Nutritional Status and Potentially Inappropriate Medications in Elderly: Real-World Experience

(1) Background: The association between polypharmacy and malnutrition has been investigated in several studies; however, few of these specifically deepened the relationship between potentially inappropriate medication and malnutrition. With a descriptive approach, the primary aim of our study was to evaluate the impact of the nutritional status, assessed with the Mini Nutritional Assessment (MNA), on potentially inappropriate medications (PIM), estimated 10-year survival, and the risk of adverse drug reactions in elderly patients; the secondary aim was to evaluate how the Screening Tool of Older People’s Prescriptions (STOPP), Screening Tool to Alert to Right Treatment (START), and BEERS 2019 criteria identify PIM compared to nutritional status. (2) Methods: In this study, 3091 subjects were enrolled, of whom 2748 (71.7%) were women; the median age was 80 years, with an interquartile range between 75 and 85 years of age. The subjects were assessed at the outpatient service for frail older people of the University Hospital of Cagliari. The study population was evaluated for their: MNA, Charlson Comorbidity Index, 10-year survival estimation, BEERS 2019, STOPP and START criteria, and ADR Risk scores. (3) Results: We divided the study population into three groups: MNA1 (MNA score ≥ 24), MNA2 (23.5–17), and MNA3 (<17): the severity of comorbidities, STOPP and START alerts, and BEERS 2019 criteria were significantly worse in both MNA2 and MNA3 compared to MNA1—with the exception of BEERS “non-anti-infective medications that should be avoided or have their dosage reduced with varying levels of kidney function in older adults”. Moreover, the estimated 10-year survival was significantly higher in MNA1 than in MNA2 and MNA3, and also in MNA2 compared to MNA3. Finally, the ADR risk scores were significantly lower in MNA1 than in MNA2 and MNA3. (4) Conclusions: Our study demonstrated the association between nutritional status and PIM checked with the BEERS 2019 criteria, and, for the first time, with the STOPP and START criteria

AIRE polymorphism, melanoma antigen-specific T cell immunity, and susceptibility to melanoma

AIRE is involved in susceptibility to melanoma perhaps regulating T cell immunity against melanoma antigens (MA). To address this issue, AIRE and MAGEB2 expressions were measured by real time PCR in medullary thymic epithelial cells (mTECs) from two strains of C57BL/6 mice bearing either T or C allelic variant of the rs1800522 AIRE SNP. Moreover, the extent of apoptosis induced by mTECs in MAGEB2-specific T cells and the susceptibility to in vivo melanoma B16F10 cell challenge were compared in the two mouse strains. The C allelic variant, protective in humans against melanoma, induced lower AIRE and MAGEB2 expression in C57BL/6 mouse mTECs than the T allele. Moreover, mTECs expressing the C allelic variant induced lower extent of apoptosis in MAGEB2-specific syngeneic T cells than mTECs bearing the T allelic variant (p < 0.05). Vaccination against MAGEB2 induced higher frequency of MAGEB2-specific CTL and exerted higher protective effect against melanoma development in mice bearing the CC AIRE genotype than in those bearing the TT one (p < 0.05). These findings show that allelic variants of one AIRE SNP may differentially shape the MA-specific T cell repertoire potentially influencing susceptibility to melanoma

STOPP/START antiaggregation and anticoagulation alerts in atrial fibrillation

BACKGROUND Atrial Fibrillation (AF) is common in the elderly. A key component of AF management is Oral Anticoagulant Therapy (OAT), consisting of Vitamin K Antagonists (VKAs) or Direct Oral Anticoagulants (DOACs). The aim of the present study is to check, using STOPP (Screening Tool of Older Persons’ Prescriptions)/START (Screening Tool to Alert to Right Treatment) Criteria, if such drugs are potentially inappropriately prescribed/omitted in an elderly population with AF, and to determine their impact on mortality. METHODS This study included patients (n=427) with nonvalvular AF consecutively evaluated between 2013 and 2019 at the Geriatric Outpatient Service, University Hospital of Monserrato, Cagliari, Italy, and followed-up for 36 months. The OAT-group included 330 patients; the other 97 patients constituted the non-OAT-group. The sample was assessed for STOPP/START criteria. RESULTS We found no difference (p&gt;0.1) in comorbidity burden, frailty, and cardio-cerebro-vascular disease prevalence in the two groups, who also did not present difference in 36-month mortality (p=0.97). OAT was overall appropriately taken, and 62.4% of OAT-group presented the START criterion to take antiplatelets but also the STOPP criterion not to take them, because of the simultaneous anticoagulant intake. In the non-OAT-group, 69.1% presented the START criterion to take anticoagulants, and 21.6% the START criterion to take antiplatelets. CONCLUSIONS Patients with AF are often prone to under- or over-prescription, particularly of antithrombotic drugs. The STOPP/START criteria are a valid tool to assess and correct wrong therapeutic choices. In frail and comorbid subjects, survival is not correlated with the assumption of OAT

Sensing Single Molecule Penetration into Nanopores: Pushing the Time Resolution to the Diffusion Limit

To quantify small molecule penetration into and eventually permeation through nanopores, we applied an improved excess-noise analysis of the ion current fluctuation caused by entering molecules. The kinetic parameters of substrate entry and exit are derived from a two-state Markov model, analyzing the substrate concentration dependence of the average ion current and its variance. Including filter corrections allows one to detect the transition rates beyond the cutoff frequency, fc, of the instrumental ion-current filter. As an application of the method, we performed an analysis of the single-channel ion current of Meropenem, an antibiotic of the carbapenem family, interacting with OmpF, the major general outer membrane channel of Escherichia coli bacteria. At 40 °C we detected the residence time of Meropenem inside OmpF of about 500 ns - more than 2 orders of magnitude smaller than fc-1 and close to the diffusion limit of few hundred nanoseconds. We also have established theoretical limit conditions under which the substrate-induced channel blockages can be detected and suggest that submicrosecond-scale gating kinetic parameters are accessible with existing experimental equipment

HUBUNGAN ANTARA POWER OTOT LENGAN DENGAN KEMAMPUAN RNSMASH BOLA VOLI PADA SISWA SMA NEGERI 8 TAKENGON RNTAHUN AJARAN 2013/2014

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