Does COVID-19 Vaccination Warrant the Classical Principle " ofelein i mi vlaptin"?

The current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic warrants an imperative necessity for effective and safe vaccination, to restrain Coronavirus disease 2019 (COVID-19) including transmissibility, morbidity, and mortality. In this regard, intensive medical and biological research leading to the development of an arsenal of vaccines, albeit incomplete preconditioned evaluation, due to emergency. The subsequent scientific gap raises some concerns in the medical community and the general public. More specifically, the accelerated vaccine development downgraded the value of necessary pre-clinical studies to elicit medium- and long-term beneficial or harmful consequences. Previous experience and pathophysiological background of coronaviruses' infections and vaccine technologies, combined with the global vaccines' application, underlined the obligation of a cautious and qualitative approach, to illuminate potential vaccination-related adverse events. Moreover, the high SARS-CoV-2 mutation potential and the already aggregated genetical alterations provoke a rational vagueness and uncertainty concerning vaccines' efficacy against dominant strains and the respective clinical immunity. This review critically summarizes existing evidence and queries regarding SARS-CoV-2 vaccines, to motivate scientists' and clinicians' interest for an optimal, individualized, and holistic management of this unprecedented pandemic

Paradigm shift in Parkinson's disease: using continuous telemonitoring to improve symptoms control. Results from a 2-years journey

IntroductionConventional care in Parkinson's disease (PD) faces limitations due to the significant time and location commitments needed for regular assessments, lacking quantitative measurements. Telemonitoring offers clinicians an opportunity to evaluate patient symptomatology throughout the day during activities of daily living.MethodsThe progression of PD symptoms over a two-year period was investigated in patients undergoing traditional evaluation, supplemented by insights from ambulatory measurements. Physicians integrated a telemonitoring device, the PDMonitor®, into daily practice, using it for informed medication adjustments.ResultsStatistical analyses examining intra-subject changes for 17 subjects revealed a significant relative decrease of −43.9% in the device-reported percentage of time spent in “OFF” state (from 36.2 to 20.3%). Following the 24-month period, the majority of the subjects improved or exhibited stable symptom manifestation. In addition to positively impacting motor symptom control, telemonitoring was found to enhance patient satisfaction about their condition, medication effectiveness, and communication with physicians.DiscussionConsidering that motor function is significantly worsened over time in patients with PD, these findings suggest a positive impact of objective telemonitoring on symptoms control. Patient satisfaction regarding disease management through telemonitoring can potentially improve adherence to treatment plans. In conclusion, remote continuous monitoring paves the way for a paradigm shift in PD, focusing on actively managing and potentially improve symptoms control

A modal logic of knowledge, belief and estimation

The actions of an agent operating in a complex environment are based on her knowledge and beliefs. Epistemic states are typically incomplete, thus the agent has often to estimate whether a fact is true or false before proceeding to actions. We introduce a modal framework for reasoning about Knowledge, Belief and Estimation, three attitudes involved in an agent's decision-making process. In this modal account, Knowledge and Belief are captured by S4.2 which has been advocated as a `correct' logic of knowledge by W. Lenzen and R. Stalnaker. Estimation is a non-normal modal operator interpreted as a `majority' quantifier; the approach employs the `weak filters', a general notion of `big' subsets introduced within KR by K. Schlechta and V. Jauregui. Its axiomatization reveals that this `majority' operator has been introduced by J. Burgess (1969) phi and ((sic))phi used also by A. Herzig (2003). We provide a full account of the logic KBE in which estimation is complete: exactly one of. and notsign. is estimated to be true. We prove soundness and completeness with respect to a class of frames combining relational Kripke frames with Scott-Montague semantics in which neighbourhoods are `weak ultrafilters' and present a tableaux proof procedure. It comes out that believing phi can be equivalently defined in KBE as `estimating that phi is known', an interesting fact and an indication of the intuitive correctness of the introduced estimation operator. The assumption on complete estimation is rather strong; yet, it is not hard to define KBiE, a relaxed variant in which estimation is still consistent but not complete. We provide the technical details for soundness and completeness with respect to the larger class of frames where neighbourhoods are weak filters. Finally, it is proved that KBiE invalidates a rule introduced in W. Lenzen's probabilistic analysis of weak belief and thus the weak filter semantics is essentially different than its probabilistic counterpart

Peptide-Based Vaccines for Neurodegenerative Diseases: Recent Endeavors and Future Perspectives

The development of peptide-based vaccines for treating human neurodegenerative diseases has been the eventual aim of many research endeavors, although no active immunotherapies have been approved for clinical use till now. A typical example of such endeavors is the effort to develop vaccines for Alzheimer’s disease based on the beta-amyloid peptide, which continues to be intensively investigated despite previous setbacks. In this paper, recent developments in peptide-based vaccines which target beta-amyloid as well as tau protein and α-synuclein are presented. Particular focus has been directed toward peptide epitopes and formulation systems selected/developed and employed to enhance vaccine efficacy and safety. Results from both, human clinical trials and animal preclinical studies conducted mainly in transgenic mice have been included. Future perspectives on the topic are also briefly discussed

Laparoscopic Bullet Removal in a Penetrating Abdominal Gunshot

Penetrating abdominal trauma has been traditionally treated by exploratory laparotomy. Nowadays laparoscopy has become an accepted practice in hemodynamically stable patient without signs of peritonitis. We report a case of a lower anterior abdominal gunshot patient treated laparoscopically. A 32-year-old male presented to the Emergency Department with complaint of gunshot penetrating injury at left lower anterior abdominal wall. The patient had no symptoms or obvious bleeding and was vitally stable. On examination we identified 1 cm diameter entry wound at the left lower abdominal wall. The imaging studies showed the bullet in the peritoneal cavity but no injured intraperitoneal and retroperitoneal viscera. We decided to remove the bullet laparoscopically. Twenty-four hours after the intervention the patient was discharged. The decision for managing gunshot patients should be based on clinical and diagnostic findings. Anterior abdominal injuries in a stable patient without other health problems can be managed laparoscopically

Radiochemical and radiobiological evaluation of a new Tc-99m-labelled litorin derivative

WOS: 00028107510011

Interpreting Thermodynamic Profiles of Aminoadamantane Compounds Inhibiting the M2 Proton Channel of Influenza A by Free Energy Calculations

The development of novel anti-influenza drugs is of great importance because of the capability of influenza viruses to occasionally cross interspecies barriers and to rapidly mutate. One class of anti-influenza agents, aminoadamantanes, including the drugs amantadine and rimantadine now widely abandoned due to virus resistance, bind to and block the pore of the transmembrane domain of the M2 proton channel (M2TM) of influenza A. Here, we present one of the still rare studies that interprets thermodynamic profiles from isothermal titration calorimetry (ITC) experiments in terms of individual energy contributions to binding, calculated by the computationally inexpensive implicit solvent/implicit membrane molecular mechanics Poisson–Boltzmann surface area (MM-PBSA) approach, for aminoadamantane compounds binding to M2TM of the avian “Weybridge” strain. For all eight pairs of aminoadamantane compounds considered, the trend of the predicted relative binding free energies and their individual components, effective binding energies and changes in the configurational entropy, agrees with experimental measures (ΔΔ<i>G</i>, ΔΔ<i>H</i>, <i>T</i>ΔΔ<i>S</i>) in 88, 88, and 50% of the cases. In addition, information yielded by the MM-PBSA approach about determinants of binding goes beyond that available in component quantities (Δ<i>H</i>, Δ<i>S</i>) from ITC measurements. We demonstrate how one can make use of such information to link thermodynamic profiles from ITC with structural causes on the ligand side and, ultimately, to guide decision making in lead optimization in a prospective manner, which results in an aminoadamantane derivative with improved binding affinity against M2TM_Weybridge

Phospholipase Cζ rescues failed oocyte activation in a prototype of male factor infertility

Objective To determine the effect of infertility-linked sperm phospholipase Cζ (PLCζ) mutations on their ability to trigger oocyte Ca2+ oscillations and development, and also to evaluate the potential therapeutic utility of wild-type, recombinant PLCζ protein for rescuing failed oocyte activation and embryo development. Design Test of a novel therapeutic approach to male factor infertility. Setting University medical school research laboratory. Patient(s) Donated unfertilized human oocytes from follicle reduction. Intervention(s) Microinjection of oocytes with recombinant human PLCζ protein or PLCζ cRNA and a Ca2+-sensitive fluorescent dye. Main Outcome Measure(s) Measurement of the efficacy of mutant and wild-type PLCζ-mediated enzyme activity, oocyte Ca2+ oscillations, activation, and early embryo development. Result(s) In contrast to the wild-type protein, mutant forms of human sperm PLCζ display aberrant enzyme activity and a total failure to activate unfertilized oocytes. Subsequent microinjection of recombinant human PLCζ protein reliably triggers the characteristic pattern of cytoplasmic Ca2+ oscillations at fertilization, which are required for normal oocyte activation and successful embryo development to the blastocyst stage. Conclusion(s) Dysfunctional sperm PLCζ cannot trigger oocyte activation and results in male factor infertility, so a potential therapeutic approach is oocyte microinjection of active, wild-type PLCζ protein. We have demonstrated that recombinant human PLCζ can phenotypically rescue failed activation in oocytes that express dysfunctional PLCζ, and that this intervention culminates in efficient blastocyst formation