Prevalence Of Clinical Manifestations Research Articles

A New Ex Vivo Model Based on Mouse Retinal Explants for the Study of Ocular Toxoplasmosis.

Ocular toxoplasmosis is the most prevalent clinical manifestation of T. gondii infection, which causes irreversible retinal damage. Different experimental models have been developed to study this pathology. In the present study, a new, ex vivo model is proposed to contribute to the elucidation of disease mechanisms and to possible therapeutic solutions. Ex-vivo retinal explants, prepared from mouse retinas following established protocols, were incubated with T. gondii tachyzoites maintained in Vero cells. At different times, starting at 12 h up to 10 days of incubation, the explants were analyzed with immunofluorescence and Western blot to investigate their responses to parasite infection. T. gondii invasion of the retinal thickness was evident after 3 days in culture, where parasites could be detected around retinal cell nuclei. This was paralleled by putative cyst formation and microglial activation. At the same time, an evident increase in inflammatory and oxidative stress markers was detected in infected explants compared to controls. Cell death also appeared to occur in retinal explants after 3 days of T. gondii infection, and it was characterized by increased necroptotic but not apoptotic markers. The proposed model recapitulates the main characteristics of T. gondii retinal infection within 3 days of incubation and, therefore, allows for studying the very early events of the process. In addition, it requires only a limited number of animals and offers easy manipulation and accessibility for setting up different experimental conditions and assessing the effects of putative drugs for therapy.

Clinical, epidemiological and dental characterization of children with congenital heart diseases

Objective: to characterize the clinical, dental and epidemiological profile of children with congenital heart disease followed at the dental outpatient clinic of a Maternal and Child University Hospital in the city of São Luís/MA, Brazil. Methods: The present study had a descriptive, retrospective and quantitative nature. Data collection was carried out by analyzing the medical records of patients seen from January 2017 to December 2019, aged 0 to 12 years and of both sexes. Results: The majority of patients were male (51.4%), from the city of São Luís and metropolitan region (52.9%), self-declared mixed race (62.9%). Acyanotic congenital heart diseases were the most prevalent (81.4%) and half of the patients (50%) had already had an episode of toothache. The use of fluoride toothpaste and toothbrush was observed in almost all patients (90%), with the highest frequency of tooth brushing being twice a day (44.3%). Caries disease was the most prevalent oral clinical manifestation (61.4%). Conclusion: The importance of maintaining an adequate standard of oral health and its influence on the general systemic condition of these patients is reaffirmed. It is suggested that more studies be carried out in order to deepen knowledge about this population.

Scrub typhus meningoencephalitis in children: an experience from Eastern India.

Scrub typhus meningoencephalitis (STME) is an uncommon but fatal complication of scrub typhus that requires extra diligence in early identification and treatment. The goal of this study was to look at the clinical characteristics, laboratory results, and outcome of STME in children. A retrospective study was conducted in the paediatric intensive care unit of a tertiary care hospital in Eastern India between April 2021 and September 2022. It was carried out in children aged 1 month-12 years. Sixteen children were diagnosed with STME out of 75 acute encephalitis syndrome (AES) cases. The male-to-female ratio was 3:1, with a mean age of 4.28 ± 3.36 years. All the children hailed from rural areas. Fever (100%), convulsions (87.5), altered sensorium (93.75%), nuchal stiffness (25%), vomiting (75%), pallor (75%), and hepatomegaly (50%) were the most prevalent clinical manifestations. The average duration of fever upon presentation was 8.25 ± 2.11 days and the average length of hospital stay was 9.00 ± 4.59 days. The complications encountered were shock (3), interstitial pneumonia (1), myocarditis (1), raised intracranial pressure (1), and right-sided hemiplegia (1). Fifteen children recovered completely, whereas one child suffered from residual right-sided neurodeficit. A high index of suspicion needs to be maintained for STME as a possible AES entity, as anti-scrub measures administered promptly can go a long way in mitigating the related morbidity and mortality especially in resource-constrained settings.

Comparative effectiveness of high-intensity laser therapy and ultrasound therapy for hemiplegic shoulder pain in stroke patients: a randomized controlled trial“

ABSTRACT Background Hemiplegic shoulder pain (HSP) is a prevalent clinical manifestation following stroke, often causing considerable discomfort and disability. Various therapeutic approaches have been developed to address HSP. Objectives This study aimed to compare the effectiveness of HILT versus US therapy in alleviating HSP in stroke patients. Methods A double-blind randomized controlled trial enrolled stroke patients with HSP within one year post-onset. Participants were randomly assigned to HILT (with sham US) or US therapy (with sham HILT). Both groups received 10-minute sessions of their assigned therapy modality along with daily shoulder range of motion (ROM) exercises 5 times per week over two consecutive weeks. Pain reduction was the primary outcome, with shoulder ROM as secondary outcomes. Results Thirty patients (11 women, 19 men; mean age: 60.80 ± 11.51 years) were included. After the two-week intervention, significant improvements were observed in pain reduction at rest and during motion in the HILT group, and in pain reduction during motion and shoulder internal rotation in the US group compared to pre-treatment values within each group. However, there was no significant difference between the HILT and US therapy groups in any evaluated parameter. Conclusions Comparable efficacy was found between HILT and US therapy in reducing pain and improving shoulder ROM for HSP in stroke patients. Both modalities, when combined with shoulder ROM exercises, offer viable options for managing HSP in this population. Further research with larger sample sizes is needed to validate these findings and explore long-term outcomes.

Chromosome 7 Isodisomy in a Child with Silver-Russell Síndrome

Silver-Rusell syndrome is a rare genetic disease. There is evidence that the genetic causes of the disorder are heterogeneous, with predominant alterations in the imprinted regions of chromosomes 11 and 7, in addition to other genomic alterations, such as chromosomal structural aberrations, single nucleotide polymorphisms, copy number variations, and small insertions and deletions. The most prevalent clinical manifestations include prenatal and postnatal growth retardation, dysmorphic features, and feeding difficulties. We present a case of a 4-year-old boy with phenotypic features consistent with Silver-Russell syndrome. The sample was subjected to conventional karyotyping analysis. The analysis was also conducted using the SALSA MLPA Probemix ME032-A1 UDP7-UDP14 and Applied Biosystems CytoScan 750K Suite. MS-MLPA analysis revealed the presence of hypermethylation in the <em>GRB-10</em> and <em>MEST</em> genes on chromosome 7. SNP-array analysis revealed a loss of heterozygosity (LOH) at 7q11.22q31.1 (38.7 Mb). The methylation of the genes involved in this epigenetic event, in conjunction with LOH and the clinical characterization of this child, indicates that the origin of the disease is due to an isodisomy of maternal chromosome 7. This report of a child who exhibits the clinical characteristics of SRS and presents a UPD of chromosome 7, most likely originating from the mother, once again demonstrates the involvement of these genes in SRS despite the incomplete understanding of the underlying mechanism. A multidisciplinary strategy has been proposed for the follow-up and treatment of this disease according to its etiology in the proband.

Epidemiological trends, antifungal drug susceptibility and SQLE point mutations in etiologic species of human dermatophytosis in Al-Diwaneyah, Iraq

Dermatophytes show a wide geographic distribution and are the main causative agents of skin fungal infections in many regions of the world. Recently, their resistance to antifungal drugs has led to an obstacle to effective treatment. To address the lack of dermatophytosis data in Iraq, this study was designed to investigate the distribution and prevalence of dermatophytes in the human population and single point mutations in squalene epoxidase gene (SQLE) of terbinafine resistant isolates. The identification of 102 dermatophytes isolated from clinical human dermatophytosis was performed through morphological and microscopic characteristics followed by molecular analysis based on ITS and TEF-1α sequencing. Phylogeny was achieved through RAxML analysis. CLSI M38-A2 protocol was used to assess antifungal susceptibility of the isolates to four major antifungal drugs. Additionally, the presence of point mutations in SQLE gene, which are responsible for terbinafine resistance was investigated. Tinea corporis was the most prevalent clinical manifestation accounting for 37.24% of examined cases of dermatophytosis. Based on ITS, T. indotineae (50.98%), T. mentagrophytes (19.61%), and M. canis (29.41%) was identified as an etiologic species. T. indotineae and T. mentagrophytes strains were identified as T. interdigitale based on TEF-1α. Terbinafine showed the highest efficacy among the tested antifungal drugs. T. indotineae and T. mentagrophytes showed the highest resistance to antifungal drugs with MICs of 2–4 and 4 μg/mL, while M. canis was the most susceptible species. Three of T. indotineae isolates showed mutations in SQLE gene Phe397Leu substitution. A non-previously described point mutation, Phe311Leu was identified in T. indotineae and mutations Lys276Asn, Phe397Leu and Leu419Phe were diagnosed in T. mentagrophytes XVII. The results of mutation analysis showed that Phe397Leu was a destabilizing mutation; protein stability has decreased with variations in pH, and point mutations affected the interatomic interaction, resulting in bond disruption. These results could help to control the progression of disease effectively and make decisions regarding the selection of appropriate drugs for dermatophyte infections.

Chromosomal Variations and Clinical Features of Acute Lymphoblastic Leukemia in the North Indian Population: A Cross-Sectional Study.

The key prognostic markers in acute lymphoblastic leukemia (ALL) include age, leukocyte count upon diagnosis, immunophenotype, and chromosomal abnormalities. Furthermore, there was a correlation between cytogenetic anomalies and specific immunologic phenotypes of ALL, which in turn had varied outcomes. The objective of this study was to examine the occurrence of cytogenetic abnormalities in individuals diagnosed with acute lymphoblastic leukemia. The study employed a cross-sectional design to investigate genetic evaluation and clinical features in 147 ALL patients between March 2021 and August 2022. Demographic data (like age and sex), clinical manifestations, and hematological parameters were collected. Cytogenetic analysis (G-banding) was performed to identify chromosomal abnormalities. The mean±SD and analysis of variance (ANOVA) were usedtoassess associations and differences among variables usingSPSS Version 24 (IBM Corp., Armonk, NY, USA). The study shows male n=85 andfemale n=62 in ALL patients, with prevalent clinical manifestations: fever n=100 (68.03%), pallor n=123 (83.67%), and lymphadenopathy n=65 (44.22%).Thehematologicalparameters like hemoglobin (Hb) (6.14±2.5 g/dl),total leukocyte count (TLC)(1.7±1.05 cell/mm3), and platelet count (1.2±0.11 lac/mm3) show a significant variation (P<0.05) in patients aged 30-50 years.In addition,chromosomal abnormalities, particularly 46, XX, t(9;22), were prevalent, emphasizing the genetic heterogeneity of ALL. The study shows a male predominance with ALL, prevalent clinical manifestations, and significant hematological parameter variations in the 30-50 age group. Chromosomal abnormalities, notably 46, XX, t(9;22), underscore the genetic complexity of the disease, which necessitates tailored therapeutic interventions informed by genetic profiles.

Intralesional Quadrivalent Human Papilloma Virus Vaccine Versus Candida Antigen in the Treatment of Multiple Recalcitrant Non-Genital Warts.

Warts are the most prevalent clinical manifestation of Human Papilloma Virus (HPV) infections, which vary in morphological pattern depending on the site of the body affected. To evaluate the safety and efficacy of intralesional quadrivalent HPV vaccine versus candida antigen in treatment of multiple recalcitrant non-genital warts. A randomized-control clinical trial included 60 cases with multiple recalcitrant warts who were randomly distributed into three groups; Group I included 20 patients who received intralesional candida antigen at a dose of 0.3 mL of 1/1000 solution, Group II included 20 patients who received intralesional quadrivalent HPV vaccine at a dose of 0.3ml and Group III included 20 patients who received intralesional injection 0.3 ml of normal saline 0.9% as a control group). Each agent was injected at the base of the largest wart every three weeks until it was completely cleared, or for a total of four sessions. the highest response rate was detected in the quadrivalent HPV vaccine group (75% complete response) followed by the candida vaccine group (40% complete response and 15% partial response). Also, regarding the distant response rate, the highest response rate was detected in the quadrivalent HPV vaccine group (72.7% complete response and 27.3% partial response) followed by the candida vaccine group (33.3% complete response and 50% partial response). Intralesional immunotherapy appears to be effective and safe in treating multiple recalcitrant non-genital warts, with intralesional quadrivalent HPV vaccine outperforming intralesional candida antigen.

P020 Clinical characteristics, disease trajectories and management of Vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome: a systematic review

Abstract Background/Aims VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is an autoinflammatory condition, characterised by somatic mutation of UBA1 gene. To date, no systematic literature review (SLR) has been undertaken to summarise the clinical manifestations, genotypes and treatment of VEXAS. We undertook a SLR to evaluate the multisystem characteristics and genotypes associated with VEXAS syndrome. Methods Articles discussing VEXAS syndrome, published 1946 until May 2023, were included. The protocol was registered in the PROSPERO database of systematic reviews (CRD42023407547). Medline, Embase and Cochrane Databases were searched. The research questions were: 1) What are the clinical characteristics of patients diagnosed with VEXAS? 2) What are the genotypes associated with VEXAS? 3) What are the effective treatments for VEXAS? Articles meeting inclusion criteria were examined by two authors at abstract and full paper stage. Information was extracted on: demographics, type and prevalence of clinical manifestations, genetic mutations, and treatment. Meta-analysis using a random effects model was used to determine pooled estimates of serum markers. Results From 214 articles, 64 were included, comprising 273 patients with VEXAS. 96.3% were male, with a mean age of 67.2 years (SD 6.8) at disease onset. Study cohorts were from: Europe (n = 25); North America (n = 18); South America (n = 1); Asia (n = 16); Australasia (n = 4). The most frequent diagnoses made prior to VEXAS were: relapsing polychondritis (n = 48); Sweet’s syndrome (n = 24); polyarteritis nodosa (n = 11); myelodysplastic syndrome (n = 10). Fever was reported in 195 cases (71.4%) and weight loss in 69 (25.3%). Most patients had pulmonary (n = 231; 84.6%), haematological (n = 228; 83.5%) dermatological (n = 217; 79.5%) and musculoskeletal (n = 138; 50.5%) involvement, although other organ manifestations of varying prevalence were also recorded. Pooled estimates of serological investigations were: ESR 101.3 mm/hr (SE 4.8; n = 246); CRP 144.2 mg/L (SE 14.1; n = 258); Hb 91.0 g/L (SE 3.2; n = 265); MCV 107.3 fL (SE 2.3; n = 265). The most commonly reported mutations were “c.122T&amp;gt;C pMET41Thr” (n = 71), “c.121A&amp;gt;G pMET41Val” (n = 35) and “c.121A&amp;gt;C pMet41Leu” (n = 33). Most patients received glucocorticoids (n = 133, 48.7%) followed by methotrexate (n = 55, 20.1%) and IL-6 inhibitors (n = 47, 17.2%). One patient underwent splenectomy; six received bone marrow transplants. Regarding mortality, 44 patients were reported to have died due to manifestations of VEXAS syndrome. Conclusion This is the first SLR to capture clinical manifestations, genetics and treatment of cases of VEXAS reported to date. Diagnosis remains clinically challenging, as evidenced by the multiple prior diagnoses ascribed to patients, most commonly relapsing polychondritis and Sweet’s syndrome. Most patients present with haematological disorders, fever, pulmonary and dermatological involvement. Reported mortality was consistent with genetic variants strongly associated with reduced survival rates. Genetics and treatment of VEXAS continue to be an active area of research. Future studies are needed to better understand these as well as optimize treatment for people with this rare condition. Disclosure K. Kouranloo: None. M. Dey: None. J. Almutawa: None. N. Myall: None. A. Nune: None.

‘’Wait and See’’ as a Treatment Option for a Rathke’s Cleft Cyst Apoplexy in Pediatric Population: A Case Report

Introduction: Rathke cleft cyst apoplexy is exceedingly rare, particularly in infants. The most prevalent clinical manifestations include headaches, visual field defects, and endocrine dysfunction. Treatment options range from surgery to conservative methods, taking into consideration the balance of benefits and risks, especially during critical life stages such as childhood. Case Presentation: We present the case of a 12-year-old boy admitted due to the recent onset of headaches and diabetes insipidus. Magnetic resonance imaging revealed Rathke cleft cyst apoplexy. Given the absence of compressive symptoms in a child at the early stages of puberty and without abnormalities in basic endocrine tests, a conservative strategy was employed, involving regular clinical, biological, and radiological follow-ups. The child experienced normal puberty without any endocrine deficiencies except for a partial growth hormone deficiency. Conclusions: For clinically asymptomatic children diagnosed with Rathke's cleft cyst apoplexy, adopting a conservative management approach is recommended, provided there is thorough clinical, biological, and radiological surveillance.

A clinical prevalence of dermatophytic mycoses with an assessment of its clinical manifestations in a tertiary care hospital at Salem, South India.

Dermatophytosis is very common among all age groups throughout the world. The incidence of the same is increasing on a steady basis. Estimating the clinical prevalence of dermatophytes mycoses among the patients visiting the outpatient unit and assessing its distinct manifestations. A prospective observational study was conducted with the patients attending the Skin and STD outpatient unit of a tertiary care teaching hospital in Salem. A total of 3068 outpatients attended the department, of which 420 patients were diagnosed with dermatophytic mycoses and were taken for investigating the prevalence. A total of 420 dermatophytosis patients were included giving a percentage prevalence of 13.69%. There were more female patients (n = 213, 50.71%) than males (n = 207, 49.29%). The most common afflicted age group was 31-40 years (n = 99, 50.71%). Most of the patients had an atypical lesion called tinea incognita (n = 265, 63.09%) where there was no typical classic appearance of dermatophytic infections. The most prevalent clinical manifestation was tinea corporis (n = 73, 17.38%) followed by tinea cruris (n = 69, 16.43%). There were more newly diagnosed dermatophytosis cases (n = 326) than the previously diagnosed cases (n = 94). This study concludes that dermatophytic mycoses were more prevalent among females than males and among the age groups of 31-40 years. The most common clinical presentation was tinea incognita followed by tinea corporis.

Cholangiocarcinoma Insights: Established Foundations and Cutting-Edge Innovations from Dr. James Cleary’s Pioneering Research

This paper provides insights into the conventional understanding of biliary tract malignancies, with a specific focus on cholangiocarcinoma (CCA). We then delve into the groundbreaking ideas presented by Dr. James Cleary. CCA, originating from biliary tree cells, manifests diverse subtypes contingent upon anatomical localization and differentiation status. These variants exhibit discrete genetic aberrations, yielding disparate clinical phenotypes and therapeutic modalities. Intrahepatic, perihilar, and distal CCAs intricately involve distinct segments of the biliary tree, further categorized as well-differentiated, moderately differentiated, or poorly differentiated adenocarcinomas based on their histological differentiation. Understanding the etiological factors contributing to CCA development assumes paramount importance. Stratifying these factors into two groups, those unrelated to fluke infestations (e.g., viral hepatitis and fatty liver conditions) and those associated with fluke infestations (e.g., chronic liver inflammation), facilitates predictive modeling. The epidemiology of CCA exhibits global variability, with Southeast Asia notably displaying higher incidences attributed primarily to liver fluke infestations. Jaundice resulting from bile duct obstruction constitutes a prevalent clinical manifestation of CCA, alongside symptoms like malaise, weight loss, and abdominal pain. Diagnostic challenges arise due to the symptomatic overlap with other biliary disorders. Employing comprehensive liver function tests and imaging modalities such as computed tomography assumes a pivotal role in ensuring accurate diagnosis and staging. However, the definitive confirmation of CCA necessitates a biopsy. Treatment modalities, predominantly encompassing surgical resection and radiation therapy, hold curative potential, although a considerable subset of patients is deemed unresectable upon exploration. Challenges intensify, particularly in cases classified as cancer of unknown origin, underscoring the imperative for early intervention. Advancements in genomic sequencing have revolutionized precision medicine in CCA. Distinct genomic markers, including fibroblast growth factor receptor 2 (FGFR2) alterations and isocitrate dehydrogenase 1 (IDH1) mutations, have emerged as promising therapeutic targets. FGFR2 alterations, encompassing mutations and rearrangements, play pivotal roles in oncogenesis, with FGFR inhibitors demonstrating promise despite identified resistance mechanisms. Similarly, IDH1 inhibitors face challenges with resistance, despite encouraging early clinical trial results, prompting exploration of novel irreversible inhibitors. Dr. James Cleary’s illuminating discourse underscores the significance of diverse FGFR2 alterations and the potential of IDH1 inhibition in reshaping the treatment landscape for CCA. These findings unveil critical avenues for targeted therapeutic interventions, emphasizing the critical need for ongoing research to optimize outcomes in this challenging cancer subtype, incorporating innovative insights from Dr. Cleary.

CLINICAL MANIFESTATIONS AND LABORATORY PROFILE OF DENGUE FEVER CASES AT THE TIME OF PRESENTATION IN TERTIARY CARE HOSPITAL

Dengue is the most common arboviral disease worldwide in tropical and subtropical regions. Clinical manifestations of dengue fever are mild illnesses like classical dengue fever and severe illnesses like dengue shock syndrome, and dengue hemorrhagic fever. The study was aimed to determine the clinical manifestations and laboratory parameters of patients with Dengue fever Materials And Methods: This prospective study was conducted at a tertiary teaching hospital, Nellore over 6 months. All the patients above the age of 14 years who were diagnosed with Dengue with a positive result for NS1Ag or IgM or IgG antibodies were included. All the necessary clinical and laboratory investigation parameters of the patients were noted and the data was analyzed by frequency and percentage. Results: During the study period, a total of 73 dengue cases were included in the study. Of these, there were 38 (52%) males and 33 (48%) females between 15 and 80 years of age. The most common clinical presentations were fever (100%), headache 56 (76.7%), myalgia 52 (71.2%), and nausea/vomiting 46 (63%). The common hematological findings were thrombocytopenia 58 (79.4%), followed by raised liver transaminases 42 (57.5%), leucopenia 37 (50.6%), leucocytosis 22 (30.1%) and raised hematocrit 21(28.7%) Conclusion: Fever, headache, and anorexia are the most prevalent clinical manifestations of Dengue fever. Low platelet count, raised liver transaminases, and a rise in hematocrit are the most prevalent laboratory abnormalities. Early detection and monitoring of dengue cases can prevent the serious complications of dengue fever.

Molecular, Immunological, and Clinical Characterization of SARS-CoV-2 Infection in Breakthrough-Infected Healthcare Workers During the Last Wave of The Pandemic in Shiraz, Iran

Background: The coronavirus disease 2019 (COVID-19) poses a threat to the global economy and public health. Mutations in the spike protein of the virus can impact the functional characteristics and effectiveness of vaccines. Objectives: This study aimed to analyze mutations in three key regions of the spike protein, investigate clinical presentations, and assess protective immune levels in healthcare workers (HCWs) who had received full vaccine doses but were re-infected. Methods: In this cross-sectional study, 49 breakthrough-infected HCWs were included from November 2021 to May 2022. After confirming COVID-19 reinfection, the SARS-CoV-2 genome was extracted using the ROJE extraction kit, and genetic variation analysis was performed through Sanger sequencing. Blood samples were collected with prior consent, and ELISA tests were performed to determine antibody levels. Clinical presentations were recorded, and independent t-tests revealed no significant gender-based differences in the C-terminal point mutation. Results: In this study, 75.5% (37/49) of the included HCWs were female (P-value &lt; 0.05), and 25 were qualified for PCR and gene sequencing. Mutations were observed in 25, 10, and 1 sequence(s) of the C-terminal domain, N-terminal domain, and RBD regions of the S1 gene, respectively. The mutations had no significant correlation with the patient's gender, age, or occupation, but they were significantly more prevalent in those with underlying diseases. 63.3% (31/49) of patients had high or very high IgG levels, and none had undetectable antibody levels at the time of reinfection. Loss of the sense of smell (69.4% - 34/49), sore throat (65.3% - 32/49), headache (59.2% - 29/49), and cough (57.1% - 28/49) were the most prevalent clinical manifestations (P &gt; 0.05) in breakthrough-infected HCWs, aligning with the pattern of symptoms seen in the Omicron wave. However, the loss of the sense of taste showed significant results concerning clinical manifestation (P &lt; 0.05). The examination of mutations revealed the presence of the Omicron variant in the majority of individuals. Point mutations in the C-terminal region did not significantly vary based on age, gender, or vaccine type. No significant difference was observed between vaccine types and clinical symptoms. Conclusions: In conclusion, this study identified spike protein mutations in reinfections among vaccinated healthcare workers. While mutations were prevalent, no significant correlations were found with demographics or vaccine types. Symptoms resembled the Omicron variant, notably with the loss of the sense of taste as a significant marker. Detectable antibody levels post-reinfection suggest that vaccine-induced immunity remains robust. Continuous monitoring of virus variants is crucial for optimizing vaccination strategies in the face of evolving strains.

Altered Brain Functional and Effective Connectivity Induced by Electroacupuncture in Rats Following Anterior Cruciate Ligament Transection.

The chronic pain arising from knee osteoarthritis (KOA) is a prevalent clinical manifestation. As a traditional Chinese approach, electroacupuncture (EA) has a positive influence in relieving chronic pain from KOA. The study aims to explore functional connectivity (FC) and effective connectivity (EC) alterations induced by EA in anterior cruciate ligament transection (ACLT) rat model of KOA using resting-state functional magnetic resonance imaging (fMRI). After the establishment of ACLT, rats were randomly divided into the EA group and the sham-EA group. The EA group received EA intervention while the sham-EA group received sham-intervention for 3 weeks. Mechanical pain threshold (MPT) assessment was performed before and after intervention, and fMRI was conducted after intervention. EA intervention effectively relieved pain in post-ACLT rats. Results of rest-state functional connectivity (rs-FC) analysis revealed that compared with the sham-EA group, the EA group had higher FC between the right raphe and the left auditory cortex, the left caudate_ putamen and the left internal capsule (IC), as well as the right zona incerta (ZI) and the left piriform cortex, but lower FC between the right raphe and the left hippocampus ventral, as well as the right septum and the left septum. Furthermore, Granger causality analysis (GCA) found the altered EC between the right septum and the left septum, as well as the left IC and the right septum. The results confirmed the effect of EA on analgesia in post- ACLT rats. The alterations of FC and EC, mainly involving basal ganglia and limbic system neural connections, might be one of the neural mechanisms underlying the effect of EA, providing novel information about connectomics plasticity of EA following ACLT.

Clinical characteristics, disease trajectories and management of vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome: a systematic review.

VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is a newly discovered autoinflammatory condition characterised by somatic mutation of the UBA1 gene. The syndrome leads to multi-system inflammation affecting predominantly the skin, lungs and bone marrow. We undertook a systematic review of the multisystem features and genotypes observed in VEXAS syndrome. Articles discussing VEXAS syndrome were included. Medline, Embase and Cochrane databases were searched. Information was extracted on: demographics, type and prevalence of clinical manifestations, genetic mutations and treatment. Meta-analysis using a random effects model was used to determine pooled estimates of serum markers. From 303 articles, 90 were included, comprising 394 patients with VEXAS. 99.2% were male, with a mean age of 67.1 years (SD 8.5) at disease onset. The most frequent diagnoses made prior to VEXAS were: relapsing polychondritis (n = 59); Sweet's syndrome (n = 24); polyarteritis nodosa (n = 11); and myelodysplastic syndrome (n = 10). Fever was reported in 270 cases (68.5%) and weight loss in 79 (20.1%). Most patients had haematological (n = 342; 86.8%), dermatological (n = 321; 81.5%), pulmonary (n = 297; 75.4%%) and musculoskeletal (n = 172; 43.7%) involvement, although other organ manifestations of varying prevalence were also recorded. The most commonly reported mutations were "c.122T > C pMET41Thr" (n = 124), "c.121A > G pMET41Val" (n = 62) and "c.121A > C pMet41Leu" (n = 52). Most patients received glucocorticoids (n = 240; 60.9%) followed by methotrexate (n = 82; 20.8%) and IL-6 inhibitors (n = 61, 15.4%). One patient underwent splenectomy; 24 received bone marrow transplants. VEXAS syndrome is a rare disorder affecting predominantly middle-aged men. This is the first systematic review to capture clinical manifestations, genetics and treatment of reported cases. Further studies are needed to optimise treatment and subsequently reduce morbidity and mortality.

Antimicrobial Susceptibility Patterns of Klebsiella Species Causing Urinary Tract Infections in Pregnant Women

Background: Urinary tract infections (UTIs) are the most prevalent type of infection during pregnancy and are notoriously difficult to treat. Significant maternal and fetal risk is associated with UTI during pregnancy, with the most prevalent clinical manifestations being asymptomatic bacteriuria, acute cystitis, and acute pyelonephritis.&#x0D; Objectives: To identify Klebsiella species causing urinary tract infection among pregnant women and its antimicrobial susceptibility pattern by modified Kirby Bauer disc diffusion method in Rajshahi Medical College Hospital.&#x0D; Materials and Method: A descriptive cross-sectional study was conducted between July 2021 to June 2022 in the Microbiology Department of Rajshahi medical college and the Gynecology and Obstetrics Department of RMCH to determine the antimicrobial susceptibility pattern of Klebsiella species causing urinary tract infection in pregnant women. The urine samples were inoculated onto MacConkeys agar, blood agar, nutrient agar, and chromogenic UTI agar media and incubated aerobically at 370 C overnight (18-20 hrs).&#x0D; Results: In all trimesters, 294 urine samples were obtained from pregnant women with asymptomatic and symptomatic UTIs. Among the 114 (38.77%) culture-positive samples, 111 (97.36%) were single isolates, whereas 3 (2.63%) included multiple isolates. Klebsiella spp. comprised 21 out of 117 culture-positive bacterial isolates (17.94%). Regarding antimicrobial susceptibility testing, Klebsiella spp. demonstrated a significant degree of sensitivity to meropenem and nitrofurantoin. In this investigation, Klebsiella spp. was found to be the cause of bacteriuria among pregnant women.&#x0D; Conclusion: Doctors should adhere to the antimicrobial susceptibility test results when selecting the appropriate medications to treat pregnant women with UTIs.&#x0D; TAJ 2022; 36: No-1: 41-46

Characterization of phenyl propiolic acid from Proteus mirabilis DMTMMR-11 and Evaluation of its mode of action against Yersinia enterocolitica (MTCC-840) an in-Vitro and in-Vivo based approach

Foodborne illnesses are pervasive in raising public health concerns in both developed and developing nations. Yersinia enterocolitica a zoonotic bacterial species that causes food-transmitted infections, and gastroenteritis, is its most prevalent clinical manifestation. This study aims to investigate the differences, dependencies, and inhibitory mechanisms between the host and the microbiome. Proteus mirabilis DMTMMR-11, the bacterium found in the human gastrointestinal tract was used for the extraction of intracellular metabolite, because of its beneficial effects on the normal flora of the human gut. Phenyl propiolic acid was identified as the dominant compound in the metabolite after characterization using FT-IR, NMR, and LC-MS-MS. To assess its inhibitory mechanism against Yersinia enterocolitica, the pathogen was subjected to biological characterization by MBC and MIC, resulting in the rate of inhibition at 50 μg/ml. Anti-bacterial curve supports the inhibited growth of Y. enterocolitica. Mechanism of inhibition at its cellular level was indicated by the increase in alkaline phosphate content, which drastically reduced the cell membrane and cell wall potential expanding its permeability by intruding the membrane proteins, which was observed in SEM Imaging. Phenyl propiolic acid efficiently disrupts the biofilm formation by reducing the adherence and increasing the eradication property of the pathogen by exhibiting 65% of inhibition at the minimal duration of 12h. In-vivo study was carried out through host-pathogen interaction in C. elegans, an efficient model organism assessed for its life-span, physiological, and behavioral assays.

Treatment of hypophosphatasia

ypophosphatasia is a systemic metabolic disorder due to genetically determined deficient activity of the tissue non-specific alkaline phosphatase (TNAP). The phenotypic presentation is characterized by a wide spectrum of clinical manifestations regarding both, affected body systems and organs as well as the severity of associated deficits. Appropriate treatment strategies thus have to be multimodal in order to cover individual disease manifestation. For patients with disease onset before adulthood, enzyme replacement therapy with asfotase alfa is approved in Europe to treat the bone manifestations of the disease. Available data from clinical trials as well as real-word evidence confirm encouraging results of this treatment in severely affected children with substantial improvement regarding radiographic and functional outcome parameters as well as overall survival. In adult patients with disease manifestation pursuant to the label, published results also report substantial amelioration of disease-specific deficits along with functional improvements. Meanwhile, there is are also data supporting the safety and efficacy of long-term treatment with asfotase alfa over several years. While inflammatory muskuloskeletal pain - seemingly the most prevalent clinical manifestation along with exhaustion - can transiently be mitigated with on-demand NSARs, essential treatment options to causatively overcome that issue are still lacking. Accordingly, maintenance of musculoskeletal health and functionality requires sustained supportive treatment including physiotherapy and individually adjusted technical orthopedic support. The use and potential clinical impact of phosphate and vitamin B6 on the course of the disease requires further investigation. Current data regarding the use of bone-targeted compounds established for osteoporosis is critical in terms of antiresorptive, while osteoanabolic treatment strategies appear feasible. Considering further organ manifestation including orodental, gastrointestinal and neurological symptoms etc., the entirety of therapeutic measures should be coordinated among a multidisciplinary team and overlooked at an experienced center, while individual tasks can preferably be accomplished at local facilities near the patient’s home.

Epidemiology and patient journey of Rett syndrome in the United States: a real-world evidence study

BackgroundRett syndrome (RTT) is a neurodevelopmental disorder that almost exclusively affects females and is associated with high clinical burden. However, literature characterizing the real-world journey of patients with RTT is limited. This study provided an overview of the epidemiology, patient characteristics, clinical manifestations, healthcare resource utilization (HRU), costs, and treatment patterns of patients with RTT in the US.MethodsIQVIA™ Medical Claims Data and Longitudinal Prescription Data (11/01/2016–10/31/2019) were used to identify female patients with RTT, with the first observed diagnosis defined as the index date. Annual incidence and prevalence of RTT were assessed over the entire study period; clinical manifestations, all-cause and RTT-related HRU and costs, and treatment patterns were evaluated during the observation period—from the index date to end of clinical activity or end of data availability, whichever occurred first. Results were further stratified into pediatric (< 18 years) and adult (≥ 18 years) subgroups.ResultsIn 2019, prevalence and incidence of RTT was 0.32 and 0.23 per 10,000 enrollees, respectively. Among 5,940 female patients (pediatric: 3,078; adult: 2,862) with mean observation period of 2.04 years, the most prevalent clinical manifestations were neurological disorders (72.8%), gastrointestinal/nutritional disorders (41.9%), and orthopedic disorders (34.6%). The incidence rate of all-cause HRU was 44.43 visits per-patient-per-year and RTT-related HRU comprised 47% of all-cause HRU. Mean all-cause healthcare costs were $40,326 per-patient-per-year, with medical costs driven by home/hospice care visits, therapeutic services, outpatient visits, and inpatient visits. RTT-related healthcare costs comprised 45% of all-cause healthcare costs. The most prevalent supportive therapy and pharmacologic agent were feeding assistance (37.9%) and antiepileptic drugs (54.8%), respectively. Trends were similar by subgroup; although, rates of HRU were generally higher among pediatric patients relative to adult patients (all-cause: 52.43 and 35.86, respectively), which translated into higher mean healthcare costs (all-cause: $45,718 and $34,548, respectively).ConclusionsPatients with RTT have substantial disease burden, including prevalent clinical manifestations, high rates of HRU and annual healthcare costs, and reliance on pharmacologic and supportive therapies. These findings underscore the unmet need for effective therapies to target the multifactorial manifestations of RTT.