Synthesis and antitumor properties of some new 3-R-6-(5-arylfuran-2-yl-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazoles

One of the promising methods of creating antitumor drugs is the screening of potential antitumor agents among synthesized compounds. Nitrogen-based heterocycle analogues are an extremely important class of organic substances that are widely used in medical chemistry. [1,2,4]Triazolo[3,4-b][1,3,4] thiadiazoles are among the little-studied and hard-to-reach members of this class of compounds. The aim of our work was to synthesize some new 3-R-6-(5-arylfuran-2-yl-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazoles, as well as the study of their antitumor activity. The objects of study were 3-R-6-(5-arylfuran-2-yl-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazoles. The composition and structure of the synthesized compounds were confirmed by the data of elemental analysis and 1H NMR spectroscopy. The antitumor activity of the synthesized compounds was studied in the framework of the international scientific program of the National Cancer Institute (Bethesda, Maryland, USA) DTP NCI (Developmental Therapeutic Program). The synthesis of 11 derivatives of 3-R-6-(5-arylfuran-2-yl-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazoles was carried out. These substances are obtained by the interaction of 5-arylfuran-2-carboxylic acids with 5-substituted 4-amino-4H-1,2,4-triazolo-3-thiols. Primary screening revealed individual 3-R-6-(5-arylfuran-2-yl-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazoles, which showed pronounced selective antitumor activity. The most active among the tested compounds were 3 d, 3 e and 3 j, which were further investigated during secondary screening. The results of these studies confirm the high antitumor activity of these compounds. The proposed approaches and the developed synthesis protocols made it possible to obtain a series of new 3-R-6-(5-arylfuran-2-yl-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazoles. The results of studies of the antitumor activity of the synthesized compounds made it possible to single out 3 highly active compounds with high antitumor activity, which gives reason to consider this condensed system as a promising molecular framework for the design of potential antitumor agents.

ReCODE: A Personalized, Targeted, Multi-Factorial Therapeutic Program for Reversal of Cognitive Decline

Background: Alzheimer’s disease (AD) is the major cause of age-associated cognitive decline, and in the absence of effective therapeutics is progressive and ultimately fatal, creating a dire need for successful prevention and treatment strategies. We recently reported results of a successful proof-of-concept trial, using a personalized, precision medicine protocol, but whether such an approach is readily scalable is unknown. Objective: In the case of AD, there is not a single therapeutic that exerts anything beyond a marginal, unsustained, symptomatic effect. This suggests that the monotherapeutic approach of drug development for AD may not be an optimal one, at least when used alone. Using a novel, comprehensive, and personalized therapeutic system called ReCODE (reversal of cognitive decline), which proved successful in a small, proof-of-concept trial, we sought to determine whether the program could be scaled to improve cognitive and metabolic function in individuals diagnosed with subjective cognitive impairment, mild cognitive impairment, and early-stage AD. Methods: 255 individuals submitted blood samples, took the Montreal Cognitive Assessment (MoCA) test, and answered intake questions. Individuals who enrolled in the ReCODE program had consultations with clinical practitioners, and explanations of the program were provided. Participants had follow-up visits that included education regarding diet, lifestyle choices, medications, supplements, repeat blood sample analysis, and MoCA testing between 2 and 12 months after participating in the ReCODE program. Pre- and post-treatment measures were compared using the non-parametric Wilcoxon signed rank test. Results and Conclusions: By comparing baseline to follow-up testing, we observed that MoCA scores either significantly improved or stabilized in the entire participant pool—results that were not as successful as those in the proof-of-concept trial, but more successful than anti-amyloid therapies—and other risk factors including blood glucose, high-sensitivity C-reactive protein, HOMA-IR, and vitamin D significantly improved in the participant pool. Our findings provide evidence that a multi-factorial, comprehensive, and personalized therapeutic program designed to mitigate AD risk factors can improve risk factor scores and stabilize or reverse the decline in cognitive function. Since superior results were obtained in the proof-of-concept trial, which was conducted by a small group of highly trained and experienced physicians, it is possible that results from the use of this personalized approach would be enhanced by further training and experience of the practicing physicians. Nonetheless, the current results provide further support indicating the potential of such an approach for the prevention and reversal of cognitive decline.

Effectiveness of Identity-based Psychodrama Educational-therapeutic Program on Identity Styles and Neuroticism

Background: Neuroticism is one of the serious mental health problems of people. No study has been conducted on the impact of identity issues in the treatment of neurotic people. Objectives: This study aims to formulate, design, and investigate the effect of identity-based psychodrama educational program on identity styles and neuroticism. Materials & Methods: This research was a quasi-experimental study with a pre-test, post-test design using a control group. The study participants were 40 people aged 15-30 years referred to Pendare Nik Counseling Center in Najafabad City, Isfahan Province, Iran, in 2020. They were selected using a convenience sampling method and randomly assigned into the intervention (n=20) and control (n=20) groups. The data collection instruments were Berzonsky Identity Style Inventory (1992) and McCrae and Costa 5-factor inventory (1992). A Researcher-made Identity-Based Psychodrama Program (2020) was used for the intervention. The collected data were analyzed using ANCOVA in SPSS v. 23. Results: The educational-therapeutic program significantly affected identity styles and neuroticism (P<0.001). It significantly reduced the neuroticism level of people in the intervention group (F=200.71, η2=0.84). Conclusion: The identity-based psychodrama program reduced diffuse-avoidant, normative, and informational identity styles and neuroticism and promoted the achieved identity style.

Ranibizumab or Aflibercept for Neovascular Age-Related Macular Degeneration, Twelve-Month Outcomes of Therapeutic Program in Non-Tertiary Institution: A Comparative Study.

Purpose: This single center study aimed to compare the 12-month treatment outcomes of ranibizumab with that of aflibercept in routine clinical practice.Methods: Cohort of patients diagnosed with treatment-naïve neovascular AMD, treated using either ranibizumab (n = 33 eyes) or aflibercept (n = 44 eyes) monotherapy over a 12-month follow-up period was analyzed. Anonymous data were extracted from the electronic database dedicated to the drug program.Results: In the ranibizumab group, there were not statistically significant changes in BCVA (ETRDS letters) and CRT (µm), between baseline (67.9 ± 8.6 & 384.9 ± 97.9) and at 12 months (67.9 ± 12.1 & 398.9 ± 127.1; P = 0.372 & P = 0.884, respectively). In the aflibercept, there was an improvement in BCVA and reduction in CRT between baseline (64.2 ± 8.1 & 414.3 ± 97.8) and at 12 months (70.7 ± 7.4 & 342.3 ± 71.6; P <.001 & P <.001, respectively). There was no difference in BCVA between the two groups at either diagnosis (P= 0.101) or 12 months (P= 0.917). Mean number of injections in the ranibizumab group was significantly lower (4.9 ± 1.5) than in the aflibercept group (6.7 ± 1; P<.001).Conclusions: One initial injection of ranibizumab and then PRN regimen resulted in stabilization of disease progression. Drug selection and treatment scheme could influence twelve-months outcomes. In the aflibercept group, three initial monthly injections and then every two months provided both significant BCVA improvement and CRT reduction at 12 months of treatment.

Dropout from Treatment and Desistance from Crime among Released Prisoners in Jerusalem Halfway House for Prisoners with Substance Misuse Disorder

The study aims to investigate the rates of recidivism among prisoners on parole with a substance misuse disorder who participated in the Jerusalem halfway-house, which combines supervision, employment, and a comprehensive therapeutic program. The study population included all participants who have been treated in the halfway-house ( N = 125), whereas the comparison group included all prisoners with a substance misuse disorder who were released after serving their full sentences ( N = 321). To reduce possible selection biases, the Propensity Score Matching method was used. Findings show that prisoners, who were treated at the Jerusalem halfway-house, are characterized by higher and frequent rates of recidivism. However, when only completers of the halfway-house were evaluated, it was found that they had lower and slower rates of recidivism. Findings suggest that completing treatment contributes to desistance from crime in the critical post-release years among participants and indicates the importance of optimal diagnostic processes before admitting prisoners to a halfway-house.

Effective factors of addiction treatment communities in Peru, Nicaragua and Czechia

Purpose This paper aims to explore the effective factors that influence the treatment of drug addiction in therapeutic communities (TCs) and to determine its essential elements in the Peruvian, Nicaraguan and Czech context. Design/methodology/approach The qualitative data were collected during semi-structured interviews with inpatients/clients of seven TCs based in Peru (Takiwasi), Nicaragua (Centro de Especialiades en Adicciones, Centro de Rehabilitación del Alcohólico y Adicto a Otras Drogas and Albergue de Miembros Adictos en Recuperación) and the Czech Republic (Renarkon, Sejrek and Kladno-Dubi). All 90 interviews were manually transcribed, and content analysis was performed. Codes were created using the grounded theory method. Findings The effective factors of TC, treatment in Peru, Nicaragua and Czechia are identical in conditions such as the presence of a personal therapist, the use of psychotherapy and the importance of group cohesion. In Peru, the administration of medicinal plants and diet was perceived as a principal part of the treatment. Nicaraguan TCs were specific for practicing 12 steps. In Czechia, an emphasis is put on the therapeutic program, workshops and leisure activities. Spirituality and religion play a main role in the Peruvian and Nicaraguan TCs only. Originality/value The current study presents a unique insight into the factors considered effective by inpatients/clients of TCs in different socio-cultural contexts.

Assessment of Disability Progression Independent of Relapse and Brain MRI Activity in Patients with Multiple Sclerosis in Poland

The aim of the study was to verify the association of clinical relapses and brain activity with disability progression in relapsing/remitting multiple sclerosis patients receiving disease-modifying treatments in Poland. Disability progression was defined as relapse-associated worsening (RAW), progression independent of relapse activity (PIRA), and progression independent of relapses and brain MRI Activity (PIRMA). Data from the Therapeutic Program Monitoring System were analyzed. Three panels of patients were identified: R0, no relapse during treatment, and R1 and R2 with the occurrence of relapse during the first and the second year of treatment, respectively. In the R0 panel, we detected 4.6% PIRA patients at 24 months (p < 0.001, 5.0% at 36 months, 5.6% at 48 months, 6.1% at 60 months). When restricting this panel to patients without brain MRI activity, we detected 3.0% PIRMA patients at 12 months, 4.5% at 24 months, and varying from 5.3% to 6.2% between 36 and 60 months of treatment, respectively. In the R1 panel, RAW was detected in 15.6% patients at 12 months and, in the absence of further relapses, 9.7% at 24 months and 6.8% at 36 months of treatment. The R2 group was associated with RAW significantly more frequently at 24 months compared to the R1 at 12 months (20.7%; p < 0.05), but without a statistical difference later on. In our work, we confirmed that disability progression was independent of relapses and brain MRI activity.