SGLT-2 inhibitors enhance the effect of metformin to ameliorate hormonal changes and inflammatory markers in a rat PCOS model.

Polycystic ovary syndrome (PCOS) is a common endocrine, reproductive, and metabolic disorder affecting females. The management of PCOS is challenging and current interventions are not enough to deal with all consequences of this syndrome. We explored the beneficial effect of combined sodium glucose co transporter-2 inhibitor (SGLT-2i); (empagliflozin) and metformin on hormonal and metabolic parameters in an animal model of PCOS and insulin resistance (IR). Forty adult female Wistar rats divided into five groups: control, PCOS-IR, PCOS-IR treated with metformin, PCOS-IR treated with empagliflozin, and PCOS-IR treated with combined metformin and empagliflozin. Single modality treatment with metformin or empagliflozin yielded significant improvement in body mass index, insulin resistance, lipid profile, sex hormones, inflammatory markers, and ovarian cystic follicles. Combined metformin with empagliflozin expressed further significant improvement in sex hormones, inflammatory markers with disappearance of ovarian cystic follicles. The superior significant improvement with combined treatment over the single modality was in line with significant improvement in the ovarian AMPKα-SIRT1 expression.

Severe Headache in Primary Sjögren's Syndrome Responded to Rituximab.

Introduction: Primary Sjögren syndrome (pSS) is an immune systemic disease, that may affect the central nervous system. A severe headache unresponsive to treatment is the headache which is persistently nonresponsive to narcotic analgesics. Case presentation: A 48-year-old woman with a 10-year history of pSS was seen in January 2021, complaining of a headache one week previously. The headache was characterised by a dull persistent pressing intensity and was not responding to paracetamol, NSAIDs or codeine. She had no previous history, nor family history. Physical examination revealed bilateral parotid glands enlargement. Laboratory tests showed anaemia, and elevated levels of erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), with positive anti-La and anti-Ro antibodies. She was given topical treatment and different doses of Predlone, in addition to methotrexate10 mg/week. She had received three pulses of methylprednisolone and was started on azathioprine with a mild response to the headaches, so she received two initial IV doses of rituximab 375 mg/m2, then every 2 weeks, with a clinical and laboratory response. Two years later, she had no headache. Discussion: Headache that may presented in pSS are tension headaches, migraines and cluster headaches. The therapy is disease-modifying antirheumatic drugs, hydroxychloroquine, glucocorticoids and biotherapeutics. Rituximab is used in the treatment of some patients with pSS, especially where it can affect systemic symptoms. Conclusion: Rituximab treatment may be an option for severe headache in patients with pSS. The mechanism is unknown but may be due to depletion of brain auto-reactive B cells. Further research is needed. LEARNING POINTS: An unresponsive headache in a patient with primary Sjögren's syndrome treated with tryptophan, opioids and NSAIDs responded successfully to B-cell depletion with rituximab.We hypothesise that brain-autoreactive B cells were involved in the pathogenesis of the headache.

Evaluation of the Cariogenic and Anti-Cariogenic Potential of Human Colostrum and Colostrum-Derived Probiotics: Impact on S. mutans Growth, Biofilm Formation, and L. rhamnosus Growth.

Human colostrum (HC) is essential for oral health as it is rich in probiotics that could affect the growth of the cariogenic S. mutans and its biofilm formation; hindering dental caries in advance. In this study, HC was collected from 36 healthy mothers 1-3 days postpartum. The effect of HC on oral health was carried out by assessing the impact of HC and its derived probiotics' cell-free supernatants (CFS) on the growth of S. mutans (using modified well diffusion) and its biofilm formation (using microtiter plate assay). Moreover, the effect of whole HC on L. rhamnosus, a probiotic oral bacterium, was examined. Probiotics were isolated and identified phenotypically by API 50 CH carbohydrate fermentation and genotypically by 16S rRNA amplification. The in vitro study revealed that HC has cariogenic activity and is associated with biofilm formation. Biofilm strength was inversely proportional to HC dilution (p-value < 0.0001). Nevertheless, HC and colostrum-derived probiotics improve oral health by inhibiting the growth of caries-inducing S. mutans with lower inhibition to L. rhamnosus probiotics. The CFS of isolated probiotics reduced the biofilm formation via the cariogenic S. mutans. These results are not only promising for caries eradication, but they also highlight the importance of breastfeeding infants from their first hours to shape healthy oral microbiota, protecting them from various diseases including dental caries.

Genital Ulcers Associated with Systemic Lupus Erythematosus - What are the Possible Causes? A Case Report.

Systemic lupus erythematosus (SLE) is a chronic systemic autoimmune disease that affects many organs. In this report, we discuss the case of a patient with SLE who presented to an out-hospital clinic, complaining of fever and pain with genital ulcers. Negative evaluations for other causes of genital ulcers, indicated these ulcers as related to SLE. This case highlights the importance of including SLE ulcers in the differential diagnosis of genital ulcers. LEARNING POINTS: Determining the cause of genital ulceration is a clinical challenge, especially in sexually active individuals.Genital ulcers associated with SLE are often underdiagnosed. Any patient with a history of SLE presenting with genital discomfort and/or pain must be evaluated for genital ulcers without delay.

Systemic sclerosis associated with primary sclerosing cholangitis and hyperthyroidism: a case report.

The association between systemic sclerosis and other immune-mediated diseases such as primary sclerosing cholangitis and hyperthyroidism should be suspected in case the patient presents with similar symptoms. A 43-year-old woman presented to the hospital with progressive jaundice, dark urine, dyspnoea, fatigue, generalized arthralgia, weight loss, and amenorrhoea. In addition, she was diagnosed with systemic sclerosis seven years ago. The patient was diagnosed recently with primary sclerosing cholangitis and hyperthyroidism through laboratory tests and investigations such as magnetic resonance cholangiopancreatography, ultrasound, and computed tomography scan. After appropriate treatment and follow-up, the patient recovered well. Immune-mediated diseases can occur simultaneously or consequently due to the common immunological dysfunction that causes these conditions.

An Unforeseen Outcome of COVID-19: The Triggering of Adult-Onset Still's Disease.

Background: Adult-onset Still's disease (AOSD) is a rare auto-inflammatory disorder with unknown etiology by which an infectious trigger is usually responsible for the onset of the disease. It is diagnosed by exclusion when certain clinical, biochemical, and radiological criteria are met after excluding all other potential causes. Besides, SARS­CoV­2 infection is increasingly being reported to have autoimmune complications. In the literature, 3 AOSD cases have been reported to be triggered by SARS­CoV­2 infection and here we report the fourth. Case presentation: A 24-year-old female doctor suffered from fever, sore throat, and mild cough a few days after a shift in the COVID-19 ward. A week later, she developed polyarthritis, salmon-colored rash, and high-grade fever, and the laboratory findings were indicating an inflammatory syndrome. COVID-19 IgM antibodies were positive indicating recent infection. After running a battery of tests, infectious, neoplastic, and rheumatic causes of these symptoms that persisted for about 50 days were excluded which led to a diagnosis of AOSD after fulfilling its criteria with subsequent treatment with methylprednisolone. Drastic improvement was achieved with no recurrence until the date of reporting. Conclusion: This case presents a new consequence of COVID-19 and adds to the emerging cumulative experiences with this disease. We encourage health care professionals to report such cases to further understand the nature of this infection and its possible outcomes.

Evaluation of the Efficacy of Minimal Invasive Methods Versus Conventional Methods for Caries Removal in Primary Molars.

AIM: Evaluating the efficacy of two "minimal invasive methods" of caries removal (Brix 3000/ceramic bur) in comparison with the conventional method in the management of dental caries in primary molars.  Materials and methods: A sum of 60 teeth from children ranging from four to nine years old of both sexes were selected for this study and randomly assigned to three groups: Group I (Brix 3000), Group II (ceramic bur), and Group III (diamond bur), with 20 teeth per group. RESULTS: Regarding the efficacy of caries removal, the Brix 3000 group had significantly the lowest efficacy, while the ceramic bur and diamond bur groups were significantly the highest without significant differences between the ceramic and diamond groups. Regarding caries removal time, the Brix 3000 group was significantly the highest, while the diamond bur group was significantly the lowest, and the ceramic bur group was intermediate between them. Regarding pain perception, the Brix 3000 and ceramic bur groups were significantly the lowest, with insignificant differences between them, while the diamond bur group was significantly the highest. CONCLUSION: Ceramic bur is an excellent alternative treatment for caries removal in children in comparison with conventional methods and CMCR. Brix 3000®, despite being less painful in comparison with drilling methods, has lower efficacy and efficiency.

Rheumatologists' knowledge and perception of COVID-19 and related vaccines: the vaXurvey2 online survey.

The study aimed to explore the experience of coronavirus disease-2019 (COVID-19) infection and vaccine adverse events (AEs) among rheumatologists. A validated questionnaire was distributed as a Google form to rheumatologists across the country via social networking sites from late December 2021 till early January 2022. The questionnaire included questions regarding participants' socio-demographic details, COVID-19 infection and vaccination details with special emphasis on AEs. Out of 246 responses, 228 were valid. 200 (81.3%) responders had received the vaccine. The mean age of the 228 participants was 37.9 ± 8.5 years, 196 were females and 32 males (F:M 6.1:1) from 18 governorates across the country. Comorbidities were present in 54 subjects (27%). There was a history of highly suspicious or confirmed COVID-19 infection in 66.7% that were all managed at home. The COVID-19 vaccine was received by 200 and a booster dose of 18.5%. Obesity and musculoskeletal involvement co-morbidities were present only in those with AEs (9.1% and 5.5% respectively). AEs were present in 82%; 66.7% had injection-site tenderness, 50% fatigue, 35.5% fever, 15% chills, 42.5% myalgia, 14.5% arthralgia, 8% low back pain, headache 31%, dizziness 10%, sleepliness 16% and 15% developed post-vaccine. There were no differences according to the geolocation regarding the occurrence of COVID-19 infection (p = 0.19) or AEs post-vaccine (p = 0.58). The adverse events were mostly mild to moderate and tolerable which makes this work in agreement with other studies that support the broad safety of the vaccine in favor of the global benefit from mass vaccination.

Insights from ancient DNA analysis of Egyptian human mummies: clues to disease and kinship.

The molecular Egyptology field started in the mid-eighties with the first publication on the ancient DNA (aDNA) analysis of an Egyptian mummy. Egypt has been a major interest for historians, archeologists, laymen as well as scientists. The aDNA research on Egyptian biological remains has been fueled by their abundance and relatively well-preserved states through artificial mummification and by the advanced analytical techniques. Early doubts of aDNA integrity within the Egyptian mummies and data authenticity were later abated with studies proving successfully authenticated aDNA retrieval. The current review tries to recapitulate the published studies presenting paleogenomic evidence of disease diagnosis and kinship establishment for the Egyptian human remains. Regarding disease diagnosis, the prevailing literature was on paleogenomic evidence of infectious diseases in the human remains. A series of reports presented evidence for the presence of tuberculosis and/or malaria. In addition, there were solitary reports of the presence of leprosy, diphtheria, bacteremia, toxoplasmosis, schistosomiasis and leishmaniasis. On the contrary, paleogenomic evidence of the presence of rare diseases was quite scarce and mentioned only in two articles. On the other hand, kinship analysis of Egyptian human remains, including that of Tutankhamen, was done using both mitochondrial DNA sequences and nuclear DNA markers, to establish family relationships in four studies. It is clear that the field of molecular Egyptology is still a largely unexplored territory. Nevertheless, the paleogenomic investigation of Egyptian remains could make significant contributions to biomedical sciences (e.g. elucidation of coevolution of human host-microbe interrelationship) as well as to evidence-based archeology.

YOLO Based Breast Masses Detection and Classification in Full-Field Digital Mammograms.

BACKGROUND AND OBJECTIVE: With the recent development in deep learning since 2012, the use of Convolutional Neural Networks (CNNs) in bioinformatics, especially medical imaging, achieved tremendous success. Besides that, breast masses detection and classifications in mammograms and their pathology classification are considered a critical challenge. Till now, the evaluation process of the screening mammograms is held by human readers which is considered very monotonous, tiring, lengthy, costly, and significantly prone to errors. METHODS: We propose an end to end computer-aided diagnosis system based on You Only Look Once (YOLO). The proposed system first preprocesses the mammograms from their DICOM format to images without losing data. Then, it detects masses in full-field digital mammograms and distinguishes between the malignant and benign lesions without any human intervention. YOLO has three different architectures, and, in this paper, the three versions are used for mass detection and classification in the mammograms to compare their performance. The use of anchors in YOLO-V3 on the original form of data and its augmented version is proved to improve the detection accuracy especially when the k-means clustering is applied to generate anchors corresponding to the used dataset. Finally, ResNet and Inception are used as feature extractors to compare their classification performance against YOLO. RESULTS: Mammograms with different resolutions are used and based on YOLO-V3, the best results are obtained through detecting 89.4% of the masses in the INbreast mammograms with an average precision of 94.2% and 84.6% for classifying the masses as benign and malignant respectively. YOLO's classification network is replaced with ResNet and InceptionV3 to get overall accuracy of 91.0% and 95.5%, respectively. CONCLUSION: The proposed system showed using the experimental results the YOLO impact on the breast masses detection and classification. Especially using the anchor boxes concept in YOLO-V3 that are generated by applying k-means clustering on the dataset, we can detect most of the challenging cases of masses and classify them correctly. Also, by augmenting the dataset using different approaches and comparing with other recent YOLO based studies, it is found that augmenting the training set only is the fairest and accurate to be applied in the realistic scenarios.

Vitamin D deficiency and glycemic control among patients with type 2 diabetes mellitus in Jazan City, Saudi Arabia.

Background: The prevalence of vitamin D deficiency (VDD) is predicted to be high in patients with type 2 diabetes mellitus (T2DM), but the exact figure is not known in Jazan, Saudi Arabia. Emerging data suggests that VDD plays a role in glycemic control. The aim of this study was to measure the prevalence of VDD among T2DM patients and to investigate its association with patients' characteristics and glycemic control in Jazan. Methods: This is an analytical cross-sectional study which recruited 309 patients with T2DM randomly from primary health care centers in Jazan. Logistic regression analysis was conducted to determine the VDD predictors and to examine the association of VDD and glycemic control. Results: The VDD prevalence was found to be 60.8% in patients with T2DM. Age, gender, diabetic retinopathy (DR), dyslipidemia, glycemic control, and obesity were significantly associated with VDD, and all except obesity were independent predictors of VDD. There was a significant negative correlation between 25-hydroxyvitamin D and HbA1c. VDD was a significant independent predictor of poor glycemic control after adjustment for hypertension, DR, diabetic neuropathy, type of diabetes medication, diabetes duration, and education level. Conclusion: In this Saudi Arabian population, VDD is highly prevalent in people with T2DM and is associated with poor glycemic control. Health education targeting patients with T2DM and national strategies regarding vitamin D fortification are needed to prevent VDD in Saudi Arabia. Earlier VDD diagnosis by health care providers may help to improve the outcome for patients with T2DM. Establishing the causal association between VDD and glycemic control and clarifying the biological role of vitamin D in T2DM are important aims for future studies.

Toll-like receptor 9 in systemic sclerosis patients: relation to modified Rodnan skin score, disease severity, and functional status.

The objective of this study is to assess toll-like receptor-9 (TLR9) expression in CD3-positive T lymphocytes and CD19-positive B lymphocytes in systemic sclerosis (SSc) patients and to study their relation to the extent of skin fibrosis, disease characteristics, and severity as well as the functional status. Fifty-five female SSc patients and 30 matched controls were included. Skin thickness was scored according to the modified Rodnan skin score (mRss). The severity of major organ involvement was assessed using the Medsger severity score (MSS). Scleroderma health assessment questionnaire (SHAQ) was measured to evaluate patients' functional status. Expression of TLR9 in CD3-positive T lymphocytes and CD19-positive B lymphocytes was studied using flow cytometry. The mean age of the patients was 40.5 ± 9.1 years, and their disease duration was 6.7 ± 3.3 years. There were 21 (38.2%) with diffuse (dcSSc) and 34 (61.8%) with limited cutaneous (lcSSc) subtypes. There was a significant increase in the expression of TLR9/CD3 and TLR9/CD19 in the SSc patients (44.9 ± 18.1 and 24.1 ± 9.6) compared to that in the control (1.4 ± 0.97 and 1.3 ± 0.94; p < 0.0001 for both, respectively) being higher in those with dcSSc. TLR9/CD3 expression was significantly increased in SSc patients with arthralgia/arthritis and digital resorption compared to those without. The TLR9/CD3 significantly correlated with the mRss and MSS (r = 0.37, p = 0.006 and r = 0.31, p = 0.02; respectively). Both the TLR9/CD3 and TLR9/CD19 expressions were significantly correlating (r = 0.53, p < 0.0001). On regression analysis, only TLR9/CD3 was a significant risk factor of the mRss and MSS (ß = 0.43, p = 0.009 and ß = 0.33, p = 0.015, respectively). TLR9, especially TLR9/CD3, is highly expressed in SSc patients particularly those with dcSSc subtype and could form a potential marker for skin fibrosis and disease severity.

Methylene tetrahydrofolate reductase, transforming growth factor-ß1 and lymphotoxin-α genes polymorphisms and susceptibility to rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis is a widely prevalent autoimmune disorder with suggested genetic predisposition. OBJECTIVES: The aim of this study is to detect the pattern of genetic polymorphism of methylene tetrahydrofolate reductase (MTHFR C677 T and A1298 C), transforming growth factor-ß1 (TGF-ß1 T869 C) and lymphotoxin-α (LT-α A252G) in patients having rheumatoid arthritis and correlate these patterns to disease activity and serum levels of tumor necrosis factor-alpha (TNF-α), B-Cell Activating Factor (BAFF), and osteopontin. METHODS: A total of 194 subjects, 90 controls and 104 patients with rheumatoid arthritis were genotyped for MTHFR C677 T and A1298 C, TGF-ß1 T869 C and LT-α A252G polymorphisms using a methodology based on PCR-RFLP. Also serum levels of TNF-α, osteopontin and BAFF were measured by ELISA kits. RESULTS: The CT genotype and T allele of MTHFR C677 T and GG genotype and G allele of LT-α A252G are associated with the risk of RA and with higher levels of the pro-inflammatory cytokine, TNF-α in patients with rheumatoid arthritis. CONCLUSION: Our findings suggest that there is association between MTHFR C677 T and LT-α A252G genes polymorphisms and increased risk of RA in this sample of Egyptian population.

Methylene tetrahydrofolate reductase, transforming growth factor-ß1 and lymphotoxin-α genes polymorphisms and susceptibility to rheumatoid arthritis / Polimorfismos dos genes metilenotetrahidrofolato redutase, fator de crescimento transformador β1 e linfotoxina-α e susceptibilidade à artrite reumatoide

ABSTRACT Background: Rheumatoid arthritis is a widely prevalent autoimmune disorder with suggested genetic predisposition. Objectives: The aim of this study is to detect the pattern of genetic polymorphism of methylene tetrahydrofolate reductase (MTHFR C677 T and A1298 C), transforming growth factor-β1 (TGF-β1 T869 C) and lymphotoxin-α (LT-α A252G) in patients having rheumatoid arthritis and correlate these patterns to disease activity and serum levels of tumor necrosis factor-alpha (TNF-α), B-Cell Activating Factor (BAFF), and osteopontin. Methods: A total of 194 subjects, 90 controls and 104 patients with rheumatoid arthritis were genotyped for MTHFR C677 T and A1298 C, TGF-β1 T869 C and LT-α A252G polymorphisms using a methodology based on PCR-RFLP. Also serum levels of TNF-α, osteopontin and BAFF were measured by ELISA kits. Results: The CT genotype and T allele of MTHFR C677 T and GG genotype and G allele of LT-α A252G are associated with the risk of RA and with higher levels of the pro-inflammatory cytokine, TNF-α in patients with rheumatoid arthritis. Conclusion: Our findings suggest that there is association between MTHFR C677 T and LT-α A252G genes polymorphisms and increased risk of RA in this sample of Egyptian population.

RESUMO Antecedentes: A artrite reumatoide é uma doença autoimune amplamente prevalente com sugerida predisposição genética. Objetivos: Detectar o padrão de polimorfismo dos genes metilenotetrahidrofolato redutase (MTHFR C677 T e A1298 C), fator de crescimento transformador β1 (TGF-β1 T869 C) e linfotoxina-α (LT-α A252G) em pacientes com artrite reumatoide e correlacionar esses padrões com a atividade da doença e os níveis séricos de fator de necrose tumoral alfa (TNF-α), fator ativador de linfócitos B (BAFF) e osteopontina. Métodos: Foram genotipados 194 indivíduos – 90 controles e 104 com artrite reumatoide – à procura de polimorfismos dos genes MTHFR C677 T e A1298 C, TGF-β1 T869 C e LT-α A252G com uma metodologia baseada na PCR-RFLP. Mensuraram-se também os níveis séricos de TNF-α, osteopontina e BAFF com kits de Elisa. Resultados: O genótipo CT e o alelo T do MTHFR C677 T e o genótipo GG e alelo G do LT-α A252G estão associados ao risco de AR e a níveis mais elevados da citocina pró-inflamatória TNF-α em pacientes com artrite reumatoide. Conclusão Os achados do presente estudo sugerem que há associação entre os polimorfismos dos genes MTHFR C677 T e LT-α A252G e um risco aumentado de AR nessa amostra da população egípcia.

Vitamin D status in rheumatoid arthritis patients: relation to clinical manifestations, disease activity, quality of life and fibromyalgia syndrome.

AIM: To assess vitamin D levels in rheumatoid arthritis (RA) patients and to find their relation to clinical parameters, fibromyalgia syndrome (FMS), quality of life (QoL) and disease activity. METHODS: The study included 63 RA patients and 62 controls. Clinical examination and laboratory investigations were performed. For patients, the Disease Activity Score (DAS-28), QoL index, Health Assessment Questionnaire II (HAQ II) and Modified Larsen score were calculated. 25-OH-vitamin D was measured in patients and controls. RESULTS: The patients' mean age was 41.59 ± 9.69 years and disease duration 5.89 ± 3.67 years. The level of vitamin D in RA patients was significantly lower (23.11 ± 12.71 ng/mL) than that in the controls (32.59 ± 13.06 ng/mL) (P = 0.005) being deficient in 50.8%, insufficient in 23.8% and normal in 25.4%. The RA patients with FMS (n = 33) had significantly lower levels of vitamin D (19.08 ± 10.59 ng/mL) than those without (27.55 ± 13.51 ng/mL) (P = 0.008). The difference was significant on comparing those receiving hydroxychloroquine (17.39 ± 7.84 ng/mL) to those not (31.85 ± 13.85 ng/mL) (P < 0.001). Vitamin D significantly correlated with QoL index (r = 0.58, P < 0.001) and negatively with HAQ II (r = -0.36, P = 0.004) and BMI (r = -0.39, P = 0.001). CONCLUSION: Special attention is required regarding vitamin D levels in RA patients with FMS and decreased QoL. Vitamin D should be corrected and supplementation considered among the RA management armamentarium.

Musculoskeletal manifestations in patients with malignant disease.

To detect and describe the incidence of musculoskeletal manifestations in different malignant diseases as well as their relation to the treatment received whether by chemotherapy or radiation therapy. Sixty patients with different malignant diseases were included in this study, 45 with solid tumors and 15 patients with hematological malignancy. The mean age was 46.55 +/- 11.04 years and the mean disease duration was 2 +/- 0.75 years. The patients were fully examined for any rheumatologic involvement, laboratory investigations were performed as well as dual energy X-ray absorptiometry study for bone densitometry. Treatment strategies were assessed including the chemotherapeutics, radiation therapy, and/or surgery. Myalgias and arthralgias were the most frequent followed by flexor tenosynovitis, frozen shoulder, and fibromyalgia syndrome. Hypertrophic osteoarthropathy was seen in five patients, cutaneous vasculitis in two patients as well as arthritis. Osteonecrosis was present in one of the lunate carpal bones of a patient with non-Hodgkin's lymphoma (1.67%) and receiving high dose steroids. Rheumatoid factor was positive in four patients, three of which had hepatitis C virus positivity and cryoglobulins. Anti-neutrophil cytoplasmic antibody was negative in all the studied patients. The bone mineral density was significantly reduced in the patients with malignancy compared to the control. Mild to moderate osteoporosis was present, being more evident in the spine and forearm. The bone loss was higher in those with solid tumors and even more obvious in those receiving aromatase inhibitors. Musculoskeletal manifestations occurring during malignancies and following the treatment represent a significant percentage of symptoms and signs which may raise a clue to differential diagnosis.