The impact of cycling infrastructure on consumers' perceptions of bicycle transport

Метою роботи є дослідження впливу розвитку інфраструктури на вибір споживачами велосипедів як альтернативного екологічного транспорту. В статті розглянуто проблеми та перспективи розвитку велотранспорту. Проведено аналіз причин вибору споживачів щодо використання велосипедів як транспортного засобу для повсякденного життя. Розглянуто позитивний досвід розвитку велотранспортної інфраструктури у провідних країнах Європи. Досліджено основні вимоги для розвитку велосипедної інфраструктури та визначено основні критерії її розбудови, зокрема у місті Києві.The aim of the article is to research the influence of developing the cycling infrastructure on the consumer's choice of bicycles as an alternative to eco transportation. The article talks about the problems and perspectives of developing a cycling infrastructure. An analysis of reasons was conducted in regards to the consumer's choice using bicycles as means of everyday transportation. Also, a positive experience in developing the cycling infrastructure in leading European countries was discussed. The article researched key requirements for developing the cycling infrastructure and identified basic criteria of its development, in particular in Kyiv city

Evolution of the CDK4/6 inhibitor abemaciclib: from palliative to adjuvant therapy. Clinical experience with abemaciclib in patients with hormone-receptor-positive, HER2-negative breast cancer

Introduction. Cyclin-dependent kinase 4/6 inhibitors are indicated in endocrine therapy for the treatment of hormone receptorpositive, HER2-negative, advanced, or metastatic breast cancer. In the recent past, abemaciclib made its debut as a combinatorial partner for adjuvant therapy in hormone-dependent breast cancer. This article demonstrates the analysis of our own experience of introducing abemaciclib into clinical practice.Aim. The aim of the study was to evaluate the preliminary results of treatment of patients with hormone receptor-positive HER2-negative metastatic breast cancer using abemaciclib outside the framework of clinical trials, in the real clinical practice of an oncological dispensary.Materials and methods. A retrospective analysis of the results of treatment was carried out in 27 patients who were prescribed abe-maciclib in various regimens and lines from April 2021 to January 2022 in the conditions of routine practice in the Krasnodar region.Results and discussion. Analysis of the total population of 27 patients at a median follow-up of 8 months showed that the median PFS was not reached. The one-year PFS was 68.8%. Treatment outcomes were independent of prescribing abemaciclib to treat baseline metastatic disease or breast cancer progression after previous radical treatment (p = 0.60). The PFS did not depend on the expression of progesterone receptors in the tumor tissue (p = 0.326) and the proliferative activity index Ki-67 (p = 0.618). Patients who received no more than 2 lines of previous drug treatment for a history of metastatic breast cancer had the greatest benefit from abemaciclib therapy (p = 0.001).Conclusions. Despite a relatively difficult group of patients (96% of patients with visceral metastases), abemaciclib has demonstrated efficacy and safety. The effectiveness did not depend on the analyzed factors: Ki-67, the level of expression of progesterone receptors, the type of metastatic disease (de novo metastatic or progressive breast cancer). In view of the best results, it is advisable to prescribe abemaciclib in the early lines of therapy

Эффективность и безопасность комбинации ленватиниба и эверолимуса у больных диссеминированным раком почки, прогрессирующим на фоне антиангиогенной таргетной терапии: второй анализ данных российского многоцентрового наблюдательного исследования

Objective. The primary endpoint was progression-free survival; secondary endpoints included overall survival, objective response rate and duration, tumor control rate and duration, as well as safety profile of lenvatinib with everolimus in consecutive patients with advanced renal cell carcinoma who had disease progression after targeted antiangiogenic therapy.Materials and methods. This observational study included 129 consecutive patients with metastatic renal cell carcinoma resistant to targeted antiangiogenic therapy. The median age was 60 years; a male to female ratio was 3.1:1. Twenty-seven patients (20.9 %) had ECOG performance status of 2—4. The majority of study participants (n = 127; 98.4 %) had multiple metastases. Tumor lesions were located in >1 organ in 104 cases (80.6 %). The primary tumor was removed in 110 (85.3 %), including 39 (30.2 %) patients undergone cytoreductive surgery. Seventy patients (54.2 %) had earlier received more than one line of therapy. Upon enrollment, there were 13 IMDC favourable-risk patients (10.1 %), 86 IMDC intermediate-risk patients (66.6 %), and 29 IMDC poor-risk patients (22.5 %). In one patient (0.8 %), the IMDC risk was not estimated. All patients received lenvatinib at a dose of 18 mg/day and everolimus at a dose of 5 mg/day. The median follow-up was 10.5 (1—30) months.Results. Median progression-free survival was 14.9 (11.9—17.9) months; overall survival was 19.9 (15.2—24.6) months. The objective response rate was 17.0 % (median duration 9.7 (2.8—16.5) months); tumor control rate was 72.9 % (median duration 10.0 (2.5—17.5) months). Adverse events were observed in 112patients (86.8 %) with grade III—IVadverse events registered in 27participants (20.9 %). Five participants (3.9 %) needed inpatient treatment of adverse events; one patient (0.8 %) died due to adverse events. Adverse events required treatment discontinuation in 4 patients (3.1 %), treatment interruption in 35 patients (27.1 %), and dose reduction in 33 patients (25.6 %).Conclusion. The results of the secondary analysis in the ROSLERCM observational study confirmed the results obtained earlier on the efficacy and safety of the lenvatinib plus everolimus combination in the second- and subsequent-line therapy for advanced renal cell carcinoma resistant to targeted antiangiogenic therapy in consecutive Russian patients.Цель. Первичной конечной точкой являлась беспрогрессивная выживаемость, вторичными — общая выживаемость, частота и длительность ответа на лечение и контроля над опухолью, а также профиль безопасности комбинации ленватиниба и эверолимуса у неотобранных пациентов с распространенным почечно-клеточным раком, прогрессирующим после антиангиогенной таргетной терапии.Материалы и методы. В наблюдательное исследование последовательно включены 129 больных диссеминированным почечноклеточным раком, резистентным к антиангиогенной таргетной терапии. Медиана возраста — 60 лет, соотношение мужчин и женщин — 3,1:1. Соматический статус расценен как ECOG 2—4у 27 (20,9 %) больных. У127 (98,4 %) пациентов имелись множественные метастазы. Опухолевые очаги локализовались в >1 органе в 104 (80,6 %) случаях. Первичная опухоль удалена у 110 (85,3 %) больных, в 39 (30,2%) наблюдениях — с циторедуктивной целью. Ранее >1 линии предшествующей терапии получали 70 (54,2 %) больных. На момент включения в исследование к группе благоприятного прогноза по шкале IMDC относились 13 (10,1 %), промежуточного — 86 (66,6 %), неблагоприятного — 29 (22,5 %) больных; группа прогноза не определена у 1 (0,8 %) пациента. Всем больным назначали ленватиниб 18мг/сут с эверолимусом 5мг/сут. Медиана наблюдения за всеми пациентами составила 10,5 (1—30) мес. Результаты. Медиана беспрогрессивной выживаемости достигла 14,9(11,9—17,9) мес, общей выживаемости — 19,9(15,2—24,6) мес. Частота объективного ответа составила 17,0 % (медиана длительности — 9,7(2,8—16,5) мес), частота контроля над опухолью — 72,9 % (медиана длительности — 10,0 (2,5—17,5) мес). Нежелательные явления зарегистрированы у 112 (86,8 %), в том числе, III—IV степеней тяжести — у 27 (20,9 %) больных. Госпитализация для коррекции нежелательных явлений потребовалась в 5 (3,9 %) случаях, 1 (0,8 %) пациент умер из-за нежелательных явлений. Нежелательные явления послужили причиной отмены терапии в 4 (3,1 %), перерыва в лечении — в 35 (27,1 %), редукции дозы — в 33 (25,6 %) случаях.Заключение. Результаты второго анализа наблюдательного исследования ROSLERCM подтвердили ранее полученные результаты применения комбинации ленватиниба с эверолимусом во 2-й и последующих линиях терапии распространенного почечно-клеточного рака, рефрактерного к антиангиогенному лечению, у неотобранных российских больных

PEROXYNITRITE CHEMISTRY

This century old area of research has been experiencing a renaissance during the last decade, with the annual number of publications on the subject increasing from only one in 1990 to nearly 200 in the late-1990s. This renewed interest is stimulated by the discovery of biological roles of nitric oxide, distinguished by the 1998 Nobel prize, and the recognition that the conversion of nitric oxide into peroxynitrite may play major roles in human diseases associated with oxidative stress and in cellular defense against invading pathogens. Peroxynitrite (ONOO{sup {minus}})is a structural isomer of nitrate (NO{sub 3}{sup {minus}}) that contains a peroxo bond. The physiological route to ONOO{sup {minus}} is provided by the combination of nitric oxide ({center_dot}NO) with superoxide ({center_dot}O{sub 2}{sup {minus}}), an extremely rapid reaction occurring upon every encounter of these radicals (the upper dot denotes radical species). Both {center_dot}NO and {center_dot}O{sub 2}{sup {minus}} are the oxygen metabolic products simultaneously generated in a number of cell types within a human body. Compared to its precursors, peroxynitrite is a much stronger oxidant capable of oxidizing proteins, nucleic acids, and lipids

Nitroxyl and its anion in aqueous solutions: Spin states, protic equilibria, and reactivities toward oxygen and nitric oxide

The thermodynamic properties of aqueous nitroxyl (HNO) and its anion (NO(−)) have been revised to show that the ground state of NO(−) is triplet and that HNO in its singlet ground state has much lower acidity, pKa((1)HNO/(3)NO(−)) ≈ 11.4, than previously believed. These conclusions are in accord with the observed large differences between (1)HNO and (3)NO(−) in their reactivities toward O(2) and NO. Laser flash photolysis was used to generate (1)HNO and (3)NO(−) by photochemical cleavage of trioxodinitrate (Angeli's anion). The spin-allowed addition of (3)O(2) to (3)NO(−) produced peroxynitrite with nearly diffusion-controlled rate (k = 2.7 × 10(9) M(−1)⋅s(−1)). In contrast, the spin-forbidden addition of (3)O(2) to (1)HNO was not detected (k ≪ 3 × 10(5) M(−1)⋅s(−1)). Both (1)HNO and (3)NO(−) reacted sequentially with two NO to generate N(3)O [Formula: see text] as a long-lived intermediate; the rate laws of N(3)O [Formula: see text] formation were linear in concentrations of NO and (1)HNO (k = 5.8 × 10(6) M(−1)⋅s(−1)) or NO and (3)NO(−) (k = 2.3 × 10(9) M(−1)⋅s(−1)). Catalysis by the hydroxide ion was observed for the reactions of (1)HNO with both O(2) and NO. This effect is explicable by a spin-forbidden deprotonation by OH(−) (k = 4.9 × 10(4) M(−1)⋅s(−1)) of the relatively unreactive (1)HNO into the extremely reactive (3)NO(−). Dimerization of (1)HNO to produce N(2)O occurred much more slowly (k = 8 × 10(6) M(−1)⋅s(−1)) than previously suggested. The implications of these results for evaluating the biological roles of nitroxyl are discussed

The Efficacy and Safety of Bilastine in the Treatment of Perennial Allergic Rhinitis in Patients with Moderate and Severe Forms of the Disease. Comparison of bilastine 20 mg with desloratadine 5 mg Сергей

Background: Bilastine is a new non-sedating H1 antihistamine approved for the symptomatic treatment of allergic rhinoconjunctivitis (ARC) and urticaria in adults and children over 12 years of age. In this paper, bilastine was compared with desloratadine in the treatment of various forms of allergic rhino-conjunctivitis classified according to the ARIA recommendations.Materials and Methods: This was an international, multi-centre, open-label, prospective randomized, parallel-group, phase III study which enrolled a total of 226 patients with ARC. The diagnosis of the allergic rhino-conjunctivitis was established on the basis of nasal and non-nasal symptoms and confirmed by the skin prick test. Patients were randomized to one of the two treatment groups: bilastine 20 mg daily or desloratadine 5 mg daily.Results: The results for the primary and secondary endpoints showed a comparable reduction in TSS, NSS, and NNSS from the baseline to the end of the treatment between the treatment groups, with slightly better effects for bilastine. Additional tests carried out in the subgroup of patients with moderate / severe persistent (MSP) ARC demonstrated comparable results for the bilastine and desloratadine groups regarding the mean change in TSS from the baseline until the 28th day, except for the sneezing score, for which bilastine showed the higher response (-1.60 ± 0.60 vs. -1.39 ± 0.63), and a statistically significant difference between the treatment groups regarding AUC for TSS ( -26.07 [95% CI: -48.6, -3.53] p = 0.024), NNSS (-10.51 [95% CI:-19.42, -1.59] p = 0.021), the sneezing score (-4.79 [95% CI:-9.06, -0.51] p = 0.028) and the ocular redness score (-5.50 [95% CI: -8.91, -2.08] p = 0.02).Conclusion: In general, bilastine and desloratadine showed a comparable efficacy profile in the treatment of ARC; however, the results obtained in the subgroup of patients with moderate / severe persistent symptoms indicate that bilastine has a stronger therapeutic effec