Individual Manifestations Research Articles

Widespread Aneurysms Secondary to Myosin Light-Chain Kinase Gene Mutation Leading to Multifocal Right Hemispheric Stroke (P3-5.001)

<h3>Objective:</h3> Familiarize providers with the presence of the Myosin Light-Chain Kinase (MYLK) and the possible vascular manifestations in individuals carrying this autosomal dominant gene mutation. <h3>Background:</h3> Myosin Light-Chain Kinase is a ubiquitously expressed kinase involved in the physiological contraction of smooth muscle cells within hollow organs. Variations in the Myosin Light-Chain Kinase (MYLK) gene lead to decrease in phosphorylation of 20kDa regulatory light-chain leading to a reduction in smooth muscle contractile function. MYLK gene mutations have been associated with autosomal dominant thoracic aortic aneurysms and dissections, however there are limited studies mentioning the involvement of other vascular structures containing these dysfunctional smooth muscle cells. In this report, we present a case of a 43-year-old individual who presented to the hospital for quadrantanopia, hearing loss and headache who was subsequently found to have an acute stroke of multiple foci involving the right ACA and MCA territories. Past medical history was significant for hemochromatosis, early onset coronary artery disease in self and close family members. Etiology workup revealed a right internal carotid artery aneurysm measuring 10cm. Complains of abdominal pain led to imaging revealing focal dissection of the abdominal aorta, a right common iliac artery 2.3cm aneurysm as well as a proximal celiac artery 1.7cm aneurysm. On outpatient genetic testing, the patient was found to be a carrier of the MYLK (p.Val509Met) gene mutation; variance was of unclear significance, however familial thoracic aneurysms/dissections have been reported in the Clinical Variance Database. The patient has since been managed with dual anti-platelet therapy and was instructed to follow closely with neurological and vascular surgery for close monitoring. <h3>Design/Methods:</h3> NA <h3>Results:</h3> NA <h3>Conclusions:</h3> This case highlights the MYLK gene mutation and its possible relationship with widespread malformations in the carotid, celiac, and mesenteric vasculature to familiarize practitioners with manifestations and clinical sequelae of individuals affected with this gene. <b>Disclosure:</b> Dr. Hamzoian has nothing to disclose. Dr. Abdelmasih has nothing to disclose. Dr. Ditamo has nothing to disclose. Dr. Kahila has nothing to disclose.

Integral testing indicators individual features of various playing roles volleyball players at the specialized basic training stage

Rationale and purpose: Volleyball has a unique feature of combining both tall attackers and small, fast liberos in one team. The purpose of the study was to develop individual programs of the educational and training process of volleyball players at the stage of specialized basic training based on factor models of their readiness.&#x0D; Material and Methods: The women's volleyball team of the Children's League of Ukraine of sports boarding school No. 1 in the city of Kharkiv took part in the study, in the number of 12 players aged 15-16 years. The testing was carried out on 10 tests of physical fitness. From the methods of statistical analysis, the method of descriptive statistics, factor analysis by the method of principal components with the determination of the individual manifestation of each factor in female athletes, and cluster analysis were used.&#x0D; Results: On the basis of the factor analysis, the structure of the preparedness of volleyball players at the stage of specialized basic training was determined, in which four pronounced factors were revealed. The model of the existing or possible belonging of the players to the role according to the determined factor structure is determined: in the forwards of the first tempo, the factors "speed-power readiness" and "power endurance" come to the fore, in the attackers of the second pace - "speed-power readiness" and "speed endurance", in "communication" - "speed endurance" and "special (aerobic-anaerobic) endurance", in libero - "power endurance" and "special (aerobic-anaerobic) endurance". Using this scheme, you can determine the individual potential opportunities of different players to play in different roles.&#x0D; Conclusions: As a result of the cluster analysis, the functions of volleyball players were clarified and the players most similar to each other in terms of their preparation structure were identified, which sometimes causes some difficulties for coaches when working with athletes with implicitly expressed game functions. Individual profiles of players were compiled and individual recommendations for training volleyball players were developed based on the individual values of readiness factors and the results of cluster analysis.

Risk factors for the femoral head aseptic necrosis development in patients with systemic lupus erythematosus

Objective: to identify risk factors for the development of the femoral head aseptic necrosis (FHAN) and osteoarthritis (OA) of the hip joint (HJ) in patients with systemic lupus erythematosus (SLE) according to a retrospective analysis.Material and methods.The retrospective study included data from the case histories of 103 patients with SLE who underwent total hip arthroplasty (HA) (unilateral in 82 patients, bilateral in 21). The total follow-up period ranged from 2 years to 21 years. Among the patients included in thestudy, the majority were women (86.4%), the ratio of women and men was 7:1. At the time of surgery, the average age of women was 36.3±13.25 years, men – 36.2±9.57 years, duration of the disease – 168.0±132.5 months. SLE activity was assessed using the SLEDAI-2K scale. All patients were taking glucocorticoids (GC). The average duration of GC treatment was 89.0±87.2 months. 71.8% of patients received immunosuppressive therapy: hydroxychloroquine – 55.3%, azathioprine – 10.7%, methotrexate – 5.8%. The functional status of hip joint was determined using the Harris scale; by the time of surgery, the average score was 45.6±13.1 points. Pain intensity was assessed using a visual analogue scale and reached an average of 70.1±16.0 mm.Results and discussion. In 58.5% of patients with SLE, the indication for HA was FHAN (Group 1) and in 41.6% – OA of HJ (Group 2). At the time of HA, the duration of the disease was longer and the age was higher in group 2 than in group 1 (p&lt;0.05). An analysis of individual clinical manifestations of SLE that preceded the development of HJ pathology revealed that arthritis and the presence of an antinuclear factor, ANF, were associated with the development of FHAN (p=0.022 and p=0.04, respectively). At the onset of the disease, patients of the 1st group, compared with patients of the 2nd group, more often had lesions of the skin, kidneys and serositis (22.9 and 20.5%; 14.5 and 11.7%; 68.7 and 64.7 %, respectively), but they were less likely to have mucous membranes and the central nervous system (CNS) involvement (14.5 and 23.5%; 10.4 and 17.6%, respectively). However, these differences did not reach statistical significance. Almost all of these disease manifestations, with the exception of the mucous membranes and the CNS lesions, were more often observed in patients with the development of FHAN, which indicates a higher activity of the disease at the onset of SLE. At the time of HA, we did not find any relationship between SLE activity and FHAN formation and hip OA. Patients of the 1st and 2nd groups in the same number of cases had mild (56.2 and 58.8%, respectively) and moderate (35.4 and 32.4%, respectively) activity according to SLEDAI-2K. No activity (SLEDAI-2K – 0 points) was also observed in patients of both groups with the same frequency (8.3 and 8.8% of cases, respectively). Associations of cumulative and daily doses of GC with the development of FHAN and OA of HJ were not revealed. In the 1st group, the average daily dose of GC was slightly higher, and the cumulative dose was less than in the 2nd group (8.59±4.75 and 7.79±5.39 mg; 20.0±11.9 and 23.8±19.2 g, respectively), but these differences were not significant (p&gt;0.05).Conclusion. In SLE patients, the incidence of FHAN and HJ OA was comparable. At the time of HA, SLE patients with HJ OA were older and had a longer duration of the disease than patients with FHAN. The risk factors for FHAN were arthritis and ANF positivity at the onset of SLE.

Validation of the French version of the Emotion and Regulation Beliefs Scale (ERBS) and Dissociation Belief Scale (DBS)

Dissociation is a recurrent symptom of post-traumatic stress disorder (PTSD) and is associated with emotional dysregulation. Beliefs about emotions seem to be involved in emotional dysregulation but have not been studied in relation to dissociation. Likewise, there is currently little empirical evidence of beliefs about dissociation. The aims of the study were to validate psychometric tools assessing these beliefs, to assess their role in dissociation, and to explore the mediating role of emotional dysregulation and beliefs about dissociation in the relationship between beliefs about emotion and dissociation. We recruited a sample from the general population (n=1009) and a sample of patients with PTSD (n=90). All participants completed self-report questionnaires to evaluate symptoms of PTSD (PTSD Checklist/Impact of Event Scale, PCL-5/IES-6), dissociation (Dissociative Experiences Scale, DES), difficulties in emotion regulation (Difficulties in Emotion Regulation Scale, DERS), beliefs about dissociation (Dissociation Beliefs Scale, DBS), and beliefs about emotion (Emotion and Regulation Beliefs Scale, ERBS). The questionnaires used to assess the beliefs about emotion (ERBS) and dissociation (DBS) had good psychometric properties. Dissociation was positively associated with positive and negative beliefs about dissociation and with negative beliefs about emotions in both the clinical and non-clinical groups. The relationship between beliefs about emotions and dissociation was mediated by emotional dysregulation and positive beliefs about dissociation in both groups. The ERBS and DBS are effective tools to assess beliefs. Beliefs about emotion and dissociation seem to be involved in dissociative manifestations in both clinical and non-clinical individuals.

Laparoscopic diaphragm repair with bioabsorbable mesh in congenital and acquired diaphragmatic hernia

Background and Aim: Congenital or acquired diaphragmatic hernias are both possible. The present study aimed to investigate the superiority of laparoscopic surgery over open repair of congenital diaphragmatic hernias with bioabsorbable mesh in congenital and acquired diaphragmatic hernia. Patients and Methods: This retrospective study was conducted on 7 diaphragmatic hernia cases in the General Surgery Unit of Federal Government Polyclinic Hospital, Islamabad from January 2015 to December 2022. Diaphragmatic hernia was diagnosed and confirmed on CT scan. Patients with Bochdalek hernia (BH), right-sided eventration of diaphragm, and left eventration of diaphragm (ED) cases were enrolled. Individual demographic details, clinical manifestations, hernia description, treatment modalities, and complications were recorded. Results: The overall mean age was 42 years with an age range 30-62 years. Of the total cases, there were 6 (85.7%) male and 1 (14.3%) female. The incidence of Bochdalek hernia (BH), left-sided ED, and right-sided ED was 2 (28.6%), 4 (57.1%), and 1 (14.3%) respectively. The major defect on left and right side was 15× 7 cm and 15× 8 cm respectively.

Dissection of a Down syndrome-associated trisomy to separate the gene dosage-dependent and -independent effects of an extra chromosome.

As an aneuploidy, trisomy is associated with mammalian embryonic and postnatal abnormalities. Understanding the underlying mechanisms involved in mutant phenotypes is broadly important and may lead to new strategies to treat clinical manifestations in individuals with trisomies, such as trisomy 21 [Down syndrome (DS)]. Although increased gene dosage effects because of a trisomy may account for the mutant phenotypes, there is also the possibility that phenotypic consequences of a trisomy can arise because of the presence of a freely segregating extra chromosome with its own centromere, i.e. a 'free trisomy' independent of gene dosage effects. Presently, there are no reports of attempts to functionally separate these two types of effects in mammals. To fill this gap, here we describe a strategy that employed two new mouse models of DS, Ts65Dn;Df(17)2Yey/+ and Dp(16)1Yey/Df(16)8Yey. Both models carry triplications of the same 103 human chromosome 21 gene orthologs; however, only Ts65Dn;Df(17)2Yey/+ mice carry a free trisomy. Comparison of these models revealed the gene dosage-independent impacts of an extra chromosome at the phenotypic and molecular levels for the first time. They are reflected by impairments of Ts65Dn;Df(17)2Yey/+ males in T-maze tests when compared with Dp(16)1Yey/Df(16)8Yey males. Results from the transcriptomic analysis suggest the extra chromosome plays a major role in trisomy-associated expression alterations of disomic genes beyond gene dosage effects. This model system can now be used to deepen our mechanistic understanding of this common human aneuploidy and obtain new insights into the effects of free trisomies in other human diseases such as cancers.

СТУДОЦЕНТРОВАНИЙ ПІДХОД ДО ОРГАНІЗАЦІЇ ОСВІТНЬОГО ПРОЦЕСУ ЯК УМОВА РОЗВИТКУ КОНКУРЕНТОСПРОМОЖНОСТІ МАЙБУТНЬОГО ВЧИТЕЛЯ

Prerequisites for the actualization of the problem of the development of the teacher's competitiveness are socio-economic and educational transformations, which were reflected in the content of state documents on the modernization of education in Ukraine. A modern teacher needs to be ready for ever-changing trends in society and the labor market. Responding to the demands of the times, higher pedagogical education should be based on the ideology of development and qualitatively change. The system of professional pedagogical training should provide for the process and result of mastering the system of general and subject competencies and the formation of the worldview and other personal qualities of the future teacher based on them, including competitiveness. We define competitiveness as a set of formed personal and professional qualities and characteristics that determine success in professional and social activities, and highlight the following characteristics of a competitive teacher: professional competence, value-motivational component; manifestation of individuality. We believe that the competitiveness of the future teacher is a dynamic characteristic of the individual, therefore we can talk about its development as a result of the formation of a set of key competencies of the individual, which make up the professional and personal basis of activity and professional competence. In our opinion, one of the conditions for the development of social and professional mobility of a future specialist is studio-centered training. Student-centered learning is a modern philosophy of educational activity, an important principle of organizing educational activities of a higher school. Orientation of higher education on the personality of the student makes it possible to increase the quality of the higher education system, to prepare a competitive specialist in the modern labor market with flexible creative thinking, proactive, stimulates him to responsible learning, develops social and professional mobility. Elective disciplines are an "indicator" of the introduction of an individual educational trajectory of a student of higher education, one of the mechanisms for improving the quality of professional training, developing the social and professional mobility of a future specialist.

공직자윤리법상 공직부패 방지에 대한 고찰

Corruption in the public service society undermines the principle of fair competition and the health of the market, undermines the public's trust in the public, and ultimately violates the basic principles and values of the Constitution, including the principle of the rule of law, which is a fundamental principle of our Constitution.&#x0D; As a public service ethics, integrity is a standard of morality that public officials should have, and the duty of integrity of a member of the National Assembly under Article 46(1) of the Constitution is a duty that applies to all public officials beyond the members of the National Assembly. Under the Ethics of Public Officials Act, the system of property registration and disclosure does not violate the Constitution because it does not regulate how public officials form property or the limits on property holdings, but rather requires them to register the formed property by declaring it to the state.&#x0D; Stocks are property rights that have a fairly small meaning for the individual's personality manifestation, but because their social associations and social functions are distinct, they can be more broadly restricted by the state. Because a stock trust is based on a substantial connection between a public official and a family member, it does not fall under the constitutionally prohibited association system. The employment restriction of retired public officials is intended to ultimately ensure the fairness of their duties by preventing the possibility of using confidential information or information obtained during their employment for certain companies re-employed after retirement, or exerting undue influence over the department in which they were employed.

Investigation of the Reasons for Motivation to Study Chinese at Confucius Institutes in Russia in the Context of Globalization.

This article is devoted to the issues of the spread of the Chinese language in Confucius Institutes in Russia in the era of globalization. It examines the main motivating factors for learning Chinese. Attention is drawn to the increasing interest in China in Russia, to the study of the Chinese language. The relevance of the research is due to the growing interest in the Chinese language in Russia due to the direct interest in China, its ancient culture, as well as for the development of professional skills and career growth. The purpose of the study is to study the reasons for the spread of the Chinese language in Confucius Institutes in Russia in the context of globalization. To achieve this goal, the activities of the Confucius Institute at the Far Eastern Federal University (FEFU) were studied, as well as a survey of students was conducted According to the results, the main motives for choosing are related to interest in Chinese culture (including its individual manifestations), possible career prospects and the desire for self-development. The results obtained make it possible to more effectively build the learning process at the Confucius Institute in Russia.

Mapping the burden of severe forms of epidermolysis bullosa – Implications for patient management

The pathophysiological processes underlying the phenotypic spectrum of severe forms of epidermolysis bullosa (EB) are complex and poorly understood. To use burden mapping to explore relationships between primary pathomechanisms and secondary clinical manifestations in severe forms of EB (junctional and dystrophic EB [JEB/DEB]) and highlight strengths and weaknesses in evidence regarding the contribution of different pathways. Literature searches were performed to identify evidence regarding the pathophysiological and clinical aspects of JEB/DEB. Identified publications and clinical experience were used to construct burden maps to visually communicate plausible connections and their relative importance by subtype. Our findings suggest that most of the clinical consequences of JEB/DEB may result from an abnormal state and/or faulty skin remodeling driven by a vicious cycle of delayed wound healing, predominantly mediated through inflammation. The quantity and quality of evidence varies by individual manifestations and disease subtype. The burden maps are provisional hypotheses requiring further validation and are limited by the published evidence base and subjectivity in clinical opinion. Delayed wound healing appears to be a key driver of the burden of JEB/DEB. Further studies are warranted to understand the role of inflammatory mediators and accelerated wound healing in patient management.

A qualitative study of the sources of chronic obstructive pulmonary disease-related emotional distress.

The aim of this study is to identify the sources of illness-related emotional distress from the perspective of individuals living with mild to severe chronic obstructive pulmonary disease (COPD). A qualitative study design with purposive sampling was applied at a Swiss University Hospital. Eleven interviews were conducted with individuals who suffered from COPD. To analyze data, framework analysis was used, guided by the recently presented model of illness-related emotional distress. Six main sources for COPD-related emotional distress were identified: physical symptoms, treatment, restricted mobility, restricted social participation, unpredictability of disease course and COPD as stigmatizing disease. Additionally, life events, multimorbidity and living situation were found to be sources of non-COPD-related distress. Negative emotions ranged from anger, sadness, and frustration to desperation giving rise to the desire to die. Although most patients experience emotional distress regardless of the severity of COPD, the sources of distress appear to have an individual manifestation. There is a need for a careful assessment of emotional distress among patients with COPD at all stages of the disease to provide patient-tailored interventions.

“Looking beyond Mental Health Stigma”: An Online Focus Group Study among Senior Undergraduate Nursing Students

Evidence highlights the need for professionals to be aware of their stigmatizing attitudes and discriminatory practices in order to minimize the negative impact on the people they take care of. However, nursing students' perceptions of these issues have been poorly studied. This study explores the perspective of senior undergraduate nursing students on mental health and the stigma around it, by considering a simulated case vignette of a person with a mental health problem. A descriptive qualitative approach was chosen and involved three online focus group discussions. The findings show various manifestations of stigma, both at an individual and collective level, which indicates that it is an obstacle to the wellbeing of people with mental illness. Individual manifestations of stigma concern its effect on the person with mental illness, while at the collective level they concern the family or society in general. Stigma is a multifactorial, multidimensional, and complex concept, in terms of identifying and fighting it. Thus, the strategies identified involve multiple approaches at the individual level, aimed at the patient and family, namely through education/training, communication, and relationship strategies. At the collective level, to intervene with the general population and specific groups, such as groups of young people, strategies suggested include education/training, use of the media, and contact with people with mental disorders as ways to fight stigma.

Integrator complex subunit 15 controls mRNA splicing and is critical for eye development.

The eye and brain are composed of elaborately organized tissues, development of which is supported by spatiotemporally precise expression of a number of transcription factors and developmental regulators. Here we report the molecular and genetic characterization of Integrator complex subunit 15 (INTS15). INTS15 was identified in search for the causative gene(s) for an autosomal-dominant eye disease with variable individual manifestation found in a large pedigree. While homozygous Ints15 knockout mice are embryonic lethal, mutant mice lacking a small C-terminal region of Ints15 show ocular malformations similar to the human patients. INTS15 is highly expressed in the eye and brain during embryogenesis and stably interacts with the Integrator complex to support small nuclear RNA 3' end processing. Its knockdown resulted in missplicing of a large number of genes, probably as a secondary consequence, and substantially affected genes associated with eye and brain development. Moreover, studies using human iPS cells-derived neural progenitor cells showed that INTS15 is critical for axonal outgrowth in retinal ganglion cells. This study suggests a new link between general transcription machinery and a highly specific hereditary disease.

Рrofessional burnout syndrome as a manifestation of stress in naval specialists of different age groups

OBJECTIVE: To assess the symptom severity and formation of professional burnout syndrome (PBS) in naval experts of different age groups.MATERIALS AND METHODS: 849 naval experts, aged 25–45 were examined. Based on generally accepted methods, there was the evaluation of professional burnout and stress, considering clinical-psychophysiological features of the respondents with a different severity level of symptom manifestation. Moreover, to assess the dynamics of professional burnout in naval experts, performing military service as part of Arctic division, subgroups by age were identified out of the total sample (N=127): the group of persons, performing military service as part of Arctic division aged 25–30 included 21 people (n1=21), aged 31–40–72 people (n2=72), aged 41–45–34 people (n3=34). Statistics: Statistic analysis of the data was conducted using the application package «STATISTICA 6.0» and spreadsheet Microsoft Excel-2010.RESULTS: The formation nature of PB syndrome in naval experts of different age showed that the persons, performing military service as part of Arctic division, aged 25–30, experienced a high rate of stress phase (68,1±7,9 points), indicating its formation, and 39,8±7,5 points in the resistance phase, indicating the process of this phase formation; yet there were normative values (28,4±5,1 points) on the exhaustion phase in this group of people. The naval experts, performing military service as part of Arctic division, aged 31–40, experienced a high rate of stress phase (72,8±7,9 points) and resistance phase (73,4±11,5 points), indicating their formation in the examined individuals; at the same time the indicators on the exhaustion phase did not overcome the normative values of 26,7±7,2 points. The naval experts, performing military service as part of Arctic division, aged 41–45, experienced average normative values on stress phase (25,9±3,8 points), resistance phase (23,9±3,9 points); yet there was formation of exhaustion phase (39,1±6,9 points).DISCUSSION: The analysis allowed to reveal age-sensitive formation of professional burnout syndrome. It is shown that individual manifestations of the syndrome form clear modal symptoms among different age groups. The specifics of neuropsychic disorders in naval experts of different age groups were identified.CONCLUSION: The data analysis allowed to conclude that prevention of PBS formation and its successful overcoming could largely be achieved by naval experts’ implementation of optimal strategies for coping with stress and using constructive and mature psychological defenses in their behavior.

Toxoplasmosis-Associated Lymphadenopathy: Description of a Series of Cases in a Reference Center

Background: Toxoplasmosis has a more severe manifestation in pregnant women and immunocompromised individuals. Up to 15% of immunocompetent individuals who have acquired the infection may be asymptomatic, however in others the symptoms may be confused with another infection and cause more severe manifestations such as ocular toxoplasmosis which is the most common cause of chorioretinitis and can lead to retinal necrosis. Considering that the clinical characteristics of lymphadenopathy-related toxoplasmosis in Colombia have not been reported despite its high frequency, it is essential to define its clinical presentation. Objective: The objective was to describe a series of cases, their evolution, clinical characteristics and response to treatment of lymphadenopathy due to toxoplasmosis in a first level health care institution in Armenia, Colombia. Methods: 106 medical records with a diagnosis of toxoplasmosis-associated lymphadenopathy were reviewed from 2006 to 2022 at the Universidad del Quindío health center. Cases that met the following criteria were included: Presence of lymphadenopathies accompanied or not by fever and positive IgM or IgG anti-Toxoplasma test. Clinical presentation, accompanying symptoms and laboratory tests were analyzed. In the patients who had follow-up, the response to treatment was analyzed. Results: Of 106 cases, 100 met the selection criteria, 59% male, 30% adolescent. Coinfections occurred in 3% with Epstein-Barr virus (EBV) and 2% Cytomegalovirus. The location was predominately of cervical adenopathies (83%). The main associated symptom was fever with 37%. The main treatment received was Pyrimethamine/Sulfadoxine with 37% having an adequate response. Conclusions: The clinical manifestations of the infection should guide us to consider the possible presence of lymph node toxoplasmosis. Timely diagnosis and treatment prevent severity and complications in our environment such as ocular involvement which greatly impacts the quality of life of the population.

A Silver Bullet or a Toolkit to Treat AUD? The Contribution of NK-1R Antagonists

AUDs (Alcohol Use Disorders) encompass pathologies with individual traits and manifestations linked to genetic backgrounds, environmental exposures, and family and social dynamics. The search for effective pharmacological treatments has frequently thrown its weight behind a single therapy: a purported “silver bullet” that may cure alcoholism. However, given the complexity of the pathologies associated with AUDs, and the individual variations, this endeavor may fail. Consequently, basic research and clinical trials have contributed strategies targeting specific facets of harmful alcohol consumption.

A mutational hotspot in AMOTL1 defines a new syndrome of orofacial clefting, cardiac anomalies, and tall stature.

AMOTL1 encodes angiomotin-like protein 1, an actin-binding protein that regulates cell polarity, adhesion, and migration. The role of AMOTL1 in human disease is equivocal. We report a large cohort of individuals harboring heterozygous AMOTL1 variants and define a core phenotype of orofacial clefting, congenital heart disease, tall stature, auricular anomalies, and gastrointestinal manifestations in individuals with variants in AMOTL1 affecting amino acids 157-161, a functionally undefined but highly conserved region. Three individuals with AMOTL1 variants outside this region are also described who had variable presentations with orofacial clefting and multi-organ disease. Our case cohort suggests that heterozygous missense variants in AMOTL1, most commonly affecting amino acid residues 157-161, define a new orofacial clefting syndrome, and indicates an important functional role for this undefined region.

The structural and dynamic analysis of the clinical-psychopathological components of emotional burnout and professional disappointment in psychiatrists during the war

In order to evaluate and meaningful structural-dynamic analysis of psychopathological manifestations of emotional burnout (EB) and professional maladjustment (MA) in psychiatrists during the war 120 psychiatrists who worked in Kyiv in the period from February 24, 2022, during 2022, were examined. The comprehensive examination included the use of clinical-psychopathological, psychodiagnostic and psychometric research methods. Psychiatrists showed a wide range of expressiveness of manifestations of EB and violations of pro- fessional MA — from their absence to a high level. In most of the examined (47.5 %), EB and MA corresponded to a moderate level (this level requires medical and psychological assistance from rehabi- litation specialists). The specific weight of doctors with a low level of EB and professional MA was also significant (30.8 %) (such doctors, it may be recommended to conduct consultative work in a preven- tive direction). The share of doctors with pronounced and high levels of EB and MA was significantly lower (21.7 %) (such doctors require the mandatory intervention of specialists to apply urgent medical and psychological measures, carry out a program for readaptation or change professional activity). Psychiatrists with manifestations of EV and professional MA of varying degrees of severity showed signs of depressive and anxiety disorders, while anxiety manifestations were more expressive than depressive ones. In doctors with individual manifestations of MA, depressive symptoms corresponded to a mild level, and anxiety symptoms corresponded to an average level, while in doctors with an estab- lished MA, signs of depressive disorders were found at a close to moderate level, and anxiety indicators were of a medium or high level. Psychiatrists with manifestations of EV and professional MA of various degrees of severity are char- acterized by manifestations of a wide spectrum of psychopathological symptoms of varying intensity and variability, the leading place among which is occupied by manifestations of depression, anxiety, somatization, and obsessive-compulsive symptoms. At the same time, among doctors without signs of MA, the indicators of expressiveness of psychopathological symptoms correspond to a low level, and among doctors with manifestations of MA — to an average and high level. The highest indicators of expressiveness of psychopathological symptoms were found in the group of doctors with an established MA, and significantly lower — in the group of doctors with individual signs of MA. The revealed regularities should be taken into account when developing treatment and preventive measures for this contingent of respondents.

The development of compulsive coping behaviour is associated with a downregulation of Arc in a Locus Coeruleus neuronal ensemble

Some compulsive disorders have been considered to stem from the loss of control over coping strategies, such as displacement. However, the cellular mechanisms involved in the acquisition of coping behaviours and their subsequent compulsive manifestation in vulnerable individuals have not been elucidated. Considering the role of the locus coeruleus (LC) noradrenaline-dependent system in stress and related excessive behaviours, we hypothesised that neuroplastic changes in the LC may be associated with the acquisition of an adjunctive polydipsic water drinking, a prototypical displacement behaviour, and the ensuing development of compulsion in vulnerable individuals. Thus, male Sprague Dawley rats were characterised for their tendency, or not, to develop compulsive polydipsic drinking in a schedule-induced polydipsia (SIP) procedure before their fresh brains were harvested. A new quantification tool for RNAscope assays revealed that the development of compulsive adjunctive behaviour was associated with a low mRNA copy number of the plasticity marker Arc in the LC which appeared to be driven by specific adaptations in an ensemble of tyrosine hydroxylase (TH)+, zif268− neurons. This ensemble was specifically engaged by the expression of compulsive adjunctive behaviour, not by stress, because its functional recruitment was not observed in individuals that no longer had access to the water bottle before sacrifice, while it consistently correlated with the levels of polydipsic water drinking only when it had become compulsive. Together these findings suggest that downregulation of Arc mRNA levels in a population of a TH+/zif268− LC neurons represents a signature of the tendency to develop compulsive coping behaviours.

Cardiovascular Disease Among Persons Living With HIV: New Insights Into Pathogenesis and Clinical Manifestations in a Global Context

Widespread use of contemporary antiretroviral therapy globally has transformed HIV disease into a chronic illness associated with excess risk for disorders of the heart and circulatory system. Current clinical care and research has focused on improving HIV-related cardiovascular disease outcomes, survival, and quality of life. In high-income countries, emphasis on prevention of atherosclerotic coronary artery disease over the past decade, including aggressive management of traditional risk factors and earlier initiation of antiretroviral therapy, has reduced risk for myocardial infarction among persons living with human immunodeficiency virus-1 infection. Still, across the globe, persons living with human immunodeficiency virus-1 infection on effective antiretroviral therapy treatment remain at increased risk for ischemic outcomes such as myocardial infarction and stroke relative to the persons without HIV. Unique features of HIV-related cardiovascular disease, in part, include the pathogenesis of coronary disease characterized by remodeling ectasia and unusual plaque morphology, the relative high proportion of type 2 myocardial infarction events, abnormalities of the aorta such as aneurysms and diffuse aortic inflammation, and HIV cerebrovasculopathy as a contributor to stroke risk. Literature over the past decade has also reflected a shift in the profile and prevalence of HIV-associated heart failure, with a reduced but persistent risk of heart failure with reduced ejection fraction and a growing risk of heart failure with preserved ejection fraction. Cardiac magnetic resonance imaging and autopsy data have emphasized the central importance of intramyocardial fibrosis for the pathogenesis of both heart failure with preserved ejection fraction and the increase in risk of sudden cardiac death. Still, more research is needed to better characterize the underlying mechanisms and clinical phenotype of HIV-associated myocardial disease in the current era. Across the different cardiovascular disease manifestations, a common pathogenic feature is that HIV-associated inflammation working through different mechanisms may amplify underlying pathology because of traditional risk and other host factors. The prevalence and phenotype of individual cardiovascular disease manifestations is ultimately influenced by the degree of injury from HIV disease combined with the profile of underlying cardiometabolic factors, both of which may differ substantially by region globally.