Ideal lag time from ovulation to oocyte aspiration using a GnRH agonist trigger.

BACKGROUND: In ART, oocyte maturation (M2) and ovulation is stimulated by a hormonal trigger. For maturation to occur, sufficient "lag time" must elapse between the trigger and aspiration, ranging from 32 to 38 hours. Premature aspiration can result in poor yields; late aspiration risks spontaneous ovulation. AIM: Our study examines optimal lag time using a GnRH antagonist protocol and GnRH agonist trigger for ICSI. METHODS AND MATERIALS: We analyzed data from 220 women undergoing GnRH antagonist protocol using a GnRH agonist trigger for ICSI at our clinic between 02/2012-03/2018. Patients were divided into 4 groups based on lag time: 34.00-34.99 hours (n = 32), 35.00-35.99 hours (n = 113), 36.00-36.99 hours (n = 57) and 37.00 h or more (n = 18). Analyses were performed with the Kruskal-Wallis test, Chi-Square, and Spearman's rho correlation. RESULTS: A positive correlation was found for the number of M2 oocytes aspirated and lag time (ρ = 0.138, p = 0.04) and for the total number of oocytes aspirated and lag time, (ρ = 0.174, p = 0.01). No correlation was found between the proportion of M2 oocytes aspirated and lag time (p = 0.217). The third group (36 h) had significantly more M2 oocytes aspirated than the second group (35 h) (12.4 ± 7.1 vs 9.4 ± 6.2; p = 0.039). The four groups did not differ for the proportion of mature M2 oocytes (H = 2.453, p = 0.484). The four groups differed in the frequency of live births per fresh embryos transferred (χ2 = 9.364, p = 0.025). CONCLUSION: Our study identified a positive correlation between lag time and both the number of M2 oocytes and the total number of oocytes aspirated-factors which lead to an increased rate of successful pregnancies. Further research is necessary.

CoViD-19 Immunopathology and Immunotherapy.

New evidence on the T-cell immuno-pathology in patient's with Corona Virus Disease 2019 (CoViD-19) was reported by Diao et al. in MedRxiv (doi: 10.1101/2020.02.18.20024364) [1]. It reports observations on 522 patients with confirmed CoViD-19 symptomatology, compared to 40 control subjects. In brief, notable T cytopoenia was recorded by flow cytometry in the CD4+ and the CD8+ populations, which were significantly yet inversely correlated with remarkably increased serum levels of the pro-inflammatory cytokines IL-6, IL-10 and TNF-a. Flow cytometry established a progressive increase in the expression of programmed cell death marker-1 (PD-1) and T cell immunoglobulin and mucin domain 3 (Tim-3) as patients (n=14) deteriorated from prodromal to symptomatic CoViD-19 requiring intensive care. Here, we interpret these observations of Diao et al from our current understanding of T cell immunophysiology and immunopathology following an immune challenge in the form of sustained viral infection, as is the case in CoViD-19, with emphasis on exhausted T cells (Tex). Recent clinical trials to rescue Tex show promising outcomes. The relevance of these interventions for the prevention and treatment of CoViD-19 is discussed. Taken together, the data of Diao et al could proffer the first glimpse of immunopathology and possible immunotherapy for patients with CoViD-19.

Metascience in Bioinformation.

Metascience refers to the systematic process that uncovers, builds, evaluates, organizes and disseminates scientific advances. It is the principal tool at the disposal of the society to combat the debilitating effects of "false information" on health related data and its constituents.

Future Innovations in Viral Immune Surveillance: A Novel Place for Bioinformation and Artificial Intelligence in the Administration of Health Care.

Novel developments in bioinformation, bioinformatics and biostatistics, including artificial intelligence (AI), play a timely and critical role in translational care. Case in point, the extent to which viral immune surveillance is regulated by immune cells and soluble factors, and by non-immune factors informs the administration of health care. The events by which health is regained following viral infection is an allostatic process, which can be modeled using Hilbert's and Volterra's mathematical biology criteria, and biostatistical methodologies such as linear multiple regression. Health regained following viral infection can be given as Y being the sum-total of the positive factors and events (∏) that inherently push allostasis forward (i.e., the orderly process of immune activation and maturation) and the negative (N) factors and events that, allostatically speaking, interfere with regaining health. Any gaps in knowledge are filled by AI-aided immune tweening. Proof of concept can be tested with the fast-gaining infection using tick-borne Bunyavirus that cause severe fever with thrombocytopenia syndrome (SFTS).

Quantitative Consensus in Systematic Reviews: Current and Future Challenges in Translational Science.

Translational science conceptualizes healthcare as a concerted set of processes that integrate research findings from the bench to the bedside. This model of healthcare is effectiveness-focused, patient-centered, and evidence-based, and yields evidence-based revisions of practice-based guidelines, which emerge from research synthesis protocols in comparative effectiveness research that are disseminated in systematic reviews. Systematic reviews produce qualitative and quantitative consensi of the best available evidence. The quantitative consensus is derived from meta-analysis protocols that are often achieved by probabilistic approach Bayesian statistical models.

Lubricin: A Principal Modulator of the Psychoneuroendocrine - Osteoimmune Interactome - Implications for Novel Treatments of Osteoarthritic Pathologies.

Lubricin is a synovial glycoprotein that contributes to joint lubrication. We propose the hypothesis that lubricin is a key modulator of the psychoneuroendocrine-osteoimmune interactome, with important clinical relevance for osteoarthritic pathologies. We consider a variety of neuroendocrine-immune factors, including inflammatory cytokines and chemokines that may contribute to the modulation of lubricin in rheumatic complications. Based on our preliminary immunocytochemistry and fractal analysis data, and in the context of translational research of modern healthcare, we propose that molecular lubricin gene expression modification by means of the novel CRISPR/Cas system be considered for osteoarthritic therapies.

Clinical Immunology of Cholera - Current Trends and Directions for Future Advancement.

Cholera remains a feared, aggressive, infectious and lethal disease today, despite several decades of intense research, concerted public health modalities designed to prevent, and to control outbreaks, availability of efficacious vaccines aimed at containing its contagious spread, and effective patient-centered medical interventions for reducing morbidity and mortality. Despite these advances, cholera still strikes communities around the world, especially in countries and regions of the globe where medical and nursing care cannot be as effectively proffered to the population at risk as in First World economies. Case in point, the number of suspected cholera cases that currently afflicts Yemen escalates at an "unprecedented rate", according to the World Health Organization. Here, following a brief introduction of the history of the medical knowledge about cholera, we discuss current trends of our understanding of clinical immune surveillance against the bacillus that causes cholera, vibrio Cholera (vCh). We cite the current state of best available evidence about anticholera vaccines, and outline certain directions for future study to characterize the clinical immunology of cholera.

Hypothalamus-Pituitary-Adrenal cell-mediated immunity regulation in the Immune Restoration Inflammatory Syndrome.

Over one third of the patients sero-positive for the human immunodeficiency virus (HIV) with signs of the acquired immune deficiency syndrome (AIDS), and under treatment with anti-retroviral therapy (ART), develop the immune reconstitution inflammatory syndrome (IRIS). It is not clear what variables are that determine whether a patient with HIV/AIDS will develop ART-related IRIS, but the best evidence base thus far indicates that HIV/AIDS patients with low CD4 cell count, and HIV/AIDS patients whose CD4 count recovery shows a sharp slope, suggesting a particularly fast "immune reconstitution", are at greater risk of developing IRIS. Here, we propose the hypothesis that one important variable that can contribute to low CD4 cell count number and function in ART-treated HIV/AIDS patients is altered hypothalamic-pituitary-adrenal (HPA) cell-mediated immune (CMI) regulation. We discuss HPA-CMI deregulation in IRIS as the new frontier in comparative effectiveness research (CRE) for obtaining and utilizing the best evidence base for treatment of patients with HIV/AIDS in specific clinical settings. We propose that our hypothesis about altered HPA-CMI may extend to the pathologies observed in related viral infection, including Zika.

Individual Patient Research (IPR) Outcomes with Alzheimer's Disease: The Psycho-neuro-immune Viewpoint.

Traditional research in the health sciences has involved control and experimental groups of patients, and descriptive and inferential statistical analyses performed on the measurements obtained from the samples in each group. As the novel model of translational healthcare, which integrates translational research and translational effectiveness, becomes increasingly established in modern contemporary medicine, healthcare continues to evolve into a model of care that is evidence-based, effectiveness-focused and patientcentered. Patient-centered care requires the timely and critical development and validation of a new research paradigm, which is referred to as "individual patient research (IPR)", as opposed as the customary group research approach. That is to say, research in geriatric disease conditions, such as Alzheimer's Disease (AD) must be performed from the viewpoint of individual patient research outcomes, and individual patient data analysis. Here, we discuss IPR in patients with AD in the context of the best available research evidence that indicates psychological symptoms, endocrine deregulation, and immune alterations in AD. We propose a clinical adaptive cluster randomized stepped wedge blinded controlled trial, with sequential with sequential roll-out of an evidence-based intervention in a crossover paradigm.