Soft tissue sarcoma mimicking an arteriovenous malformation - A case report and review of literature.

INTRODUCTION AND IMPORTANCE: Arteriovenous malformation (AVM) is a rare condition affecting less than 5/10,000 people, with high misdiagnosis due to its heterogeneity, inconsistent nomenclature, and diverse diagnostic criteria. Understanding its prevalence in this age group is crucial for effective treatment. Here we present a case report of a patient with AVM. IRB approval and patient consent were obtained. This study was done based on SCARE criteria. CASE PRESENTATION: A 53-year-old female patient was diagnosed with a right hip vascular mass suggestive of AVM. The patient reported painless swelling on the right hip for five years, initially increasing in size but significantly increasing in the last six months. The patient had no history of trauma, neurological or pelvic symptoms, or constitutional symptoms. An examination of the lower limbs revealed a firm, non-tender mass measuring approximately 15 × 15 cm. A thigh MRI revealed a sizable, well-rounded, lobulated soft tissue mass with a stromal structure and pronounced vascularity, indicative of a soft tissue tumor. CLINICAL DISCUSSION: AVMs misdiagnosis is a significant issue, with 40 % of soft tissue sarcomas still misdiagnosed delaying care and leading to unnecessary measures. A 2015 study found 42.5 % of AMV patients were misdiagnosed, and 71 % were misdiagnosed as hemangiomas. Management involves multidisciplinary approaches, including radiology, sclerotherapy, surgical resection, and chemo/radiotherapy. Sirolimus may improve AVM prognosis. CONCLUSION: Misdiagnosis of AVMs is a significant issue, with 40 % of soft tissue sarcomas still misdiagnosed. Management involves multidisciplinary approaches, including interventional radiology, sclerotherapy, surgical resection, and chemo/radiotherapy.

The Effects of Cataract Surgery on Children's Vision: A Systematic Review.

Background: Five-fifths of all incidents of blindness in Saudi Arabia may be attributed to cataracts. Cataracts are the second major cause of blindness, responsible for 35.5% of cases. Therefore, the purpose of the research was to measure the visual acuity improvement after cataract surgery in children. Materials and Methods: This systematic review followed PRISMA guidelines for reporting systematic reviews. All procedures followed the recommendations of the Cochrane handbook. Studies of varying study designs, both published and unpublished, are included. Retrospective studies with outcomes of pediatric cataract surgery were identified from various databases. Result: After an initial screening, 108 out of 167 items were deemed unsuitable for publication. There were 59 full-text papers assessed for inclusion, and only seven matched the criteria. All the articles included were of a very high standard. Both the duration of therapy and the target population varied widely between the studies. Conclusion: The results indicated that the majority of childhood cataracts are hereditary. Primary posterior capsulectomy and anterior vitrectomy combined with cataract extraction and intra-ocular lens implantation is the treatment of choice for pediatric cataracts. It is recommended that surgery be performed in a properly equipped facility staffed by trained, cooperative personnel and that different procedures be used to enhance post-operative follow-up.

Gastroesophageal Cancer After Laparoscopic Sleeve Gastrectomy.

Obesity has been linked to many types of cancers, and this association has received much attention. Here, we are reporting the case of a 41-year-old male patient, the second case diagnosed in our hospital with advanced metastatic gastroesophageal cancer eight years after laparoscopic sleeve gastrectomy. Routine preoperative endoscopy for all patients planned for bariatric surgery can play an important role in preoperative surgery selection, detection of abnormal pathology/lesions, as well as in postoperative follow-up/esophagogastroduodenoscopy surveillance plans, especially for patients identified as high-risk to develop cancer.

Satisfaction Rate After Laser Correction of Presbyopia (Presbyond) Among Patients Aged 40 Years and Older in Taif, Saudi Arabia.

Background Presbyopia is a physiological condition arising due to the loss of accommodation within the crystalline lens. One of the most widely accepted theories of the mechanism of accommodation was that in response to ciliary muscle contraction, the crystalline lens thickness increases, the lens diameter decreases, and both the anterior and posterior curvature of the lens increase, resulting in an increase in lenticular power therefore, accommodation. A contrasting theory suggests that ciliary muscle contraction leads to a selective increase in equatorial zonular tension, with the lens equator moving toward the sclera and the equatorial diameter of the lens increasing. This results in a change of lens optical power. Until now, clinical approaches to correct presbyopia have included monovision, multifocality, and extended depth of focus, all three of which can be achieved surgically on the cornea or by lens surgery. Methods This was a cross-sectional study adopted among patients who had Presbyond surgery in Taif City, Saudi Arabia, and were aged 40 years and older. The data was collected by conducting phone interviews to increase the response rate with a prepared questionnaire that was studied to achieve equality between participants to determine whether they were satisfied or not about the results after this surgery. The contact information was retrieved based on hospital records about patients who underwent Presbyond surgery. Data was analyzed using IBM SPSS Statistics for Windows, Version 22 (Released 2013; IBM Corp., Armonk, New York, United States). The data was collected for the period beginning on the first of January 2019 until the first of February 2023. Results From the study findings, a significant number of participants (28.1%, n=25) reported experiencing complete improvement and returning to normal life within 1-30 days after surgery. A slightly larger percentage (39.2%, n=35) experienced this within 1-3 months. Most of the participants (80.9%, n=72) reported an overall improvement in their quality of life after the surgery. This included activities such as reading and using a mobile phone. This indicates that the surgery had a positive impact on their daily lives and activities. In terms of recommendations, a total of 49 (55.1%, n=49) participants stated that they were very likely to recommend refractive surgery to a family member or friend experiencing vision problems. The study found that the mean patients' satisfaction score after one month of surgery is 2.494 units higher than the mean satisfaction score before surgery. This difference was statistically significant (p < .001). Conclusion The majority of participants did not experience any problems during the surgery, and most were able to resume their normal activities within a relatively brief period of time. The surgery achieved its goals for the majority of participants, resulting in an improvement in their quality of life. However, some short-term discomfort or adjustment period was reported. Overall, the participants were satisfied with the surgery, with the majority being very likely to recommend it to others. There is room for improvement in addressing concerns such as blurred vision, the need for glasses, and dry eyes. The study also found that patient satisfaction increased significantly after one month of surgery, and the timing of complete improvement and perception of achieving surgical goals were strongly associated with perceived outcomes.

Risk factors for severe morbidity and definitive stoma after elective surgery for sigmoid diverticulitis: a multicenter national cohort study.

BACKGROUND: In the decision to perform elective surgery, it is of great interest to have data about the outcomes of surgery to individualize patients who could safely undergo sigmoid resection. The aim of this study was to provide information on the outcomes of elective sigmoid resection for sigmoid diverticular disease (SDD) at a national level. METHODS: All consecutive patients who had elective surgery for SDD (2010-2021) were included in this retrospective, multicenter, cohort study. Patients were identified from institutional review board-approved databases in French member centers of the French Surgical Association. The endpoints of the study were the early and the long-term postoperative outcomes and an evaluation of the risk factors for 90-day severe postoperative morbidity and a definitive stoma after an elective sigmoidectomy for SDD. RESULTS: In total, 4617 patients were included. The median [IQR] age was 61 [18.0;100] years, the mean ± SD body mass index (BMI) was 26.8 ± 4 kg/m2, and 2310 (50%) were men. The indications for surgery were complicated diverticulitis in 50% and smoldering diverticulitis in 47.4%. The procedures were performed laparoscopically for 88% and with an anastomosis for 83.8%. The severe complication rate on postoperative day 90 was 11.7%, with a risk of anastomotic leakage of 4.7%. The independent risk factors in multivariate analysis were an American Society of Anesthesiologists (ASA) score ≥ 3, an open approach, and perioperative blood transfusion. Age, perioperative blood transfusion, and Hartmann's procedure were the three independent risk factors for a permanent stoma. CONCLUSIONS: This series provides a real-life picture of elective sigmoidectomy for SDD at a national level. TRIAL REGISTRATION: Comité National Information et Liberté (CNIL) (n°920361).

Investigation and drug design for novel molecules from natural products as inhibitors for controlling multiple myeloma disease using in-silico tools.

Multiple myeloma (MM) is a disease that causes plasma cell growth in the bone marrow and immune globulin buildup in blood and urine. Despite recent advances in MM therapy, many still die due to its high mortality rate. A study using computational simulations analyzed 100 natural ingredients from the SANC database to determine if they inhibited the IgH domain, a known cause of multiple myeloma. Natural component Diospyrin inhibited the IgH enzyme with the best binding energy of -10.3 kcal/mol and three carbon-hydrogen bonds, followed by Parviflorone F complex with a binding energy of -10.1 kcal/mol and two conventional-hydrogen bonds. As a result, the Molecular Dynamic simulation was used to test the stability of the two complexes. During the simulation, the Diospyrin molecule dissociated from the protein at roughly 67.5 ns, whereas the Parviflorone F molecule stayed attached to the protein throughout. The latter was the subject of the investigation. The analysis of the production run data revealed that the Parviflorone F molecule exhibits a variety of conformations within the binding pocket while keeping a relatively constant distance from the protein's center of mass. The analysis of the production run data revealed that the Parviflorone F molecule exhibited a variety of conformations within the binding pocket while keeping a relatively constant distance from the protein's center of mass. The root mean square deviation (RMSD) plots for both the protein and complex showed a stable and steady average value of 4.4 Å for the first 82 nanoseconds of manufacture. As a result, the average value increased to 8.3 Å. Furthermore, the components of the binding free energy, as computed by MM-GBSA, revealed that the mean binding energy of the Parviflorone F molecule was -23.88 kcal/mol. Finally, after analyzing all of the examination data, Parviflorone F was identified as a powerful inhibitor of the IgH domain and hence of the MM disease, which requires further in-vivo conformation.Communicated by Ramaswamy H. Sarma.

Saccharomyces cerevisiae supplemented diets mitigate the effects of waterborne cadmium toxicity on gilthead seabream (Sparus aurata L.): growth performance, haemato-biochemical, stress biomarkers, and histopathological investigations.

Yeast, Saccharomyces cerevisiae, has been utilized as a probiotic in aqua-feeds to promote growth and alleviate the stress in aquatic animals. On the other hand, cadmium (Cd) toxicity causes serious retardation of growth and welfare status of aquatic animals. The present study was conducted to evaluate the protective role of dietary yeast in mitigating the waterborne Cd toxicity effects on the growth, haemato-biochemical, stress biomarkers, and histopathological investigations of gilthead seabream (Sparus aurata L.). In a 3 × 3 factorial design, the acclimated fish (20-24 g) were randomly distributed into nine treatments in triplicates where they were fed on 0.0% (control), 0.5%, and 1.0% of yeast along with exposure to 0.0, 1.0, and 2.0 mg Cd/L for 60 days. All growth parameters and mRNA expressions of IGF-1 and GH genes as well as haematological parameters were markedly increased with the increase of dietary yeast levels; meanwhile these variables were significantly retarded with Cd exposure. Contradictory effects on the above-mentioned variables were observed with Cd toxicity. In contrast, blood cortisol, glucose, total cholesterol, and triglyceride, lactate dehydrogenase, alanine transaminase, aspartate transaminase, alkaline phosphatase, in addition to DNA fragments % were noticeably increased with Cd toxicity especially at the treatment of 2.0 mg Cd/L, while decreasing with increasing dietary yeast levels. Compared with the control fish group, Cd concentrations in the gill, liver, and muscle tissues of gilthead seabream were higher in Cd-exposed treatments, especially at the treatment of 2.0 mg Cd/L. Deposition of Cd in fish liver was higher than that in gill tissues but lowest Cd residue was observed in muscle tissues. No significant changes in Cd residues in fish organs were observed in yeast-fed fish with no Cd exposure. The Cd exposure negatively affected histological status of gill, liver, and kidney tissues of S. aurata; while feeding Cd-exposed fish on yeast diets lowered the Cd residues in fish organs and recovered the adverse effects of Cd toxicity. Hence, this study recommends the addition of bakery yeast (1.0%) to fish diets to improve the performance, overall welfare, and histopathological status of gilthead seabream, S. aurata.

Top 50 Highly Cited Publications in Facelift Surgery: A 50-Year Bibliometric Analysis Review.

INTRODUCTION: Facelift surgery, also known as rhytidectomy, is a commonly performed procedure to address aging-related changes in the face and neck. Over the years, its techniques and methodologies have evolved. This study aimed to provide a bibliometric analysis of the top 50 most cited publications related to facelift surgery over a fifty-year period (1973-2023). METHODS: The authors obtained data from the Web of Science Core Collection on July 15, 2023. Using a predefined search strategy, the most cited articles from 1973 to 2023 on facelift surgery were identified. The publications were analyzed for their type of study, journal of publication, geographic origin, and primary outcomes. Furthermore, the authorship gender distribution was assessed. RESULTS: The majority of the publications (34 out of 50) were published in the "Plastic and Reconstructive Surgery" journal. The USA contributed to 72% of the research, followed by the UK, Mexico, Australia, and Germany. The primary outcomes varied from surgical techniques, anatomical studies, risk factors, patient-specific outcomes, and facial rejuvenation techniques, to comparative and historical progression of techniques. Notably, male authors dominated the field with 47 out of 50 papers having both a first and senior male author. CONCLUSION: Facelift surgery has seen substantial research development over the past fifty years. The USA has been at the forefront of this research, with a predominant focus on surgical techniques and anatomical studies. Male dominance in authorship indicates potential scope for increased gender diversity in this specialty. Annual updates are recommended for continued insights. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Unveiling Phytoconstituents with Inhibitory Potential Against Tyrosine-Protein Kinase Fyn: A Comprehensive Virtual Screening Approach Targeting Alzheimer's Disease.

BACKGROUND: Tyrosine-protein kinase Fyn (Fyn) is a critical signaling molecule involved in various cellular processes, including neuronal development, synaptic plasticity, and disease pathogenesis. Dysregulation of Fyn kinase has been implicated in various complex diseases, including neurodegenerative disorders such as Alzheimer's and Parkinson's diseases, as well as different cancer types. Therefore, identifying small molecule inhibitors that can inhibit Fyn activity holds substantial significance in drug discovery. OBJECTIVE: The aim of this study was to identify potential small-molecule inhibitors among bioactive phytoconstituents against tyrosine-protein kinase Fyn. METHODS: Through a comprehensive approach involving molecular docking, drug likeliness filters, and molecular dynamics (MD) simulations, we performed a virtual screening of a natural compounds library. This methodology aimed to pinpoint compounds potentially interacting with Fyn kinase and inhibiting its activity. RESULTS: This study finds two potential natural compounds: Dehydromillettone and Tanshinone B. These compoundsdemonstrated substantial affinity and specific interactions towards the Fyn binding pocket. Their conformations exhibitedcompatibility and stability, indicating the formation of robust protein-ligand complexes. A significant array of non-covalentinteractions supported the structural integrity of these complexes. CONCLUSION: Dehydromillettone and Tanshinone B emerge as promising candidates, poised for further optimization as Fynkinase inhibitors with therapeutic applications. In a broader context, this study demonstrates the potential of computationaldrug discovery, underscoring its utility in identifying compounds with clinical significance. The identified inhibitors holdpromise in addressing a spectrum of cancer and neurodegenerative disorders. However, their efficacy and safety necessitatevalidation through subsequent experimental studies.

Glioblastoma with Primitive Neuroectodermal Tumor like Component: Rare and Enigmatic.

Glioblastoma (GBM) with Primitive Neuroectodermal tumor (PNET) like features is an extremely rare tumor showing dual features of malignant glioma and primitive neuroectodermal tumour occurring mostly in adults. It poses diagnostics dilemma to the neuropathologist and treating oncologist team because of its rarity, tendency to spread to cerebrospinal fluid and dismal prognosis. We have described this tumor in a 11 years old male child in this case report. Keywords: glioma,glioblastoma,primitive neuroectodermal tumor, variant, pediatric.

The opposing effects of two gene defects in STX11 and SLP76 on the disease in a patient with an inborn error of immunity.

BACKGROUND: Inborn errors of immunity are mostly monogenic. However, disease phenotype and outcome may be modified by the coexistence of a second gene defect. OBJECTIVE: We sought to identify the genetic basis of the disease in a patient who experienced bleeding episodes, pancytopenia, hepatosplenomegaly, and recurrent pneumonia that resulted in death. METHODS: Genetic analysis was done using next-generation sequencing. Protein expression and phosphorylation were determined by immunoblotting. T-cell proliferation and F-actin levels were studied by flow cytometry. RESULTS: The patient harbored 2 homozygous deletions in STX11 (c.369_370del, c.374_376del; p.V124fs60∗) previously associated with familial hemophagocytic lymphohistiocytosis and a novel homozygous missense variant in SLP76 (c.767C>T; p.T256I) that resulted in an approximately 85% decrease in SLP76 levels and absent T-cell proliferation. The patient's heterozygous family members showed an approximately 50% decrease in SLP76 levels but normal immune function. SLP76-deficient J14 Jurkat cells did not express SLP76 and had decreased extracellular signal-regulated kinase signaling, basal F-actin levels, and polymerization following T-cell receptor stimulation. Reconstitution of J14 cells with T256I mutant SLP76 resulted in low protein expression and abnormal extracellular signal-regulated kinase phosphorylation and F-actin polymerization after T-cell receptor activation compared with normal expression and J14 function when wild-type SLP76 was introduced. CONCLUSIONS: The hypomorphic mutation in SLP76 tones down the hyperinflammation due to STX11 deletion, resulting in a combined immunodeficiency that overshadows the hemophagocytic lymphohistiocytosis phenotype. To our knowledge, this study represents the first report of the opposing effects of 2 gene defects on the disease in a patient with an inborn error of immunity.

Antitumor Activity of Ferulic Acid Against Ehrlich Solid Carcinoma in Rats via Affecting Hypoxia, Oxidative Stress and Cell Proliferation.

Background Ferulic acid is a natural compound commonly found in fruits and vegetables like tomatoes, sweet corn, rice bran, and dong quai. It has various beneficial effects on the body, such as anti-inflammatory, anti-apoptotic, hepatoprotective, cardioprotective, and neuroprotective properties. Aims We conducted a study to investigate the antitumor activity of ferulic acid against Ehrlich solid carcinoma (ESC), specifically by affecting hypoxia-inducible factor (HIF)-1α and its subsequent effects on other factors like nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), cellular Myc (cMyc), cyclin D1, mammalian target of rapamycin (mTOR), and signal transducer and activator of transcription 3 (STAT3). Materials and methods The study involved implanting rats with ESC cells and administering 50 mg/kg of ferulic acid orally daily for eight days. Sections of the muscles with ESC were stained with toluidine blue or immunostained with anti-HIF-1α antibodies. The tumor samples were used to evaluate the expression of HIF-1α, Nrf2, HO-1, cMyc, cyclin D1, mTOR, and STAT3. Results Ferulic acid increased mean survival time, reduced tumor volume and weight, and improved the appearance of the tumor tissue. Furthermore, ferulic acid significantly elevated the expression of Nrf2 and HO-1, while reducing the expression of HIF-1α, Nrf2, HO-1, cMyc, cyclin D1, mTOR, and STAT3. Conclusions Ferulic acid can reduce tumor size and weight while improving the structure of muscle cells, suggesting it may have antineoplastic activity against ESC. Further investigation revealed that ferulic acid downregulates HIF-1α, increasing the expression of antioxidant proteins Nrf2 and HO-1. Additionally, ferulic acid decreases the expression of proliferation markers cMyc and cyclin D1 and downregulates cellular regulators mTOR and STAT3.

Biologic Therapies in Chronic Rhinosinusitis with Nasal Polyposis: Overview of Systematic Reviews and Updated Systematic Review.

Objectives: Chronic rhinosinusitis with nasal polyposis (CRSwNP) is a highly prevalent and challenging disease to manage. Several systematic reviews (SRs) have been carried out to evaluate the efficacy and safety of biologic therapies. We aimed to evaluate the current and available evidence of the biologics in treating CRSwNP. Data Source: Systematic Review of three electronic databases. Review Methods: Following the PRISMA Statement, the authors explored three main databases through February 2020 for pertinent SRs and meta-analyses (MAs) as well as experimental and observational studies. A Measurement Tool to Assess Systematic Reviews Version-2 (AMSTAR-2), was employed to evaluate the quality of methodology of SRs and MAs. Results: A Total of five SRs were included in this overview. The AMSTAR-2 final summary was moderate to critically low. Although conflicting findings were reported, anti-immunoglobulin E (Anti-IgE) and anti-interleukin-4 (Anti-IL-4) were superior to placebo for improving total nasal polyp (NP) score, particularly in patients with asthma. Findings of the included reviews revealed that both sinus opacification and the Lund-Mackay (LMK) total scores significantly improved after biologics use. Subjective quality-of-life (QoL) assessment provided by general and specific questionnaires illustrated favorable results of biologics for CRSwNP, whereas no significant adverse events were reported. Conclusion: The current findings support the use of biologics for CRSwNP patients. However, the evidence for their use in such patients should be cautiously adopted because of the questionable evidence. Supplementary Information: The online version contains supplementary material available at 10.1007/s12070-022-03144-8.

Dietary Chlorella vulgaris effectively alleviates oxidative stress, immunosuppression, and enhances the resistance to Streptococcus agalactiae infection in cadmium-intoxicated Nile tilapia fingerlings.

Aquatic pollutants, including cadmium (Cd), cause oxidative stress on aquatic animals. The use of probiotics, including microalgae as a feed additive to alleviate the toxic impacts of heavy metals, is a much more interesting point. Hence, the current study investigated the oxidative stress and immunosuppression in Nile tilapia (Oreochromis niloticus) fingerlings caused by Cd toxicity as well as the preventive function of dietary Chlorella vulgaris against Cd toxicity. Accordingly, fish were fed on 0.0 (control), 5, and 15 g/kg diet of Chlorella up to satiation thrice a day, along with being exposed to 0.0 or 2.5 mg Cd/L for 60 days. Following the experimental procedure, fish from each group were intraperitoneally injected with Streptococcus agalactiae, and their survivability was observed for further ten days. Chlorella-supplemented diets meaningfully (P < 0.05) boosted the antioxidative capability of fish, which was evidenced by higher activities of hepatic superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione-S-transferase (GST) as well as higher levels of reduced glutathione (GSH) along with significant reductions in hepatic malondialdehyde levels. Moreover, the innate immunity indices [phagocytic activity (PA), respiratory burst activity (RBA), and alternative complement activity (ACH50)] were significantly higher in Chlorella-fed fish, particularly in the group of 15 g/kg diet. Additionally, serum of Chlorella-fed fish showed potent bactericidal activities against S. agalactiae, particularly at the treatment of a 15 g/kg diet. Feeding Chlorella diets to Nile tilapia fingerlings upregulated SOD, CAT, and GPx genes expression alongside the down-regulation of IL-1ß, IL-8, IL-10, TNF-α, and HSP70 genes expression. Conversely, Cd toxicity caused oxidative stress and suppressed the fish's innate immunity with upregulation of the expression of IL-1ß, IL-8, IL-10, TNF-α, and HSP70 genes. Feeding Cd-exposed fish on Chlorella-containing diets attenuated these adverse effects. The current research revealed that supplementing feeds with the treatment of 15 g/kg diet of C. vulgaris supports the antioxidant-immune responses and alleviates the Cd toxicity effects on Nile tilapia fingerlings.

Knowledge, Attitude, and Practice Regarding Fibromyalgia Among Primary Care Physicians in Tabuk, Saudi Arabia.

BACKGROUND: Adequately informed family physicians have the greatest potential to correctly identify the diagnosis of fibromyalgia (FM) and develop an initial treatment plan. Therefore, it is substantial to determine the levels of weakness and inaccuracy among primary care physicians regarding FM diagnostic criteria and management strategies. AIM: This study aimed to assess the knowledge, attitude, and practices regarding FM among primary care physicians in Tabuk, Saudi Arabia. METHODS: This cross-sectional study included family physicians who were board-certified or registered in the family medicine training program and working at the government family healthcare centers in Tabuk. A pre-designed, structured questionnaire was distributed either in written form or as an online survey. RESULTS: This study included 52 primary healthcare physicians. Twenty-two (42.3%) participants incorrectly recorded localized pain as a diagnostic symptom, and 45 (86.5%) incorrectly recorded nonsteroidal anti-inflammatory drugs (NSAIDs), prednisolone, and/or opioids as drugs that are used for treating FM. Only 59.6% were confident in recognizing the symptoms of FM, and 55.8% were confident in differentiating FM from other similar diseases. CONCLUSIONS: The primary healthcare physicians working in the government's primary healthcare centers in Tabuk City, Saudi Arabia, have low levels of knowledge about diagnostic criteria and treatment strategies for FM. These findings highlight the need for continuous professional development involving family physicians in the primary healthcare setting with suitable continuous medical education (CME) programs concerning FM.

The IL-4Rα Q576R polymorphism is associated with increased severity of atopic dermatitis and exaggerates allergic skin inflammation in mice.

BACKGROUND: Atopic dermatitis (AD) is characterized by TH2-dominated skin inflammation and systemic response to cutaneously encountered antigens. The TH2 cytokines IL-4 and IL-13 play a critical role in the pathogenesis of AD. The Q576->R576 polymorphism in the IL-4 receptor alpha (IL-4Rα) chain common to IL-4 and IL-13 receptors alters IL-4 signaling and is associated with asthma severity. OBJECTIVE: We sought to investigate whether the IL-4Rα R576 polymorphism is associated with AD severity and exaggerates allergic skin inflammation in mice. METHODS: Nighttime itching interfering with sleep, Rajka-Langeland, and Eczema Area and Severity Index scores were used to assess AD severity. Allergic skin inflammation following epicutaneous sensitization of mice 1 or 2 IL-4Rα R576 alleles (QR and RR) and IL-4Rα Q576 (QQ) controls was assessed by flow cytometric analysis of cells and quantitative RT-PCR analysis of cytokines in skin. RESULTS: The frequency of nighttime itching in 190 asthmatic inner-city children with AD, as well as Rajka-Langeland and Eczema Area and Severity Index scores in 1116 White patients with AD enrolled in the Atopic Dermatitis Research Network, was higher in subjects with the IL-4Rα R576 polymorphism compared with those without, with statistical significance for the Rajka-Langeland score. Following epicutaneous sensitization of mice with ovalbumin or house dust mite, skin infiltration by CD4+ cells and eosinophils, cutaneous expression of Il4 and Il13, transepidermal water loss, antigen-specific IgE antibody levels, and IL-13 secretion by antigen-stimulated splenocytes were significantly higher in RR and QR mice compared with QQ controls. Bone marrow radiation chimeras demonstrated that both hematopoietic cells and stromal cells contribute to the mutants' exaggerated allergic skin inflammation. CONCLUSIONS: The IL-4Rα R576 polymorphism predisposes to more severe AD and increases allergic skin inflammation in mice.

Macrophages of the M1 and M2 types play a role in keloids pathogenesis.

The pathophysiology of keloid formation is unknown, however, macrophages are thought to play a role in keloid formation. Understanding the mechanism(s) of keloid development might be crucial in developing a new treatment regimen for keloids. The aim of this study was to understand possible status of M1 and M2 type macrophages in the pathogenesis of keloid. Thirty cases of Keloid tissues were selected according to our inclusion and exclusion criteria, as well as 30 normal scars, were enrolled in our study as a control group. An excisional biopsy was harvested and ELISA was done on keloid tissue and normal scar samples, with CD68, the surface marker for M1 and CD163 representing M2. The results revealed the low expression of M1 (CD68) in keloid tissue meanwhile high levels of M1 were detected in normal scars. We also detected that higher tissue expression of M2 (CD163) was significantly associated with keloid cases when compared to low M2 expression in the control group. An important finding that was discovered during our study is that the M1 and M2 are significant predictors of keloid. Every increase of 1 ng/mL in M1 decreases the risk of keloid by 0.99 while every increase of one unit in M2 increases the risk of keloid by 2.01. This study concluded that the keloid formation could be a result of an abnormal response to tissue injury where there is an excessive entry of inflammatory cells into the wound, including macrophages and that the keloid incidence might be related to a decrease in M1 and an increase in M2.

Knowledge, Attitude, and Practice of Colorectal Cancer Screening Among Primary Healthcare Physicians in Riyadh Second Health Cluster.

BACKGROUND: Colorectal cancer is the third common cancer, and the second common cause of cancer death in the world. According to the 2014 Cancer Incidence Report of the Kingdom of Saudi Arabia, colorectal cancer account for 11.5% from all cancers reported among Saudi nationals. By the year 2030, the incidence of colorectal cancer could increase fourfold among both genders. AIM: The study aimed to conduct to understand the knowledge, attitude, and practice of primary healthcare physicians regarding colorectal cancer screening in Riyadh Second Health Cluster in the city of Riyadh, Saudi Arabia. MATERIALS AND METHODS: A cross-sectional study design, probability proportional to size sampling at the cluster zones level and convenient sampling for the physicians, were used among physicians working in the primary healthcare centers in the city of Riyadh between October 2022 and November 2022. RESULT: Of the 213 respondents, the mean age of the physician was 35, the majority were males (59%), Saudi Arabian nationality (60%), Resident Physicians (54%) and ≤ five years' work experience (45%). Sixty-four percent of the study participants believe that the majority of asymptomatic average-risk patients have to start the screening at the age of 45 years old. Ninety-seven percent believe that colorectal cancer screening for asymptomatic average-risk patients aged 45 years and older is effective. Ninety-two percent of the physicians perform colorectal cancer screening for asymptomatic average-risk patients aged 45 years. The mean knowledge score is 4.65 (SD=2.33) with a range of 0 to 10. The mean attitude score is 4.19 (SD=1.28) with a range of 0 to 6. CONCLUSION: The study found that the physicians had higher attitude and practice towards colorectal cancer screening and adequate knowledge towards colorectal cancer screening. The knowledge and attitude scores are associated with practicing colorectal cancer screening.

CPHEN-016: Comprehensive phenotyping of human regulatory T cells.

Peripheral immunological tolerance is mainly maintained by regulatory T (Treg) cells, a specific CD4 T cells subset that expresses the transcription factor Foxp3. Treg cells are crucial to control autoimmunity and inflammation and to limit tissue destruction arising from inflammatory responses. Loss of functions mutations in FOXP3 in humans induces a fatal autoimmune lymphoproliferative disorder, known as Immune dysregulation, Polyendocrinopathy, Enteropathy, X-linked (IPEX). Specific Treg cell differentiation and activation states have been linked to several human diseases. Indeed, Treg cells play a crucial role in different diseases including colitis, multiple sclerosis, autoimmunity, and infection. Characterization of Treg cell functions and understanding the role of different Treg cell subsets are crucial to the development of novel Treg cell-specific therapeutics for inflammatory diseases. In this phenotype report, we will describe laboratory methods to effectively study and characterize human Treg cells.

A Stk4-Foxp3-NF-κB p65 transcriptional complex promotes Treg cell activation and homeostasis.

The molecular programs involved in regulatory T (Treg) cell activation and homeostasis remain incompletely understood. Here, we show that T cell receptor (TCR) signaling in Treg cells induces the nuclear translocation of serine/threonine kinase 4 (Stk4), leading to the formation of an Stk4-NF-κB p65-Foxp3 complex that regulates Foxp3- and p65-dependent transcriptional programs. This complex was stabilized by Stk4-dependent phosphorylation of Foxp3 on serine-418. Stk4 deficiency in Treg cells, either alone or in combination with its homolog Stk3, precipitated a fatal autoimmune lymphoproliferative disease in mice characterized by decreased Treg cell p65 expression and nuclear translocation, impaired NF-κB p65-Foxp3 complex formation, and defective Treg cell activation. In an adoptive immunotherapy model, overexpression of p65 or the phosphomimetic Foxp3S418E in Stk3/4-deficient Treg cells ameliorated their immune regulatory defects. Our studies identify Stk4 as an essential TCR-responsive regulator of p65-Foxp3-dependent transcription that promotes Treg cell-mediated immune tolerance.