Therapeutic Efficacy and Outcomes of Remdesivir versus Remdesivir with Tocilizumab in Severe SARS-CoV-2 Infection

The infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) generated many challenges to find an effective drug combination for hospitalized patients with severe forms of coronavirus disease 2019 (COVID-19) pneumonia. We conducted a retrospective cohort study, including 182 patients with severe COVID-19 pneumonia hospitalized between March and October 2021 in a Pneumology Hospital from Cluj-Napoca, Romania. Among patients treated with standard of care, 100 patients received remdesivir (R group) and 82 patients received the combination of remdesivir plus tocilizumab (RT group). We compared the clinical outcomes, the inflammatory markers, superinfections, oxygen requirement, intensive care unit (ICU) admission and mortality rate before drug administration and 7 days after in R group and RT group. Borg score and oxygen support showed an improvement in the R group (p < 0.005). Neutrophiles, C-reactive protein (CRP) and serum ferritin levels decreased significantly in RT group but with a higher rate of superinfection in this group. ICU admission and death did not differ significantly between groups. The combination of remdesivir plus tocilizumab led to a significantly improvement in the inflammatory markers and a decrease in the oxygen requirement. Although the superinfection rate was higher in RT group than in R group, no significant difference was found in the ICU admission and mortality rate between the groups.     

Prediction of Drug Synergism between Peptides and Antineoplastic Drugs Paclitaxel, 5-Fluorouracil,and Doxorubicin Using In Silico Approaches

Chemotherapy is the main treatment for most early-stage cancers; nevertheless, its efficacy is usually limited by drug resistance, toxicity, and tumor heterogeneity. Cell-penetrating peptides (CPPs) are small peptide sequences that can be used to increase the delivery rate of chemotherapeutic drugs to the tumor site, therefore contributing to overcoming these problems and enhancing the efficacy of chemotherapy. The drug combination is another promising strategy to overcome the aforementioned problems since the combined drugs can synergize through interconnected biological processes and target different pathways simultaneously. Here, we hypothesized that different peptides (P1–P4) could be used to enhance the delivery of chemotherapeutic agents into three different cancer cells (HT-29, MCF-7, and PC-3). In silico studies were performed to simulate the pharmacokinetic (PK) parameters of each peptide and antineoplastic agent to help predict synergistic interactions in vitro. These simulations predicted peptides P2–P4 to have higher bioavailability and lower T_max, as well as the chemotherapeutic agent 5-fluorouracil (5-FU) to have enhanced permeability properties over other antineoplastic agents, with P3 having prominent accumulation in the colon. In vitro studies were then performed to evaluate the combination of each peptide with the chemotherapeutic agents as well as to assess the nature of drug interactions through the quantification of the Combination Index (CI). Our findings in MCF-7 and PC-3 cancer cells demonstrated that the combination of these peptides with paclitaxel (PTX) and doxorubicin (DOXO), respectively, is not advantageous over a single treatment with the chemotherapeutic agent. In the case of HT-29 colorectal cancer cells, the combination of P2–P4 with 5-FU resulted in synergistic cytotoxic effects, as predicted by the in silico simulations. Taken together, these findings demonstrate that these CPP6-conjugates can be used as adjuvant agents to increase the delivery of 5-FU into HT-29 colorectal cancer cells. Moreover, these results support the use of in silico approaches for the prediction of the interaction between drugs in combination therapy for cancer.     

Delay classical conditioning in young and older rabbits: Initial acquisition and retention at 12 and 18 months.

Classical conditioning of the nictitating membrane-eyeblink response in young (age 7 mo) and older (age 36 mo) New Zealand white rabbits in a delay paradigm with 400-msec CS–unconditioned stimulus/stimuli (UCS) interval was examined for initial acquisition and retention. Older animals required significantly more acquisition trials to reach learning criterion. Age differences in acquisition were temporary. Older rabbits responded at a level comparable to that of young rabbits such that total performance over the 630 trials of acquisition was not different. Rabbits in the explicitly unpaired control groups exhibited no age differences in unconditioned response (UCR) amplitude or latency measures. 12- and 18-mo retests demonstrated no significant age effects on retention. Patterns of retention differed between age groups. Older rabbits required fewer trials to obtain the learning criterion at each phase of testing. Younger rabbits maintained a stable performance throughout training. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The relationship between the extent of reciprocity with social supporters and measures of depressive symptomatology, impairment, disability, and handicap in persons with spinal cord injury.

140 adults (aged 19–77 yrs) were randomly selected from a sampling frame of 661 persons with spinal cord injury. They completed a questionnaire assessing amount of social support, degree of reciprocity with supporters, and satisfaction with relationships with supporters; the Center for Epidemiologic Studies Depression Scale; a self-report version of the Functional Independence Measure; and the Craig Handicap Assessment and Reporting Technique. A physician assessed the degree of paralytic impairment by means of the ASIA Total Motor Index Score. Relationships in which the supporter gave more than the participant were associated with more satisfaction with the relationship and more social support. The number of reciprocal relationships was positively associated with more desirable outcomes in the handicap dimensions of mobility, occupation, social integration, and economic self-sufficiency. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A stochastic optimal feedback control problem with random-sized jumps

An optimal feedback control problem for a partially observed linear system with noise of fixed-sized jumps occurring at random times driven by a Poisson process is extended to include noise with random-sized jumps. The control structure is appropriately modified to compensate for the mean behavior of the system jumps via an additional deterministic term. Editor: N.U. Ahmed     

Distribution damage measurement,analysis and correction

Distribution damage is a symptom of underlying problems—a quality system out of adjustment. The purpose of this paper is to develop a management method for controlling distribution damage. Such a system includes setting standards and managing conformance through appraisal and corrective action, including package improvement through damage reproduction test method evaluation.     

Towards an educational Superlnterface

Abstract  It is presumed that recent technological innovations, combined with three more established (educational) technologies, could cause a drastic change in university education, if adequate organizational conditions could be created. Such conditions are needed to structure, channel and manage an as yet undreamed of flow of information. Closely related to the metaphor of the 'Info Highway', an educational 'Superlnterface' is described. Based upon networked computer platforms, such a human-computer-human interface is to support large scale telestudy (and teleworking). The Superlnterface is to be designed or is to evolve in such a way that reliable and valid organizational foundations for university education can be established. As the organizational foundation is so paramount, the authors would like to see serious research into the modelling of Superlnterface structures, resources, and dynamics. Indications of some such research issues are presented.     

Psychological assessment of interpersonal victimization effects in adults and children.

Because clinical awareness of victimization effects is a relatively recent phenomenon, the field is only now developing assessment methodologies relevant to victims of interpersonal violence. This article reviews current information on the psychological assessment of children and adults with victimization histories, both in terms of general psychological tests such as the MMPI, Rorschach, and Child Behavior Checklist, and trauma-specific measures such as the Trauma Symptom Inventory, Trauma Symptom Checklist for Children, and Child Sexual Behavior Inventory. In addition, issues associated with overlapping traumas, symptom underreporting and overreporting, measurement distortion and misidentification effects, and psychometric quality are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Research using intentional deception: Ethical issues revisited.

Reviews ethical issues concerning the use of intentional deception in research with human participants 10 yrs after the publication of the American Psychological Association's (1973) guidelines on the conduct of research with human Ss. Intentional deception is defined. The present status of guidelines concerning intentional deception and the incidence and extremity of deception being used are reviewed, leading to the conclusion that the former has not decreased the latter. The present author's position proscribing intentionally deceptive research is grounded in rule-utilitarian meta-ethics. Three ethical rules proscribing intentional deception in the research setting are presented. The costs to Ss, the profession, and society are reviewed, and arguments are presented against the scientific benefits claimed for deceptive instructions. In this context, the scientific problems with social psychological experimentation are discussed. Recommendations for research strategies in lieu of deception paradigms and for appropriate debriefing are offered. (50 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)