Clinical Manifestations Of Disease Research Articles

Radiological assessment of extremity bone involvement in Erdheim-Chester disease: a systematic review of case reports.

To describe the clinical presentations and radiological manifestations of Erdheim-Chester disease (ECD) in the extremities, with particular emphasis on radiologic findings, as radiographs are typically the initial imaging modality used in clinical practice. Following the PRISMA guidelines, a comprehensive systematic search was performed across Scopus, PubMed, Web of Science, and Embase databases, covering case reports from inception until August 1, 2024. Included were studies with pathologically confirmed ECD (CD68 positive and CD1a negative) that were evaluated with at least one imaging modality and provided detailed descriptions of radiological findings. Out of 401 identified articles, 20 articles comprising 20 histologically confirmed cases of ECD met the inclusion criteria following screening and full-text review. Pathological reports were assessed for the presence of lipid-laden cells and Touton giant cells, which were identified in 84.2% and 75% of cases, respectively. Upper extremities were affected in 65% of cases and lower extremities in all cases. Symmetric involvement was observed in 84.6% of upper extremity cases and 84.2% of lower extremity cases. Radiological findings were categorized as pure sclerosis (53.3%) and cortical thickening (42.8%) identified as the most common findings. Clinical manifestations were assessed, with pain and swelling in the extremities being the most common symptoms, occurring in 70% of cases. The hallmark of ECD is bilateral, symmetric diaphyseal and/or metaphyseal osteosclerosis in the long tubular bones of the lower extremities. Epiphyseal sparing is observed in more than half of the patients.

A patient with a PTPN11 gene variant complicated with Chiari I malformation and syringomyelia and a review of literatures.

According to previous literature reports, PTPN11 gene variants account for approximately 50% of Noonan syndrome (NS) cases and 85% of Leopard syndrome (LS) cases. Several patients who were diagnosed with NS or LS complicated with Chiari I malformation (CIM) and/or syringomyelia have been reported to have a PTPN11 variant. However, it is not always clear whether the association between CIM and/or syringomyelia and PTPN11 variants is real or random. We try to explain this phenomenon by reporting a clinical case and making a mini-review. We retrospectively described a clinical case in detail and made a genetic test on the proband and her family members using whole-exome sequencing. And made a review of the related literatures. The patient was manifesting progressive abnormal gait and muscle weakness for more than 2 years before she was admitted to our hospital at the age of 5 years and 2 months. On examination, she looked frail and slender. She had short stature, mild intellectual disability, decreased muscle strength in the left limb, thinner left limb, left hollow foot and foot drop, weakened left knee and Achilles tendon reflexes and a positive left Babinski sign. She looked timid and had very little expressive language. MRI of the brain and spine revealed CIM and syringomyelia with hydrops. Cardiac ultrasonography revealed an ostium secundum defect. ECG examination showed no abnormalities. She received a spinal cavity subarachnoid shunt; the symptoms were relieved to some extent, and the cavity in the lumbar vertebrae was significantly reduced after the surgery. Genetic testing found a variant, c. 922A>G (p. Asn308Asp) in the PTPN11 gene. Both parents were wild-type at this locus. A literature review found that 31 patients with NS or LS were complicated with CIM, syringomyelia or both. Together with our patient, a total of six patients in this group had the PTPN11 gene variant. Among them, four were complicated with both CIM and syringomyelia, and two were complicated with CIM only. We report another case with a PTPN11 variant that was complicated with both CIM and syringomyelia. It suggests that CIM and syringomyelia may be clinical manifestations of PTPN11 variation-related diseases. This phenomenon may be underrated due to limitations of genetic diagnostic methods in the past. We strongly suggest routine craniocerebral and spinal MRI scans and genetic testing for patients suspected of having NS or LS.

Development of Serum Plate Agglutination Antigen using Mycoplasma gallisepticum Field Isolate

Mycoplasma gallisepticum is an important pathogen responsible for respiratory tract infections in poultry. Clinical manifestation of disease varies from mild respiratory infection to chronic respiratory disease (CRD) in case of co-infections with other viral or bacterial pathogens. Mycoplasma infections cause huge economic losses due to reduction in hatchability and egg production as well as due to increased morbidity and mortality in a flock. Early screening of infection is done by using serological assays including Serum Plate Agglutination Assay (SPA) and Enzyme Linked Immunsorbent Assay (ELISA). The present study was aimed to prepare SPA antigen using M. gallisepticum isolate recovered from the field. In house developed antigen was compared with commercially available antigen using sera collected from the suspected flocks. Results revealed 205/300 (68.35%) positive reactions using locally developed antigen and 198/300 (66%) positive reactions while using commercially available imported antigen. After statistical analysis by using Fisher’s exact test, it was inferred that difference between detection rate of both antigens was non-significant (P =1.0000). Local antigen was assessed for cross reactivity and it gave suitable results till four months. Local antigen appears to provide a cheaper and easy method for initial screening of M. gallisepticum infection.

The Beneficial Effects of Curcumin on Lipids: Possible Effects on Dyslipidemia-induced Cardiovascular Complications.

Dyslipidemia and altered lipid metabolism are closely involved in the pathogenesis and clinical manifestation of many metabolic and non-metabolic diseases. Therefore, mitigation of pharmacological and nutritional factors together with lifestyle modifications is paramount. One potential nutraceutical exhibiting cell signaling and lipid-modulating properties implicated in dyslipidemias is curcumin. Specifically, recent evidence suggest that curcumin may improve lipid metabolism and prevent dyslipidemia-induced cardiovascular complications via several pathways. Although the exact molecular mechanisms involved are not well understood, the evidence presented in this review suggests that curcumin can provide significant lipid benefits via modulation of adipogenesis and lipolysis, and prevention or reduction of lipid peroxidation and lipotoxicity via different molecular pathways. Curcumin can also improve the lipid profile and reduce dyslipidemia- dependent cardiovascular problems by impacting important mechanisms of fatty acid oxidation, lipid absorption, and cholesterol metabolism. Although only limited direct supporting evidence is available, in this review we assess the available knowledge regarding the possible nutraceutical effects of curcumin on lipid homeostasis and its possible impacts on dyslipidemic cardiovascular events from a mechanistic viewpoint.

DEVELOPMENT AND VALIDATION FOR INTRA-SPECIES CLASSIFICATION OF HHV6A AND HHV6B MOLECULAR GENETIC DIVERSITY

Human herpesvirus 6A (HHV6A) and human herpesvirus 6B (HHV6) are ubiquitous viruses that infect more than 95% of the population. Clinical manifestations of HHV6 infection and associated diseases are diverse, which may depend on virus molecular genetic characteristics (genovariants). Estimating the significance of the molecular genetic diversity is complicated due to the lack of proper classification. The aim of the study was to develop an intraspecies HHV6A and HHV6B classification. Using 50 and 207 HHV6A and HHV6B full-genome sequences retrieved from the NCBI Nucleotide database, various fragments of virus genome were analyzed. Multiple sequence alignment was performed using MAFFT L-INS-i algorithm; F81 nucleotide substitution model and maximum likelihood method were used to construct dendrograms. Nucleotide substitutions were determined relative to reference sequences X83413 (HHV6A) and AF157706 (HHV6B). Genovariants were defined based on the nucleotide substitutions in variable positions of the genomic fragment. The results were confirmed by constructing dendrograms. An opportunity of using fragments of HHV6A and HHV6B genomes to construct an intraspecies classification was assessed. Fragments U90 (part206) and U90B(part431) were selected as optimal. Based on the nucleotide sequences of the fragments, the intraspecies classification for HHV6A and HHV6B was constructed, including seven genovariants of each virus. The genovariants were characterized by unique nucleotide composition in the signature positions. A minimum (0.001 or less for both viruses) nucleotide diversity within the isolated genovariants was established. The classification reflects the phylogenetic relationships of circulating and inherited chromosomally integrated forms of HHV6A and HHV6B: divergence of HHV6A genovariants depending on its persistence form and integration site and coevolution of two HHV6B forms within several genovariants. Further studies on virus molecular genetic diversity in different regions of Russia and abroad may supplement the classification. The method of HHV6A and HHV6B classification is characterized by simplicity, technological accessibility and can be implemented in laboratories of different levels of technical equipment. The classification can be used to analyze an effect of virus molecular genetic diversity on the clinical characteristics of associated diseases, optimize the epidemiological surveillance system and develop new approaches for diagnostics, prevention, and treatment of HHV6 infection.

Visium spatial transcriptomics and proteomics identifies novel hepatic cell populations and transcriptomic signatures of alcohol-associated hepatitis.

Alcohol-associated hepatitis (AH) is the clinical manifestation of alcohol-associated liver disease (ALD). AH is a complex disease encompassing the dysregulation of many cells and cell subpopulations. This study used a hepatic spatial transcriptomic and proteomic approach (10X Genomics Visium) to identify hepatic cell populations and their associated transcriptomic and proteomic alterations in human AH. Formalin-fixed paraffin-embedded liver tissue from AH patients (n = 2) and non-ALD controls (donors) (n = 2) were used for Visium spatial transcriptomic and proteomic analysis. AH cell clusters and cell markers were drastically different in regard to tissue pattern and number of cell types compared to non-ALD controls. Cholangiocytes, endothelial cells, macrophages, and stellate cells were more profuse in AH relative to non-ALD controls. Transcriptionally, proliferating cell nuclear antigen-positive (PCNA+) hepatocytes in AH more closely resembled cholangiocytes suggesting they were non-functional hepatocytes derived from cholangiocytes. Furthermore, mitochondria protein-coding genes were reduced in AH versus non-ALD control hepatocytes, suggesting reduced functionality and loss of regenerative mechanisms. Macrophages in AH exhibited elevated gene expression involved in exosomes as compared to non-ALD controls. The most upregulated macrophage genes observed in AH were those involved in exosome trafficking. Gene and protein signatures of disease-associated hepatocytes (ANXA2+/CXCL1+/CEACAM8+) were elevated in AH and could visually identify a pre-malignant lesion. This study identified global cell type alterations in AH and distinct transcriptomic changes between AH and non-ALD controls. These findings characterize cellular plasticity and profuse transcriptomic and proteomic changes that are apparent in AH and contribute to the identification of novel therapeutics.

Role of Resveratrol in Endotoxin Induced Uveitis: Literature Review

Uveitis is defined by a range of diverse clinical manifestations of ocular disease and involves inflammation of the uveal tissue, which includes the iris, choroid and ciliary body. Uveitis is characterized by a variety of heterogeneous clinical manifestations of ocular diseases. Corticosteroid and immunosupressive medication are required for non-infectious uveitis since they can successfully control inflammation. This study investigates role of Resveratrol as a promosing treatment in endotoxin induced uveitis as a mimic human anterior uveitis. Resveratrol is acknowledged as an antioxidant polyphenol discovered in grape skin and red wine. Anti-inflammatory, anti-cancer, and antioxidant properties are only a few of Resveratrol many biological and medicinal potentials. Our study evaluated the role of Resveratrol in potential therapy of uveitis. Results demonstrate significant reduce of inflammatory cytokine and cells suggesting the potential therapeutic effect of Resveratrol.

THE IMPACT OF EXOGENOUS AND ENDOGENOUS FACTORS ON VASCULAR WALL ELASTICITY AND POTENTIAL CLINICAL EFFECTS (Review Article)

Vascular aging is associated with profound changes in the structural properties of the arterial wall. Arterial hypertension, diabetes mellitus, and chronic kidney disease are the primary determinants of the loss of elasticity and reduced compliance of the vascular wall. Arterial stiffness is a key parameter for assessing the elasticity of the arterial wall and can be easily evaluated using non-invasive methods such as pulse wave velocity. Early assessment of arterial stiffness is critical, as its changes may precede the clinical manifestations of cardiovascular disease. With age, arterial walls become stiffer, leading to an increase in systolic blood pressure and an increased risk of cardiovascular events such as stroke, myocardial infarction, or heart failure. The gradual decrease in vascular elasticity is accompanied by remodeling of their structure, an increase in collagen fibers, and a decrease in elastin, which exacerbates the problem. In addition, the mechanical stress on the vascular wall, which increases with age, worsens its condition, provoking the formation of atherosclerotic plaques. Arterial stiffness, as an important biomarker of vascular aging, is also an indicator of increased cardiovascular risk, independent of other factors such as blood pressure or the presence of comorbidities. Therefore, timely diagnosis of arterial stiffness can help prevent serious complications and adjust treatment for patients at risk. Important are also preventive measures, including a healthy lifestyle, physical activity, and control of the underlying diseases that contribute to the acceleration of vascular aging processes. Moreover, the influence of endogenous and exogenous factors, such as diet, the presence of chronic diseases, and bad habits (in particular, smoking), contribute to the acceleration of these processes. Innovative diagnostic methods, such as magnetic resonance imaging (MRI) or ultrasound, allow detecting these changes at early stages and, accordingly, adapting treatment.

Comorbidity problems in patients with osteoporosis

BACKGROUND: Osteoporosis is a metabolic skeletal disease characterized by decreased bone mass, impaired microarchitecture of bone tissue and, as a consequence, fractures with minimal trauma. The social significance of osteoporosis is determined by its consequences — fractures of the vertebral bodies and bones of the peripheral skeleton, leading to high medical costs and causing a high level of disability, including disability and mortality. Osteoporosis is most often combined with cardiovascular diseases caused by atherosclerosis, which are widespread and are the leading cause of disability and mortality. A small number of studies have been devoted to the study of the features of clinical manifestations of cardiovascular diseases in the combination of coronary heart disease and osteoporosis. AIM: To identify the frequency and severity of comorbid diseases and their risk factors in postmenopausal osteoporosis. MATERIALS AND METHODS: A retrospective and prospective cohort study was conducted from 2013 to 2023. 8250 women with postmenopausal osteoporosis were examined and the data from the medical records of these patients who applied to the Osteoporosis Center of the North-Western State Medical University named after I.I. Mechnikov of the Ministry of Health of the Russian Federation from 2013 to 2020 were analyzed. At the prospective stage, two comparison groups of 100 patients with and without postmenopausal osteoporosis were formed from 500 patients with comorbid diseases (coronary heart disease, hypertension, type 2 diabetes, stroke, transient ischemic attack). Bone mineral density was assessed based on the Hologic Discoveri Wi dual-energy X-ray absorptiometry at 2 points in the lumbar spine (L1–L4) and the femoral neck. Along with traditional laboratory examination methods, bone metabolism markers (total calcium, phosphorus, vitamin D, urine analysis for deoxypyridinoline, C-terminal telopeptide of type 1 collagen, osteocalcin, alkaline phosphatase, parathyroid hormone) were assessed dynamically. In all the patients, along with a general clinical examination, an assessment of risk factors for cardiovascular disease and osteoporosis was performed. RESULTS: Body mass index was higher in the group of patients with osteoporosis — 28.4 (26.9–32.4) kg/m2 (p 0.001), versus 27.64 (25.8–30.0) kg/m2 (p 0.05). Bone mineral density in the group of patients with osteoporosis was statistically lower than in the group without osteoporosis. In the group of patients with osteoporosis, the risk of fractures was high and amounted to 37 (95% confidence interval 15.0–38.50) %, p 0.001), versus in the control group 9.55 (95% confidence interval 7.67–15.0) % (p 0.001) according to the FRAX questionnaire for the Russian Federation. In the group of patients with osteoporosis, the Charlson index values were 5.1 (95% confidence interval 4.7–5.6) points. As a result of the correlation analysis, a reliable positive relationship was revealed between low bone mineral density L1–L4 and hip with bone metabolism: alkaline phosphatase, C-terminal telopeptide of type 1 collagen, vitamin D, osteocalcin, urinary deoxypyridinoline. We found a negative relationship between bone mineral density and the Charlson index, absolute ten-year risk of hip fracture and the duration of early menopause, and the level of hypertension. To assess the dependence of QRISK3-2018 on osteoporosis risk factors in the group of patients with osteoporosis, multiple linear regression was performed. This model was characterized by a statistically significant correlation between the factors and the dependent variable of high tightness. The coefficient of determination was 0.608, indicating a 60.8% contribution of the factors taken into account in the model to the variance of QRISK3-2018. CONCLUSIONS: In women with postmenopausal osteoporosis, comorbid pathology is more common, aggravating the course of the disease. Knowledge of the prevalence of concomitant pathology and joint risk factors will make it possible to simultaneously form groups at increased risk of development, which will ensure prevention of both diseases with the same non-medical means and drugs.

Orbital and peri-ocular parffinoma: case series and literature review

BackgroundParaffinoma is a rare and intriguing condition in medicine. In this disorder, an orbital lipogranulomatosis reaction is caused by the penetration of mineral oils (particularly paraffin) into the tissues surrounding the eye.MethodsIn this report, we discuss six cases of paraffinoma affecting the eye socket following sinus surgery. For previous cases literature review, we obtained articles from searching in the PubMed, Scopus, Scholar Google and, Science of Web databases.ResultsAfter the reporting of 6 paraffinoma cases and literature review, the data related to the disease were categorized into the categories of disease definition, differential diagnosis, clinical manifestation, radiological manifestation, and histopathological diagnosis and treatment methods.ConclusionsParaffinoma is a rare and time-delayed diagnosis after various surgeries and therefore may challenge the physician to make the correct diagnosis at first. It is necessary for ophthalmologists to consider this diagnosis in cases of masses around the eyelid and orbit in patients with a history of sinus and nose surgery in other differential diagnoses.

Factors Influencing Endoscopic Dacryocystorhinostomy Outcomes: A Comprehensive Clinical and Histopathological Analysis and Review of the Literature.

The main challenge in maintaining long-term success of endoscopic dacryocystorhinostomy is preventing fibrosis and scarring at the anastomosis site. Despite numerous studies on surgical techniques, research on histological factors linked to postoperative scarring is limited. This study evaluated long-term (range, 12-18 months) outcomes and systematically examined clinical and histopathological factors that may contribute to restenosis. This retrospective study included 47 patients who underwent a unilateral surgery intervention for primary acquired lacrimal duct obstruction. The following clinical and histopathological variables were considered to assess the risk factors for the development of restenosis: sex, age, duration of disease, clinical manifestation of disease, clinical features of the lacrimal sac perceived intraoperatively, fibrosis, and mononuclear cell infiltrates. Statistical analysis showed that only patient sex (Pearson's chi-squared test, p = 0.007) and severity of intraoperative adhesions in the lacrimal sac (Pearson's chi-square test, p = 0.029) were significantly linked to restenosis. However, the skewed male-to-female ratio, few surgical failures make the conclusion that sex is a risk factor speculative. Thus, only adhesion intensity can be considered a risk factor. Additionally, fibrosis assessed using trichrome staining and T-cell lymphocytic infiltration showed potential negative prognostic value in a larger cohort. Our findings indicate that patients with significant lacrimal sac adhesions, identified during endoscopic dacryocystorhinostomy, are particularly prone to postoperative restenosis. Although histological and immunohistochemical studies did not reveal a correlation between the analyzed data and restenosis, a larger patient cohort might show that fibrosis and T-cell lymphocytic infiltration could potentially have a negative prognostic value. The poorer treatment outcomes in women, seen in our study as well as in other investigations, may be due to anatomical and physiological traits of the female lacrimal drainage system that predispose them to stenosis. This hypothesis requires further study in a larger cohort.

Assessment of metabolic markers of cardiorenal disorders in patients with arterial hypertension and metabolic syndrome

Introduction. Cardiorenal disorders (CRN) in arterial hypertension (AH) occur with interdependent dysfunction of the cardiovascular and renal systems. The concept of cardio-reno-metabolic health (CRMH) defines a dependent relationship between the clinical and pathogenetic manifestations of heart and kidney diseases in patients with metabolic disorders (MN).Aim. To study the metabolic markers of CRN in patients with hypertension and in combination with metabolic syndrome (MS).Materials and methods. The functions of the heart, kidneys, and lipid profile were studied in patients aged 40 to 69 years with hypertension and with hypertension in combination with MS.Results. The average eGFR values (estimated glomerular filtration rate) based on cystatin C are 53,5% lower than those based on creatinine (p = 0.0001). Patients with hypertension combined with MS were 42.7% more likely to have chronic kidney disease (CKD) C3aA2, 21.2% more likely to have C3bA2; the level of highly sensitive C–reactive protein (hs-CRP) was 42.8% higher compared with patients with hypertension without MN (p = 0.0001). Cystatin C values positively correlate with systolic blood pressure (SAD); eGFR has a negative association with SAD in both groups (p < 0.05). The presence of chronic heart failure with a low ejection fraction (CHF) in combination with chronic kidney disease (CKD) with moderate (C3a A2) and significantly reduced (C3b A2) renal function allows us to state the presence of CRN in 13.3% of patients with hypertension and in 17.7% of patients with hypertension combined with MS (p = 0.0001). Dyslipidemia and atherogenic lipid levels are 122% higher in patients with hypertension combined with MS, hyperlipoproteinemia (a) is 79% more common in patients with CRN on the background of MN (p = 0.0001).Conclusion. Elevated lipoprotein (a) (LP (a)) concentrations and dyslipidemia in patients with hypertension are associated with cardiorenal and metabolic disorders.

An Overview of Pediatric Pulmonary Complications During COVID-19 Pandemic: A Lesson for Future.

The pediatric community is considered a suitable target for controlling the spread and mortality of viral diseases. In late December 2019, a respiratory disease due to the novel coronavirus, later COVID-19, hit the globe. The COVID-19 global disruption had direct and indirect impacts on different aspects of child health. Therefore, surveillance, preventive approaches, and treatment plans for children came into the spotlight. This study aims to discuss the clinical pictures as well as laboratory and radiological findings of the infected children during the COVID-19 pandemic. The focus of this study is to express the clinical manifestations of respiratory disease in pediatric SARS-CoV-2, available therapeutic options, vaccine recommendations, and long COVID sequelae in affected children. This review could serve as a hint for upcoming challenges in pediatric care during future pandemics. The clinical presentation of COVID-19 in pediatrics can range from mild pulmonary disease to acute respiratory distress syndrome (ARDS). Supportive care is a crucial component of the management of pediatric COVID-19. However, the importance of specializing in how to treat patients with more severe conditions cannot be overstated. Additionally, clinicians must consider prevention strategies as well as potential complications. Although the infected patients are dipping day by day, there is a lack of clinical guidelines for pediatric SARS-CoV-2-associated pulmonary diseases. Understanding of the physicians about all aspects of pediatric care during the COVID-19 pandemic could lead to enhanced quality of future patient care and safety, reduced costs of health policies, and surveil the risk that patients with respiratory viruses can expose to society.

Influenza and non-influenza ARVI in children. A relationship between cytokine profile, parameters of the “lipid peroxidation – antioxidant defense system” as well as clinical and laboratory indicators

Influenza and acute respiratory viral infections (ARVI) impose a substantial damage to the population health in the Russian Federation due to their seasonal circulation and predominantly affect young children. A very few data on the cytokine profile, the nonspecific LPO — AOD system and their relationships with clinical characteristics in such diseases in preschool children are available. The aim of this study was to assess the cytokine profile, LPO — AOD system parameters and their relationship with the clinical and laboratory characteristics of diseases in preschool children with influenza and other ARVI. 86 preschool children (3–6 years old) were examined: with an established diagnosis of influenza (n = 31), non-influenza ARVI (n = 28), apparently healthy children (control group (n = 27). All pediatric samples were analyzed by enzyme-linked immunosorbent assay assessing blood serum concentrations of C-reactive protein and cytokines IL-1β, IL-4, IL-6, IL-8, TNFα, IFNα, IFNγ. Spectrophotometric, fluorometric and enzyme immunoassay methods to assess the state of the “LPO — AOD” system were used. In the group of children with influenza vs other ARVI, a higher incidence of intoxication syndrome was revealed. Cytokine profile in children from both clinical groups compared with control cohort was featured with higher indicators of both pro-inflammatory and anti-inflammatory origin. Children with non-influenza ARVI, had increased magnitude of LPO final products in the nonspecific LPO — AOD system along with lowered concentration of fat-soluble vitamins, general antioxidant activity, GSH level, and SOD activity. In the group with influenza, the level of primary and final lipid peroxidation products was increased, whereas that of for retinol,α-tocopherol, and total antioxidant activity was decreased paralleled with higher GSSG and SOD levels. Numerous correlations were noted in the group of children with ARVI: IL-1β/ketones, IL-6/ketones, IL-8/ketones, TNFα/ketones, IL-4/ketones, IFNg/shortness of breath, IFNα/cough, double bonds/fever, double bonds/AST, SO/intoxication, retinol/fever, GSSG/cough. The influenza group differed in the following relationships: IL-4/ketones, IL-4/fever, IFNα/ketones, CDs/AST. It can be concluded that in preschool children with ARVI and influenza, changes in the cytokine profile are accompanied by increased pro- and anti-inflammatory cytokine levels, increased intensity of lipid peroxidation reactions along with reduced magnitude of antioxidant factors. In the group with ARVI, there was a relationship between the final toxic products of lipid peroxidation — Schiff bases — and the intoxication index, as well as the presence of protective mechanisms in the form of connections between interferons and disease clinical manifestations. The group with influenza was distinguished by the presence of protective relations, which may have a beneficial effect in the context of developing pathological process. The data obtained will help expand the understanding of the pathogenetic mechanisms related to immune reactivity and nonspecific lipid peroxidation reactions in preschool patients and formulate appropriate measures for correction.

AYURVEDIC MANAGEMENT OF KRIMI: A CASE STUDY WITH SPECIAL REFERENCE TO RAKTAJA KRIMI

One of the most prevalent illnesses afflicting children in low- and middle-income nations continues to be worm infestation. While the majority of helminthic infections are mild and frequently asymptomatic, children from endemic locations are typically associated with growth retardation, nutritional compromise, anaemia, and poor academic achievement when they have moderate to heavy worm infestations. Case presentation: A 12-year-old male child was brought to Kaumarabhrithya OPD of Matrusri Davalba Ayurved Hospital, Vadodara, Gujarat, India, with symptoms of whitish patches on the face, trunk and both upper and lower limbs since 6 months associated with reduced appetite and severe constipation for 3 months. As per Ayurvedic classics, this condition can be correlated to Krimi (worms) and specifically Raktaja krimi (worms originating from vitiated blood) caused by Kushta samaana hetus (causative factors similar to skin diseases). The clinical characteristics of the illness were used to make the diagnosis. Anthelminthic drugs and hygienic practices were a part of the therapeutic strategy, including deepana (appetizer), pachana (digestive), apakarshana (to remove), prakruti vighata (destroying favourable environment)and nidana parivarjana (avoiding causative factors). Outcome: The disease's clinical manifestations significantly improved, and appetite increased. Discussion: Satisfactory outcomes were attained, oral medicine was taken upon discharge, and follow-up visits were made. This case emphasizes the use of Ayurveda in treating paediatric diseases, where effective outcomes can be achieved with accurate diagnosis, oral medication, and panchakarma treatments.

The hybrid immunity defined by weaker immune imprinting of people living with HIV has a stronger neutralizing response against Omicron variants. A suggested explanation for fewer symptoms in people living with HIV after SARS-CoV-2 variants breakthrough infection

AimsHuman immunodeficiency virus(HIV) co-infection may cause different immune imprinting, which leads to different hybrid immunity and clinical manifestations of coronavirus disease 2019. This study aims to evaluate the immune imprinting from wild-type(WT) vaccination in people living with HIV(PLWH) and analyze its effect on hybrid immunity and clinical manifestations. Materials and methodsWe enrolled 118 PLWH to compared the differences of BA.5-specific immune response in different immune modes. 20 vaccinated healthy individuals(HC) and 30 vaccinated PLWH were matched to compare the differences of the status of Omicron infection, serum neutralizing antibody levels against WT and BA.5, and specific lymphocytes expression, separately. Key findingsHybrid immunity had a higher level of BA.5 IgG than either vaccine immunity only or natural immunity only in PLWH but didn't have a higher level of BA.5-specific lymphocytes responses. PLWH had fewer symptoms than HC after breakthrough infection. The neutralizing inhibition rate of PLWH was higher for BA.5 and lower for WT, while the neutralizing inhibition rate of HC was higher for WT and lower for BA.5. The difference value of specific B lymphocytes/memory B cells/follicular helper T cells of PLWH was greater than that of HC. SignificanceHybrid immunity of PLWH has a higher level of Omicron-specific IgG without a higher level of Omicron-specific lymphocytes due to immune imprinting. However, there is a stronger neutralizing ability against variants of PLWH due to the weaker immune imprinting of PLWH than that of healthy people, which may lead to fewer symptoms in PLWH after breakthrough infection.

Moyamoya disease: insights into the clinical implications of the RNF213 gene

Moyamoya disease (MMD) is a rare cerebrovascular disorder characterized by progressive stenosis of the terminal internal carotid arteries and the formation of compensatory collateral vessels, which appear as a “puff of smoke” on cerebral angiography. It is a significant cause of stroke in East Asia, with an incidence of 0.5 to 1.5 cases per 100,000 people annually. The etiology of MMD remains unclear; however, the identification of the RNF213 gene, particularly the R4810K variant, as a major susceptibility factor among the East Asian population, has provided crucial insights into the disease's pathophysiology and clinical manifestations. MMD typically presents with transient ischemic attacks, ischemic and hemorrhagic strokes, seizures, headaches, and cognitive deficits. Diagnostic criteria have evolved to emphasize advanced imaging techniques. Pathological features include fibrocellular intimal thickening, irregular undulation of the elastic lamina, and the formation of moyamoya vessels. The mutation in the RNF213 gene impairs the degradation of proteins involved in vessel development, leading to abnormal angiogenesis. Genotype-phenotype studies indicate that the RNF213 variant is associated with an earlier onset, transient ischemic attacks, infarctions, and involvement of the posterior cerebral artery, although its effects vary between regions. Additionally, the homozygous RNF213 variant consistently correlates with an earlier age of onset and a higher risk of cerebral infarction. However, further research is necessary to fully understand its long-term impacts and its relationship with revascularization outcomes. Ongoing research is crucial to fully comprehend the pathophysiology and genetics of MMD, improve prognostic predictions, and develop novel therapies.

FDG PET/CT in large vessel vasculitis.

Large vessel vasculitides (LVV) such as giant cell arteritis, Takayasu arteritis and aortitis/periaortitis are characterised by immune-mediated inflammation of medium to large arteries. Clinical disease manifestations can be non-specific and diagnostic imaging plays an important role in the diagnostic pathway. In recent years, FDG PET/CT has proven to be a powerful metabolic tool that can provide a wholed body, non-invasive assessment of vascular inflammation. This review outlines the clinical features of large vessel vasculitis and the closely related entity of polymyalgia rheumatica, summarises the evidence for FDG PET/CT in the assessment of these conditions, and provides guidance for patient preparation, image acquisition and interpretation.

Delineating three distinct spatiotemporal patterns of brain atrophy in Parkinson's disease.

The clinical manifestation of Parkinson's disease exhibits significant heterogeneity in the prevalence of non-motor symptoms and the rate of progression of motor symptoms, suggesting that Parkinson's disease can be classified into distinct subtypes. In this study, we aimed to explore this heterogeneity by identifying a set of subtypes with distinct patterns of spatiotemporal trajectories of neurodegeneration. We applied Subtype and Stage Inference (SuStaIn), an unsupervised machine learning algorithm that combined disease progression modelling with clustering methods, to cortical and subcortical neurodegeneration visible on 3 T structural MRI of a large cross-sectional sample of 504 patients and 279 healthy controls. Serial longitudinal data were available for a subset of 178 patients at the 2-year follow-up and for 140 patients at the 4-year follow-up. In a subset of 210 patients, concomitant Alzheimer's disease pathology was assessed by evaluating amyloid-β concentrations in the CSF or via the amyloid-specific radiotracer 18F-flutemetamol with PET. The SuStaIn analysis revealed three distinct subtypes, each characterized by unique patterns of spatiotemporal evolution of brain atrophy: neocortical, limbic and brainstem. In the neocortical subtype, a reduction in brain volume occurred in the frontal and parietal cortices in the earliest disease stage and progressed across the entire neocortex during the early stage, although with relative sparing of the striatum, pallidum, accumbens area and brainstem. The limbic subtype represented comparative regional vulnerability, which was characterized by early volume loss in the amygdala, accumbens area, striatum and temporal cortex, subsequently spreading to the parietal and frontal cortices across disease stage. The brainstem subtype showed gradual rostral progression from the brainstem extending to the amygdala and hippocampus, followed by the temporal and other cortices. Longitudinal MRI data confirmed that 77.8% of participants at the 2-year follow-up and 84.0% at the 4-year follow-up were assigned to subtypes consistent with estimates from the cross-sectional data. This three-subtype model aligned with empirically proposed subtypes based on age at onset, because the neocortical subtype demonstrated characteristics similar to those found in the old-onset phenotype, including older onset and cognitive decline symptoms (P < 0.05). Moreover, the subtypes correspond to the three categories of the neuropathological consensus criteria for symptomatic patients with Lewy pathology, proposing neocortex-, limbic- and brainstem-predominant patterns as different subgroups of α-synuclein distributions. Among the subtypes, the prevalence of biomarker evidence of amyloid-β pathology was comparable. Upon validation, the subtype model might be applied to individual cases, potentially serving as a biomarker to track disease progression and predict temporal evolution.

Radiation-Induced Macrovessel/Microvessel Disease.

Radiation therapy (RT) is a cornerstone in cancer treatment (used in 50% of cases), yet challenges persist because damage to normal tissue through direct impact of radiation or bystander effects is inevitable. Injury of macrovessels by RT manifests as obstructive disease, which is akin to atherosclerotic disease. Historically observed in coronary arteries of patients treated for breast cancer and lymphoma, it also affects patients receiving contemporary therapy for lung and chest cancers. Moreover, radiation at various sites can lead to peripheral vascular disease. An aspect of radiation-induced injury that has received little attention is microvascular injury, which typically results from damage to the endothelium and is considered the primary driver of RT-induced toxicity in the skin, kidney, and brain. This review delves into the clinical manifestations of RT-induced vascular disease, signaling pathways, cellular targets affected by radiation injury, and preclinical models of RT-induced vascular injury. The goal is to inspire the development of innovative strategies to prevent RT-related cardiovascular disease.