormonal imbalances. These well ultimately result in female infertility, which could complicate natural conception efforts and request considering assisted reproductive technology (ART) in such couples.

Should a Couple with Failed In Vitro Fertilization or Intracytoplasmic Sperm Injection and Elevated Sperm DNA Fragmentation Use Testicular Sperm for the Next Cycle?

There is growing evidence indicating that intracytoplasmic sperm injection with testicular sperm rather than ejaculated sperm might be advantageous in achieving pregnancy for couples in which the male has high levels of sperm DNA fragmentation (SDF). Meta-analysis has shown that SDF rates are markedly lower in testicular sperm than in ejaculated sperm, and the odds of achieving pregnancy and a live birth are significantly higher.

Clinical relevance of genetic variants of gonadotrophins and their receptors in controlled ovarian stimulation: a systematic review and meta-analysis.

Background: Genotype has been implicated in the outcome of ovarian stimulation. The analysis of patient-specific genotypes might lead to an individualized pharmacogenomic approach to controlled ovarian stimulation (COS). However, the validity of such an approach remains to be established.

Sensitive vs. tolerant Nitzschia palea (Kützing) W. Smith strains to atrazine: a biochemical perspective.

Organic contaminants, and herbicides in particular, represent a risk for aquatic ecosystems. The primary target of herbicides are producers, the base of food webs, but frequently they end up far from the application point affecting non-target species. Its presence can work as sub-lethal stimulus, which sort the genetic and phenotypic differences within a species.

Association Between Progesterone Elevation on the Day of Human Chronic Gonadotropin Trigger and Pregnancy Outcomes After Fresh Embryo Transfer in Fertilization/Intracytoplasmic Sperm Injection Cycles.

Progesterone elevation (PE) during the late follicular phase of controlled ovarian stimulation in fresh embryo transfer fertilization (IVF)/intracytoplasmic sperm injection cycles has been claimed to be associated with decreased pregnancy rates. However, the evidence is not unequivocal, and clinicians still have questions about the clinical validity of measuring P levels during the follicular phase of stimulated cycles. We reviewed the existing literature aimed at answering four relevant clinical questions, namely (i) Is gonadotropin type associated with PE during the follicular phase of stimulated cycles? (ii) Is PE on the day of human chorionic gonadotropin (hCG) associated with negative fresh embryo transfer IVF/intracytoplasmic sperm injection (ICSI) cycles outcomes in all patient subgroups? (iii) Which P thresholds are best to identify patients at risk of implantation failure due to PE in a fresh embryo transfer? and (iv) Should a freeze all policy be adopted in all the cycles with PE on the day of hCG? The existing evidence indicates that late follicular phase progesterone rise in gonadotropin releasing analog cycles is mainly caused by the supraphysiological stimulation of granulosa cells with exogenous follicle-stimulating hormone.

Recombinant luteinizing hormone supplementation in assisted reproductive technology: a systematic review.

Objective: To assess the role of recombinant human LH (r-hLH) supplementation in ovarian stimulation for ART in specific subgroups of patients.

Design: Systematic review.

Setting: Centers for reproductive care.

Surgery vs. primary radiotherapy in early-stage oropharyngeal cancer.

Background: Early-stage oropharyngeal squamous cell carcinoma (OPSCC) can currently be treated by surgical resection or definitive radiotherapy (RT). The aim of this study is to review the outcomes of early-stage OPSCC submitted to surgery or primary RT. Preliminary results have shown similar overall survival (OS) and locoregional recurrence-free survival (LRFS).

Effect of varicocele repair on sperm DNA fragmentation: a review.

Varicocele, the leading cause of male infertility, can impair sperm quality and fertility via various oxidative stress mechanisms. An imbalance between excessive reactive oxygen species production and antioxidant protection causes alterations in nuclear and mitochondrial sperm DNA, thus rendering a subset of varicocele men less fertile. In particular, sperm DNA fragmentation is usually elevated in men with clinical varicocele in both abnormal and normal semen parameters by the current World Health Organization criteria.

Proteomic Signatures of Sperm Mitochondria in Varicocele: Clinical Use as Biomarkers of Varicocele Associated Infertility.

Purpose: Varicocele may disrupt testicular microcirculation and induce hypoxia-ischemia related degenerative changes in testicular cells and spermatozoa. Superoxide production at low oxygen concentration exacerbates oxidative stress in men with varicocele. Therefore, the current study was designed to study the role of mitochondrial redox regulation and its possible involvement in sperm dysfunction in varicocele associated infertility.

Individualized controlled ovarian stimulation in expected poor-responders: an update.

Controlled ovarian stimulation with subsequent multi-follicular development continues to be a keystone in ART. Evidence supports an individualized approach to ovarian stimulation, usually involving combinations of ovarian reserve tests, body mass index and age to tailor the exogenous gonadotropin dose, and potentially adjuvant treatment aiming for high safety and a shortening of time to live birth. While stimulation and trigger concepts have been developed successfully in normo- and hyperresponder patients, the poor responder patient remains difficult to manage.