Role of the JP45-Calsequestrin Complex on Calcium Entry in Slow Twitch Skeletal Muscles

We exploited a variety of mouse models to assess the roles of JP45-CASQ1 (CASQ, calsequestrin) and JP45-CASQ2 on calcium entry in slow twitch muscles. In flexor digitorum brevis (FDB) fibers isolated from JP45-CASQ1-CASQ2 triple KO mice, calcium transients induced by tetanic stimulation rely on calcium entry via La3+- and nifedipine-sensitive calcium channels. The comparison of excitation-coupled calcium entry (ECCE) between FDB fibers from WT, JP45KO, CASQ1KO, CASQ2KO, JP45-CASQ1 double KO, JP45-CASQ2 double KO, and JP45-CASQ1-CASQ2 triple KO shows that ECCE enhancement requires ablation of both CASQs and JP45. Calcium entry activated by ablation of both JP45-CASQ1 and JP45-CASQ2 complexes supports tetanic force development in slow twitch soleus muscles. In addition, we show that CASQs interact with JP45 at Ca2+ concentrations similar to those present in the lumen of the sarcoplasmic reticulum at rest, whereas Ca2+ concentrations similar to those present in the SR lumen after depolarization-induced calcium release cause the dissociation of JP45 from CASQs. Our results show that the complex JP45-CASQs is a negative regulator of ECCE and that tetanic force development in slow twitch muscles is supported by the dynamic interaction between JP45 and CASQs

Laparoscopic Hysterosacropexy: Is it a Safe Option for Fertility Spearing?

Objective: In case of uterine prolapse, hyseroxacropexy, a conservative surgical approach, which allows the sparing of body image and sexuality, could be the choice in fertile women. Few information are reported on subsequent pregnancy after surgery. Case report: A 33 years-old women with symptomatic prolapse underwent a laparoscopic hysterosacropexy. Subsequently she expressed her pregnancy desire and she got pregnant. A scheduled caesarean section was performed without complication. The subsequent follow-up was regular: the patient was asymptomatic and presented no sign of prolapse recurrence. Conclusion: In motivate and well counselled patient, informed about the risk of prolapse recurrence, pregnancy could be considered after hysterosacropexy

Management of discordant body stalk anomaly in monochorionic twin pregnancies

A 31-year-old woman, gravida 4 para 1 was referred to our center at 11(+1) weeks of gestation: the ultrasound examination revealed a monochorionic monoamniotic twin pregnancy, and one fetus was affected by body stalk anomaly. Chorionic villus sampling revealed a 46,XX karyotype. Extensive counselling about the prognosis of the affected fetus and possible complications of the pregnancy was provided

Changes of consultation-liaison psychiatry practice in Italian general hospitals: A comparative 20-year multicenter study

Conducted under the auspices of the Italian Society of Consultation Liaison Psychiatry (SIPC) the aim of this study was to describe the characteristics of Consultation Liaison Psychiatry (CLP) activity in Italy (SIPC-2-2018) over the past 20 years by comparing with data from the first Italian nation-wide study (SIPC-1-1998)

Sequential steps and checkpoints in the early exocytic compartment during secretory IgM biogenesis

The biogenesis of secretory IgM occurs stepwise under stringent quality control, formation of μ2L2 preceding polymerization. How is efficiency of IgM secretion coupled to fidelity? We show here that ERp44, a soluble protein involved in thiol-mediated retention, interacts with ERGIC-53. Binding to this hexameric lectin contributes to ERp44 localization in the ER-golgi intermediate compartment. ERp44 and ERGIC-53 increase during B-lymphocyte differentiation, concomitantly with the onset of IgM polymerization. Both preferentially bind μ2L2 and higher order intermediates. Their overexpression or silencing in non-lymphoid cells promotes or decreases secretion of IgM polymers, respectively. In IgM-secreting B-lymphoma cells, μ chains interact first with BiP and later with ERp44 and ERGIC-53. Our findings suggest that ERGIC-53 provides a platform that receives μ2L2 subunits from the BiP-dependent checkpoint, assisting polymerization. In this process, ERp44 couples thiol-dependent assembly and quality control

The Impact of COVID-19 Quarantine on Patients With Dementia and Family Caregivers: A Nation-Wide Survey

Introduction: Previous studies showed that quarantine for pandemic diseases is associated with several psychological and medical effects. The consequences of quarantine for COVID-19 pandemic in patients with dementia are unknown. We investigated the clinical changes in patients with Alzheimer’s disease and other dementias, and evaluated caregivers’ distress during COVID-19 quarantine. Methods: The study involved 87 Italian Dementia Centers. Patients with Alzheimer’s Disease (AD), Dementia with Lewy Bodies (DLB), Frontotemporal Dementia (FTD), and Vascular Dementia (VD) were eligible for the study. Family caregivers of patients with dementia were interviewed by phone in April 2020, 45 days after quarantine declaration. Main outcomes were patients’ changes in cognitive, behavioral, and motor symptoms. Secondary outcomes were effects on caregivers’ psychological features. Results: 4913 patients (2934 females, 1979 males) fulfilled the inclusion criteria. Caregivers reported a worsening in cognitive functions in 55.1% of patients, mainly in subjects with DLB and AD. Aggravation of behavioral symptoms was observed in 51.9% of patients. In logistic regression analysis, previous physical independence was associated with both cognitive and behavioral worsening (odds ratio 1.85 [95% CI 1.42–2.39], 1.84 [95% CI 1.43–2.38], respectively). On the contrary, pandemic awareness was a protective factor for the worsening of cognitive and behavioral symptoms (odds ratio 0.74 [95% CI 0.65–0.85]; and 0.72 [95% CI 0.63–0.82], respectively). Approximately 25.9% of patients showed the onset of new behavioral symptoms. A worsening in motor function was reported by 36.7% of patients. Finally, caregivers reported a high increase in anxiety, depression, and distress. Conclusion: Our study shows that quarantine for COVID-19 is associated with an acute worsening of clinical symptoms in patients with dementia as well as increase of caregivers’ burden. Our findings emphasize the importance to implement new strategies to mitigate the effects of quarantine in patients with dementia