Mutations in proteins involved in E-C coupling and SOCE and congenital myopathies

In skeletal muscle, Ca2+ necessary for muscle contraction is stored and released from the sarcoplasmic reticulum (SR), a specialized form of endoplasmic reticulum through the mechanism known as excitation-contraction (E-C) coupling. Following activation of skeletal muscle contraction by the E-C coupling mechanism, replenishment of intracellular stores requires reuptake of cytosolic Ca2+ into the SR by the activity of SR Ca2+-ATPases, but also Ca2+ entry from the extracellular space, through a mechanism called store-operated calcium entry (SOCE). The fine orchestration of these processes requires several proteins, including Ca2+ channels, Ca2+ sensors, and Ca2+ buffers, as well as the active involvement of mitochondria. Mutations in genes coding for proteins participating in E-C coupling and SOCE are causative of several myopathies characterized by a wide spectrum of clinical phenotypes, a variety of histological features, and alterations in intracellular Ca2+ balance. This review summarizes current knowledge on these myopathies and discusses available knowledge on the pathogenic mechanisms of disease

Evaluation of trueness and precision of removable partial denture metal frameworks manufactured with digital technology and different materials

PURPOSE. The aim of this study is to evaluate the accuracy of removable partial denture (RPD) frameworks produced using different digital protocols. MATERIALS AND METHODS. 80 frameworks for RPDs were produced using CAD-CAM technology and divided into four groups of twenty (n = 20): Group 1, Titanium frameworks manufactured by digital metal laser sintering (DMLS); Group 2, Co-Cr frameworks manufactured by DMLS; Group 3, Polyamide PA12 castable resin manufactured by multi-jet fusion (MJF); and Group 4, Metal (Co-Cr) casting by using lost-wax technique. After the digital acquisition, eight specific areas were selected in order to measure the Δ-error value at the intaglio surface of RPD. The minimum value required for point sampling density (0.4 mm) was derived from the sensitivity analysis. The obtained Δ-error mean value was used for comparisons: 1. between different manufacturing processes; 2. between different manufacturing techniques in the same area of interest (AOI); and 3. between different AOI of the same group. RESULTS. The Δ-error mean value of each group ranged between -0.002 (Ti) and 0.041 (Co-Cr) mm. The Pearson’s Chi-squared test revealed significant differences considering all groups paired two by two, except for group 3 and 4. The multiple comparison test documented a significant difference for each AOI among group 1, 3, and 4. The multiple comparison test showed significant differences among almost all different AOIs of each group. CONCLUSION. All Δ-mean error values of all digital protocols for manufacturing RPD frameworks optimally fit within the clinical tolerance limit of trueness and precision

Pregnancy, fertile life factors, and associated clinical course in PRKN early-onset Parkinson’s disease

introduction: as the most common cause of autosomal recessive early onset parkinson’s disease (EOPD), parkin type parkinson’s disease (PRKN-PD) may affect female patients in childbearing age. accordingly, issues related to fertility must be adequately addressed. here, we landscaped fertile life factors and pregnancy course of a PRKN-PD cohort, including both novel cases directly observed at our center and published ones. methods: six patients with confirmed PRKN-PD were examined by a structured interview on reproductive factors and associated modifications of PD disturbances, including one case followed up throughout pregnancy which was described in greater detail. six studies reporting fertile life factors of nine PRKN-PD patients were reviewed collecting homogeneous data on fertile life and pregnancy course. results: PRKN-PD female patients experienced motor fluctuations with the menstrual cycle, pregnancy, and puerperium, which suggests a role for sex hormones in PD clinical burden. In some cases, abortion and miscarriages occurred during the organogenesis phase in patients receiving oral antiparkinsonian therapy; however, levodopa/benserazide monotherapy resulted to be the safest choice in pregnancy. conclusion: collectively these data disclose the importance of pre-conception counseling in childbearing age PRKN-PD patients and EOPD in general

Medication use in Italian nursing homes: preliminary results from the national monitoring system

Background: The aging population has increased concerns about the affordability, quality, and nature of long-term care for older people, emphasizing the role of nursing homes. Unlike acute hospital and primary care, there is a lack of drug consumption data in long-term care to understand regional or national healthcare policies. Objectives: This study aimed to describe medication consumption by older adults and expenditure in Italian nursing homes (NHs). Methods: Data on drug consumption and costs from the administrative medicine informational flows that detect medicines packages supplied to patients in health facilities and NHs were used. Data on the characteristics of the healthcare residence were from the Italian Health Ministry. Records for the year 2019, selecting the nursing homes exclusively providing elderly or mixed (elderly and disabled) were used. Results: In 2019, the total expenditure on medicines in NHs amounted to 25.38 million euros, the average cost to 1.30 and the expenditure per bed to 436.18 euros. Cardiovascular drugs were the highest-consuming therapeutic class (177.0 defined daily doses—DDDs/100 days of NH stay; 22.2% of total) followed by drugs acting on the alimentary tract and metabolism (167.6% and 21.0%) and blood drugs (160.4% and 20.1%). The treatment of hypertension and heart failure was widely the most frequently used, with the consumption being driven mainly by furosemide and ramipril. Antiulcer drugs were used on average in more than half of the days of NH stay (58.5 DDDs/100 days of NH stay), representing a therapeutic category for which deprescribing initiatives are recommended. On average, almost all patients received a dose of benzodiazepines, antipsychotics and antidepressants (37.6, 35.9, and 17.7 DDDs/100 days of NH stay, respectively), confirming the high prevalence of use for these medicines. Antibiotics reached 6.8 DDDs/100 days of NH stay. Conclusion: The availability of data in this specific setting allows the identification of the main interventions toward improving appropriateness and represents a challenge for drug utilization research. Data from this study suggest that proton pump inhibitors (PPIs), benzodiazepines and antibacterials can be areas of improving prescribing appropriateness

Homovanillic acid in CSF of mild stage Parkinson's disease patients correlates with motor impairment.

In Parkinson's disease (PD), several efforts have been spent in order to find biochemical parameters able to identify the progression of the pathological processes at the basis of the disease. It is already known that advanced PD patients manifesting dyskinesia are featured by the high homovanillic acid (HVA)/dopamine (DA) ratio, suggesting the increased turnover of DA in these patients. Less clear is whether similar changes affect mild and moderate stages of the disease (between 1 and 2.5 of Hoehn & Yahr -H&Y- stage). Hence, here we tested whether cerebrospinal fluid (CSF) concentrations of DA and its major metabolites, either 3,4-dihydroxyphenylacetic acid (DOPAC) or HVA, correlate with motor performance in mild and moderate PD patients. CSF samples were collected after 2 days of anti-PD drugs washout, via lumbar puncture (LP) performed 130 min following administration of oral levodopa (LD) dose (200 mg). LP timing was determined in light of our previous tests clarifying that 2 h after oral LD administration CSF DA concentration reaches a plateau, which was un-respective of PD stage or duration. DA, DOPAC and HVA were assayed by high performance liquid chromatography in a group of 19 patients, distributed in two groups on the basis of the H&Y stage with a cut-off of 1.5. In these PD patients, HVA was correlated with DOPAC (R = 0,56, p < 0,01) and both HVA and DOPAC CSF levels increased in parallel with the motor impairment. More importantly, HVA correlated with motor impairment measured by the Unified Parkinson's Disease Score -III (UPDRS) (R = 0.61; p < 0.0001). The present findings showed the early alteration of the DA pre-synaptic machinery, as documented by the progressive increase of CSF HVA concentrations, which also correlated with PD motor impairment. Therefore, we suggest the potential use of measuring the CSF HVA level as a possible biomarker of PD stage changes in order to monitor the effectiveness of PD-modifying pharmacological therapies

Medication Use and Costs Among Older Adults Aged 90 Years and Older in Italy

Older adults are often affected by multiple chronic conditions and experience geriatric syndromes that may affect the risk/benefit profile of medications. Little is known about the use of such medications in the older population. This article describes medication use and costs in Italian adults aged ≥90&nbsp;years. Data from the 2019 Pharmaceutical Prescriptions database, concerning data on medications reimbursed by the Italian National Health Service, were analyzed in terms of prevalence and amount of use expressed as defined daily dose/1,000 users (DDD/1,000 users/day), accounting for different age-groups and sex. All individuals aged ≥90&nbsp;years used at least one medication, with a mean number of 3128 DDD/1,000 users/day corresponding to an annual cost of 683 euros per user. Both use and costs linearly decreased with increasing age, with men accounting for a higher amount of DDD/1,000 users and costs than women across all age-groups. Antihypertensives (1330 DDD/1,000 inhabitants), antiplatelet agents (337 DDD/1,000 inhabitants), medications for peptic ulcer and gastroesophageal reflux (328 DDD/1,000 inhabitants), and lipid-lowering agents (166 DDD/1,000 inhabitants) were the most frequently used medications. We observed a progressive decrease in the usage of the majority of medications with increasing age, with the exception of antibiotics and antipsychotics. Individuals aged ≥90&nbsp;years used a lower DDD/1,000 users, with an associated decrease in annual costs. The persistent use of preventive medications highlights the potential lack of awareness regarding medication rationalization and guidance for optimizing prescriptions. Our findings highlight the need for further initiatives to improve medications’ appropriateness in these older age-groups

Involvement of subcortical brain structures during olfactory stimulation in multiple chemical sensitivity

Multiple chemical sensitivity (MCS) patients usually react to odour compounds and the majority of neuroimaging studies assessed, especially at the cortical level, many olfactory-related correlates. The purpose of the present study was to depict sub-cortical metabolic changes during a neutral (NC) and pure (OC) olfactory stimulation by using a recently validated 18F-2-fluoro-2-deoxy-D-glucose (FDG)-positron emission tomography/computer tomography procedure in 26 MCS and 11 healthy (HC) resting subjects undergoing a battery of clinical tests. Twelve subcortical volumes of interest were identified by the automated anatomical labeling library and normalized to thalamus FDG uptake. In both groups, when comparing OC to NC, the within-subjects ANOVA demonstrated a relative decreased metabolism in bilateral putamen and hippocampus and a relative increased metabolism in bilateral amygdala, olfactory cortex (OLF), caudate and pallidum. The between-groups ANOVA demonstrated in MCS a significant higher metabolism in bilateral OLF during NC. As in HC subjects negative correlations were found in OC between FDG uptake in bilateral amygdala and hippocampus and odor pleasantness scale, the latter positively correlated with MCS subjects\u27 bilateral putamen FDG uptake in OC. Besides FDG uptake resemblances in both groups were found, for the first time a relative higher metabolism increase in OLF in MCS subjects at rest with respect to HC was found. When merging this aspect to the different subcortical FDG uptake correlations patterns in the two groups, the present study demonstrated to describe a peculiar metabolic index of behavioral and neurological aspects of MCS complaints