Effective Inhibition of TNF-α/mTOR Axis-Mediated Liver Inflammation and Fibrosis Induced by TAA Using a Combination of Metformin and Resveratrol in Association with the Inhibition of the Profibrotic Gene and Protein Expression

SUMMARY: The response of the immune system to harmful stimuli leads to inflammation, and the adverse effects of the toxic hepatitis chemical, thioacetamide (TAA) on the human body are well documented. This article investigated the degree of protection provided by the combined pleotropic drug, metformin (Met) and the plant polyphenolic and the antiinflammatory compound, resveratrol (Res) on liver tissue exposed to TAA possibly via the inhibition of the inflammatory cytokine, tumor necrosis factor-α (TNF-α) / mammalian target of rapamycin (mTOR) axis-mediated liver fibrosis, as well as amelioration of profibrotic gene and protein expression. Rats were either given TAA (200 mg/kg via intraperitoneal injection) for 8 weeks beginning at the third week (experimental group) or received during the first two weeks of the experiment combined doses of metformin (200 mg/kg) and resveratrol (20 mg/kg) and continued receiving these agents and TAA until experiment completion at week 10 (treated group). A considerable damage to hepatic tissue in the experimental rats was observed as revealed by tissue collagen deposition in the portal area of the liver and a substantial increase (p<0.0001) in hepatic levels of the inflammatory marker, tumor necrosis factor-α (TNF-α), as well as blood levels of hepatocellular injury biomarkers, alanine aminotransferase (ALT) and aspartate aminotransferase (AST). TAA also augmented hepatic tissue levels of the signalling molecule that promotes liver fibrosis (mTOR), and profibrogenic markers; alpha-smooth muscle actin (α-SMA) protein, tissue inhibitor of metalloproteinases-1 (TIMP-1) mRNA, and matrix metalloproteinase-9 (MMP-9) mRNA. All these parameters were protected (p≤0.0016) by Met+Res. In addition, a significant correlation was detected between liver fibrosis score and inflammation, liver injury enzymes, mTOR, and profibrogenesis markers. Thus, these findings suggest that Met+Res effectively protect the liver against damage induced by thioacetamide in association with the downregulation of the TNF-α/mTOR/fibrosis axis.

La respuesta del sistema inmunológico a estímulos dañinos conduce a la inflamación y los efectos adversos de la tioacetamida (TAA), una sustancia química tóxica para el hígado, están bien documentadas. Este artículo investigó el grado de protección proporcionado por el fármaco pleotrópico combinado metformina (Met), el polifenólico vegetal y el compuesto antiinflamatorio resveratrol (Res) en el tejido hepático expuesto a TAA, posiblemente a través de la inhibición de la citoquina inflamatoria, factor de necrosis tumoral α (TNF-α)/objetivo de la fibrosis hepática mediada por el eje de rapamicina (mTOR), así como mejora de la expresión de genes y proteínas profibróticas. Las ratas recibieron TAA (200 mg/kg mediante inyección intraperitoneal) durante 8 semanas a partir de la tercera semana (grupo experimental) o recibieron durante las dos primeras semanas del experimento dosis combinadas de metformina (200 mg/kg) y resveratrol (20 mg/kg) y continuaron recibiendo estos agentes y TAA hasta completar el experimento en la semana 10 (grupo tratado). Se observó un daño considerable al tejido hepático en las ratas experimentales, como lo revela el depósito de colágeno tisular en el área portal del hígado y un aumento sustancial (p<0,0001) en los niveles hepáticos del marcador inflamatorio, el factor de necrosis tumoral-α (TNF- α), así como los niveles sanguíneos de biomarcadores de lesión hepatocelular, alanina aminotransferasa (ALT) y aspartato aminotransferasa (AST). TAA también aumentó los niveles en el tejido hepático de la molécula de señalización que promueve la fibrosis hepática (mTOR) y marcadores profibrogénicos; proteína actina del músculo liso alfa (α- SMA), inhibidor tisular de las metaloproteinasas-1 (TIMP-1) mRNA y matriz metaloproteinasa-9 (MMP-9) mRNA. Todos estos parámetros fueron protegidos (p≤0.0016) por Met+Res. Además, se detectó una correlación significativa entre la puntuación de fibrosis hepática y la inflamación, las enzimas de lesión hepática, mTOR y los marcadores de profibrogénesis. Por lo tanto, estos hallazgos sugieren que Met+Res protege eficazmente el hígado contra el daño inducido por la tioacetamida en asociación con la regulación negativa del eje TNF-α/mTOR/fibrosis.

Trajectory, Perceived Causes and Efforts in Diabetes Selfmanagement: A Qualitative Study Among Young People With Type 2 Diabetes Mellitus and Caregivers

@#Introduction: Previous studies have suggested that young individuals with type 2 diabetes mellitus (T2DM) face challenges in achieving optimal diabetes self-management, leading to difficulties in attaining the recommended glycaemic target. The reasons behind these suboptimal practices remain unclear due to the limited number of studies conducted in Malaysia that focused on diabetes self-management among young people. This qualitative study aimed to understand the lived experience of young people with T2DM on self-management in Malaysia. Methods: Young people at the age of 10 to 24 years, who had been diagnosed with T2DM and the caregivers who managing young people with T2DM were interviewed. Data were thematically analysed with the aid of QSR NVivo version 12. Results: Sixteen young informants and eleven caregivers participated in this study. Three major themes conceptualised the lived experience of diabetes self-management: (1) the trajectory to T2DM diagnosis; (2) perceived causes of T2DM; (3) the efforts in diabetes self-management. The route of diagnosis and experiential knowledge about T2DM might determine their efforts in the self-management among the young people. Healthy eating, medication taking and physical activity were perceived as important tasks in diabetes self-management. The involvement of the caregivers in diabetes self-management evolved over time. Conclusion: The study highlighted the experience of young people and caregivers since the beginning of the diagnosis and their strategies in diabetes self-management. More understanding of the lived experiences of patients and caregivers in disease management within the socio-ecological context could help to improve health-care services and intervention for this population.

Kajian Rintis Penilaian Literasi Digital: Kesediaan Guru Prasekolah Menggunakan Platform Pembelajaran dalam Talian untuk Pendidikan Pemakanan (A Pilot Study Assessing Digital Literacy: Preschool Teachers’ Readiness to Use Online Learning Platforms in Nutrition Education) / Jurnal Sains Kesihatan Malaysia

@#eToyBox is a learning management system for preschool teachers to improve their health literacy, which ultimately aims to improve children’s obesity-related behaviour. As part of the development process of eToyBox, assessment on digital literacy, acceptance of digitization of education materials, and perceived barriers in adopting online learning is needed. Fifty-four preschool teachers under the Community Development Department (KEMAS) in Kuala Lumpur, Selangor, and Sarawak, who participated in ToyBox Study Malaysia intervention in 2018, took part in this cross-sectional study. An online self-administered questionnaire was used to assess sociodemographic background, use of communication tools and media, and teacher’s views on adapting the ToyBox modules to digital education materials. Respondents were contacted, and questionnaire link was shared through WhatsApp messages. Most participants (74.0%) were Malay females aged 31 to 40 years old. Most participants had internet access (94.4%) and owned at least a smart phone, laptop or tablet (94.4%). Participants perceived their computer skills to be average (75.0%). Majority of respondents (65.0%) reported advanced and higher abilities in word processing and email, but only 22.0% in spreadsheet skills. The main barrier to accessing online material was unstable internet connection (74.1%). Most respondents (90.0%) agree that adapting effective modules to online learning will be beneficial for professional development and teaching practices. In conclusion, most participants supported digitizing Toybox Study Malaysia educational content and were comfortable 72 with its implementation via an online learning platform. The findings from this study can advise future development of online learning materials for preschool teachers in Malaysia.

Molecular characterization and incidence of new tospovirus: Soybean Vein Necrosis Virus (SVNV) in Egypt / Caracterização molecular e incidência de novo tospovírus: Vírus da Necrose da Veia da Soja (SVNV) no Egito

Abstract Field survey study was conducted season (2017). Soybeans and weeds were weekly sampled randomly. Thrips adults were identified and counted. Detection of the virus isolate and the natural incidence was determined using; Mechanical transmission, host range, DAS-ELISA, RT-PCR. The natural incidence thrips individuals was detected depending on the SVNV% in thrips individuals and weeds hosts. Ten thrips species were associated with soybean plants in the field. The most abundant species was T. tabaci, average 256.5 average no.of individuals, followed by F. occidentalis (142.5 average no. of individuals), then N. variabilis (86.6/ average no. of individuals). Fourteen thrips species occurred on 5 legumes field crops and 41 weed plant species within soybean field. The highest average number 40.6.of individuals were recorded on Ammi majus. While the lowest one 3.3 average no. of individuals were on Urtica urens. Only 21diagnostic plant species were susceptible to infection with SVNV. G. max and Vigna radiate, were the highest percentage of infection 80% followed by V. unguilata & N. benthamiana, 75%. Egyptian isolate of Soybean vein necrosis virus (SVNV) in this study showed a high degree of similarity and it is closely related to TSWV from Egypt (DQ479968) and TCSV from USA (KY820965) with nucleotide sequence identity of 78%. Four thrips species transmitted SVNV (F. fusca 4.0%, F. schultzei 4.3%, F. tritici 3.3% and N. variabilis 68.0% transmission). Both C. phaseoli and M. sjostedti can acquire the virus but unable to transmit it. The following species; T. tabaci, F. occidentalis, S. dorsallis and T. palmi cannot acquire or transmit SVNV. The incidence of SVNV in the field started by the end of July then increased gradualy from 12.7 to 71.3% by the end of the season. In conclusion, few thrips individuals invaded soybean crops are enough to transmit high rate of SVNV within the crop. Furthermore, several vector species are also abundant on weeds, which are the major sources of soybean viruses transmitted to the crops. This information might be important for control and reduce the incidence of SVNV infection.

Resumo O estudo de pesquisa de campo foi realizado na temporada (2017). A soja e as ervas daninhas foram amostradas semanalmente de forma aleatória. Tripes adultos foram identificados e contados. A detecção do vírus isolado e a incidência natural foram determinadas usando transmissão mecânica, gama de hospedeiros, DAS-ELISA, RT-PCR. A incidência natural de tripes em indivíduos foi detectada dependendo da % de SVNV em tripes e hospedeiros infestantes. Dez espécies de tripes foram associadas a plantas de soja no campo. A espécie mais abundante foi T. tabaci, com média de 256,5 número médio de indivíduos, seguida por F. occidentalis (142,5) e N. variabilis (86,6 / número médio de indivíduos). Catorze espécies de tripes ocorreram em 5 culturas de leguminosas e 41 espécies de plantas daninhas dentro de campos de soja. O maior número médio de 40,6 indivíduos foi registrado em Ammi majus. Enquanto o mais baixo, 3,3 número médio de indivíduos, foi no Urtica urens. Apenas 21 espécies de plantas diagnosticadas foram suscetíveis à infecção com SVNV. G. max e Vigna radiate foram os maiores percentuais de infecção, 80%, seguidos por V. unguilata e N. benthamiana, 75%. O isolado egípcio neste estudo mostrou um alto grau de similaridade e está intimamente relacionado ao TSWV do Egito (DQ479968) e ao TCSV dos EUA (KY820965), com identidade de sequência de nucleotídeos de 78%. Quatro espécies de tripes transmitiram SVNV (F. fusca 4,0%, F. schultzei 4,3%, F. tritici 3,3% e N. variabilis 68,0% de transmissão). Tanto C. phaseoli quanto M. sjostedti podem adquirir o vírus, mas não podem transmiti-lo. As seguintes espécies, T. tabaci, F. occidentalis, S. dorsallis e T. palmi não podem adquirir ou transmitir SVNV. A incidência de SVNV no campo, iniciada no final de julho, aumentou gradativamente de 12,7 para 71,3% no final da temporada. Em conclusão, poucos indivíduos de tripes invadiram a cultura da soja e são suficientes para transmitir alta taxa de SVNV dentro da cultura. Além disso, várias espécies de vetores também abundam em ervas daninhas, que são as principais fontes dos vírus da soja transmitidos às lavouras. Essas informações podem ser importantes para controlar e reduzir a incidência de infecção por SVNV.

Molecular characterization and incidence of new tospovirus: Soybean Vein Necrosis Virus (SVNV) in Egypt

Abstract Field survey study was conducted season (2017). Soybeans and weeds were weekly sampled randomly. Thrips adults were identified and counted. Detection of the virus isolate and the natural incidence was determined using; Mechanical transmission, host range, DAS-ELISA, RT-PCR. The natural incidence thrips individuals was detected depending on the SVNV% in thrips individuals and weeds hosts. Ten thrips species were associated with soybean plants in the field. The most abundant species was T. tabaci, average 256.5 average no.of individuals, followed by F. occidentalis (142.5 average no. of individuals), then N. variabilis (86.6/ average no. of individuals). Fourteen thrips species occurred on 5 legumes field crops and 41 weed plant species within soybean field. The highest average number 40.6.of individuals were recorded on Ammi majus. While the lowest one 3.3 average no. of individuals were on Urtica urens. Only 21diagnostic plant species were susceptible to infection with SVNV. G. max and Vigna radiate, were the highest percentage of infection 80% followed by V. unguilata & N. benthamiana, 75%. Egyptian isolate of Soybean vein necrosis virus (SVNV) in this study showed a high degree of similarity and it is closely related to TSWV from Egypt (DQ479968) and TCSV from USA (KY820965) with nucleotide sequence identity of 78%. Four thrips species transmitted SVNV (F. fusca 4.0%, F. schultzei 4.3%, F. tritici 3.3% and N. variabilis 68.0% transmission). Both C. phaseoli and M. sjostedti can acquire the virus but unable to transmit it. The following species; T. tabaci, F. occidentalis, S. dorsallis and T. palmi cannot acquire or transmit SVNV. The incidence of SVNV in the field started by the end of July then increased gradualy from 12.7 to 71.3% by the end of the season. In conclusion, few thrips individuals invaded soybean crops are enough to transmit high rate of SVNV within the crop. Furthermore, several vector species are also abundant on weeds, which are the major sources of soybean viruses transmitted to the crops. This information might be important for control and reduce the incidence of SVNV infection.

Resumo O estudo de pesquisa de campo foi realizado na temporada (2017). A soja e as ervas daninhas foram amostradas semanalmente de forma aleatória. Tripes adultos foram identificados e contados. A detecção do vírus isolado e a incidência natural foram determinadas usando transmissão mecânica, gama de hospedeiros, DAS-ELISA, RT-PCR. A incidência natural de tripes em indivíduos foi detectada dependendo da % de SVNV em tripes e hospedeiros infestantes. Dez espécies de tripes foram associadas a plantas de soja no campo. A espécie mais abundante foi T. tabaci, com média de 256,5 número médio de indivíduos, seguida por F. occidentalis (142,5) e N. variabilis (86,6 / número médio de indivíduos). Catorze espécies de tripes ocorreram em 5 culturas de leguminosas e 41 espécies de plantas daninhas dentro de campos de soja. O maior número médio de 40,6 indivíduos foi registrado em Ammi majus. Enquanto o mais baixo, 3,3 número médio de indivíduos, foi no Urtica urens. Apenas 21 espécies de plantas diagnosticadas foram suscetíveis à infecção com SVNV. G. max e Vigna radiate foram os maiores percentuais de infecção, 80%, seguidos por V. unguilata e N. benthamiana, 75%. O isolado egípcio neste estudo mostrou um alto grau de similaridade e está intimamente relacionado ao TSWV do Egito (DQ479968) e ao TCSV dos EUA (KY820965), com identidade de sequência de nucleotídeos de 78%. Quatro espécies de tripes transmitiram SVNV (F. fusca 4,0%, F. schultzei 4,3%, F. tritici 3,3% e N. variabilis 68,0% de transmissão). Tanto C. phaseoli quanto M. sjostedti podem adquirir o vírus, mas não podem transmiti-lo. As seguintes espécies, T. tabaci, F. occidentalis, S. dorsallis e T. palmi não podem adquirir ou transmitir SVNV. A incidência de SVNV no campo, iniciada no final de julho, aumentou gradativamente de 12,7 para 71,3% no final da temporada. Em conclusão, poucos indivíduos de tripes invadiram a cultura da soja e são suficientes para transmitir alta taxa de SVNV dentro da cultura. Além disso, várias espécies de vetores também abundam em ervas daninhas, que são as principais fontes dos vírus da soja transmitidos às lavouras. Essas informações podem ser importantes para controlar e reduzir a incidência de infecção por SVNV.

Adiponectin serum levels and ADIPOQ (rs2241766) polymorphism in alopecia areata Egyptian patients

Abstract Background Alopecia Areata (AA) is an acquired autoimmune form of non-scarring hair loss. Adiponectin and its gene polymorphism were related to many autoimmune disorders. Objective Assessment of adiponectin serum levels and adiponectin gene (ADIPOQ) (rs2241766) Single Nucleoid Polymorphism (SNP) in AA patients and correlating the results with the disease severity in those patients. Methods This study included 75 AA patients and 75 age and gender-matched healthy subjects (controls). The severity of Alopecia Tool (SALT) score assessment to evaluate AA severity was done. Adiponectin serum levels by ELISA and ADIPOQ (rs2241766) SNP using PCR were performed. Results Adiponectin serum levels were significantly lower in AA patients than controls (p = 0.001). ADIPOQ (rs2241766) TG genotype and G allele were significantly predominant in AA patients increasing its risk by 5 and 4 folds (OR = 5.17, p = 0.001), (OR = 3.82, p = 0.001) respectively. Serum adiponectin levels were negatively correlated with SALT score (r = -0.435, p = 0.001) and associated with alopecia totalis (p = 0.016). ADIPOQ (rs2241766) TG genotype was significantly associated with low serum adiponectin levels and higher SALT score (p = 0.001). Study limitations The small sample size. Conclusions ADIPOQ (rs2241766) gene polymorphism (TG genotype and G allele) may modulate AA risk and contribute to the development of AA in Egyptian populations. Decreased circulating adiponectin levels may have a dynamic role in AA etiopathogenesis. Adiponectin serum concentration can be considered a severity marker of hair loss in AA.

Assessment of humoral immune response to different COVID-19 vaccines in patients undergoing maintenance hemodialysis / Avaliação da resposta imune humoral a diferentes vacinas contra a COVID-19 em pacientes submetidos à hemodiálise de manutenção

ABSTRACT Introduction: The immune response to different Coronavirus Disease 2019 (COVID-19) vaccines is under-investigated in end-stage kidney disease (ESKD) patients, especially in the Middle East and North Africa. We carried out this research to estimate the effectiveness of COVID-19 immunization in ESKD patients on regular hemodialysis (HD). Methods: In this prospective observational study, we enrolled 60 ESKD patients on regular HD who had completed COVID-19 vaccination and 30 vaccinated healthy participants. Serum levels of severe acute respiratory syndrome coronavirus 2 immunoglobulin G (SARS-COV2 IgG) were quantified 1 month after completing the vaccination schedule, and all participants were followed up from October 2021 to March 2022. The vaccines used in the study were from Pfizer-BioNTech, AstraZeneca, and Sinopharm. Results: The median level of SARS-COV2 IgG was lower in HD patients than in healthy participants (p < 0.001). Regarding the type of COVID-19 vaccination, there was no statistical difference in SARS-COV2 IgG levels among HD patients. During the observation period, none of the HD patients had COVID-19. Conclusion: COVID-19 vaccination appeared to be protective in HD patients for 6 months and the side effects of vaccines were tolerable.

RESUMO Introdução: A resposta imune a diferentes vacinas contra a doença do coronavírus 2019 (COVID-19) é pouco investigada em pacientes com doença renal em estágio terminal (DRET), especialmente no Oriente Médio e norte da África. Realizamos esta pesquisa para estimar a eficácia da imunização contra a COVID-19 em pacientes com DRET em hemodiálise regular (HD). Métodos: Nesse estudo observacional prospectivo, inscrevemos 60 pacientes com DRET em HD regular que haviam concluído o esquema de vacinação contra a COVID-19 e 30 participantes saudáveis vacinados. Os níveis séricos de imunoglobulina G da síndrome respiratória aguda grave do coronavírus 2 (SARS-COV2 IgG) foram quantificados um mês após a conclusão do esquema vacinal, e todos os participantes foram acompanhados de outubro de 2021 a março de 2022. As vacinas utilizadas no estudo eram da Pfizer-BioNTech, AstraZeneca e Sinopharm. Resultados: O nível mediano de SARS-COV2 IgG foi menor em pacientes em HD do que em participantes saudáveis (p < 0,001). Com relação ao tipo de vacinação contra a COVID-19, não houve diferença estatística nos níveis de SARS-COV2 IgG entre pacientes em HD. Durante o período de observação, nenhum dos pacientes em HD teve COVID-19. Conclusão: A vacinação contra a COVID-19 pareceu ser eficaz na proteção de pacientes em HD por 6 meses e os efeitos colaterais das vacinas foram toleráveis.

Endoscopic Orientation of Juxta-pituitary Carotid in Transsphenoidal Approaches: Critical Considerations for Clinical Applications

Abstract Introduction In sphenoid sinuses with ill-defined carotid bony landmarks, accidental injury of the internal carotid artery (ICA) remains one of the most challenging complications, which is particularly reported in the endoscopic endonasal transsphenoidal approaches (EETAs). Objectives To describe an anatomical model for the endoscopic orientation of the juxta-pituitary segment of the ICA in relation to the lateral opticocarotid recess (OCR) as a nearby bony landmark. Methods Dissection was performed progressively, simulating the EETA, in twenty fresh adult cadavers. After reducing the posterior and lateral walls of the sphenoid sinuses, various measurements were taken from both lateral OCRs to "contact points" on the juxta-pituitary segment of the ICA and lateral margins of the pituitary gland. Results The current results have enabled us to divide the region between the lateral OCRs into 3 compartments: 2 lateral parasellar compartments contain juxta-pituitary segments of the ICA with a mean width of 8 mm and a narrow range from 7 mm to 10 mm; and a central intercarotid sellar compartment represents the safe region for bone drilling, showing widely variable widths ranging from 9 mm to 20 mm. In all specimens, the variation in the width of the intercarotid compartment correlated with the distance between both lateral OCRs. Conclusion The present study improves surgeon awareness of the variations in the course of the ICA through the EETA along sphenoid sinuses with ill-defined bony landmarks. An appreciation of the measurements taken in the present study can help in operative training, and can also provide a base for future studies to confirm ICA courses associated with a higher risk of injury.

MTHFR C677T Polymorphism, Plasma Homocysteine, and PDGF-AA Levels and Transcranial Doppler Velocity in Children With Sickle Cell Disease

Objective: To evaluate the effect of methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism on plasma homocysteine (tHcy) and platelet-derived growth factor (PDGF-AA) levels in children with sickle cell disease (SCD), and ascertain their role in predicting high transcranial doppler velocity (TCD). Methods: We estimated MTHFRC677T gene polymorphism, plasma tHyc and PDGF-AA in 44 SCD patients and 44 healthy children. Results: The prevalence of mutant homozygous MTHFR (C677TT) in SCD was 13.6%. Significantly higher plasma tHcy was observed in mutant homozygous MTHFRC677TT patients. Significantly higher plasma tHcy and PDGF-AA levels were observed in SCD patients than in controls. Median (IQR) PDGF-AA levels were significantly higher in conditional and high-risk TCD patients as compared to low-riskTCD patients [325 (93.1-368) and 368 (111-480) vs 111 (56-201) pg/mL, respectively; P<0.001]. Mean (SD) tHcy levels were significantly higher in high-risk TCD children than low-risk TCD children (12.9 (2.7) vs 9.9 (2.5) µmol/L; P=0.006). The receiver operating characteristic revealed that the area under the curve (AUC) of PDGF-AA for high TCD velocity was 0.934 (95% CI 0.845-1.00; P<0.001) and tHcy had an AUC of 0.675 (95% CI 0.517-0.833; P=0.04). Conclusion: PDGF-AA and tHcy levels could be used as predictive markers for stroke in SCD children. MTHFR Polymorphism contributes to elevated tHcy levels.

The efficacy of anti–TNF-? agents in the treatment of juvenile idiopathic arthritis-associated uveitis in a pediatric cohort

Purpose: Biologic therapy has shown promising control in children with often intractable juvenile idiopathic arthritis (JIA)?associated uveitis (JIA?U). Methods: This is a retrospective cohort study of 35 eyes of 35 children who received biologics for JIA?U. Pretreatment and posttreatment data (at 3, 6, 9, 12, 18, 24, and >24 months) were analyzed to determine functional success (stable/improved visual acuity), quiescence success (?0.5 cells in the anterior chamber), complete steroid success (termination of systemic, periocular therapy and decreased topical drops to ?2/day) or systemic steroid success (termination of systemic steroids only), and complete success (all of the above). Results: This study included 35 eyes up to 12 months and 21 eyes beyond 24 months. Steroid?sparing, functional, and quiescence success showed a rate of success of 52.43%, 77%, and 91%, respectively, at 12 months and 66.67%, 85.7%, and 76.2%, respectively, beyond 24 months. Complete success was 34.29% at 12 months, peaking at 18 months (65.62%) and reached 57.14% beyond 24 months. In their final follow?up, the best corrected visual acuity (BCVA) remained the same in 45.71%, improved in 37.14%, and worsened in 17.14% children. Conclusion: Biologic therapy is effective in JIA?U, especially in termination of systemic steroids, stabilization of vision, and maintaining quiescence

Tzanck cytology smear in diagnosis of cutaneous talaromycosis (penicilliosis)

Talaromyces marneffei infection is an AIDS-defining illness in South and Southeast Asia. Travel-related talaromycosis is being increasingly recognized in non-endemic areas too. It is a potentially fatal infection with rapid deterioration, if left untreated. Usage of Tzanck cytology smear for rapid diagnosis of T. marneffei is rarely described. In this case study, we report a man who presented with altered behaviour, headache, fever and cutaneous lesions. Tzanck smear test, skin biopsy and blood culture showed presence of T. marneffei. The cytomorphology findings of T. marneffei in Tzanck cytology smear were described. In conclusion, Tzanck smear is a simple and inexpensive test in establishing a rapid clinical diagnosis of talaromycosis before the culture is reported

A rat model of rheumatoid arthritis: TDZD-8 is associated with the protection against the induction of the synovium knee joint IL-17A/GSK3beta/ROS/alpha-SMA axis of fibrosis / Un modelo de rata de artritis reumatoide: TDZD-8 está asociado con la protección contra la inducción del eje de fibrosis de la articulación sinovial de la rodilla IL-17A/GSK3ß/ROS/α-SMA

SUMMARY: Rheumatoid arthritis (RA) that affects the synovial knee joint causes swelling of the synovial membrane and tissue damage. Interleukin-17A (IL-17A) and the enzyme glycogen synthase kinase-3β (GSK3β) are involved in the pathogenesis of RA. The link between IL-17A, GSK3β, the oxidative stress, and the profibrogenic marker alpha-smooth muscle actin (α-SMA) with and without TDZD-8, GSK3β inhibitor has not been studied before. Consequently, active immunization of rats was performed to induce RA after three weeks using collagen type II (COII) injections. The treated group received daily injection of 1 mg/kg TDZD-8 for 21 days following the immunization protocol (COII+TDZD-8). Blood and synovium tissue samples were harvested at the end of the experiment. RA development was confirmed as corroborated by a substantial increase in blood levels of the highly specific autoantibody for RA, anti-citrullinated protein antibody as well as augmentation of reactive oxidative species (ROS) levels measured as lipid peroxidation. RA induction also increased synovium tissue levels of IL-17A and the profibrogenic marker, α-SMA. All these parameters seemed to be significantly (p<0.0001) ameliorated by TDZD-8. Additionally, a significant correlation between IL-17A, ROS, and α-SMA and biomarkers of RA was observed. Thus, knee joint synovium RA induction augmented IL-17A/GSK3β/ROS/α-SMA axis mediated arthritis in a rat model of RA, which was inhibited by TDZD-8.

La artritis reumatoide (AR) que afecta la articulación sinovial de la rodilla provoca inflamación de la membrana sinovial y daño tisular. La interleucina-17A (IL-17A) y la enzima glucógeno sintasa quinasa-3β (GSK3β) están involucradas en la patogenia de la AR. No se ha estudiadol vínculo entre IL-17A, GSK3β, el estrés oxidativo y el marcador profibrogénico actina de músculo liso alfa (α-SMA) con y sin inhibidor de TDZD-8, GSK3β. En consecuencia, se realizó una inmunización activa de ratas para inducir la AR después de tres semanas usando inyecciones de colágeno tipo II (COII). El grupo tratado recibió una inyección diaria de 1 µg/ kg de TDZD-8 durante 21 días siguiendo el protocolo de inmunización (COII+TDZD-8). Se recogieron muestras de sangre y tejido sinovial al final del experimento. El desarrollo de AR se confirmó como lo corroboró el aumento sustancial en los niveles sanguíneos del autoanticuerpo altamente específico para AR, el anticuerpo antiproteína citrulinada, así como el aumento de los niveles de especies oxidativas reactivas (ROS) medidos como peroxidación lipídica. La inducción de AR también aumentó los niveles de tejido sinovial de IL-17A y el marcador profibrogénico, α-SMA. Todos estos parámetros parecían mejorar significativamente (p<0,0001) con TDZD-8. Además, se observó una correlación significativa entre IL- 17A, ROS y α-SMA y biomarcadores de AR. Por lo tanto, la inducción de AR en la sinovial de la articulación de la rodilla aumentó la artritis mediada por el eje IL-17A/GSK3β/ROS/α-SMA en un modelo de rata de AR, que fue inhibida por TDZD-8.

Human beta-defensin 1 circulating level and gene polymorphism in non-segmental vitiligo Egyptian patients

Abstract Background: Vitiligo is an acquired depigmented skin disorder. It has a genetic and autoimmune background. Human beta defensin-1(HBD-1) plus its gene polymorphism were linked to some autoimmune disorders. Objectives: To elucidate the possible role of HBD-1 in the pathogenesis of non-segmental vitiligo (NSV) through evaluation of HBD-1 serum levels and its single nucleotide polymorphism (SNP) in patients having NSV, in addition, to correlating the results with the extent of vitiligo in those patients. Methods: A current case-control study included 50 patients having NSV and 50 controls. The authors used Vitiligo Area Scoring Index (VASI) score to assess vitiligo severity and laboratory investigations to assess serum HBD-1 level using ELISA and defensin-beta1 (DEFB1) SNP using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results: There were significantly lower HBD-1 serum levels in NSV cases than in controls (p < 0.001). There was a significant predominance of GG DEFB1 genotype and G allele in NSV patients in comparison to controls (p < 0.001). The levels of serum HBD-1 and DEFB1 genotypes were not associated or correlated significantly with any of the personal and clinical parameters of vitiligo patients. Study limitations: The small sample size. Conclusions: DEFB1 gene polymorphism (GG genotype and G allele) may modulate vitiligo risk and contribute to vitiligo development in Egyptian populations. Decreased circulating HBD-1 levels might have an active role in vitiligo etiopathogenesis that could be mediated through its possible anti-inflammatory effects.

A Rat Model of Rheumatoid Arthritis: TDZD-8 is Associated with the Protection Against the Induction of the Synovium Knee Joint IL-17A/GSK3β/ROS/α-SMA Axis of Fibrosis

SUMMARY: Rheumatoid arthritis (RA) that affects the synovial knee joint causes swelling of the synovial membrane and tissue damage. Interleukin-17A (IL-17A) and the enzyme glycogen synthase kinase-3β (GSK3β) are involved in the pathogenesis of RA. The link between IL-17A, GSK3β, the oxidative stress, and the profibrogenic marker alpha-smooth muscle actin (α-SMA) with and without TDZD-8, GSK3β inhibitor has not been studied before. Consequently, active immunization of rats was performed to induce RA after three weeks using collagen type II (COII) injections. The treated group received daily injection of 1 mg/kg TDZD-8 for 21 days following the immunization protocol (COII+TDZD-8). Blood and synovium tissue samples were harvested at the end of the experiment. RA development was confirmed as corroborated by a substantial increase in blood levels of the highly specific autoantibody for RA, anti-citrullinated protein antibody as well as augmentation of reactive oxidative species (ROS) levels measured as lipid peroxidation. RA induction also increased synovium tissue levels of IL-17A and the profibrogenic marker, α-SMA. All these parameters seemed to be significantly (p<0.0001) ameliorated by TDZD-8. Additionally, a significant correlation between IL-17A, ROS, and α-SMA and biomarkers of RA was observed. Thus, knee joint synovium RA induction augmented IL-17A/GSK3β/ROS/α-SMA axis mediated arthritis in a rat model of RA, which was inhibited by TDZD-8.

La artritis reumatoide (AR) que afecta la articulación sinovial de la rodilla provoca inflamación de la membrana sinovial y daño tisular. La interleucina-17A (IL-17A) y la enzima glucógeno sintasa quinasa-3β (GSK3β) están involucradas en la patogenia de la AR. No se ha estudiadol vínculo entre IL-17A, GSK3β, el estrés oxidativo y el marcador profibrogénico actina de músculo liso alfa (α-SMA) con y sin inhibidor de TDZD-8, GSK3β. En consecuencia, se realizó una inmunización activa de ratas para inducir la AR después de tres semanas usando inyecciones de colágeno tipo II (COII). El grupo tratado recibió una inyección diaria de 1 µg/ kg de TDZD-8 durante 21 días siguiendo el protocolo de inmunización (COII+TDZD-8). Se recogieron muestras de sangre y tejido sinovial al final del experimento. El desarrollo de AR se confirmó como lo corroboró el aumento sustancial en los niveles sanguíneos del autoanticuerpo altamente específico para AR, el anticuerpo antiproteína citrulinada, así como el aumento de los niveles de especies oxidativas reactivas (ROS) medidos como peroxidación lipídica. La inducción de AR también aumentó los niveles de tejido sinovial de IL-17A y el marcador profibrogénico, α-SMA. Todos estos parámetros parecían mejorar significativamente (p<0,0001) con TDZD-8. Además, se observó una correlación significativa entre IL- 17A, ROS y α-SMA y biomarcadores de AR. Por lo tanto, la inducción de AR en la sinovial de la articulación de la rodilla aumentó la artritis mediada por el eje IL-17A/GSK3β/ROS/α-SMA en un modelo de rata de AR, que fue inhibida por TDZD-8.

A Long-Term Follow-up Study for the Treatment of Snoring after Using Patterned Non-Ablative Erbium: YAG 2,940 nm Laser

Abstract Introduction Laser uvulopalatoplasty is an established operation for the treatment of snoring with good results on a short-term basis, while long-term follow-up studies, in addition to their scarcity, had conflicting results regarding recurrence, the change of snoring quality, and complications. Objective To assess the long-term follow-up results of using nonablative 2,940 nm Erbium: YAG for the treatment of snoring regarding outcomes and recurrence. Methods This 2-year follow-up study was conducted on 76 patients operated upon by non-ablative 2940 nm Erbium: yttrium-aluminum-garnet (YAG) using a PS01 patterned headpiece. Subjective evaluation of the treatment was performed relying on a smartphone application to record snoring in addition to a questionnaire specially designed to report recurrence and change in the quality of snoring reported by a patient's spouse. The objective evaluation was done by computed tomography (CT) imaging of the soft palate. The patients were evaluated preoperatively, 6 weeks postoperatively and after a 2-year follow-up period. Results Six week after the procedure, there was a significant improvement in 52 patients (68.4%). Out of the 52 patients, only 43 completed the 2-year follow-up; however, 15 of them complained of recurrence. Nevertheless, the patients who suffered from recurrence showed subjective improvement in snoring quality. Conclusions The nonablative mode of Erbium: YAG 2,940 nm laser proved to be efficient in soft palate tightening for the management of snoring. However, there was recurrence in 34.8% of the patients who presented objective and subjective improvement of the complaints, 6 weeks postoperatively and after a 2-year follow-up period.

Relationship between Aortic Root Diameter and Type 2 Diabetes in Hypertensive Patients

Background: Diabetes mellitus (DM) involves a series of metabolic conditions associated with hyperglycaemia which is caused by defects in insulin secretion and./or insulin action. The aim of this work was assessment of the relationship between Aortic Root (AOR) diameter and type 2 diabetes mellitus (T2DM) in Hypertension (HTN) cases. Methods: This prospective case control study was carried out on 80 HTN cases. Cases were divided in to three groups: Group A (30 HTN cases) with type 2 DM with good metabolic control (Hb AIC ? 7.0), group B: (30 HTN cases) with type 2 DM with poor metabolic control (Hb AIC > 7.0) and C (Control group) 20 HTN, non-DM subjects of the same age and sex group with no other comorbid conditions. Results: FS had a significant decline in group A (P2 = 0.001) and in group B (P3 <0.001) than C. EF had a significant difference among all groups (P <0.001). Early wave declaration time (DT) had a significant decline in group A (P2 = 0.049) and in group B (P3= 0.023) than C. Tissue doppler early velocity wave had a significant difference among all groups (P = 0.004). Tissue doppler early velocity wave had a significant decline in group A and B than C. (P2 = 0.038. P3 = 0.003). Conclusions: AOR in HTN cases had a significant decline in DM cases compared with non-DM cases. In our results, glycaemic control didn’t play a significant role in aortic root.

Hemoglobin Level as a Predictor of Major Adverse Cardiovascular Events and Short-term Outcomes in Stemi Patient Treated with Pharmacoinvasive Strategy versus Primary PCI

Background: Anaemia is prevalent among cases with acute coronary syndrome (ACS) and has been linked to poor clinical prognosis. Guidelines for cases with ST-segment elevation myocardial infarction (STEMI) recommend timely primary percutaneous coronary intervention (pPCI) as the preferred reperfusion strategy. If timely pPCI cannot be performed, a pharmacoinvasive strategy (PI) is recommended within 12 hours of symptom onset. The aim of this work was to study and assess the impact of hemoglobin level as a predictor of MACE and short-term outcomes in cases treated with Primary PCI vs pharmacoinvasive strategy. Methods: This prospective case-control observational study was conducted on 100 cases that were divided into 2 groups. Group I consisted of 50 anaemic cases & group II consisted of 50 cases that were not anaemic. Both groups were subdivided into A subgroups that underwent revascularization by pPCI and B subgroups that underwent revascularization by pharmacoinvasive strategy. Results: There was no significant difference in LVEF, infarct site and final TIMI flow, the anaemic groups showed statistically significant more total MACE than non-anaemic groups whether revascularized by pPCI or pharmacoinvasive strategy. As expected, anaemic cases tended to have higher bleeding complications especially those undergoing pharmacoinvasive strategy. The anaemic cases also were less likely to be discharged on RAAS and beta blockers. Conclusions: Anaemic cases whether revascularized with pPCI or pharmacoinvasive strategy tend to have higher incidence of MACE and major bleeding with no significant difference in mortality. There was no significant difference between LVEF between the study groups.

Coronary Artery Ectasia as a Predictor of Major Adverse Cardiac Events in Patients with Acute ST Elevation Myocardial Infarction

Background: Coronary artery ectasia (CAE) is characterised as localised or widespread non-obstructive lesions of the epicardial coronary arteries with a luminal dilation more than 1.5 times the neighbouring normal segments or vessel diameter. Isolated CAE is CAE in the absence of severe coronary artery stenosis. This aberrant dilatation of coronary arteries can produce angina pectoris and even myocardial infarction in people without coronary artery disease owing to vasospasm, dissection, or thrombus. The purpose of this study was to evaluate the connection between CAE and major adverse cardiac events (MACE) following acute myocardial infarction with ST elevation. Methods: This was a prospective cohort study which was carried out on 300 cases. Cases were divided into two groups: Group I: including about 22 STEMI cases with CAE and Group II: including about 278 STEMI cases without CAE. All cases in this study were subjected to full history taking, clinical examination, laboratory tests, standard 12-leads ECG, resting transthoracic echocardiography (TTE), and coronary angiography. Results: Regarding MACE in the studied groups, Incidence of reinfarction and cardiac death were significant higher in cases with STEMI and CAE than cases with STEMI alone. In univariate regression analysis, CAE (OR: 3.59, p value =0.022) was a significant predictor of cardiac death but age, male sex, and EF were not. Also, in multivariate regression analysis CAE (OR: 3.49, p value =0.029) was a significant predictor of cardiac death but age, male sex, and EF were not smoking with high warfarin consumption. Further, Markis classification 1 and 3 were the most frequent phenotype among cases. In STEMI cases, the incidence of reinfarction and cardiac death were significantly higher in cases with STEMI and CAE than cases with STEMI alone. So, CAE is a significant predictor of cardiac death.

Role of P Wave Duration and Tissue Doppler Imaging as Predictive Indicators for Paroxysmal Atrial Fibrillation in Hypertensive Patients

Background: Atrial fibrillation (AF) is the most prevalent chronic arrhythmia in the heart. AF accounts for one-third of rhythm disorder hospitalizations. AF increases profoundly the risk of stroke, heart failure, and death. This study used P-wave and transthoracic echocardiography with tissue Doppler imaging (TDI) to determine paroxysmal AF predictors in hypertensive individuals. Methods: This case control study was performed on 100 hypertensive adult patients. They were classified into two equal group: Group I included hypertensive patients diagnosed to have paroxysmal AF. Group II (control group) included hypertensive patients with normal sinus rhythm. All subjects were subjected to electrocardiographic and conventional and tissue Doppler Imaging measurements. Results: Pmax had significantly increased in PAF patients compared to sinus rhythm patients. PAL, PAR, PAI, LR, LI and IR had significantly increased in PAF patients compared to sinus rhythm patients. In Multivariate logistic regression analysis, Pmax, PAL, PAI, PAR, LR, LI and IR were found to be independent predictors for PAF. Therefore, Pmax, PAL PAI, PAR, LR, LI and IR were found to be significant predictors for PAF. Best cut-off values for Pmax, PAL, PAI, PAR, LR, LI and IR were: (118, 81, 61, 49.9, 34, 20 and 16 ms) with sensitivity (76, 96, 96, 88, 82, 86 and 77.5 ), specificity (84, 100, 98, 92, 78, 82 and 76) and the AUC of (0.850, 0.979, 0.987, 0.961, 0.836, 0.891 and 0.798) respectively. Conclusions: Electrocardiographic P-wave analysis and echocardiographic TDI may identify hypertension patients at risk for paroxysmal AF, since the combination of Pmax and TDI may help in predicting the development of AF in hypertensive individuals.

Self-assumed Neurologic Related Condition Deviated Metoclopramide-Induced Acute Dystonic of Oculogyric Crisis in a Woman of Childbearing Age: A Case Report

A 26-year-old Malaysian woman (childbearing age) attended a private primary care clinic with a known case of gastroesophageal reflux disease (GERD) and complained of persistent nausea and a few episodes of vomiting. She had no known drug allergy, no surgical history, no hospitalization in the last two years, was a non-smoker, and no history of drug or alcohol abuse. The patient was prescribed Tab metoclopramide 10 mg TDS and Tab ranitidine 150 mg BD for five days. About 30 min after oral administration of both medicines, her eyes rolled involuntary upward, leading to lateral deviation of the eyes, and mouth jaws clenched as if “dislocated jaws.” The patient was immediately brought into an emergency department (ED) of a public tertiary care hospital. A drug challenge test was done which resulted in the withdrawal of metoclopramide. The accompanied sister later disclosed that the patient had taken metoclopramide and ranitidine from a private clinic earlier in the day. The patient self-assumed to have a sudden seizure, due to excessive hot weather and dehydration. A slow intravenous infusion of 50 mg/mL diphenhydramine hydrochloride in 0.9% w/v NaCl 100 mL was administered stat. Consequently, the symptoms vanished after approximately 30 min of the therapy, devoid of relapse. The patient was discharged from ED post 8 hours of monitoring with complete recovery. Physicians frequently prescribe metoclopramide to treat nausea and vomiting, which may cause adverse drug reaction of acute dystonic oculogyric crisis (OGC). Due to its unwanted and unpredictable extrapyramidal symptoms, metoclopramide should be prescribed and dispensed with caution. Thorough history taking at ED is imperative for correct early diagnosis and treatment, as metoclopramide-induced dystonic OGC has a high probability of confusion with other causes of dystonia such as conversion and seizures, encephalitis, tetanus, and hypercalcemic tetany.