Mild Manifestations Research Articles

Human enteroviruses and the long road to acute flacid paralysis eradication.

Enteroviruses (EVs) are a highly diverse group of viruses multiplying primarily in the gastrointestinal tract and/or the upper respiratory tract, initially distributed in two separate genera: Enterovirus and Rhinovirus, respectively. According to the similarities in genome organization and particle structure, rhinovirus species were later reclassified as also belonging to genus Enterovirus. Human EV infections are usually asymptomatic or causing mild clinical manifestations. Nevertheless, some EV infections may derive in severe neural complications, including acute flaccid paralysis (AFP) such as poliomyelitis, whose etiological agent is poliovirus, a member of the Enterovirus C species. The inactivated polio vaccine (IPV) and particularly the oral attenuated polio vaccine (OPV) have contributed to the virtual eradication of the disease. However, sustained global circulation of vaccine-derived poliovirus 2 (cVDPV2), originated from the genetic instability of OPV strain 2 and intertypic recombination between Sabin OPV strains and members of the Enterovirus C species, still causes outbreaks of AFP worldwide. In addition, humanitarian crises, in particular armed conflicts, hamper polio vaccination campaigns and facilitate the occurrence of cases. Additionally, besides poliovirus, other EV may also cause AFP, among them EV A71 or EV D68, and it is highly advisable to implement wastewater surveillance to elucidate the occurrence of not only polioviruses, but also of other EV susceptible to derive in serious neural complications, since the screening of viral RNA in cerebrospinal fluid samples in patients suffering from AFP is not a reliable diagnostic tool.

Clinicopathologic Effects of Xenogeneic GvHD Induced by Adoptively Transferred Human-Derived T Cells in Severely Immunodeficient Mice

Background: Xenogeneic graft-versus-host disease (xGvHD) is an inevitable confounder of preclinical evaluation of adoptive immunotherapies on tumor-bearing immunodeficient mouse models. This study was designed to appraise the clinical and histopathological effects caused by xGvHD in severely immunodeficient mice considering the T cell dosage. Methods: Fifty NOG mice underwent intraperitoneal injection of three different doses of human-derived total T cells, a high dose of CD8+T cells, or vehicle (as control). Clinical and histopathological status of the study subjects were evaluated and compared according to scoring systems. Results: In mice receiving higher doses of total T cells, the clinical severity of xGvHD was greater. However, recipients of CD8+T cells developed none to mild xGvHD manifestations. Higher doses of T cells were associated with poorer outcomes including premature death and more severe histopathologic damages. Greater CD3+T cell tissue engraftment (immunohistochemical CD3 positivity) was associated with more severe xGvHD-induced histopathological damages. Clinical xGvHD scores were significantly correlated with histopathological xGvHD scores in total and in each tissue. Mice with severe cutaneous symptoms had higher scores of xGvHD-induced histopathologic changes in the skin. Lethargy was associated with higher histopathological scores in the lungs, liver and spleen. Conclusion: In preclinical evaluations, lower doses of T cell-based therapies are associated with milder xGvHD. Development of xGvHD may be averted by the use of CD4+T cell-depleted grafts. Histopathological and clinical scoring systems for evaluating xGvHD are significantly correlated. The lungs and liver are reliable organs for histopathological assessment and scoring of xGvHD.

A Review of Arshoghna Mahakashaya in the Charaka Samhita

Arsha, one of the most prevalent ano-rectal disorders, can manifest at any stage of life and is extensively described in Ayurvedic literature. These texts elucidate its etiology, pathology, symptomatology, classifications, and therapeutic approaches. Arsha denotes the abnormal proliferation of muscle tissue in various forms that arise in the rectum and adjacent areas, often as a consequence of imbalances in the doshas associated with the skin, muscle, and adipose tissues. Manifesting at the opening of the guda marga (anal passage), Arsha can be as problematic as an adversary, even in its mildest manifestations, leading to considerable discomfort and distress. The Mahakashaya, an Ayurvedic classification of medications based on their therapeutic actions (Karmas), provides valuable insights into the management of Arsha. Acharya Charaka categorizes Arsha into two types: Ardra (wet) and Shushka (dry). In the Charaka Samhita, Sutrastana, Chapter 4, the Arshoghna Mahakashaya group enumerates ten potent herbs known for their efficacy in the management of Arsha. These herbs include Kutaja, Bilva, Chitraka, Shundi, Ativisha, Abhaya, Dhanvayasa, Daruharidra, Vacha, and Chavya. Each plant in this category possesses specific Rasa (taste), Guna (qualities), Veerya (potency), and Vipaka (post-digestive effect), which collectively contribute to its therapeutic efficacy against Arsha. In the treatment of Arshas, Tikta, Katu, and Kashaya rasa pradhana dravyas are of critical importance. These medications are classified based on their pharmacological properties, thereby offering targeted relief to individuals affected by this condition.

Higher burden of cerebral small vessel disease is associated with risk of incident stroke in community dwelling individuals.

Mild manifestations of individual cerebral small vessel disease (CSVD) markers are common and may not denote increased risk, but high CSVD burden identifies individuals at increased risk of stroke and dementia. Scores incorporating multiple individual CSVD markers may better identify a person's risk. We related a multi-marker CSVD score to risk of incident stroke and compared it with the Framingham Stroke Risk Profile (FSRP) in community-dwelling individuals. Framingham Heart Study participants aged ≥55 years, free of stroke and dementia and with brain magnetic resonance imaging ratings of CSVD markers were included. A multi-marker CSVD score reflecting increasing CSVD burden was used, assigning one point each for presence of cerebral microbleeds, severe perivascular spaces, extensive white matter hyperintensities, covert brain infarcts, and cortical superficial siderosis. Multivariable Cox proportional hazards regression analyses were used to relate CSVD score to incident stroke. Among 1,154 participants (46% male, mean age 70.9±8.7), 92 (8%) developed stroke over a median follow-up of 8.6 years (Q1-Q3: 5.1-12.5). In models adjusting for age, sex, time interval between clinic exam and MRI, FHS cohort, and FSRP, those with three or more markers had increased risk of stroke (HR: 2.62; 95% CI: 1.17-5.88). In comparison, a 5-percent increase in FSRP was also associated with increased risk (aHR: 1.16; 95% CI: 1.04-1.29). The FSRP and CSVD score had similar model discrimination metrics. Higher CSVD burden is associated with increased risk of stroke, beyond the effect explained by risk factors in the FSRP. These findings support consideration of CSVD burden to identify risk of stroke in community-dwelling individuals for early implementation of preventive strategies.

Brain abscess caused by Streptococcus pyogenes with atypical symptoms: a case report and literature review

BackgroundStreptococcus pyogenes is a common gram-positive bacterium, belonging to group A Streptococcus (GAS), and is responsible for causing a range of clinical conditions. Brain abscess caused by GAS is uncommon in pediatric infectious diseases, and GAS brain abscess without acute infectious symptoms has been rarely reported.Case presentationWe present a case of one GAS brain abscess in a previously healthy child with unusual clinical manifestations of decreased muscle strength in the left limbs. The right frontal lobe mass lesion was resected using a microscope-based neuronavigation system. A sole defectively beta-hemolytic Streptococcus pyogenes was isolated from the lesion. The patient’s peripheral blood whole-exome and the pathogen’s whole-genome sequencing were performed respectively, revealing a heterozygous mutation in the interferon regulatory factor-8 (IRF8) gene in the patient and lack of hyaluronic acid capsules in Streptococcus pyogenes (genotype emm22). The patient eventually recovered after prompt surgical drainage of the abscess and appropriate antibiotic treatment.ConclusionsIt is important to pay attention to Streptococcus pyogenes brain abscesses with mild clinical manifestations. Upon reviewing all the cases of pediatric GAS brain abscess reported in the published literature, we discovered that early diagnosis and treatment are crucial factors that impact the prognosis of GAS brain abscess.

P44 An acutely unwell and rare presentation of systemic lupus erythematosus; a case report

Abstract Introduction Systemic lupus erythematosus (SLE) is a systemic autoimmune disease with multisystem involvement. The condition has varying clinical presentations from mild mucocutaneous manifestations to severe multiorgan and central nervous system involvement. It is challenging to diagnose someone with SLE during acute admission. Apart from infection and malignancies, autoimmune and connective tissue diseases should always be one of our differentials in an acutely unwell patient with multisystem involvement. This case demonstrates how unwell and rare a patient with SLE can present. We also acknowledge the need to further understand and raise awareness of this uncommon condition. Case description A 48 year old Thai lady with no known medical illness presented with 2-3 weeks history of viral like illness. On admission, she was tachycardic, hypotensive and hypoxic. Clinical examination revealed bi-basal crepitations and elevated JVP. Her ECG showed sinus tachycardia. Admission bloods showed anemia, raised white cell count, lymphopenia, thrombocytopenia, raised inflammatory markers and acute kidney injury (AKI). CT scan revealed evidence of pericardial effusion with small free fluid in abdomen and pelvis. ECHO showed large pericardial effusion and pericardiocentesis was performed which drained purulent fluid. Blood culture was positive for E. Coli. 3rd Day blood tests were strongly positive for CTD screening. She was reviewed by the rheumatology team and was diagnosed as acute presentation of SLE causing serositis having fulfilled the SLICC criteria with E. Coli bacteremia. SLE DAI – 2K score was 11. She reported history of Raynaud’s since moving to UK, hair loss and two miscarriages in the past. She denied history of oral ulcers, facial rash or significant joint involvement. Renal team advised that AKI was due to infection rather than lupus. She was commenced on high dose oral prednisolone (40 mg/day) and antibiotics. Her condition responded to steroids and subsequently was commenced on mycophenolate as outpatient. Discussion SLE is an autoimmune disease that affects multiple organ systems. Symptoms and signs can vary although majority of patients present with cutaneous manifestation. Most of the clinical manifestations of the disease are due to abnormal inflammatory response. Patients with SLE are usually diagnosed at outpatient settings although they can present acutely unwell as seen in this patient. Serositis refers to inflammation of serous tissue which includes pleura, pericardium and peritoneum. It is considerably a rare condition which is only seen in only around 10% of patients with SLE. Patients can present with shortness of breath, abdominal pain, diarrhoea, fatigue chest pain and even cardiac tamponade. Due to the heterogeneity of SLE presentations, it is challenging for clinicians to diagnose and manage the symptoms. Besides infection and malignancies, it is always important to consider connective tissue disease as one of the differentials in an acutely unwell patient presenting with multisystem involvement. SLICC criteria can be used as a diagnosing tool for SLE which includes clinical and immunological criteria. SLEDAI-2K score can be used to assess disease activity. Her biochemical parameters as well as clinical symptoms drastically improved following steroid initiation. Early recognition and treatment initiation can improve mortality and morbidity significantly. Despite how unwell she was during admission; she improved quickly and was discharged relatively early. Her condition continues to improve on DMARDs, and she is on regular clinic follow up. Key learning points • A good clinical history and examination is essential and aids reaching a diagnosis. As reflected in this case, our patient was a female at childbearing age, south Asian (non-Caucasian ethnicity) who presented with multisystem involvement. Her initial finding of serositis, acute kidney injury, anemia, raised ESR and E. coli bacteremia were not fitting with a typical sepsis picture. There should be strong grounds for considering SLE during such clinical presentations. Suspecting SLE in an acute setting is really challenging due to various reasons, like wide symptomology of SLE, minimal exposure of SLE to physicians and their tendency of leaning towards other common conditions, like sepsis. As SLE is mostly diagnosed as outpatient, inpatient presentations are rare. Furthermore, blood results for connective tissue disease which is a major criteria for diagnosis, can take between 3 to 5 working days to be reported. However, early and appropriate consideration of autoimmune conditions as differentials of an acutely ill patient with multisystem involvement can expedite the process of diagnosis, involvement of related specialty and commencement of appropriate treatment. This approach will benefit patients producing favourable outcomes and minimal hospital stay.

Doxycycline with or without famciclovir for infectious ophthalmic and respiratory disease: a prospective, randomized, masked, placebo-controlled trial in 373 kittens.

The aim of this study was to prospectively evaluate in a randomized, triple-masked, placebo-controlled trial, outcomes for kittens with ocular manifestations of infectious upper respiratory disease (IURD) treated with an ophthalmic and oral antibiotic only vs those also treated with famciclovir. Kittens were stratified into three age (1 to <4, 4 to <8 or 8-12 weeks) and two disease severity ('mild' [total disease score 1-11] or 'severe' [total disease score 12-23]) groups and randomized to receive approximately 5 mg/kg doxycycline either with placebo (group D) or with approximately 90 mg/kg famciclovir (group DF) PO q12h. Caregivers scored clinical signs once daily for 21 days. Ophthalmic examinations and scoring by veterinarians were completed on days 1 and 21. Ophthalmic and clinical resolution were defined as scores of zero for all ocular signs and all ocular and respiratory signs, respectively. Ophthalmic and clinical recovery were defined by absence of active inflammation. For kittens with mild disease, those in group D were slower than those in group DF to achieve clinical recovery (P = 0.049) and clinical resolution (P = 0.030), but not ophthalmic recovery (P = 0.064) or ophthalmic resolution (P = 0.089). Kittens with mild disease and receiving famciclovir achieved predicted 75% clinical resolution 4-5 days earlier than kittens with mild disease and receiving doxycycline alone, and kittens with severe disease (regardless of treatment group). Significantly fewer kittens in group DF developed corneal disease than in group D (P = 0.016). All five kittens whose clinical signs worsened sufficiently to be removed from the study were in group D. The addition of famciclovir to standard antibiotic treatment may reduce corneal disease, length of stay and time to adoption for shelters and rescue groups, thereby increasing capacity for care. Early administration of famciclovir in kittens exhibiting mild ocular manifestations of IURD may be preferable to delaying this treatment until the disease progresses to a severe stage.

Clinical and Epidemiological Features of Pediatric COVID-19: A Retrospective Study.

There is a demand for additional data regarding the impact of coronavirus disease 2019 (COVID-19) on the pediatric population. This study sought to determine the clinical and epidemiological features of pediatric COVID-19 in Iran. A retrospective study was performed to assess medical records of children with COVID-19 admitted to Abuzar Hospital in Ahvaz (Iran). Their clinical and demographic data were recorded. In this study, 600 medical records of pediatric COVID-19 patients were evaluated. Over 50% of them were boys. Mild, moderate, and severe manifestations of COVID-19 were identified in 250, 200, and 150 children, respectively. Patients with severe or moderate COVID-19 had substantially higher levels of various inflammatory markers (C-reactive protein (CRP), fibrinogen, and d-dimer), alanine transaminase (ALT), creatine kinase (CPK), blood urea nitrogen (BUN), neutrophils, lactate dehydrogenase (LDH), aspartate aminotransferase (AST), creatinine (Cr), bilirubin, and gamma-glutamyl transferase (GGT) compared to children with mild COVID-19 (p < 0.001); they also had lower levels of lymphocytes, hemoglobin (Hb), and vitamin D than patients with mild COVID-19 (p < 0.001). In addition, children with severe or moderate COVID-19 had a notably higher incidence of fever or dry cough and longer hospital stays than those with mild COVID-19 (p < 0.001). The prevalence of malnutrition and anemia in patients was 50.6% and 31.5%, respectively. A significant proportion of children who were underweight and stunted experienced moderate to severe COVID-19. Furthermore, there was a considerably higher prevalence of malnutrition, anemia, and vitamin D insufficiency, or deficiency in children with moderate-to-severe COVID-19 compared to patients with mild COVID-19 (p < 0.001). The outcomes of this study revealed a significantly higher prevalence of malnutrition, anemia, vitamin D insufficiency or deficiency, elevated liver and kidney function test results, and increased inflammatory markers in children with moderate to severe COVID-19 compared to those with mild COVID-19.

Molecular and Clinical Heterogeneity in Hungarian Patients with Treacher Collins Syndrome-Identification of Two Novel Mutations by Next-Generation Sequencing.

Treacher Collins syndrome (TCS) is a rare congenital craniofacial disorder with variable penetrance and high genetic and phenotypic heterogeneity. It is caused by pathogenic variants in the TCOF1, POLR1D, POLR1C, and POLR1B genes, and its major characteristic features are malar and mandibular hypoplasia, downward slanting of the palpebral fissures, and conductive hearing loss. In this study, five patients (two males and three females, age range from 2 to 29 years) with TCS were tested by Next-Generation Sequencing (NGS)-based sequencing and clinically characterized. Genetic analyses detected two deletions and one insertion in the TCOF1 gene and one missense variant in the POLR1D gene. Two novel mutations, c.1371_1372insT (p.Lys458*) in the TCOF1 gene and c.295 G>C (p.Gly99Arg) in the POLR1D gene, were identified. Moreover, two already known mutations, c.4369_4373del (p.Lys1457Glufs*12) and c.2103_2106del (p.Ser701Argfs*9) in the TCOF1 gene, were detected. The novel TCOF1 c.1371_1372insT mutation was associated with mild craniofacial manifestations and very rare symptoms of TCS, i.e., developmental delay and moderate intellectual disability. Although incomplete penetrance is a known phenomenon in TCS, surprisingly, the majority of our patients inherited the disease-causing variants from an asymptomatic mother. The unique feature of our study is the observation of causative mutation transmission between asymptomatic family members. Our results expanded the clinical and mutational spectrum of TCS and further confirmed the inter- and intra-familial variability of this disorder.

8620 Prevalence of Osteopenia of Prematurity and Risk Factors in Neonatal of Maternity Hospital

Abstract Disclosure: D.M. Bastos: None. J.G. Bastos: None. A.C. Bastos: None. Introduction: The osteometabolic disease of prematurity (ODP), formerly known as osteopenia of prematurity, corresponds to a disorder of bone mineralization in the neonatal period in very low birth weight premature newborns. The estimated prevalence is about 30% when the birth weight is less than 1,500 grams and around 60% when it is less than 1,000 grams. There is no specific clinical picture, and it can present with mild manifestations, growth deficit, or even evolve with severe rickets and fractures. To qualify the care of premature newborns (NB) in our Service, we question what is the local prevalence of ODP and what are the clinical, biochemical, or imaging risk factors that are potentially related to a greater predisposition to this condition. Objective: Evaluate the prevalence of ODP and recognize potential risk factors in NBs in a neonatal ICU of a reference maternity hospital in Curitiba/ PR. Method: Retrospective longitudinal study, with analysis of medical records of patients born with a gestational age less than 34 weeks and birth weight less than 1,500 grams, born between January/2013 to August/2016. Discussion: Prematurity is the significant factor, followed by low birth weight, for osteopenia. Newborns (NB) with a birth weight below 1500g should receive 40mg/Kg of calcium and 50 mg/Kg of phosphorus. Supplementation of human milk should be started from 15 days of life or when oral intake reaches 100ml/Kg per day (1g/20 ml of milk). In this study, the classification of the growth curve and prevalence by sex were divergent with the literature. The most vulnerable are those with parenteral nutrition or prolonged fasting, as the adequate diet is the basis of prevention and treatment, similar data being found, as well as association with prolonged use of diuretic, presence of sepsis diagnosis and bronchopulmonary dysplasia. However, there is still a lack of specific and sensitive markers for early diagnosis and treatment. Conclusion: The prevalence of Osteopenia of Prematurity was lower than that found in the literature. The risk factors bronchopulmonary dysplasia and use of diuretics were statistically significant when evaluated in patients with osteopenia. However, no relationship was found between ODP and sepsis, as well as a relationship between ODP and Necrotizing Enterocolitis. Regarding the days kept fasting, use of TPN and Use of antibiotics, a longer duration of use was obtained when compared with the group that did not develop the disease. Presentation: 6/3/2024

Association of C4 and CH50 levels with cough and rhinorrhea in COVID-19 patients: A retrospective analysis in the Iranian population

IntroductionThe wide spectrum of COVID-19 symptoms, ranging from mild manifestations to severe pulmonary damage and mortality, prompted this study to investigate the relationship between clinical symptoms and complement system (CS) activation in COVID-19 patients. Materials and methodThis retrospective study focused on 100 PCR-positive COVID-19 individuals admitted to Imam Khomeini and Bu Ali hospitals in Sari City from April to June 2021. The levels of C3 and C4 proteins in their blood were measured using nephelometry, and CH50 tests were done with single radial immunodiffusion to determine the activity of CS. ResultsThe study found that high blood pressure, smoking, and diabetes were the most common underlying conditions among the patients, with prevalence rates of 29%, 24%, and 23%, respectively. Positive correlations were found between C4 and CH50 levels and the presence of cough and rhinorrhea in the subjects. Stratifying patients into 2 groups based on cough or rhinorrhea revealed a significant difference in CH50. ConclusionThe findings suggest that COVID-19 patients with hypertension or diabetes mellitus may benefit from targeting CS for disease management.

Assessment of the Quality of Life of Men with Premature Ejaculation

Sexual health is an integral part of the quality of life of every person, as it is of great importance for the physical and mental well-being of individuals, couples, families, and, accordingly, for the social and economic development of communities and countries. The objective: to assess the impact of premature ejaculation (PE) on the quality of life of men depending on the degree of clinical manifestations. Materials and methods. 89 men who had premature ejaculation were under observation. The average age of the patients was 32.6±4.2 years. The average duration of the disease was 4.6±2.4 years. 22 (24.7%) patients had secondary (acquired) premature ejaculation against the background of chronic prostatitis or prostatic vesiculitis. Other 67 (75.3%) men had a primary (congenital) form of premature ejaculation, which began with the beginning of sexual life. The premature ejaculation diagnostic tool (PEDT) was used to determine the severity of premature ejaculation. Quality of life was assessed on the basis of Quality of Life Enjoyment and Satisfaction Questionnaire – Short Form (Q-LES-Q-SF) (). Hospital Anxiety and Depression Scale (HADS) was used for screening detection of anxiety and depression. Study of medical and social characteristics based on the developed program was performed and the sensitivity of the penis was also assessed using biotensiometry. Results. It was established that men with premature ejaculation have a low satisfaction with life (76.4%), against the background of complete (55.1%) or partial (44.9%) dissatisfaction with their sexual life. Premature ejaculation has a negative impact on their daily life, as it leads to negative experiences (92.1%), reduced work capacity (41.6%), deterioration of relations with a wife or partner (48.3%), a feeling of exhaustion and fatigue (32.6%). When evaluating the results of the PEDT diagnostic test, according to the severity of the manifestations, men had a mild (50.5%), medium (31.5%) or severe (18%) degree. A clear correlation between the decline in men’s quality of life and the severity of premature ejaculation was noted (Spearman’s r = –0.938; p&lt;0.01). The data of anxiety and depression scales indicated their high level, which also depended on the degree of severity of premature ejaculation manifestations (Spearman’s r = 0.790; p&lt;0.01) and negatively affected the quality of life (Spearman’s r = –0.760; p&lt;0,01). According to the data of biotensiometry, hypersensitivity of the head of the penis was noted in men with premature ejaculation, in comparison with the data in the control group of men who did not have sexual disorders: 4.2±1.6 W and 12.4±2.6 W respectively (p&lt;0.05). More pronounced indicators of penile hypersensitivity were observed in men with severe PE with a statistically significant difference compared to the indicators in the group of men with mild manifestations of PE (p&lt;0.05) and without a significant difference compared to the indicators in the group of men with average by the degree of PE (p&gt;0.05). Somewhat more pronounced indicators of penile hypersensitivity were observed in men with PE under the age of 30. Conclusions. Premature ejaculation is characteristic of men of young working age, which is accompanied by a negative impact on various areas of their life, and the development of anxiety and depression, as well as a decrease in the quality of life. This requires improving the organization of providing medical and psychological assistance to such patients.

Problems of depression in neurological practice

Introduction. Depressive disorders have ceased to be only the task of psychiatrists. Depression is detected in patients with a somatic and neurological profile as a reaction to the disease, and may be the cause of the disease. The number of above-mentioned pathologies remains unknown to date. The main task for health care organizers is the need to build an algorithm for the identification, registration and treatment of depressive disorders in patients with combined pathologies. This article discusses depressive disorders in patients with multiple sclerosis. The purpose of the study: to study depressive disorders and factors influencing depression in patients with multiple sclerosis. Materials and methods. 203 patients with clinically confirmed diagnosis of MS participated. Taking into account the course of the disease, MS patients were distributed: with a remitting (RRS) type of MS course 88.2 % (179 people) and 11.8 % (24 people) with a secondary progressive course (RRS). The average age of the examined patients with remitting course (RRS) ranged from 15 to 63 years, on average 38 ± 10 years. The age of the examined patients with HPV is in the range from 29 to 65 years, on average (46 ± 9.00) years. The majority of patients had a disease duration of less than 20 years, on average 8.23±6.57 years. The average age of onset of the disease is 30.2±10.5 years. The duration of the disease is 9.84 ± 0.73 years, while the level of disability of patients (score in points on the Expanded Disability Status Scale/EDSS) at the time of examination was 2.89 ± 0.16 points. The disability index varied in patients with RRS2.89 ± 0.16 points, in patients with RRS (5.0 ± 0.24) points. Results and discussion. 55.7 % (113 people) of MS patients were diagnosed with depression, of which 80.5 % (91 people) and 19.5% (22 people) of patients with a remitting (RRS) course and a secondary progressive course of the disease (RRS). More than 54.8 % (62 people) had mild and moderate depressive manifestations, 39.8 % (45 people) most often had mixed anxiety-depressive disorder, recurrent depressive disorder, then depressive episodes. It was revealed that the development of depression in patients with a remitting course is influenced by: «disease duration» PC p = 0.00333**, «disability level» p = 0.0457* and «personal anxiety» p = 0.0194. In patients with a secondary progressive course, depression is influenced by the following factors: «situational» p = 0.0398* and «personal anxiety» p = 1.740. The social status determined that patients with «MS without depression» who were married were statistically less likely to suffer from depression and maintained their working capacity longer (p &lt; 0.001). Conclusion. Depressive disorders are the leading disorders in neurological patients, but their number and severity of symptoms are often ignored by specialists. Therefore, the health authorities are faced with the task of building a clinical and organizational algorithm for the identification of depressive disorders, as well as their timely medical correction.

Uncommon culprit artery leading to atypical de winter electrocardiographic changes: a case report

BackgroundA subset of patients with acute coronary artery occlusion requiring emergency revascularization, does not present with the typical ECG features of ST-segment elevation myocardial infarction (STEMI).Timely identification of these atypical presentations is crucial.Case presentationThis report describes a 55-year-old male patient who was admitted to the emergency department with chest pain. The electrocardiogram (ECG) recorded atypical de Winter electrocardiographic changes and their evolution.ResultsCoronary angiography confirmed the occlusion of the second diagonal branch (D2). The patient’s condition improved after D2 balloon angioplasty.ConclusionDe Winter electrocardiographic changes can also be observed in D2 occlusions and may present with milder manifestations. Timely recognition of these changes holds significant clinical value.

Characterization of Clinical Phenotypes in Congenital Myasthenic Syndrome Associated with the c.1327delG Frameshift Mutation in CHRNE Encoding the Acetylcholine Receptor Epsilon Subunit.

Congenital myasthenic syndromes (CMS) are a group of rare but often treatable inherited disorders of neuromuscular transmission characterized by fatigable skeletal muscle weakness. In this paper we present the largest phenotypic analysis to date of a cohort of patients carrying the pathogenic variant c.1327delG in the CHRNE gene, leading to CHRNE-CMS. This study aims to identify the phenotypic variability in CMS associated with c.1327delG mutation in the CHRNE gene. Disease specific symptoms were assessed using specific standardized tests for autoimmune myasthenia (Quantitative Myasthenia Gravis score) as well as patient-reported scales for symptom severity. Evaluated clinical manifestations included ocular symptoms (ophthalmoparesis and ptosis), bulbar weakness, axial muscle weakness, proximal and distal muscle weakness, and respiratory function. Patients were allocated into three groups according to clinical impression of disease severity: mild, moderate, and severe. We studied 91 Bulgarian Roma patients, carrying the same causative homozygous CHRNE c.1327delG mutation. Bulbar weakness was present in patients throughout all levels of severity of CHRNE-CMS in this study. However, difficulties in eating and swallowing are more prominent characteristics in the moderate and severe clinical phenotypes. Diplopia and ptosis resulting from fatigue of the extraocular muscles were permanent features regardless of disease severity or age. Levels of axial, proximal and distal muscle weakness were variable between disease groups. The statistical analysis showed significant differences between the patients in the three groups, emphasizing a possible variation in symptom manifestation in the evaluated patient population despite the disease originating from the same genetic mutation. Impairment of respiratory function was more prominent in severely affected patients, which might result from loss of compensatory muscle function in those individuals. Results from our study indicate significant phenotypic heterogeneity leading to mild, moderate, or severe clinical manifestation in CHRNE-CMS, despite the genotypic homogeneity.

Effects of the oxoaporphine alkaloid hernandonine on dengue virus. Evidence for its mechanisms of action

BackgroundDengue, caused by the dengue virus (Orthoflavivirus dengue, encompassing DENV types 1-4), is a member of the Flaviviridae family. The symptoms of dengue range from subclinical or mild manifestations to potentially fatal complications. The management of severe dengue is exceptionally challenging due to the absence of effective antiviral medications. In this context, natural products, whether in the form of pure compounds or standardized plant extracts, have emerged as a promising source for the development of novel antiviral therapeutics. Hernandonine, an oxoaporphine alkaloid found in Hernandia nymphaeifolia (C. Presl) Kubitzki. serves both as a metabolite and an inhibitor of human immunodeficiency virus type 1 (HIV-1) integrase. PurposeThis study investigated the ability of hernandonine to inhibit DENV infection and explored its potential mechanisms. Study designTo assess the in vitro anti-DENV activity, cells or induced pluripotent stem cell (iPSC)-derived cerebral organoids were exposed to hernandonine before or after infection with DENV. Along with hernandonine, the endocytosis modulators, genistein, wortmannin, Methyl-β-cyclodextrin (MβCD) and lovastatin, were used in the assays. MethodsThe DENV infectivity and virion production in cells or cerebral organoids treated with compounds were determined. Various methods, including cell and cerebral organoids imaging, protein and gene detection were conducted to explore their antiviral mechanisms. ResultsThe results revealed notable antiviral properties of hernandonine, particularly in inhibiting DENV during the early stages of infection. Mechanistic analysis demonstrated that, akin to genistein, wortmannin, methyl-β-cyclodextrin (MβCD), and lovastatin, hernandonine exerted an influence on cholesterol-rich lipid rafts. It also restrained the pseudopodial movement ability of cells, potentially through the downregulation of cytoskeleton and endocytosis regulatory genes or protein expression. Moreover, hernandonine's virucidal activity was demonstrated. Hernandonine's inhibition of DENV infection was further validated in a disease-relevant iPSC-derived cerebral organoids model, a novel DENV-2 infection system worthy of further application. ConclusionThis study evidenced the potential of hernandonine as a novel candidate in the fight against DENV infection.

Incidence of acute transfusion reactions and associated factors among adult blood-transfused patients at Jimma University Medical Center, southwest Ethiopia: A cross-sectional study.

Acute transfusion reaction is mainly related to the infusion of blood or blood products resulting at any time within a day of the intervention. It ranges from a non-specific febrile episode to a life-threatening intravascular hemolysis. The severity of the reaction and the degree of morbidity are usually related to the degree of ABO incompatibility and the volume of blood transfused. Therefore, this study aimed to determine the incidence of acute transfusion reactions and its associated factors in Jimma University Medical Center, southwest Ethiopia. Institution-based cross-sectional study was conducted from 1 October to December 30, 2020. A total of 384 transfused patients were followed in this study. Socio-demographic and clinical data were collected through a structured questionnaire. Baseline measurement and 24-hour periodic vital signs monitoring were conducted after each transfusion. Four milliliters of venous blood were drawn after transfusion intervention from each distrusted patient for complete blood count, blood group phenotype, direct antihuman globulin test (DAT), and crossmatching. Data were entered into Epi data version 3.1 and analyzed using Statistical Package for Social Science software (SPSS) version 20. Descriptive statistics, and bivariable and multivariable logistic regression were employed to test the association between independent and dependent variables. A P value ≤ .05 was considered to indicate statistical significance. Acute transfusion reactions were diagnosed in 5.7% of patients, with most of these reactions were febrile nonhemolytic reactions (63.6%) followed by allergic (36.4%) reactions with mild clinical manifestations (27.3%). Transfusion history, transfused blood that was kept for more than 13 days, abortion history, and number of transfused units (≥3 units of blood/blood component) have 3.3, 3.85, 4.2, and 3.9 times greater odds, respectively, besides their significant association with the incidence of acute transfusion reactions. Patients with a history of previous transfusion, abortion, multi-unit transfusion, and patients transfused with blood stored for ≥14 days should be closely monitored. Starting a hemovigilance system of monitoring, collecting, and evaluating data on adverse effects of blood transfusion locally and nationally will decrease the occurrence of acute transfusion reactions.

Awareness and Knowledge of Medical Interns in the Diagnosis and Management of Anaphylaxis in Medina Region, Saudi Arabia.

Background Anaphylaxis is a severe hypersensitivity reaction caused by IgE-mediated mechanisms. This life-threatening condition affects multiple body systems. Global lifetime prevalence estimates for anaphylaxis range from 0.3% to 5.1%, with increasing incidence noted, particularly among young individuals. Symptoms range from mild skin manifestations like urticaria and pruritus to severe respiratory distress and hypotension. Objectives This study aimed to assess the knowledge level of medical interns in the Medina region, Saudi Arabia, regarding the diagnosis and management of anaphylaxis. Method A prospective cross-sectional study was conducted in hospitals in Saudi Arabia by delivering a questionnaire designed to assess the level of awareness and knowledge (including signs, symptoms, and management of anaphylaxis) among medical interns in the Medina region. The data collected were coded and analyzed using IBM SPSS Statistics for Windows, Version 22.0 (released 2013, IBM Corp., Armonk, NY). Results The study involved 291 interns from the universities in the Medina region. Most participants (275, 94.5%) correctly defined anaphylaxis and identified food allergies or insect stings as the main triggers (254, 87.3%). The participants demonstrated good knowledge of health education practices and anaphylaxis symptoms, such as the importance of carrying an adrenaline auto-injector (269, 92.4%) and recognizing syncope as a cardiovascular symptom (196, 67.4%). Regarding management, most correctly identified the initial step as removing the allergen (226, 77.7%) and epinephrine as the preferred medication (256, 88.0%). Significant gender differences were observed in the knowledge of management aspects (P = 0.001, P = 0.002, P = 0.049, P = 0.004, P = 0.001). Conclusion The study found that most participants had a good understanding of the definition of anaphylaxis and its most common triggers. The participants also demonstrated knowledge of symptoms and signs associated with anaphylaxis and the appropriate management of anaphylaxis. However, there were some differences in knowledge between females and males, suggesting that further education and awareness campaigns may be needed to ensure an accurate and consistent understanding of anaphylaxis among both genders. Overall, the study highlights the importance of education and awareness in effectively managing anaphylaxis and preventing its complications.

The prevalence of inflammatory process in placentas from premature births in different gestational periods

Premature birth (PB) is the birth in less than 37 weeks, which can be spontaneous and iatrogenic, its frequency reaches 10% of all births. The pathogenesis of premature labor is based on the inflammatory reaction of the chorion, amnion and decidual membrane, but the origin of the inflammatory reaction is different depending on the gestational age.The objective: to study the prevalence of the inflammatory response in placenta samples from very early preterm, early preterm and term births.Materials and methods. Placenta samples from 203 parturient women who gave birth in the gestational period of 22–27 weeks – very early PB (I group – 101 parturient women with premature rupture of membranes (PROM), II group – 102 parturient women with the onset of labor with intact membranes) and 202 parturient women were examined with deliveries in the period of 28–34 weeks – early PB (III group – 100 women in labor with PROM and IV group – 102 women in labor with the onset of labor with intact fetal membranes) and 60 women in labor with term deliveries.Immunohistochemical detection of CD8, CD3 and CD14 antigens in villi was used to assess the prevalence of the inflammatory process and compare it between groups.Results. In 56.7% of placentas from term deliveries no markers of villousitis were detected, a mild form of villousitis was found in another third of cases. In placentas of woman with the onset of labor between the 28th and 34th weeks with intact fetal membranes there were signs of villousitis in 54.9%, and its mild manifestations in 33.3%. In the case of premature rupture of the membranes, the prevalence of villousitis reached 65%, its severe forms were more often observed.On the other hand, in the groups of very early PB only 14.9 and 15.7% of placentas had no signs of vilouisitis, one in five placentas from these groups had severe focal or diffuse villousitis. In the group of early PB and intact amniotic membranes, one third of the placentas demonstrated an isolated CD3 lymphocyte marker, no antigen was detected in 47.1% of placentas, and only in every tenth placenta antigens of macrophages of fetal origin were determined. A similar distribution was found in placentas from early PB with PROM.In placentas from very early PB the highest frequency of CD14 detection was found – every second placenta contained this marker in isolation and in 22.5% – in combination with maternal lymphocyte markers. In the group of very early PB on the background of PROM placentas with a positive CD14 test dominated – 31.7% isolated and 45.5% in combination with CD3.Conclusions. 1. In placentas from premature births (PB) at 28–34 weeks, villousitis was detected in 54.9% of cases against the background of intact amniotic membranes and in 65.0% – on the background of premature rupture of the membranes, from very early PBs – in 85.1% and 83.3%, respectively. Placentas from deliveries with premature rupture of the fetal membranes more often had signs of severe villousitis – in 21% of cases at 28–34 weeks and in 20.6% at 22–27 weeks.2. In placentas from early PB, macrophage antigen of fetal origin was detected in 22% of cases in the cases of premature rupture of the fetal membranes and in 21.6% of cases of childbirth with intact membranes; these samples were dominated by infiltration by lymphocytes of maternal origin. On the other hand, placentas from very early PB and ruptured fetal membranes in 77.2% of cases contained antigen of fetal macrophages and in 71.6% of cases of onset of labor with intact membranes.Such results indicate the fetal origin of the inflammatory process in very early PB.

Phenotypic Expansion of Autosomal Dominant LZTR1-Related Disorders with Special Emphasis on Adult-Onset Features.

Leucine zipper-like transcription regulator 1 (LZTR1) acts as a negative factor that suppresses RAS function and MAPK signaling; mutations in this protein may dysregulate RAS ubiquitination and lead to impaired degradation of RAS superfamily proteins. Germline LZTR1 variants are reported in Noonan syndrome, either autosomal dominant or autosomal recessive, and in susceptibility to schwannomatosis. This article explores the genetic and phenotypic diversity of the autosomal dominant LZTR1-related disorders, compiling a cohort of previously published patients (51 with the Noonan phenotype and 123 with schwannomatosis) and presenting two additional adult-onset cases: a male with schwannomatosis and Parkinson's disease and a female with Noonan syndrome, generalized joint hypermobility, and breast cancer. This review confirms that autosomal dominant LZTR1-related disorders exhibit an extreme phenotypic variability, ranging from relatively mild manifestations to severe and multi-systemic involvement, and offers updated frequences of each clinical feature. The aim is to precisely define the clinical spectrum of LZTR1-related diseases, using also two new emblematic clinical cases. Gaining insight into the mechanisms underneath this variability is crucial to achieve precision diagnostics and the development of therapeutic interventions.