Electronic witness system in IVF—patients perspective

Objective The objective of this study is to evaluate patient concerns about in vitro fertilization (IVF) errors and electronic witness systems (EWS) satisfaction. Design The design of this study is a prospective single-center cohort study. Setting The setting of this study was located in the private IVF center. Patient(s) Four hundred eight infertile patients attending an IVF cycle at a GENERA center in Italy were equipped with an EWS. Intervention(s) Although generally recognized as a very rare event in IVF, biological sample mix-up has been reported in the literature. For this reason, some IVF laboratories have introduced EWS with the aim to further reduce the risk of error during biological samples handling. Participating patients received a questionnaire developed through a Likert scale ranging from 1 to 6. Main outcomes measure(s) Patient concerns about sample mix-up without and with an EWS were assessed. Result(s) 90.4 % of patients expressed significant concerns relating to sample mix-up. The EWS reduced these concerns in 92.1 % of patients, 97.1 % of which were particularly satisfied with the electronic traceability of their gametes and embryos in the IVF laboratory. 97.1 % of patients felt highly comfortable with an IVF center equipped with an EWS. Female patients had a significantly higher appreciation of the EWS when compared to their male partners (p = 0.029). A significant mix-up event occurred in an Italian hospital during the study and patient's satisfaction increased significantly towards the use of the EWS after the event (p = 0.032). Conclusion(s) EWS, by sensibly reducing the risk for sample mix-up in IVF cycles, has been proved to be a trusted strategy from patient's perspective

Blood baseline values in female alpine and nera di verzasca goats reared in italy.

The Italian goat autochthonous breeds are appreciated for their milk and characteristics, especially for the rusticity, frugality, fertility and longevity. For these reasons the local goat breeds play an important role in the livestock sector, and it is important to guarantee sanitary strategies control, prevention or treatment of diseases. It is well known that the hematological parameters in goats undergo changes in relation with many factors like breed, age (Piccione et al. 2014), physiological/reproductive status environmental factors and stress (Waziri M.A. et al. 2010).  Based on these differences it is necessary to establish appropriate physiological baseline values for every single breed which could be used in the realistic evaluation physiological or pathological status of the animal (Arfuso et al. 2016). The aim of this work was to evaluate the differences between a local goat breed (Verzasca) and a cosmopolite one (Alpine) from the hematological point of view, and to establish hematological reference values. A total number of 71 female goats, of Alpine (n=37), and Verzasca (n=34) were enrolled for this study, for a total of 716 blood samples. Data were processed by a mixed model-repeated measures ANCOVA in order to evaluate the effects of breed, parity, and season, while baseline values for each breed have been calculated by evaluating the 2.5-97.5th  percentile of variables distribution.The results showed that the breeds differ in a significant manner (Table 1). Verzasca goat shows significantly higher values in the erythroid parameters, whereas the Alpine goat shows higher mean values of leucocyte count and absolute neutrophil count. A further interesting result is the neutrophil lymphocyte ratio which is 0.96  in the Alpine and 0,57 in the Verzasca.The results here presented can add some knowledge to the definition of the health status of the two breeds, evidencing some environmental and physiological variation mechanisms.

Endoscopic endonasal approach for loco-regional recurrent clivus chordomas

Introduction. Role of surgery for loco-regional recurrences of clivus chordomas (CCs) is still debated. It has been proposed in selected cases with a curative or with palliative intent, eventually followed by radiation or chemo/radiation treatments. Only limited data on the endoscopic endonasal approach (EEA) are available. Research question. To assess the role of EEA for loco-regional recurrent CCs. Materials and Methods. All consecutive loco-regional recurrent CCs operated by EEA at our Institution from 1998 to 2021 were identified. The extension of tumor resection, symptoms control, overall survival (OS), and progression free survival (PFS) were assessed. Results. Series includes 54 patients (53.7% females, mean age 55± 14 years). Surgery was planned with a resective aim in 35 (64.8%) patients, while it was palliative in 19 (35.2%). Gross tumor removal was achieved in 24 cases (44.4%). Main complications consisted of 2 (3.7%) CSF leaks. Further local relapses were observed in 30 (55.5%) patients after 25± 24 months; 29 (53.7%) patients deceased after 34 ± 31 months. OS and PFS were lower in these cases than primary surgeries (p<0.001 and p<0.001), but cases undergone surgery with a resective aim had a significant better OS and PFS than for those treated for palliation (p<0.001). Determinants of recurrences were tumoral size (p=0.48) and previous radiotherapy (p=009). Discussion and Conclusions. EEA has proven to be effective for loco-regional recurrent CCs alleviating patients symptoms and preserving their quality of life with limited morbidities. However, because overall prognosis is poor, EEA should be reserved to selected recurrent cases

Role of endoscopic endonasal approach for craniopharyngiomas extending into the third ventricle in adults

Introduction. Recent advancements in endoscopic endonasal approach (EEA) have favored its adoption for craniopharyngiomas extended to 3rd ventricle (3VCPs). However, for lack of extensive series, its outcome, limits, and indications remain debated. Research question. To assess the EEA results of for 3VCPs and identify those factors determining the choice of this approach. Material and Methods. Records of patients with 3VCPs, consecutively operated through an EEA at our Institution were retrospectively analyzed. Demographic and clinico-radiological data, rate of tumor resection, complications and outcome at follow-up were collected. Results. Thirty-six patients (19 females, mean age: 51.1 ± 15.9 yrs) were included. Extended transplanum-transtuberculum approach was performed in all cases Radical resection was achieved in 33 patients (91.7%). At follow-up, visual deficits improved/normalized in 21 cases (58.3%), and 35 (97.2%) presented with panhypopituitarism and DI. Anatomical (displacement of the chiasm and hypothalamus), clinical (age and pre-operative visual and endocrinological function) and tumoral (consistency, presence of hydrocephalus) parameters resulted relevant in determining the choice of this approach. Discussion and Conclusion. EEA offers a valid and direct route for 3VCPs, which permits to safely manage these tumors. In our series, EEA was chosen for tubero-infundibular forms with chiasm displaces antero-superiorly, and preferred in younger patients, with visual disturbances, comprimesed endocrinological function and no hydrocephalus. It requires a specific training and should be reserved in dedicated centers. Because no single approach is ideal for every 3VCP, all surgical options should be considered as complementary and selected basing on clinical, anatomical and tumoral features of each case

Machine learning-based clinical outcome prediction in surgery for acromegaly

Purpose Biochemical remission (BR), gross total resection (GTR), and intraoperative cerebrospinal fluid (CSF) leaks are important metrics in transsphenoidal surgery for acromegaly, and prediction of their likelihood using machine learning would be clinically advantageous. We aim to develop and externally validate clinical prediction models for outcomes after transsphenoidal surgery for acromegaly. Methods Using data from two registries, we develop and externally validate machine learning models for GTR, BR, and CSF leaks after endoscopic transsphenoidal surgery in acromegalic patients. For the model development a registry from Bologna, Italy was used. External validation was then performed using data from Zurich, Switzerland. Gender, age, prior surgery, as well as Hardy and Knosp classification were used as input features. Discrimination and calibration metrics were assessed. Results The derivation cohort consisted of 307 patients (43.3% male; mean [SD] age, 47.2 [12.7] years). GTR was achieved in 226 (73.6%) and BR in 245 (79.8%) patients. In the external validation cohort with 46 patients, 31 (75.6%) achieved GTR and 31 (77.5%) achieved BR. Area under the curve (AUC) at external validation was 0.75 (95% confidence interval: 0.59–0.88) for GTR, 0.63 (0.40–0.82) for BR, as well as 0.77 (0.62–0.91) for intraoperative CSF leaks. While prior surgery was the most important variable for prediction of GTR, age, and Hardy grading contributed most to the predictions of BR and CSF leaks, respectively. Conclusions Gross total resection, biochemical remission, and CSF leaks remain hard to predict, but machine learning offers potential in helping to tailor surgical therapy. We demonstrate the feasibility of developing and externally validating clinical prediction models for these outcomes after surgery for acromegaly and lay the groundwork for development of a multicenter model with more robust generalization

Alpha-synuclein/synapsin III pathological interplay boosts the motor response to methylphenidate

: Loss of dopaminergic nigrostriatal neurons and fibrillary α-synuclein (α-syn) aggregation in Lewy bodies (LB) characterize Parkinson's disease (PD). We recently found that Synapsin III (Syn III), a phosphoprotein regulating dopamine (DA) release with α-syn, is another key component of LB fibrils in the brain of PD patients and acts as a crucial mediator of α-syn aggregation and toxicity. Methylphenidate (MPH), a monoamine reuptake inhibitor (MRI) efficiently counteracting freezing of gait in advanced PD patients, can bind α-syn and controls α-syn-mediated DA overflow and presynaptic compartmentalization. Interestingly, MPH results also efficient for the treatment of attention deficits and hyperactivity disorder (ADHD), a neurodevelopmental psychiatric syndrome associated with Syn III and α-syn polymorphisms and constituting a risk factor for the development of LB disorders. Here, we studied α-syn/Syn III co-deposition and longitudinal changes of α-syn, Syn III and DA transporter (DAT) striatal levels in nigrostriatal neurons of a PD model, the human C-terminally truncated (1-120) α-syn transgenic (SYN120 tg) mouse, in comparison with C57BL/6J wild type (wt) and C57BL/6JOlaHsd α-syn null littermates. Then, we analyzed the locomotor response of these animals to an acute administration of MPH (d-threo) and other MRIs: cocaine, that we previously found to stimulate Syn III-reliant DA release in the absence of α-syn, or the selective DAT blocker GBR-12935, along aging. Finally, we assessed whether these drugs modulate α-syn/Syn III interaction by fluorescence resonance energy transfer (FRET) and performed in silico studies engendering a heuristic model of the α-syn conformations stabilized upon MPH binding. We found that only MPH was able to over-stimulate a Syn III-dependent/DAT-independent locomotor activity in the aged SYN120 tg mice showing α-syn/Syn III co-aggregates. MPH enhanced full length (fl) α-syn/Syn III and even more (1-120) α-syn/Syn III interaction in cells exhibiting α-syn/Syn III inclusions. Moreover, in silico studies confirmed that MPH may reduce α-syn fibrillation by stabilizing a protein conformation with increased lipid binding predisposition. Our observations indicate that the motor-stimulating effect of MPH can be positively fostered in the presence of α-syn/Syn III co-aggregation. This evidence holds significant implications for PD and ADHD therapeutic management

DOPAL initiates αSynuclein-dependent impaired proteostasis and degeneration of neuronal projections in Parkinson’s disease

Dopamine dyshomeostasis has been acknowledged among the determinants of nigrostriatal neuron degeneration in Parkinson’s disease (PD). Several studies in experimental models and postmortem PD patients underlined increasing levels of the dopamine metabolite 3,4-dihydroxyphenylacetaldehyde (DOPAL), which is highly reactive towards proteins. DOPAL has been shown to covalently modify the presynaptic protein αSynuclein (αSyn), whose misfolding and aggregation represent a major trait of PD pathology, triggering αSyn oligomerization in dopaminergic neurons. Here, we demonstrated that DOPAL elicits αSyn accumulation and hampers αSyn clearance in primary neurons. DOPAL-induced αSyn buildup lessens neuronal resilience, compromises synaptic integrity, and overwhelms protein quality control pathways in neurites. The progressive decline of neuronal homeostasis further leads to dopaminergic neuron loss and motor impairment, as showed in in vivo models. Finally, we developed a specific antibody which detected increased DOPAL-modified αSyn in human striatal tissues from idiopathic PD patients, corroborating the translational relevance of αSyn-DOPAL interplay in PD neurodegeneration

Myasthenia gravis imitating pituitary apoplexy in macroprolactinoma

Myasthenia gravis (MG) is an autoimmune disease affecting neuromuscular transmission that manifests with muscle weakness and typically involves the eye muscles, often producing diplopia and ptosis. Recent studies suggest that hyperprolactinaemia may have a role in the development of MG, although its association with prolactinoma is extremely rare. We report the unusual case of a 71-year-old male affected with macroprolactinoma, who presented at our Center 2\ua0weeks after starting cabergoline treatment because of acute onset of headache, diplopia, and ptosis. On admission, he presented with drowsiness, dropped head, swallowing impairment and bilateral ptosis, which rapidly worsened. Based on clinical manifestation and history, emergency surgery was performed on suspicion of pituitary apoplexy (PA), the typical complication occurring in patients with macroadenomas who present these symptoms. No pituitary haemorrhage was found. The symptoms initially resolved after surgery, but soon returned and worsened day by day, especially in the evening, despite the increase of cortisone replacement doses. MG was thus suspected and confirmed by the detection of antibodies to the acetylcholine receptor. Pyridostigmine was started with prompt improvement of neurological symptoms. In conclusion, although very rare, MG should be considered in the differential diagnosis of patients with macroprolactinomas and suggestive neurological symptoms in order to provide early and appropriate treatment. The role of hyperprolactinaemia in MG onset and evolution is also discussed

Mitochondria and alpha-synuclein: Friends or foes in the pathogenesis of Parkinson's disease?

Parkinson’s disease (PD) is a movement disorder characterized by dopaminergic nigrostriatal neuron degeneration and the formation of Lewy bodies (LB), pathological inclusions containing fibrils that are mainly composed of α-synuclein. Dopaminergic neurons, for their intrinsic characteristics, have a high energy demand that relies on the efficiency of the mitochondria respiratory chain. Dysregulations of mitochondria, deriving from alterations of complex I protein or oxidative DNA damage, change the trafficking, size and morphology of these organelles. Of note, these mitochondrial bioenergetics defects have been related to PD. A series of experimental evidence supports that α-synuclein physiological action is relevant for mitochondrial homeostasis, while its pathological aggregation can negatively impinge on mitochondrial function. It thus appears that imbalances in the equilibrium between the reciprocal modulatory action of mitochondria and α-synuclein can contribute to PD onset by inducing neuronal impairment. This review will try to highlight the role of physiological and pathological α-synuclein in the modulation of mitochondrial functions