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The causes of punishment including violence are perceived, first and foremost, as in the nature of family relations. The authors' survey focused on children's interaction with their parents, and the risk of violence is clearly present. Russian sociological research on violence against children within families shows a lack of consensus on what constitutes violence, the extent to which it should be avoided, and what its consequences are. (Contains 1 table and 5 notes.)

Introduction: Poly (adenosine diphosphate-ribose) polymerase inhibitors can up-regulate programmed cell death-ligand 1 expression and promote immune-mediated responses and may improve efficacy of first-line anti‒programmed cell death protein 1‒based therapies in patients with metastatic squamous NSCLC., Methods: In this randomized, double-blind, phase 3 trial (NCT03976362), adults with previously untreated stage IV squamous NSCLC received four cycles of induction therapy (pembrolizumab 200 mg every 3 weeks plus carboplatin and paclitaxel or nab-paclitaxel). Patients with disease control were randomized to 31 cycles of pembrolizumab 200 mg every 3 weeks plus olaparib 300 mg orally twice daily or placebo. Dual primary end points were progression-free survival (PFS) and overall survival (OS). PFS was tested at interim analysis 2 (the final PFS analysis); OS was tested at final analysis., Results: A total of 851 patients received induction treatment; 296 were randomized to pembrolizumab plus olaparib and 295 to pembrolizumab plus placebo. At interim analysis 2, with median follow-up of 27.1 months, median (95% confidence interval [CI]) PFS was 8.3 (6.7‒9.7) months in the pembrolizumab plus olaparib group and 5.4 (4.1‒5.6) months in the pembrolizumab plus placebo group (hazard ratio = 0.77, 95% CI: 0.63‒0.93, p = 0.0040 [not significant at a one-sided superiority boundary of p = 0.003]). At final analysis, with median follow-up of 33.4 months, median (95% CI) OS was 19.1 (15.9‒22.2) and 18.6 (16.0‒21.6) months, respectively (hazard ratio = 1.01, 95% CI: 0.83‒1.24, p = 0.5481). Treatment-related adverse events occurred in 76.5% and 65.1% of patients, respectively., Conclusions: Adding olaparib to pembrolizumab as maintenance therapy for metastatic squamous NSCLC did not significantly improve PFS versus pembrolizumab plus placebo; neither PFS nor OS met the prespecified statistical significance boundary. No new safety signals were identified., Trial Registration: ClinicalTrials.gov, NCT03976362., Competing Interests: Disclosure Dr. Hochmair reports having financial interests, personal, other, speaker’s bureau, and consulting or advisory role from Takeda, Roche, Eli Lilly, AstraZeneca/Daiichi Sankyo, and Merck Sharp & Dohme. Dr. Schenker reports receiving research grants from AbbVie, Amgen, Astellas, AstraZeneca, Bayer, BeiGene, Clovis, Daiichi Sankyo, EISAI, Eli Lilly, Five Prime, Gilead, GlaxoSmithKline, Mylan, Novartis, Pfizer, PharmaMar, Samsung, and Takeda. Dr. Cobo Dols reports receiving honoraria from Novartis, AstraZeneca, Boehringer Ingelheim, Roche, Bristol-Myers Squibb, Eli Lilly, Merck Sharp & Dohme, Takeda, Kyowa, Pierre Fabre, Novocure, Sanofi, and Jansen; serving on the data safety monitoring or advisory board for Novartis, AstraZeneca, Boehringer Ingelheim, Roche, Bristol-Myers Squibb, Eli Lilly, Merck Sharp & Dohme, Takeda, Pfizer, Kyowa, Sanofi, and Jansen. Dr. Kim reports receiving clinical trial funding to institution from AbbVie, Amgen, AstraZeneca/Medimmune, Bayer, Black Diamond Therapeutics, Blueprint Medicines, Boryung, Bristol Myers Squibb, Celgene, Dizal, EMD Serono Inc., Enliven Therapeutics, F. Hoffmann-La Roche Ltd./Genentech, Inc., Fore Biotherapeutics, Hanmi, Genmab, Janssen, Merck & Co. Inc., Novartis, Pfizer, RAPT Therapeutics, Regeneron, Sanofi, Takeda, Taiho, and Yuhan; serving as a consultant to AstraZeneca, Daiichi Sankyo, HK inno.N, IMBDx. Inc., Janssen, Regeneron, Roche/Genentech, Samsung Bioepis, and Takeda; and serving on the data safety monitoring or advisory board for AstraZeneca, Janssen, Regeneron, Roche/Genentech, Samsung Bioepis, and Takeda. Dr. Ozyilkan reports serving as a consultant to Roche and Merck Sharp & Dohme; receiving honoraria from Merck Sharp & Dohme and Sanofi; receiving support for attending meetings from Pfizer, Merck Sharp & Dohme, AstraZeneca, and Roche; and serving on the data safety monitoring or advisory board for Merck Sharp & Dohme. Dr. Leonova reports receiving research grants from Bio-Thera Solutions, Ltd., Roche, Shanghai Henlius Biotech, Incyte Corporation, IPSEN BIOSCIENCE, Merck Serono, and Janssen Research & Development. Dr. Kato reports receiving research grants to institution from AbbVie, Amgen, Arrivent, AstraZeneca, Bayer, BeiGene, BluePrint, Bristol Myers Squibb, Chugai, Daiichi Sankyo, Eli Lilly, Gilead, GlaxoSmithKline, Haihe, Janssen, Merck KGaA, Merck Sharp & Dohme, Novartis, Pfizer, Regeneron, and Takeda; receiving honoraria from Amgen, AstraZeneca, BeiGene, Boehringer Ingelheim, Bristol Myers Squibb, Chugai, Daiichi Sankyo, Eli Lilly, GlaxoSmithKline, Janssen, Merck KGaA, Merck Sharp & Dohme, Novartis, Ono, Pfizer, Taiho, and Takeda; serving on the data safety monitoring or advisory board for AstraZeneca, BeiGene, Chugai, Daiichi Sankyo, Janssen, Merck KGaA, Merck Sharp & Dohme, Novartis, and Pfizer; and receiving other support from Eli Lilly (spouse’s employer). Dr. Aggarwal reports being an employee of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA; a shareholder of Merck & Co., Inc., Rahway, NJ, USA; and a stockholder of Eli Lilly and Company. Dr. De Angelis reports receiving honoraria for lectures, presentations, and advisory boards from Merck, Pfizer, Bristol Myers Squibb, AstraZeneca, and GlaxoSmithKline. Dr. Gray reports receiving research grants from AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, EMD Serono – Merck KGaA, Genentech, Gilead Sciences, G1 Therapeutics, Ludwig Institute of Cancer Research, Merck & Co., Inc., Novartis, Panbela Therapeutics, Pfizer, and Regeneron; serving as a consultant for: AbbVie, AstraZeneca, Blueprint Medicines, Coherus, Daiichi Sankyo, EMD Serono, Gilead Sciences, Inc., IDEOlogy Health, Janssen Scientific Affairs, LLC, Jazz Pharmaceuticals, Loxo Oncology Inc., Merck & Co., Inc., Novartis, OncoCyte Biotechnology, Regeneron, Spectrum ODAC, Takeda Pharmaceuticals, Triptych Health Partners, and Zai Lab (US) LLC; receiving honoraria from AbbVie, AstraZeneca, Blueprint Medicines, Coherus, Daiichi Sankyo, EMD Serono, Gilead Sciences, Inc., IDEOlogy Health, Janssen Scientific Affairs, LLC, Jazz Pharmaceuticals, Loxo Oncology Inc., Merck & Co., Inc., Novartis, OncoCyte Biotechnology, Regeneron, Spectrum ODAC, Takeda Pharmaceuticals, Triptych Health Partners, and Zai Lab (US) LLC; and having leadership role on a committee or board for ASCO (Board of Directors Member), ASCO (Education Committee Ex-Chair), SWOG (Lung Committee Chair), and IASLC (Board of Directors Member). Dr. Greystoke reports serving as a consultant for Merck Sharp & Dohme, Bristol Myers Squibb, AstraZeneca, Boehringer Ingelheim, Merck, Pfizer, Takeda, Roche, Janssen, and Novartis; receiving honoraria from Merck Sharp & Dohme, Bristol Myers Squibb, AstraZeneca, Boehringer Ingelheim, Merck, Pfizer, Takeda, Roche, Janssen, and Novartis; and receiving support for attending meetings from Takeda and Roche. Mr. Huang reports being an employee of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA and a shareholder of Merck & Co., Inc., Rahway, NJ, USA. Dr. Lara-Guerra reports being an employee of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA and a shareholder of Merck & Co., Inc., Rahway, NJ, USA. Dr. Nadal reports receiving research grants from Roche, Pfizer, Bristol Myers Squibb, and Merck Serono; serving as a consultant for Roche, Bristol Myers Squibb, Merck Sharp & Dohme, Merck Serono, Sanofi, Pfizer, Eli Lilly, Amgen, Daiichi Sankyo, Boehringer Ingelheim, Genmab, AstraZeneca, Takeda, Johnson & Johnson, Pierre Fabre, and Qiagen; receiving honoraria from Roche, Bristol Myers Squibb, Merck Sharp & Dohme, Sanofi, Pfizer, Eli Lilly, Amgen, Janssen, Boehringer Ingelheim, AstraZeneca, Takeda, Sanofi, Janssen, and Qiagen; receiving support for attending meetings from Takeda, Pfizer, Merck Sharp & Dohme, AstraZeneca, and Roche; and serving on the data safety monitoring or advisory board for Apollomics, Roche, Transgene, and Merck Sharp & Dohme. Dr. Rittmeyer reports serving as an advisor to AbbVie, AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Daiichi Sankyo, Eli Lilly, Gilead, GlaxoSmithKline, Merck Sharp & Dohme, Novartis, Pfizer, and Roche. Dr. Zhao reports being an employee of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, and a shareholder of Merck & Co., Inc., Rahway, NJ, USA. The remaining authors declare no conflict of interest., (Copyright © 2024 Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, The Author(s). Published by Elsevier Inc. All rights reserved.)

Study Aim: ModraDoc006, an oral formulation of docetaxel, is co-administered with the cytochrome P450-3A4 and P-glycoprotein inhibitor, ritonavir (r): ModraDoc006/r. The preliminary efficacy and safety of oral ModraDoc006/r was evaluated in a global randomized phase II trial and compared to the current standard chemotherapy regimen of intravenous (i.v.) docetaxel and prednisone., Methods: 103 mCRPC patients, chemotherapy-naïve with/without abiraterone and/or enzalutamide pretreated, with adequate organ function and evaluable disease per RECIST v1.1 and PCWG3 guidelines were randomized 1:1 into two cohorts. In Cohort 1, 49 patients received docetaxel 75 mg/m 2 i.v. every 3 weeks (Q3W). In Cohort 2, 52 patients received ModraDoc006/r; 21 patients with a starting dose of ModraDoc006 30 mg with ritonavir 200 mg in the morning and ModraDoc006 20 mg with ritonavir 100 mg in the evening (30-20/200-100 mg) bi-daily-once-weekly (BIDW) on Days 1, 8, and 15 of a 21-day cycle. To alleviate tolerability, the starting dose was amended to ModraDoc006/r 20-20/200-100 mg in another 31 patients. All patients received prednisone 10 mg daily. Primary endpoint was rPFS., Results: There was no significant difference in rPFS between the 2 arms (p = 0.1465). Median rPFS was 9.5 months and 11.1 months (95% CI) for ModraDoc006/r and i.v. docetaxel, respectively. Partial response was noted in 44.1% and 38.7% measurable disease patients, and 50% decline of PSA was seen in 23 (50%) and 26 (56.5%) evaluable cases treated with ModraDoc006/r and i.v. docetaxel, respectively. The safety profile of ModraDoc006/r 20-20/200-100 mg dose was significantly better than i.v. docetaxel, with mild (mostly Grade 1) gastrointestinal toxicities, no hematologic adverse events, and neuropathy and alopecia incidence of 11.5% and 25%, respectively., Conclusions: ModraDoc006/r potentially represents a widely applicable, convenient, effective, and better tolerated oral taxane therapy option for mCRPC. Further investigation of ModraDoc006/r in a large randomized trial is warranted., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Modra Pharmaceuticals BV was founded as a spin-off company of the Netherlands Cancer Institute, enabling the further clinical development of novel oral taxane formulations, after their pharmaceutical and preclinical development in the Netherlands Cancer Institute. Marianne Keessen is a full-time employee of Modra Pharmaceuticals BV. The other authors declare no relevant conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Anti-pathogenic protection of potatoes remains one of the most pressing problems of sustainable agronomy and plant protection. For this purpose, we propose to use a new type of synthetic hydrogels filled with amphiphilic recipients (dispersed peat, humates) and modern plant protection products. We assumed that the introduction of swollen gel structures into the rhizosphere of potatoes will allow us: to optimize the water supply and productivity of potatoes; to protect the fertile layer and potato tubers from the main pathogens; to fix modern plant protection products in the rhizosphere, keeping them from leaching and entering the environment. Preliminary laboratory experiments tested the anti-microbial activity of gel structures, as well as their water retention, dispersity and hydraulic conductivity with subsequent computer modeling of the water exchange and root uptake in the system of "soil-gel-potato". Field trials were carried out in humid (European Russia) and arid (Uzbekistan) conditions under the atmospheric precipitation and irrigation on different soils and potato varieties with instrumental monitoring of environment, potato growth and quality. All experimental results confirmed the high efficiency of water-accumulative and plant protective synthetic gel structures. Their usage sufficiently (up to 6-15 t/hct) increases the potato yield with 1.3-2 times water saving, complete retention of agrochemicals in the rizosphere, and its actually total protection against major potato pathogens, including late blight (Phytophthora infestans).

1-[(3-chlorophenyl)phenylmethyl]urea--a compound possessing anticonvulsant activity, which has been selected by screening among 100 linear and cyclic urea derivatives, produces synchronization of spontaneous bioelectric activity, increased convulsion threshold in the motor cortex, dorsal hippocampus, and basolateral nuclei of amygdala, increased the index of low-frequency flicker acquisition, and reduced response to high-frequency oscillations in the visual cortex of rabbits. This compound also increased the extracellular content of sodium ions and reduced intracellular content of potassium ions in the motor cortex, dorsal hippocampus, and amygdala.

We investigated association of polymorphisms of interleukin IA (IL-1A), interleukin 4 (IL-4), interleukin 5 (IL-5), interleukin-8 (1L-8) genes in elderly patients with predisposition to the development of chronic lym,nphocytic leukemia (CLL). Risk factor of chronic lymphocytic leukemia is a genetic variant -590T IL-4 (OR = 1,45) and protective factor -590S IL-4 (OR = 0,68). Genetic markers -590T IL-4 (OR = 2,46), -590TT IL-4 (OR = 6,65) and mix-590TT genotype of IL-4 allele 703S-IL-5 (OR = 6.70) were associated with stage 0-1 chronic lymphocytic leukemia whereas genetic markers -889T IL-1A (OR = 1,51), -703T IL-5 (OR = 1,52) and a combination of genotype -703ST IL-5 allele-251A IL-8 (OR = 2.85) were related to the development of stage II of the disease. Risk factor for the formation of II-IV stages of chronic lymphocytic leukemia is a genetic variant -703T IL-5 (OR = 1,95).

In chronic experiments on conscious rabbits with bipolar electrodes implanted into the brain it was found that galodiph suppresses the spontaneous bioelectrical activity of the motor and visual regions of the brain cortex and somewhat decreases electrical excitability of the cortical motor region, basolateral nuclei of the amygdala and dorsal hippocampus.

The experiments on rabbits revealed the depressant effect of anticonvulsant drug halonal on spontaneous bioelectrical activity and electroexcitability of the motor area of the cerebral cortex, caudate nucleus, intralaminar nuclei of the thalamus and midbrain reticular formation. The drug exerts no effect on the amygdala and hippocamp. The mechanism of the anticonvulsant effect of halonal involves inhibition of the caudo-thalamo-cortical synchronizing system that presumably disorders the occurrence of the hypersynchronous charge in the cortical neurons and prevents the development of a convulsive fit.