Optimizing sgRNA to Improve CRISPR/Cas9 Knockout Efficiency: Special Focus on Human and Animal Cell

During recent years, clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein 9 (Cas9) technologies have been noticed as a rapidly evolving tool to deliver a possibility for modifying target sequence expression and function. The CRISPR/Cas9 tool is currently being used to treat a myriad of human disorders, ranging from genetic diseases and infections to cancers. Preliminary reports have shown that CRISPR technology could result in valued consequences for the treatment of Duchenne muscular dystrophy (DMD), cystic fibrosis (CF), β-thalassemia, Huntington’s diseases (HD), etc. Nonetheless, high rates of off-target effects may hinder its application in clinics. Thereby, recent studies have focused on the finding of the novel strategies to ameliorate these off-target effects and thereby lead to a high rate of fidelity and accuracy in human, animals, prokaryotes, and also plants. Meanwhile, there is clear evidence indicating that the design of the specific sgRNA with high efficiency is of paramount importance. Correspondingly, elucidation of the principal parameters that contributed to determining the sgRNA efficiencies is a prerequisite. Herein, we will deliver an overview regarding the therapeutic application of CRISPR technology to treat human disorders. More importantly, we will discuss the potent influential parameters (e.g., sgRNA structure and feature) implicated in affecting the sgRNA efficacy in CRISPR/Cas9 technology, with special concentration on human and animal studies

Factors of the Development of Fear of Disease Progression in Patients with Breast Cancer

BACKGROUND: The issue of the influence of psychics on somatic diseases, including cancer, becomes more and more relevant. In cases with cancer, patients face a vital threat, which, in its turn, is manifested as a range of biopsychosocial consequences. AIM: The aim of the study was to reveal the factors of the formation of fear of cancer progression or recurrence in breast cancer patients. METHODS: The sampling included patients from clinical hospitals of Moscow and Saint Petersburg (Russia). The study involved 690 patients aged 30–79 years old. The study was performed with specially selected diagnostic tools that allowed the authors to evaluate the intensity and reveal peculiarities of the development of fear of cancer progression. Statistical analysis was performed by the calculation of the mean arithmetic of the general sampling, the rate, and the ratio distribution by the intensity of fear of cancer progression, and Spearman correlation. RESULTS: Statistically significant associations were revealed between the parameters of intensity and peculiarities of fear of cancer progression and such characteristics of personality as viability, integrated personality, and experiences in a close relationship. CONCLUSION: The obtained results were used to develop methodical recommendations on the improvement of a psychoemotional condition of women diagnosed with breast cancer

Индивидуально-психологические детерминанты пищевого поведения студентов высших учебных заведений

The article is devoted to the problem of eating disorders of young people. The study focuses on the identification of psychological factors that determine the styles of eating behavior. The empirical results of the survey are presented, in which 937 students aged 18 to 25 took part. The aim of the study was to identify the relationship between the characteristics of the self-structure of students' personality, reflecting the state of their identity, and the characteristics of their eating behavior. As a result, it was revealed that constructive, destructive, and deficit self-functions (as unconscious personality constructs) find their expression not only in behavior and interpersonal social relations, but also in the style of eating behavior, tendencies to eating disorders and deviations.El artículo se centra en el problema del trastorno del comportamiento alimentario de las personas jóvenes. El estudio se centra en la detección de los factores psicológicos que determinan los estilos del comportamiento alimentario. Se presentaron los resultados empíricos de la encuesta, en la que participaron 937 estudiantes de 18 a 25 años. El observatorio del estudio fue identificación de la relación entre las características de la estructura del autoconcepto de la personalidad de los estudiantes, que reflejan el estado de su identidad, y las características de su comportamiento alimentario. Como resultado, se reveló que las funciones constructivas, destructivas y deficientes del autoconcepto, (como los diseños de personalidad inconscientes), encuentran su expresión no solo en el comportamiento y las relaciones sociales interpersonales, sino también en el estilo del comportamiento alimentario, las inclinaciones a los desarreglos alimentarios y los trastornos.Статья посвящена проблеме нарушения пищевого поведения людей молодого возраста. В исследовании акцентируется внимание на выявлении психологических факторов, детерминирующих стили пищевого поведения. Представлены эмпирические результаты опроса, в котором приняли участие 937 студентов в возрасте от 18 до 25 лет. Целью исследования стало выявление взаимосвязи между особенностями Я-структуры личности студентов, отражающими состояние их идентичности, и особенностями их пищевого поведения. В результате было выявлено, что конструктивные, деструктивные и дефицитарные Я-функции, (как неосознаваемые конструкты личности), находят свое выражение не только в поведении и межличностных социальных отношениях, но и в стиле пищевого поведения, склонностях к пищевым расстройствам и нарушениям

Влияние взаимодействия в системе «Врач – Пациент» на состояние больных

The study focuses on the search for ways to solve the problem of improving the quality of medical care for heart disease patients; the effectiveness of patients’ treatment is determined by the science-oriented medicine achievements and the general psycho-emotional states arising in various situations of doctor-patient interaction. The aim of the study is to identify the types of doctors and their impacts on patients’ psycho-emotional states and attitudes toward the disease. The study was conducted in a number of clinical hospitals in Moscow (Russia). It involved 167 doctors and 1,248 patients with arterial hypertension, coronary heart disease, and arrhythmias, aged 43 to 82 years. The study was carried out using valid psychodiagnostic techniques. There were statistically significant differences in the characteristics of the response to the disease in heart disease patients, whose physicians established with them collaborative, caring, directive, authoritarian and alienated relationships.El estudio se centra en la búsqueda de formas de resolución el problema de mejorar la calidad de la asistencia médica a los pacientes con enfermedades cardiovasculares, cuya eficacia del tratamiento se determina por los logros de la medicina naturalmente orientada a la ciencia y la condición psique-emocional general que se produce en situaciones diversas de su interacción con el médico tratante. El observatorio del estudio es identificación de los tipos de médicos tratantes y sus efectos sobre la condición psique-emocional y la actitud hacia la enfermedad de los pacientes.  El estudio se llevó a cabo sobre la base de la serie de hospitales clínicos en Moscú (Rusia). En el estudio participaron 167 médicos y 1248 pacientes con hipertensión arterial, enfermedad isquémica coronaria y arritmias, de 43 a 82 años. El estudio se realizó con la ayuda de técnicas psiquediagnósticas validas. Se han obtenido las diferencias estadísticamente fidedignas en los indicadores de la respuesta a la enfermedad en pacientes con enfermedades cardiovasculares, cuyos médicos tratantes establecen relaciones cooperativas, de tutela, directivas, autoritarias y suspendidas con ellos.Исследование ориентировано на поиск способов решения проблемы повышения качества оказания медицинской помощи пациентам с сердечно-сосудистыми заболеваниями, эффективность лечения которых определяется как достижениями естественно-научно ориентированной медицины, так и общим психоэмоциональным состоянием, возникающим в различных ситуациях его взаимодействия с лечащим врачом. Цель исследования – выявление типов лечащих врачей и их влияния на психоэмоциональное состояние и отношение к болезни пациентов.  Исследование проводилось на базе ряда клинических больниц г. Москвы (Россия). В исследовании приняли участие 167 врачей и 1248 пациентов с артериальной гипертонией, ишемической болезнью сердца и аритмиями, в возрасте от 43 до 82 лет. Исследование осуществлялось с помощью валидных психодиагностических методик. Были получены статистически достоверны различия в показателях особенностей реагирования на болезнь у пациентов с сердечно-сосудистыми заболеваниями, лечащие врачи которых устанавливают с ними сотруднические, опекающие, директивные, авторитарные и отстраненные отношения

Mortality Rate Due to Circulatory and Alcohol-Dependent Diseases in Different Climatic Zones of Russia

AIM: Evaluation of the impact of climatic factors on the formation of mortality due to circulatory diseases and a group of diseases related to alcohol consumption identified as alcohol-dependent. METHODS: The study subject was the adult population residing in different climatic zones of Russia: in the second, third and fourth zones, with different conditions: average annual temperature (5.2°C; 1-2°C; -2.0°C), snow cover duration (≤ 150 days, ≤ 180 days, ≈ 220 days) sunshine duration and the presence of polar night and polar day in the territory of the fourth climatic zone. The assessment “impact-case of death†was carried out by calculating the standardized incidence ratio (SIR) with 95% confidence intervals (CI) for circulatory system diseases (CSD) and alcohol-dependent diseases (ADD) in accordance with the international classification of diseases (ICD-X). RESULTS: The SIR of death from alcohol-dependent diseases for the female population in the 4th climatic zone (Murmansk Region) was the highest: the SIR of death from ADD 1.87; 95% CI (1.5-2.7), the SIR of death from CSD 1.3; 95% CI (1.2-2.3). For the female population in the 3rd climatic zone (Novosibirsk Region), the SIR of death has amounted to: SIRADD 1.52; 95% CI (1.2-1.87), SIRCSD 1.14; 95 CI (1.01-1.3). Living in the 3rd climatic zone was not so important for the health of the male population: the SIR of death from CSD 1.1; 95% CI (1.05-1.13); the SIR of death from ADD 0.8; 95% CI (0.65-0.98). However, living in the 4th climatic zone (Murmansk Region) poses a higher risk of death for the male population: SIRCSD 1.22 (22.0%); 95% CI (1.02-3.95); SIRADD 1.45 (45.0%); 95% CI (0.98-2.1). CONCLUSION: Living in high northern latitudes contributes to higher levels of mortality, both female and male, from circulatory and alcohol-dependent diseases

Combined Antirelapse Therapy in Patients with Schizoaffective Disorder: A Prospective Cohort Study

Background: In most studies, patients with schizoaffective disorder (SAD) are often combined into one group along with schizophrenia patients or less commonly with those suffering from affective disorders, which makes it difficult to obtain data about the peculiarities of SAD treatment. Articles dedicated to SAD treatment in the interictal period are rare. Methods and Results: The prospective cohort study was conducted from 2011 to 2015. The study involved 86 patients diagnosed with SAD according to ICD-10. Patients received neuroleptics (NLs) as antirelapse therapy for 2 years (NL therapy); then mood stabilizers (MSs) were added to the antirelapse treatment (NL+MS therapy). The results of this combined therapy with MSs were evaluated after 2 years of treatment. Our results suggest that the use of combination therapy that includes antipsychotics and MSs leads to maintenance of a higher quality remission. Remission becomes more prolonged and affective swings less pronounced, resulting in improved quality of life in SAD patients. Improving the quality of remission can be attributed to the following characteristics of the combined therapy: a) the use of lower doses of neuroleptics; b) a reduction in the frequency and severity of mood swings; and c) an increase in patient compliance. Conclusion: The use of combined pharmacotherapy including antipsychotics and MSs produces a longer, high-quality remission. The inclusion of MSs in the scheme of treatment increases the patient adherence to a medication regimen. The use of MSs in combination therapy reduces affective fluctuations, thereby increasing the probability of maintaining remission with complete symptom relief

Efficacy and safety of metformin for the treatment of gestational diabetes: a new approach to the problem

Historically, the following two methods were used to treat gestational diabetes mellitus: non-medical life-style interventions (diet and increased physical activity) and insulin treatment when other interventions were not effective. The possibility of alternative types of treatment such as oral anti-diabetic drugs has been the source of debate in recent years. Metformin is an oral anti-diabetic drug that reduces insulin resistance, which is common during gestation and is considered one of the main pathways of glucose metabolism alteration during pregnancy. The main concern is that metformin can cross the placenta and is found unchanged in foetal blood. This is the reason why oral anti-diabetic drugs are contraindicated during pregnancy in many countries, including Russia (according to the 2012 Russian recommendations for gestational diabetes treatment). In recent years, many studies investigating the safety and efficacy of metformin for maternal and foetal health have been published. We will review recent randomized clinical trials and discuss new international clinical recommendations (FIGO, 2015) and new opportunities for gestational diabetes mellitus treatment