Induction of ovulation in rabbits by pure urinary Iuteinizing hormone

In 18-week-old nulliparous rabbit dose, ovulation was inducedwith 50 IU of pure urinary luteinizing hormone (LH; LHgroup),or 50 IU of ohuman chorionic gonadotrophin (HCG; HCG group),in order to detemine the effect of these treatments on 17-oestradioland progesterone concentrations, and on oocyte and embryo quality.Luteinizing follicles, recovered oocytes, progesteronoe concentrationand grade 5 embryos were significantly reduced when pure urinaryLH was used. Statistically significant correlations were found:(i) between oestradiol concentration and number of degeneratedoocytes in both groups (positive); (ii) between oestradiol concentrationand grade 1 and 2 embrayos (negative), and grade 5 embryos (positive)in the HCG group; (iii) between progesteronoe concentrationand metaphase II oocytes(negatice), and between progesteroneand grade 5 sembryos (positive), in the HCG group; and (iv)between progesterone and oestradiol concentrations (negative)in the LH group. It seems that the oestrsdiol to progegsteroneratio improves during the early luteal phase when ovulationis induced with LH, and that oestradiol and progesterone concentrationscould play a role in dtermining oocyte and embryo quality     

Social Distancing in Chronic Migraine during the COVID-19 Outbreak: Results from a Multicenter Observational Study

Background: The restrictions taken to control the rapid spread of COVID-19 resulted in a sudden, unprecedented change in people’s lifestyle, leading to negative consequences on general health. This study aimed to estimate the impact of such changes on migraine severity during 2020 March–May lockdown. Methods: Patients affected by migraine with or without aura, diagnosed by expert physicians, completed a detailed interview comprehensive of: assessment of migraine characteristics; measure of physical activity (PA) levels; measure of the intake frequency of main Italian foods; the Insomnia Severity Index (ISI) questionnaire investigating sleep disorders. Results: We included 261 patients with a mean age of 44.5 ± 12.3 years. During social distancing, 72 patients (28%) reported a headache worsening, 86 (33%) an improvement, and 103 (39%) a stable headache frequency. A significant decrease of the PA levels during COVID-19 quarantine in the whole study sample was observed (median total metabolic equivalent task (METs) decreased from 1170 to 510; p < 0.001). Additionally, a significant difference was reported on median ISI scores (from 7 to 8; p < 0.001), which were increased in patients who presented a stable or worsening headache. Conclusions: Our study confirmed that the restrictions taken during the pandemic have affected the practice of PA levels and sleep quality in migraine. Hence, PA and sleep quality should be assessed to find strategies for an improvement in quality of life.     

The role of external ventricular drainage for the management of posterior cranial fossa tumours: a systematic review

Neurosurgical Review - Posterior cranial fossa tumours frequently develop hydrocephalus as first presentation in up to 80% of paediatric patients and 21.4% of adults, although it resolves after...     

Human liver stem cell-derived extracellular vesicles reduce injury in a model of normothermic machine perfusion of rat livers previously exposed to a prolonged warm ischemia

Livers from donors after circulatory death (DCD) are a promising option to increase the donor pool, but their use is associated with higher complication rate and inferior graft survival. Normothermic machine perfusion (NMP) keeps the graft at 37°C, providing nutrients and oxygen supply. Human liver stem cell-derived extracellular vesicles (HLSC-EVs) are able to reduce liver injury and promote regeneration. We investigated the efficacy of a reconditioning strategy with HLSC-EVs in an experimental model of NMP. Following total hepatectomy, rat livers were divided into 4 groups: (i) healthy livers, (ii) warm ischemic livers (60 min of warm ischemia), (iii) warm ischemic livers treated with 5 × 10⁸ HLSC-EVs/g-liver, and (iv) warm ischemic livers treated with a 25 × 10⁸ HLSC-EVs/g-liver. NMP lasted 6 h and HLSC-EVs (Unicyte AG, Germany) were administered within the first 15 min. Compared to controls, HLSC-EV treatment significantly reduced transaminases release. Moreover, HLSC-EVs enhanced liver metabolism by promoting phosphate utilization and pH self-regulation. As compared to controls, the higher dose of HLSC-EV was associated with significantly higher bile production and lower intrahepatic resistance. Histologically, this group showed reduced necrosis and enhanced proliferation. In conclusion, HLSC-EV treatment during NMP was feasible and effective in reducing injury in a DCD model with prolonged warm ischemia.     

Baseline Assessment of Circulating MicroRNAs Near Diagnosis of Type 1 Diabetes Predicts Future Stimulated Insulin Secretion

Type 1 diabetes is an autoimmune disease resulting in severely impaired insulin secretion. We investigated whether circulating microRNAs (miRNAs) are associated with residual insulin secretion at diagnosis and predict the severity of its future decline. We studied 53 newly diagnosed subjects enrolled in placebo groups of TrialNet clinical trials. We measured serum levels of 2,083 miRNAs, using RNA sequencing technology, in fasting samples from the baseline visit (<100 days from diagnosis), during which residual insulin secretion was measured with a mixed meal tolerance test (MMTT). Area under the curve (AUC) C-peptide and peak C-peptide were stratified by quartiles of expression of 31 miRNAs. After adjustment for baseline C-peptide, age, BMI, and sex, baseline levels of miR-3187-3p, miR-4302, and the miRNA combination of miR-3187-3p/miR-103a-3p predicted differences in MMTT C-peptide AUC/peak levels at the 12-month visit; the combination miR-3187-3p/miR-4723-5p predicted proportions of subjects above/below the 200 pmol/L clinical trial eligibility threshold at the 12-month visit. Thus, miRNA assessment at baseline identifies associations with C-peptide and stratifies subjects for future severity of C-peptide loss after 1 year. We suggest that miRNAs may be useful in predicting future C-peptide decline for improved subject stratification in clinical trials.     

Range of motion of foot joints following total ankle replacement and subtalar fusion

BackgroundIn severe cases of ankle and subtalar arthritis, arthrodesis of the subtalar joint is performed in combination with ankle arthroplasty. In these special cases gait analysis reveals real motion at the replaced tibiotalar joint.MethodsTwenty-three patients affected by ankle and subtalar arthritis, treated either with a 3-component or a 2-component prosthesis in combination with subtalar arthrodesis, were clinically evaluated preoperatively and at a minimum of 1-year follow-up. Gait analysis was performed postoperatively using a multi-segment foot protocol. Foot kinematics were compared to corresponding data from a healthy control group.ResultsClinical scores significantly improved from preoperative to follow-up. The clinically measured passive ankle dorsiflexion/plantarflexion significantly improved at the follow-up. Patients’ normalized walking speed and stride length were significantly lower than those in control. With exception of the ankle frontal-plane motion, sagittal-plane mobility of foot joints was about 50% than that in healthy joints.ConclusionsImprovement in clinical scores was found for both prostheses. Normal spatio-temporal parameters were not restored. In these patients, fusion of the subtalar joint appeared to be compensated by larger frontal-plane motion at the tibiotalar joint.Level of evidenceLevel III- retrospective comparative study.The study was approved by the local Ethics Committee as protocol MAT (protocol registration at clinicaltrials.gov NCT03356951).     

Adeno-associated viral vectors for retinal gene transfer and treatment of retinal diseases

Retinal gene transfer holds big promises for the treatment of inherited and non-inherited blinding diseases, such as retinitis pigmentosa or age-related macular degeneration. Key to the development of successful gene-based therapies for the eye are efficient tools for retinal gene transfer. Vectors based on adeno-associated viruses (AAV) are able to transduce robustly and persistently different retinal cell types of animal models after a single intraocular administration. Recombinant AAV (rAAV) vectors are versatile gene transfer tools in that capsid proteins from dozens of AAV serotypes can be easily interchanged, resulting in the creation of recombinant vectors with unique transduction properties. This has allowed successful proof-of-principle studies using rAAV-mediated gene transfer to restore retinal morphology and function in small and large animal models of retinal diseases. In addition, gene delivery using rAAV vectors in the eye seems to have appropriate biosafety characteristics to rapidly move it from bench to bedside. All the above aspects will be reviewed and discussed in detail below.     

Effects of 6-hydroxydopamine on pre- and post-junctional 5-HT1-like receptor-mediated responses in dog saphenous vein

Summary To investigate whether 5-HT₁-like receptor-mediated inhibition of adenosine 3 : 5-cyclic monophosphate (cyclic AMP) accumulation occurs in nerves or smooth muscle of saphenous vein, infusions of 6-hydroxydopamine (6-OHDA) were administered to dogs with the aim of inducing sympathetic nerve damage. The effects of 6-OHDA on other 5-HT₁-like receptor-mediated responses at the pre- and post-junctional level were investigated for comparison by studying 5-hydroxytryptamine (5-HT)-induced inhibition of ³H-noradrenaline release and contraction of smooth muscle respectively.Disruption of nerve function by 6-OHDA was revealed by the lack of catecholaminergic fluorescence and neurogenic contractile responses in saphenous veins from dogs treated with 6-OHDA. In addition, severe impairment of neuronal uptake mechanisms were apparent since basal efflux of ³H-noradrenaline, electrically-evoked release of ³H-noradrenaline and remaining ³H-noradrenaline content were considerably reduced. Some ³H-noradrenaline was taken up and released in 6-OHDA treated tissues which is consistent with the existence of nerve varicosities resistant to the present dosing regime of 6-OHDA, an observation substantiated by electron microscopy studies showing inconsistent lesions of nerve terminals.6-OHDA pre-treatment potentiated the smooth muscle contractile responses mediated by 5-HT₁-like receptors as well as potentiating 5-HT-evoked inhibition of prostaglandin E₂-stimulated cyclic AMP accumulation. It did not, however, affect 5-HT-induced inhibition of ³H-noradrenaline release. The present results suggest that inhibition of cyclic AMP accumulation by 5-HT occurs predominantly in smooth muscle. Correspondence to A. J. Kaumann at the above address