DSP missense variant in a Scottish Highland calf with congenital ichthyosis, alopecia, acantholysis of the tongue and corneal defects

Background Ichthyosis describes a localized or generalized hereditary cornification disorder caused by an impaired terminal keratinocyte differentiation resulting in excessive stratum corneum with the formation of more or less adherent scales. Ichthyosis affects humans and animals. Two rare bovine forms are reported, the severe harlequin ichthyosis and the less severe congenital ichthyosis, both characterized by a severe orthokeratotic lamellar hyperkeratosis. Results A 2-weeks-old purebred Scottish Highland calf was referred because of a syndrome resembling congenital ichthyosis. The clinical phenotype included diffuse alopecia and a markedly lichenified skin covered with large and excessive scales. Additionally, conjunctivitis and ulceration of the cornea were noted. Post-mortem examination revealed deep fissures in the diffusely thickened tongue and histopathological findings in the skin confirmed the clinical diagnosis. Whole-genome sequencing of the affected calf and comparison of the data with control genomes was performed. A search for private variants in known candidate genes for skin phenotypes including genes related with erosive and hyperkeratotic lesions revealed a single homozygous protein-changing variant, DSP: c.6893 C>A, or p.Ala2298Asp. The variant is predicted to change a highly conserved residue in the C-terminal plakin domain of the desmoplakin protein, which represents a main intracellular component of desmosomes, important intercellular adhesion molecules in various tissues including epidermis. Sanger sequencing confirmed the variant was homozygous in the affected calf and heterozygous in both parents. Further genotyping of 257 Scottish Highland animals from Switzerland revealed an estimated allele frequency of 1.2%. The mutant allele was absent in more than 4800 controls from various other cattle breeds. Conclusions This study represents the first report of combined lesions compatible with congenital ichthyosis, alopecia, acantholysis of the tongue and corneal defects associated with a DSP missense variant as the most likely underlying cause. To the best of our knowledge, this study is also the first report of a DSP-related syndromic form of congenital ichthyosis in domestic animals. The results of our study enable genetic testing to avoid the unintentional occurrence of further affected cattle. The findings were added to the Online Mendelian Inheritance in Animals (OMIA) database (OMIA 002243-9913).

ACUTE VIRAL INFECTIONS WITH COMBINED LESIONS OF THE RESPIRATORY AND GASTROINTESTINAL TRACT - A SCOURGE OF OUR TIME

Viral infections continue to cause significant morbidity and mortality worldwide. The association of pathogens often changes not only the typical clinical picture of the infection, but also its course, which often becomes the reason for the delayed diagnosis and lack of adequate treatment. The variety and discovery of new respiratory viruses, their variability, the rapid formation of strains resistant to antiviral agents and modifying adaptive immune responses in humans, lead to an increase in the frequency of mixed viral infections, which dictates the need to develop and implement new diagnostic and treatment algorithms. This review is devoted to the problem of acute viral infections with combined lesions of the respiratory tract and gastrointestinal tract (GIT) among the population of children. The etiological structure of causative agents of acute respiratory infections (ARI), acute intestinal infections (AII) and infections with combined lesions of the respiratory tract and GIT in children is presented. The features of the pathogenesis and clinical features of rotavirus, coronavirus infections are considered. An algorithm for making a decision on the appointment of a treatment-and-prophylactic complex for children with AII and ARI is proposed.

Distributed learning episodes create a context fear memory outside the hippocampus that depends on perirhinal and anterior cingulate cortices

Damage to the hippocampus (HPC) typically causes retrograde amnesia for contextual fear conditioning. Repeating the conditioning over several sessions, however, can eliminate the retrograde amnesic effects. This form of reinstatement thus permits modifications to networks that can support context memory retrieval in the absence of the HPC. The present study aims to identify cortical regions that support the nonHPC context memory. Specifically, the contribution of the perirhinal cortex (PRH) and the anterior cingulate cortex (ACC) were examined because of their established importance to context memory. The findings show that context memories established through distributed reinstatement survive damage limited only to the HPC, PRH, or ACC. Combined lesions of the HPC and PRH, as well as the HPC and ACC, caused retrograde amnesia, suggesting that network modifications in the PRH and ACC enable context fear memories to become resistant to HPC damage.

Results of a six-year prospective study of surgical treatment of patients with combined atherosclerosisof coronary and brachiocephalic arteries based on differentiated approach

Objective. To present the results of surgical treatment of patients with multifocal atherosclerosis based on a differential approach of surgical strategy. Materials and methods. During the period of 20142021 in the S.G. Sukhanov Federal Center for Cardiovascular Surgery, Perm, we operated 243 patients with combined atherosclerosis of coronary and carotid arteries; 104 (42.8 %) patients underwent a one-stage coronary and carotid artery surgeries, and 139 (57.2 %) patients underwent a staged correction of pathology. Critical lesion of the coronary arteries was revealed in 16 (6.6 %) patients, single-vessel critical lesion in 24 (9.9 %), two-vessel and three-vessel critical lesion was detected in 87 (35.8 %) and 79 (32.5 %) patients, respectively. 145 (59.7 %) patients had a critical lesion of the carotid arteries, and 16 (6.58 %) had a bilateral critical lesion. We have developed an algorithm for choosing treatment tactics in patients with concomitant atherosclerotic lesions of the coronary and carotid arteries. Depending on our differential approach, we selected 104 (42.8 %) patients who underwent a one-stage surgery, and 139 (42.8 %) patients who were subjected to a staged treatment. Results. A total hospital mortality was 0 %. In the staged group, 1 case of transitory ischemic attack (TIA) (0.7 %) was recorded, in the group of combined interventions there was no TIA. In the group of combined interventions, there were 3 (2.9 %) cases of the perioperative stroke and 1 (0.9 %) case of myocardial infarction. In the group that underwent staged interventions, there were 2 (1.4 %) cases of perioperative stroke and 2 (1.4 %) cases of myocardial infarction. Both groups had similar combined results (death, acute MI, stroke) 5 (3.6 %) for the staged group and 4 (3.8 %) for the combined one. There was no significant difference in any of the endpoints. Conclusions. The proposed approach to the choice of techniques for treatment of combined lesions of the carotid and coronary arteries based on the differential approach is safe and permits to adequately eliminate the lesions.

Outcome of Pulmonary Autograft After the Ross Procedure

Background: The purpose of this study was to assess autograft function after the Ross procedure and to review surgical outcomes associated with autograft reoperations. Methods: This is a retrospective study of patients undergoing the Ross procedure since 1993. Autograft function and autograft reoperation were studied. Autograft failure was defined as more than moderate autograft regurgitation or autograft dilatation to more than 50 mm diameter or z-score of more than +4 in children. One hospital death was excluded from analysis as were patients with unknown late autograft status. Results: Among 75 patients analyzed, preoperative diagnosis before the Ross procedure included aortic regurgitation in 26, aortic stenosis in 19, combined lesions in 28, and 2 mechanical valve malfunctions. Median age at the Ross procedure was 12.1 (0.4-43.6) years with 44 children less than 15 years old. Six patients had greater than mild autograft regurgitation at post-Ross hospital discharge. During median follow-up of 14.9 years, there were 23 autograft failures. Eighteen autograft reoperations were performed on 17 patients (13 children), including 12 aortic valve replacements, 5 aortic root replacements (including 1 valve-sparing root replacement), and 1 Konno procedure. Freedom from autograft failure and autograft reoperation at 20 years after the Ross procedure was 52.0% and 66.3%, respectively. Multivariate analysis identified greater than mild autograft regurgitation at hospital discharge from Ross procedure as a risk factor for autograft failure ( P < .01). All patients who underwent autograft reoperation survived and had good health status at a median of 6.9 years after the reoperation. Conclusions: The Ross procedure is effective in delaying prosthetic aortic valve replacement, although the time-related risk of autograft failure is a real consideration.

SIGNS OF DISEASES OF THE GASTROINTESTINAL TRACT IN THE ORAL CAVITY OF CHILDREN

The question of combined lesions of the oral cavity and internal organs occupy a prominent place among the problems of dentistry nowadays. They allow to reflect the genesis of many diseases that manifest themselves in the oral cavity. Aim of the study was to analyze information on the relationship of diseases of oral cavity and various diseases of gastrointestinal tract. Anatomical and physiological proximity, common innervation and humoral regulation leads to the involvement of organs of oral cavity in the pathological process. Catarrhal gingivitis, stomatitis are often caused by deficiency of vitamins of group B. Above-mentioned deficiency is caused, according to many scientists, by the diseases of gastrointestinal tract. And such diseases of the oral cavity as chronic recurrent stomatitis, lichen planus, chronic recurrent herpetic stomatitis, chronic periodontitis depends on the pathology of the digestive tract. Conclusions. Thus, anatomical and physiological characteristics of children, who suffers from chronic gastrointestinal diseases, make us study the clinical manifestations of dental diseases in these patients. Prospects for further research. Further study of the dental status of children with diseases of the gastrointestinal tract is very valuable.

ROLE OF ULTRASOUND SCANNING IN DIAGNOSIS OF CONDITIONS OF KNEE JOINT SOFT TISSUES IN ACUTE AND CHRONIC INJURY IN FOOTBALL PLAYERS

Traumatic injuries of the knee joint are one of the main factors resulting in the loss of mobility among football players. According to the reports of many researchers, the damage to the soft tissues predominates in the structure of traumatic injuries of the knee joint; therefore, such diagnostic technique as ultrasound scanning is very helpful in determining the nature and extent of injuries and in making decision on the necessity of the surgical intervention. The aim of this study is to investigate and systematize ultrasound criteria for various types of traumatic injuries of the soft tissues of the knee joint in acute and chronic trauma in football players. The analysis of the findings of ultrasound scan of the knee joints in 36 football players with sports injury was carried out. The following echographic data were assessed: homogeneity, echogenicity, integrity of the tendon contours, the presence of effusion in the bursae and tendon sheaths, the number of vascular signals in the affected area. In the first group of patients, the analysis of ultrasound signs revealed the following structural changes: separate meniscus ruptures were diagnosed in 6 (27, 3%) athletes; combined lesions of the menisci and ligamentous apparatus – in 9 (40, 9%) with signs of damage to the menisci and ligaments characteristic of acute trauma; separate ligament ruptures were diagnosed in 7 (31, 8%) athletes. In the second group of the patients, sonography confirmed suffered meniscus tears in 3 (21, 4%) athletes; combined lesions of the menisci and ligaments in 7 (50,1%) footballers; rupture of the ligamentous apparatus in 4 (28,5%) individuals. Fresh injuries to the menisci and ligaments against the background of previous ruptures were not diagnosed during past ultrasound examinations and resulted in the impairment of the ratio of the load distribution on the limb that could provoke repeated trauma to the menisci and ligaments. Ultrasound scanning for acute and chronic injury of the knee joint in football players can be considered a reliable informative imaging technique, which allows assessing the severity of damage to the menisci, ligaments, soft tissues and makes it possible to choose the proper tactics of further treatment.

Clinical characteristics and prognostic significance of extramedullary involvement in childhood acute myeloid leukemia

Background. Extramedullary infiltration (EI) is relatively common in children with acute myeloid leukemia (AML) (up to 20-25 %). However, its clinical and prognostic significance remains poorly understood.Objective: to describe clinical features and to define prognostic significance of EI in children with AML.Materials and methods. The subjects of retrospective observational study were 228 children with de novo AML. The median age was 6.6 years. All of them were treated according to the protocol AML-MM-2006 from April 2007 to June 2018.All patients with EI were divided into three cohorts according to the localization of the lesions: 1) central nervous system (CNS) involvement (CNS group), 2) other localizations apart from CNS (myelosarcomas (MS) group), 3) combined lesions (CNS + MS group).Results. EI was diagnosed in 84 patients (36.84 %) with de novo AML. Among them 47 (55.95 %) had CNS involvement, 20 (23.81 %) had MS, 15 (17.86 %) had both CNS involvement and MS. 5-year overall survival (OS) rate was slightly higher in patients with CNS involvement than in children without EI - 80 ± 12 % vs 71 ± 9 %, p = 0.26, however OS in patients with MS was significantly lower - 45 ± 16 % vs 71 ± 9 %, p <0.001. In addition, OS in high-risk patients according to the protocol AML-MM-2006 who underwent allogenic hematopoietic stem cell transplantation (HSCT) without EI and with MS (± CNS involvement) was similar to OS in main groups - 81 ± 11 % and 42 ± 26 % respectively, p = 0.004. 5-year event-free survival in patients with MS was also lower than in children without EI - 38 ± 16 % vs 51 ± 8 %, p = 0.011.Conclusion. Patients with MS had worse 5-year OS and EFS than children without EI according to our study. Moreover allogenic HSCT conducted in first clinical remission did not improve the survival rate. Neuroleukemia as the only EI was not an unfavorable prognostic factor in our cohort of AML patients and was more often associated with inv(16).

Surgical treatment of a patient with combined lesion of the coronary and carotid arterial systems

A clinical case of surgical treatment of a patient with atherosclerotic combined lesions of the coronary and carotid areas is presented. A staged surgery was performed. The first stage was carotid endarterectomy sequentially on both sides. The second stage is three-vessel coronary artery bypass grafting. The patient was examined 2 years after the operation. There are no data on restenosis of the reconstruction zone of the carotid system. The return of angina pectoris is not noted.

Approach to Asymptomatic Case of Bicuspid Aortic Valve with Coarctation and Massive Aortic Arteriopathy: a Ticking Time Bomb

The combination of aortic coarctation (CoA) and bicuspid aortic valve (BAV) is associated with high risk of ascending aortic dilatation and type A aortic dissection. Most of the patients having combined lesions remain asymptomatic until adulthood and are incidentally diagnosed. Several questions regarding their treatment strategies remain unanswered. Both single-and two-stage surgical procedures have been described in medical literature, to treat CoA and BAV. Lately, combined endovascular therapy (Balloon angioplasty or Stent implantation) and surgery, has become a good alternative in selected cases. Here, we describe such a asymptomatic case of BAV with massive aneurysmal root dilatation and CoA, which was managed with endovascular stenting and surgery.