Novel COL5A1 variants and associated disease phenotypes in dogs with classical Ehlers-Danlos syndrome.

BACKGROUND: Human patients with Ehlers-Danlos syndrome (EDS) are categorized into subtypes based on causative genetic variants and phenotypes. The classical form of EDS, primarily caused by variants in COL5A1 or COL5A2, is a very common subtype in people but is poorly characterized in dogs. OBJECTIVE: Describe likely causal COL5A1 variants in dogs with classical EDS, summarize clinical histories, discuss potential disease mechanisms, and draw conclusions about disease prognosis. ANIMALS: Seven client-owned dogs that exhibited clinical signs of classical EDS. METHODS: Clinical information was recorded from medical records and communication with attending veterinarians and dog owners. To identify potential causal gene sequence variants whole-genome sequence analyses (n = 6) or Sanger sequencing (n = 1) were performed on DNA isolated from the probands. Pathological abnormalities in skin biopsy samples were assessed using histology and electron microscopy in 3 dogs. RESULTS: Six distinct heterozygous COL5A1 sequence variants were identified. The most common clinical signs included fragile skin (n = 7), hyperextensible skin (n = 7), joint hypermobility (n = 6), and atrophic scars (n = 5). The median age at last follow-up or death was 12 years (range, 6.5-14 years). Ultrastructural abnormalities in dermal collagen differed among dogs with different COL5A1 variants. CONCLUSION AND CLINICAL IMPORTANCE: We describe the genotypic and phenotypic spectrum of the classical subtype of EDS by identifying 6 novel COL5A1 variants in conjunction with detailed clinical histories that included long-term follow-up information in 7 dogs.

[Recognan (citicoline) in the correction of asthenic and anxiety-depressive disorders]. / Rekognan (tsitikolin) v korrektsii astenicheskikh i trevozhno-depressivnykh narushenii.

The article reflects the results of a number of studies that demonstrate the therapeutic effectiveness of Recognan (citicoline) in anxiety-depressive and asthenic disorders against the background of somatic and neurological diseases, in the correction of post-stroke depression. Recent experimental animal studies prove the effect of citicoline on anxiety and depression. In the complex effect, Recognan potentiates the main pharmacological effect of antidepressants and anxiolytics. In some studies, a dose-dependent change in animal behavior has been observed in response to the analgesic and antidepressant effects of citicoline. The effectiveness of citicoline in combination with transcranial direct current stimulation in the treatment of depression has been shown. The analysis of these research materials allows us to recommend Recognan in the complex therapy of asthenic and anxiety-depressive disorders in response to such pathological conditions as anxiety, asthenia, depression.

Effect of Coenzyme Q10 on Physical Performance in Older Adults with Statin-Associated Asthenia: A Double-Blind, Randomized, Placebo-Controlled Clinical Trial.

Background: Available evidence from randomized clinical trials is contrasting and definitely inconclusive in determining whether or not CoQ10 dietary supplementation is advisable in patients with statin intolerance or poor statin tolerability. Methods: This randomized, double-blind, placebo-controlled clinical study aimed at investigating the effect of chronic dietary supplementation with coenzyme Q10 (CoQ10) phytosome on physical performance in older adults with a ≥3-month history of statin-associated asthenia. The study's participants were randomized to either a placebo or 300 mg daily CoQ10 phytosome (equivalent to 60 mg CoQ10; Ubiqsome®, Indena SpA, Milan, Italy). Asthenia, handgrip strength (HGs), 2-min step test (2MST), and 1-min sit-to-stand (STS) repetitions were assessed at baseline and at 8-week follow-up. Results: After the first 4 weeks of dietary supplementation, individuals taking CoQ10 phytosome showed a greater improvement in asthenia compared to the placebo group (p < 0.05). Even more significantly, at 8-week follow-up, participants receiving CoQ10 showed substantial improvements in asthenia (-30.0 ± 20.0%), HGS (+29.8 ± 3.6%), 2MST (+11.1 ± 1.8%), and 1-min STS repetitions (+36.4 ± 3.9%) compared to both baseline and placebo (p < 0.05). Conclusions: According to our findings, chronic dietary supplementation with CoQ10 phytosome significantly enhances physical performance in older adults with statin-associated asthenia. This could have relevant implications for improving the compliance of older adults with statin treatment.

[Asthenia in young patients and possibilities for its correction]. / Asteniya u molodykh patsientov i vozmozhnosti ee korrektsii.

OBJECTIVE: To investigate the effect of using the drug Brainmax on various manifestations of asthenic syndrome. MATERIAL AND METHODS: 30 patients, average age 29 years (20-44 years) took part in the study. The duration of treatment was 15 days. Subjective indicators on the asthenic state scale, hospital anxiety and depression scale, daytime sleepiness scale, as well as objective indicators of the corrective test were analysed. RESULTS: It was found that after treating patients with Brainmax, the severity of asthenic syndrome, anxiety, and depression significantly decreased, the quality of sleep increased, and the results of the correction test improved. CONCLUSION: The drug Brainmax can be recommended for the correction of asthenic syndrome in patients with functional diseases of the nervous system.

Ehlers-Danlos syndrome (cutaneous asthenia) in a Campbell's dwarf hamster (Phodopus campbelli).

A case of cutaneous asthenia in a Campbell's dwarf hamster is described. The animal was found to have hyperextensible skin, glaucoma and lens dislocation. Histopathological examination revealed an irregular, haphazard arrangement of collagen fibres in the dermis. The animal underwent surgical reduction of the skin folds which provided only temporary relief.

Un cas d'asthénie cutanée chez un hamster nain de Campbell est décrit. L'animal présente une peau hyperextensible, un glaucome et une luxation du cristallin. L'examen histopathologique révèle une disposition irrégulière et désordonnée des fibres de collagène dans le derme. L'animal a subi une réduction chirurgicale des plis cutanés qui n'a apporté qu'un soulagement temporaire.

Descreve­se um caso de astenia cutânea em um hamster anão de Campbell. O animal apresentou hiperextensibilidade cutânea, glaucoma e deslocamento de lentes. Ao exame histopatológico, observou­se um arranjo irregular e aleatório das fibras colágenas na derme. O animal foi submetido à redução cirúrgica das dobras cutâneas que resultou em alívio apenas temporário.

Se describe un caso de astenia cutánea en un hámster enano Campbell. Se examinó al animal obsevando piel hiperextensible, glaucoma y luxación del cristalino. El examen histopatológico reveló una orientación aleatoria e irregular de las fibras de colágeno en la dermis. Se utilizó una técnica de reducción quirúrgica de los pliegues de la piel que solo indujo una mejora temporal.

[Asthenic disorders correction with Recognan]. / Korrektsiya astenicheskikh sostoyanii preparatom Rekognan.

Asthenia, asthenic syndrome, asthenic condition, asthenic reaction, asthenic disorders are terms that describe the state of «impotence¼. Fatigue that occurs against the background of habitual physical or intellectual stress for a person, and persists after rest, is asthenia. For people of the older age group, the term senile asthenia syndrome is used. Asthenia manifests itself with increased fatigue and exhaustion, mood instability, increased irritability, sleep disorders. Asthenic conditions manifest themselves along with a decrease in physical activity, increased cognitive and mental fatigue. Asthenic syndrome (AS) are considered as an integral part of cardiovascular diseases (CVD), as one of the manifestations of cerebrovascular pathology. Senile asthenia syndrome (SAS) is a geriatric syndrome characterized by an age-associated decrease in the physiological reserve and functions of many body systems, including cognitive functions. One of the drugs that has a positive effect on the severity of AS and improves the state of cognitive functions is the domestic drug Recognan (citicoline). The effectiveness of Recognan in the treatment of AS in patients with CVD, SAS, and post-COVID asthenia has been shown. It is recommended to prescribe Recognan orally at 500 mg / day for 30 days. Recognan has a nootropic and antiasthenic effect.

A Multi-Center Study Investigating Long COVID-19 in Healthcare Workers from North-Eastern Italy: Prevalence, Risk Factors and the Impact of Pre-Existing Humoral Immunity-ORCHESTRA Project.

Introduction: The impact of long-COVID-19 syndrome is rather variable, since it is influenced by several residual confounders. This study aimed to investigate the prevalence of long COVID-19 in healthcare workers (HCWs) from four university hospitals in north-eastern Italy: Trieste, Padua, Verona, and Modena-Reggio Emilia. Methods: During the period June 2022-August 2022, HCWs were surveyed for past COVID-19 infections, medical history, and any acute as well as post-COVID-19 symptoms. The prevalence of long COVID-19 was estimated at 30-60 days or 61+ days since first negative swab following first and second COVID-19 episode. Furthermore, the risk of long COVID-19 was investigated by multivariable logistic regression. Results were expressed as the adjusted odds ratio (aOR) with a 95% confidence interval (95%CI). Results: 5432 HCWs returned a usable questionnaire: 2401 were infected with SARS-CoV-2 at least once, 230 were infected at least twice, and 8 were infected three times. The prevalence of long COVID-19 after a primary COVID-19 infection was 24.0% at 30-60 days versus 16.3% at 61+ days, and 10.5% against 5.5% after the second SARS-CoV-2 event. The most frequent symptoms after a first COVID-19 event were asthenia (30.3%), followed by myalgia (13.7%), cough (12.4%), dyspnea (10.2%), concentration deficit (8.1%), headache (7.3%), and anosmia (6.5%), in decreasing order of prevalence. The risk of long COVID-19 at 30-60 days was significantly higher in HCWs hospitalized for COVID-19 (aOR = 3.34; 95%CI: 1.62; 6.89), those infected with SARS-CoV-2 during the early pandemic waves-namely the Wuhan (aOR = 2.16; 95%CI: 1.14; 4.09) or Alpha (aOR= 2.05; 95%CI: 1.25; 3.38) transmission periods-and progressively increasing with viral shedding time (VST), especially 15+ days (aOR = 3.20; 95%CI: 2.07; 4.94). Further determinants of long COVID-19 at 30-60 days since primary COVID-19 event were female sex (aOR = 1.91; 95%CI: 1.30; 2.80), age >40 years, abnormal BMI, or administrative services (reference category). In contrast, HCWs vaccinated with two doses before their primary infection (aOR = 0.57; 95%CI: 0.34; 0.94), undergraduate students, or postgraduate medical trainees were less likely to experience long COVID-19 at 30-60 days. Apart from pandemic waves, the main determinants of long COVID-19 at 30-60 days were confirmed at 61+ days. Conclusions: The risk of long COVID-19 following primary infection increased with the severity of acute disease and VST, especially during the initial pandemic waves, when more virulent viral strains were circulating, and susceptibility to SARS-CoV-2 was higher since most HCWs had not been infected yet, COVID-19 vaccines were still not available, and/or vaccination coverage was still building up. The risk of long COVID-19 therefore decreased inversely with humoral immunity at the individual level. Nevertheless, the prevalence of long COVID-19 was remarkably lower after SARS-CoV-2 reinfections regardless of vaccination status, suggesting that hybrid humoral immunity did not increase protection against the syndrome compared to immunity mounted by either natural infection or vaccination separately. Since the risk of long COVID-19 is currently low with Omicron and patients who developed the syndrome following SARS-CoV-2 infection in the early pandemic waves tend to return to a state of full health with time, a cost-effective approach to screen post-COVID-19 symptoms during the Omicron time could be restricted to vulnerable individuals developing severe disease and/or with prolonged VST.

[Frailty and chronic kidney disease - the real problem of modern nephrology: A review].

The article deals with the syndrome of frailty or senile asthenia in patients with chronic kidney disease. The questions of prevalence, diagnosis, pathogenesis of this syndrome and its clinical consequences in chronic kidney disease are discussed.

[Structure and dynamics of depressive disorders in patients with a new coronavirus infection]. / Struktura i dinamika depressivnykh rasstroistv u patsientok, perenesshikh novuyu koronavirusnuyu infektsiyu (COVID-19).

OBJECTIVE: To analyze the dynamics of depressive disorders in patients who underwent COVID-19. MATERIAL AND METHODS: The study included female patients (n=30) with mean age 35.4±3.0 years, who received inpatient treatment of depressive spectrum symptoms in accordance with ICD-10 rubrics F31-F34 and who have undergone COVID-19 (U04.9, U07.1, U07.2). Clinical-psychopathological and statistical methods were used. RESULTS: Among all patients, who underwent inpatient treatment for affective disorders, the most common symptoms were: low mood (96.7%), anxiety (83.3%), decreased interest in daily activities (40%), loss of appetite (36.7%). In patients who have had depressive symptoms before COVID-19, an increase in the number of affective spectrum symptoms (suicidal thoughts - 83.3%), as well as in asthenic manifestations in the form of increased fatigue (60%), sleep disorders (73.3%), feelings of fatigue, weakness (60%), emotional lability (40%). CONCLUSION: In patients with depressive disorders who underwent COVID-19, hypothymia is most often accompanied by anxiety, suicidal thoughts, as well as asthenic manifestations in the form of fatigue, sleep disturbances, and emotional lability. An increase in the number of asthenic spectrum symptoms in patients with depressive disorders may indicate a possible link between COVID-19 and affective pathology. The impact of coronavirus infection on the structure and dynamics of depressive disorders requires further study, taking into account the severity of affective symptoms, the impact of psychopharmacotherapy, and the severity of the infectious disease.

[Cognitive impairment in patients of cardiac surgery with senile asthenia syndrome and preastenia]. / Narusheniya kognitivnykh funktsii u patsientov kardiokhirurgicheskogo profilya s sindromom starcheskoi astenii i preastenii.

OBJECTIVE: To identify the features of the cognitive status in patients with cardiac surgery profile with senile asthenia syndrome (SAS) and preasthenia. MATERIAL AND METHODS: A study included 272 patients admitted for coronary artery bypass grafting (CABG). Screening for preasthenia and SAS in patients before surgery was performed using the Brief Battery of Physical Functioning Tests. SAS and preasthenia were detected in 15% of patients (n=41). Seventy-five patients were selected in the comparison group without asthenia. Assessment of the state of cognitive functions was carried out using screening neuropsychological scales - the Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA). RESULTS: The median of the MMSE score (27 [26; 28] and 28 [27; 29], p=0.04), and the MoCA score (23 [19; 25] and 25 [23; 27], p=0.0085) was significantly lower in patients with asthenia and pre-asthenia compared to patients without asthenia. According to the MoCA, about 60% of patients in the pre-asthenia-asthenia group had severe cognitive impairment, while in the group without asthenia, more than 30% of cases had normal cognitive functions (p=0.003). Significant intergroup differences were found in MoCA subtests, reflecting visuospatial skills, abstraction, verbal fluency and working memory (p=0.01-0.04). Regression analysis showed that age and physical functioning index (severity of asthenia) most significantly contributed to the basic cognitive status assessed by MoCA. CONCLUSION: Features of the cognitive status in patients of cardiac surgery with the SAS and preasthenia are impairments of visuospatial thinking, verbal fluency, abstract thinking and working memory. The MoCA was shown to be informative in determining the basic cognitive status of cardiac surgical patients. At the same time, the greatest contribution to the basic cognitive status is made by age and the indicator of physical functioning, which characterizes the degree of asthenia.

[Therapy of asthenic disorders after psychotic conditions in patients with cognitive impairment: results of an observational non-interventional program]. / Terapiya astenicheskikh rasstroistv posle perenesennykh psikhoticheskikh sostoyanii u patsientov s kognitivnymi narusheniyami: rezul'taty nablyudatel'noi neinterventsionnoi programmy.

OBJECTIVE: An observational non-interventional study was conducted to obtain data on the efficacy and safety of Prospekta in the treatment of postpsychotic asthenia in patients with cognitive impairment (CI). MATERIAL AND METHODS: We selected 69 patients aged 18-75 years with asthenic disorders that developed after suffering psychotic conditions and CI, who were prescribed Prospekta. At four visits (at baseline, after 2, 4 and 8 weeks), the doctor collected complaints, anamnesis, examined the patient, assessed the severity of asthenia on the MFI-20 (The Multidimensional Fatigue Inventory-20) scale, CI - on the MMSE (The Mini-mental state examination). Concomitant diseases and maintenance therapy of the underlying disease were recorded, and the safety of treatment with Prospect was evaluated. At the last visit, the doctor's clinical impression was assessed using the CGI-I (Clinical Global Impression - Global Improvement Scale). RESULTS: The analysis included data from 69 patients (mean age 45.7 years), of which 27 (33.4%) were women. Prospekta reduced the severity of asthenia on the MFI-20 scale from 85.7±6.6 to 51.6±7.1 points, including general asthenia, mental and physical asthenia, and contributed to an increase in activity and motivation (p<0.001). 8-week treatment with Prospekta improved cognitive function on the MMSE scale from 25.7±3.7 to 28.8±1.5 points (p<0.001). There was no effect of the drug on blood pressure, heart rate. 76 adverse events (AEs) were detected in 22 patients, of which 62 AEs (82%) were of mild severity, 14 AEs (18%) were of moderate severity. A causal relationship of AEs with taking Prospekta, according to doctors, was absent in 48 (63%) cases. CONCLUSION: Prospekta is an effective and safe drug for the treatment of asthenic disorders that have developed after suffering psychotic conditions in patients with CI.

[Cognitive impairment in children with organic asthenic disorder]. / Kognitivnye narusheniya u detei s organicheskim astenicheskim rasstroistvom.

OBJECTIVE: To study cognitive impairment and neurophysiological characteristics in children with organic asthenia, as well as the effectiveness of the drug Cogitum in the treatment of this pathology. MATERIAL AND METHODS: The main study group included 40 children aged 8 to 10 years with a diagnosis of «Organic asthenic disorder¼ (F06.6). The control group consisted of 30 children aged 8 to 10 years without manifestations of asthenia. The following research methods were used in the work: the asthenic state scale (ASS) by L.D. Malkova to assess the severity of asthenic syndrome, the S. Lee «SCT¼ (sluggish cognitive tempo) scale to assess manifestations of low cognitive tempo, the «Random Access Memory¼ method to quantify working memory, the TOVA (The Test of Variables of Attention) computer test to quantify assessment of attention disorders and impulsivity level, electroencephalogram (routine and spectral analysis) (p<0.05). For the treatment of patients from the study group, the drug Cogitum was used at a dose of 10 ml of a drinking solution per day for 30 days. RESULTS: In was shown that children from the study group were characterized by a decrease in working memory (7.8±2.9 vs 14.9±5.4), a statistically significant increase in SCT scores (p<0.05), a significantly greater degree of inattention and impulsivity with a tendency to an increase in the number of errors in the second half of the TOVA test (p<0.05). Comparative analysis of EEG relative power data showed a statistically significant increase in the power of waves in the alpha and theta ranges in the fronto-central leads of both hemispheres in the group of children with organic asthenic disorder (p<0.05). When re-evaluating the condition of children after treatment, a statistically significant decrease in the manifestations of asthenia on the ASS scale was recorded in 77.5% of cases. At the same time, there was a significant improvement in attention, memory, and indicators characterizing a low cognitive pace. The results of an electroencephalographic study after a course of treatment showed a decrease in the relative power of the EEG in the theta and alpha ranges in the anterior sections of the cerebral cortex (p<0.05), which indicates an increase in the level of activation of neocortical structures. CONCLUSION: Thus, the use of the drug Cogitum for the treatment of organic asthenic disorder leads not only to a decrease in asthenia and cognitive impairment, but also to an improvement in the functional state of the brain.

Psychometric validation of the French Multidimensional Chronic Asthenia Scale (MCAS) in a sample of 621 patients with chronic fatigue.

BACKGROUND: Psychometric validation of the Multidimensional Chronic Asthenia Scale (MCAS) was conducted in order to provide an effective tool for assessing the health-related quality of life of French-speaking patients with chronic asthenia (CA). METHODS: Items resulting from the initial formulation of the self-reported MCAS (along with other materials) were completed by French-speaking volunteers with inactive or active inflammatory bowel disease (IBD-I vs. IBD-A) or chronic fatigue syndrome (CFS). Responses from 621 participants (180 patients with IBD-A, 172 with IBD-I, 269 with CFS) collected in a single online survey were divided into three subsamples to test the construct validity of the MCAS (Step 1, N = 240), to confirm its factorial structure (Step 2, N = 204) and to explore its convergent-discriminant validity with the Fatigue Symptoms Inventory (FSI) and revised Piper Fatigue Scale (r-PFS, Step 3, N = 177). RESULTS: Steps 1 and 2 showed that, as expected, MCAS has four dimensions: feeling of constraint (FoC), physical (PC), life (LC) and interpersonal consequences (IC), which are also related to the duration of CA (i.e., the longer it lasts, the more the dimensions are impacted). The results further showed that the MCAS is sensitive enough to capture between-group differences, with the CFS group being the most impaired, followed by IBD-A and IBD-I. While convergent-discriminant validity between the 4 factors of MCAS and FSI and r-PFS, respectively, was satisfactory overall, Step 3 also pointed to some limitations that call for future research (e.g., shared variances between the PC and IC dimensions of MCAS and behavioral dimension of r-PFS). CONCLUSION: Despite these limitations, the MCAS clearly constitutes a promising tool for measuring quantitative differences (i.e., severity/intensity) in CA associated with various diseases, but also, and importantly, the clinically important differences in domains of its expression (i.e., qualitative differences).

[Therapeutic approaches to comorbid pathology in episodic migraine and tension-type headache]. / Terapiya komorbidnoi patologii pri epizodicheskoi migreni i golovnoi boli napryazheniya.

OBJECTIVE: To assess the severity of anxiety, depression, insomnia and asthenia in patients with episodic migraine and tension-type headache before and after treatment. MATERIAL AND METHODS: 104 patients aged 18 to 74 years were examined. Patients were divided into two groups: the 1st - 41 patients diagnosed with episodic migraine, the 2nd - 63 patients with episodic tension-type headache. The intensity of headache was assessed using the visual analog scale (VAS). The Hospital Anxiety and Depression Scale (HADS), the Levin questionnaire, and the Multidimensional Fatigue Inventory scale (MFI-20) were used to identify comorbid affective pathology, insomnia, and asthenia, respectively. RESULTS: Headache severity according to VAS in the 1st group was higher (5.8±1.3 points) than in 2nd (3.8±1.2 points). Clinical anxiety was detected in 66.3% of patients without statistically significant differences between groups. The mean HADS anxiety score was 13.9±3.5 in 1st group, 12.7±3.7 - in 2nd. Clinical depression was detected in 45.2% of patients, more often in the 2nd group - 50.8% than in the 1st (36.6%). The mean depression score according to HADS was 9.0±4.4 and 9.7±3.6 in the 1st and 2nd groups respectively. The intensity of headache was statistically significantly higher in patients with clinical anxiety. Both groups were found to have insomnia and asthenia. The majority of patients - 67.3% had myofascial pain syndrome. When re-evaluating the severity of disorders after treatment (using anxiolytics, antidepressants, muscle relaxants, magnesium and neurometabolics), a significant positive trend was noted. Reducing the intensity of headaches to 3.2±0.9 points (according to VAS scale) was in patients with migraine and 1.9±0.8 points in 2nd group. Relief of anxiety and depressive disorders was observed (HADS) in 1st (4.3±3.9) and 2nd (4.5±3.3) groups, the severity of depression (HADS) - 2.1±2.2 in 1st and 2.8±3.2 in 2nd groups, as well as a decrease in asthenia and normalization of sleep. The decrease in the severity of asthenia during treatment was more significant in patients treated with Cytoflavin. CONCLUSION: Identification and treatment of comorbid pathology leads to positive results in the treatment of primary headaches such as episodic migraine and TTH.

Precision medicine using whole genome sequencing in a cat identifies a novel COL5A1 variant for classical Ehlers-Danlos syndrome.

BACKGROUND: Ehlers-Danlos syndromes (EDS) are a heterogeneous group of heritable connective tissue disorders occurring in both human and veterinary patients. The genetics of these disorders are poorly described in small animal patients. HYPOTHESIS/OBJECTIVES: Define the clinical manifestations and genetic cause of a suspected form of EDS in a cat. ANIMALS: A 14-week-old male domestic medium hair cat was presented with skin hyperextensibility and fragility. The classic tragic facial expression was observed as well as chronic pruritus and mild hyperesthesia. METHODS: Blood samples and a skin biopsy sample were collected from the affected cat. Clinical examinations, histology, electron microscopy and whole genome sequencing were conducted to characterize the clinical presentation and identify possible pathogenic DNA variants to support a diagnosis. Criteria defining variant pathogenicity were examined including human disease variant databases. RESULTS: Histology showed sparse, disorganized collagen and an increase in cutaneous mast cells. Electron microscopy identified ultrastructural defects commonly seen in collagen type V alpha 1 chain (COL5A1) variants including flower-like collagen fibrils in cross-section. Whole genome sequencing and comparison with 413 cats in the 99 Lives Cat Genome Sequencing Consortium database identified a novel splice acceptor site variant at exon 4 in COL5A1 (c.501-2A>C). CONCLUSIONS AND CLINICAL IMPORTANCE: Our report broadens the current understanding of EDS in veterinary patients and supports the use of precision medicine techniques in clinical veterinary practice. The classification of variants for pathogenicity should be considered in companion animals.

[Asthenia, mental fatigue and cognitive dysfunction]. / Asteniya, psikhicheskaya utomlyaemost' i kognitivnaya disfunktsiya.

Conditions associated with asthenia are usually characterized by increased fatigue, impaired activities of daily living and decreased productivity. In clinical practice it is important to distinguish between idiopathic chronic fatigue (primary or functional asthenia) and chronic fatigue syndrome (CFS). Fatigue can also be classified by neuromuscular and/or cognitive and mental fatigue. The article discusses the neuroanatomical basis and focuses on the neurocognitive theory of pathological fatigue. In addition the relationship between mental stress, fatigue and cognitive impairments such as subjective cognitive impairment (SCI) and mild cognitive impairment (MCI) are also discussed. We discuss the rationale that for treatment of asthenic conditions accompanied by cognitive dysfunction it is justified to use combination therapy - fonturacetam and a preparation containing nicotinoyl-GABA and Ginkgo Biloba.

[Concepts of modern gerontology and geriatrics and the role of nutrition in their achievement].

Many factors take part in increasing the healthy period of life - the quality of the environment, drinking water, psychological attitudes in society, dietary patterns, comfort of living, quality of housing, economic relations in the state and society, the degree of landscaping and much more. Collectively, the factors that lead to a healthier and longer life are called the environment that promotes longevity. The scientific study of such an environment, changing everyday life in terms of its quality related to health and increasing duration, is the newest trend in anti-aging medicine. Individual viability (intrinsic capacity) is one of the 4 concepts of geriatrics. The main concept is senile asthenia, the second is premature aging, the third is age viability, which is a psychological state of aging. It seems promising to study the effect of nutrition on individual vitality and longevity. Objective - to study the influence of nutrition on the aging process, to develop further preventive programs based on the data obtained. Methods. Search for literature on nutrition and age problems was held in the databases of RSCI, PubMed, Google Scholar by keywords: aging, ageism, nutrition, individual viability, age-related changes, resilience diet, age-related viability, senile asthenia, domain approach, age. Results. Domain-based assessment is a modern diagnosticis of the condition of people of older age groups, which forms the basis for the development of gerontological preventive programs, in which nutrition plays an important role. Modern studies indicate that the transition in nutrition from «Western¼ patterns to diets with a high content of plant products, as well as fish, vegetable protein (nuts), reduced salt content prevents the development of complications of age-associated diseases by the mechanism of reducing inflammation and hyperinsulinemia, replenishing micronutrient deficiency. Conclusion. Many studies have confirmed the relationship between compliance with optimal nutrition and longevity, as well as a reduced risk of early development of ageassociated diseases. Further research in the field of gerontology will help in the future to develop a comprehensive system of measures aimed at increasing life expectancy and increasing individual viability.

[Efficacy of potassium N-acetylaminosuccinate (Cogitum) in the treatment of asthenic syndrome: results of double-blind placebo-controlled trial]. / Effektivnost' kaliya N-atsetilaminosuktsinata (Kogitum) pri lechenii astenicheskogo sindroma: rezul'taty dvoinogo slepogo platsebo-kontroliruemogo issledovaniya.

OBJECTIVE: Study of the effectiveness of monotherapy with potassium N-acetylaminosuccinate (Cogitum) for asthenic syndrome (fatigue) in individuals, uncharacteristic somatic, neurological diseases, anxiety disorders, depression and other diseases that may interfere with asthenia. MATERIAL AND METHODS: Patients with fatigue scores of 22 or more on the Fatigue Assessment Scale (FAS) were randomly divided into the main group (MG) - 37 people, mean age 22 years [21; 24] and the control group (CG) - 34 people, mean age 21 years [19; 23]. The Trail Making Test (TMT-A and TMT-B), the assessment of general well-being on a visual analogue scale (VAS), where 0 is the worst state of health, 10 is the state of absolute well-being, was assessed. MG patients received a solution of potassium N-acetylaminosuccinate (Cogitum) 750 mg per day in a sterile container, CG patients received sterile water with banana flavor in a sterile container. The duration of the study was 21 days. RESULTS: Prior to the start of the study, there were no statistically significant differences in FAS, TMT, and VAS between MG and CG. After 21 days, the FAS score in the MG decreased (p=0.00001), the time of TMT-A (p=0.000012) and TMT-B (p=0.000033) decreased, the VAS score increased (p=0.00024). There were no statistically significant changes in the CG. Placebo effect was noted in 10 patients of the CG (29.4%). CONCLUSION: Potassium aminosuccinate (Cogitum) at a daily dose of 750 mg and a duration of treatment of 21 days effectively eliminates the symptoms of asthenic syndrome (fatigue), while accompanied by an improvement in complex cognitive functions. The results of our study suggest that fatigue (asthenic syndrome) and cognitive impairment may have a common pathogenetic mechanism - a deficiency of systems in which mediators are N-acetylaspartate and N-acetylaspartylglutamate. Cogitum had no side effects and was well tolerated. Cogitum is superior to placebo in the treatment of fatigue (asthenic syndrome).

[Frequency of selected chronic noncommunicable diseases in older patients with senile asthenia syndrome.]

An important area of medical and social research is prospective studies of a cohort of older patients with chronic non-communicable diseases aimed at studying the level of mortality, taking into account the presence/absence of senile asthenia syndrome. A prospective clinical and epidemiological study was conducted on 1 261 people aged 80 years and older receiving medical care on an outpatient basis. Three groups of patients were formed: without senile asthenia syndrome (7,6%), in a state of pre-asthenia (23,5%), with senile asthenia (68,9%). After a calendar year, an analysis was made of the causes of death of respondents in all three groups. A high statistically significant incidence of chronic diseases in patients with senile asthenia syndrome compared with those without signs of this syndrome was noted in arterial hypertension, chronic heart failure, osteoarthritis, age-related macular degeneration, chronic kidney disease, dementia, cancer, anemia, uncomplicated diabetes mellitus. In the structure of causes of death in patients aged 80 years and older, diseases of the circulatory system, nervous system, neoplasms, liver diseases, and diabetes mellitus predominated. The odds ratio of the risk of dying within a year in patients without frailty syndrome is 0,32 (compared to patients with frailty, in which the risk is taken as 1).

[Pharmacoepidemiological analysis of antihypertensive therapy in older age groups with senile asthenia syndrome].

AIM: To conduct a pharmacoepidemiological study to determine the characteristics of antihypertensive therapy in older patients with senile asthenia syndrome (SSA) and compliance of this therapy with modern clinical recommendations. MATERIALS AND METHODS: The study included 146 patients diagnosed with stage I-III hypertension who underwent inpatient treatment in the therapeutic department of the Krasnoyarsk Regional Hospital for War Veterans, the subjects were divided into two groups. The first group included 55 elderly patients (WHO, 2012) with hypertension and SSA. The second group included 35 elderly patients (WHO, 2012) with hypertension and SSA. The comparison group consisted of 56 patients aged 60 to 84 years with hypertension without SSA. Evaluation of the pharmacotherapy was carried out based on extracts from the medical histories of inpatient patients. RESULTS: The most commonly taken groups of antihypertensive drugs in patients of older age groups with hypertension and SSA according to the study are diuretics and ß-blockers. Diuretics were taken by 88.6% of elderly patients and 83.6% of senile patients. The main combinations of antihypertensive drugs in patients with hypertension and SSA were: a two-component scheme of combination of an ACE inhibitor and a diuretic, a three-component scheme of combination of an ACE inhibitor, a ß-blocker and a diuretic, four-component schemes of combination of an ACE inhibitor, a ß-blocker, a calcium channel blocker and a diuretic, as well as a combination of an angiotensin II receptor blocker, a ß-blocker, calcium channel blocker and diuretic with combined medications. CONCLUSION: The prescribed antihypertensive therapy in patients of older age groups with hypertension and SSA in most cases is represented by a combination of several drugs. Many patients take three-component antihypertensive therapy regimens. There were no statistically significant differences between patients of older age groups with hypertension and SSA, as well as patients of older age groups with hypertension without SSA. Therefore, it can be concluded that the presence of senile asthenia syndrome does not affect the tactics of treatment of hypertension and regardless of the presence or presence of SSA, patients receive the same hypotensive therapy, which contradicts existing clinical guidelines.