Tadalafil versus pentoxifylline in the management of diabetic kidney disease: a randomized clinical trial.

AIMS: To investigate the efficacy and safety of tadalafil (TAD) versus pentoxifylline (PTX) in the management of diabetic kidney disease (DKD). Some animal studies and clinical trials reported that tadalafil and pentoxifylline have a reducing effect on different blood glucose parameters and lipid profiles which contribute to progress the patients with diabetes mellitus (DM) to DKD. METHODS: From February 2022 to March 2023, 90 patients with type 2 DM and DKD (micro-albuminuria) were enrolled in this randomized-controlled study. The patients were randomized into three equal groups: control group, TAD group, and PTX group. The three groups received traditional blood glucose lowering therapy + ramipril 10 mg PO. The TAD group also received tadalafil 20 mg PO every other day. The PTX group also received pentoxifylline 400 mg PO twice daily. RESULTS: Both TAD and PTX groups produced statistically significant improvement in the primary outcomes by a significant reduction in Urinary albumin/creatinine ratio (UACR) which was pronounced by a reduction percentage of-47.47%, -53.73% respectively. In addition to a significant decrease in Hemoglobin A1C (HbA1c) (mmol/mol), Fasting blood glucose (FBG), 2-h postprandial blood glucose (2-h PPG) (p < 0.001). Only the PTX group showed a significant increase in Cr Cl and a significant decrease in S. Cr (p < 0.001). Only the TAD group showed a significant increase in high-density lipoprotein-cholesterol (HDL-C) (p < 0.001), while the PTX group showed a significant decrease in low-density lipoprotein-cholesterol (LDL-C) (p-value 0.011), and triglyceride (p-value 0.002). Both TAD and PTX groups showed a decrease in tumor necrosis factor-α (TNF-α) which was significant only in the PTX group (p < 0.001). There was a significant increase in malondialdehyde (MDA) (p < 0.001), and an increase in urinary neutrophil gelatinase-associated Lipocalin (uNGAL) (p-value 0.850, 0.014 respectively) which was significant only in the PTX group. CONCLUSIONS: The use of tadalafil or pentoxifylline may serve as an effective adjuvant therapy for patients with diabetic kidney disease. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT05487755, July 25, 2022.

The Effect of Intra-socket Vitamin E Application on the Reduction in Postoperative Pain and Reduction in Incidence of Dry Socket in Female Patients: A Randomized Controlled Trial.

Introduction: Blum defined dry socket as the presence of postoperative pain in and around the extraction site that worsens 1-3 days after the extraction. Methods: 90 female patients seeking extraction of a single tooth in the lower posterior region were divided randomly into 45 patients who received vitamin E inside the socket after extraction (study group) and 45 patients who did not receive vitamin E after extraction (control group). Results: After 3 days, there was a decrease in pain levels in the study group compared to the control group. Only 7 patients out of 45 (16%) suffered from pain compared to 17 patients out of 45 (38%) in the control group. So, the improvement in pain was statistically significant P = 0.02. After 7 days, there was a decrease in wound healing levels in the study group compared to the control group. Only 8 patients out of 45 (17%) had poor wound healing compared to 7 patients out of 45 (16%) in the control group. However, the improvement in wound healing was not statistically significant P = 0.8. Conclusion: Based on the current results, we recommend the use of vitamin E as topical intra-socket medication in reducing the early postoperative pain.

Significant Promising Effects of Bariatric Surgery on the Biochemical Control of Glycemia and Lipidemia in Diabetic Patients in Western Saudi Arabia: A Tertiary Center Experience and a Retrospective Study.

BACKGROUND: The prevalence of obesity has increased globally and is associated with many comorbidities such as type 2 diabetes and fatty liver and cardiovascular diseases. Bariatric surgery is considered an effective intervention for achieving weight loss and controlling lipidemia and glycemia. OBJECTIVES: This Saudi retrospective observational study evaluates the clinical and biochemical benefits following bariatric surgery to obese diabetic patients.  Methodology: After gaining ethical committee approval, data was collected from the patients' medical records at a tertiary medical center (King Fahad General Hospital, Al-Madinah Al-Munawwarah, Saudi Arabia). The total sample size was 61 patients, of whom 78.33% (n=48) had a body mass index (BMI) of 40 or greater (obese class III). RESULTS: Following bariatric surgery, there were statistically significant reductions (p<0.001) in BMI and HbA1C (decreased from 45.53±7.791 kg/m2 and 7.9±1.82% to 33.42±6.18 kg/m2 and 6.06±1.35%, respectively, after surgery). Likewise, significant reductions (p<0.001) occurred to serum total cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides that decreased from 234.4±26.7 mg/dl, 152.2±19.4 mg/dl, and 187.3±24.6 mg/dl to 158.4±17.3 mg/dl, 95.6±15.7 mg/dl, and 132.5±19.5 mg/dl, respectively. Interestingly, serum high-density lipoprotein (HDL) significantly increased (p<0.001) from 43.8±6.2 mg/dl to 52.3±4.6 mg/dl. Using the novel clinical therapeutic index, bariatric surgery decreased BMI by about 26.6%. Using the novel biochemical therapeutic index, bariatric surgery decreased HbA1C, serum total cholesterol, serum LDL cholesterol, and serum triglycerides by about 22.99%, 32.42%, 37.18%, and 29.26%, respectively, while serum HDL increased by about 19.4%. CONCLUSION: Bariatric surgery is an effective intervention for obese diabetic patients resulting in weight loss, better control of diabetes and hyperlipidemia, and the metabolic profile. It is also recommended in Saudi Arabia for the high prevalence of obesity and diabetes mellitus.

Bacterial Proteins and Peptides as Potential Anticancer Agents: A Novel Search for Protein-based Therapeutics.

Tumor diseases remain among the world's primary causes of death despite substantial advances in cancer diagnosis and treatment. The adverse chemotherapy problems and sensitivity towards drugs for some cancer types are among the most promising challenges in modern treatment. Finding new anti-cancer agents and drugs is, therefore, essential. A significant class of biologically active substances and prospective medications against cancer is comprised of bacterial proteins and peptides. Among these bacterial peptides, some of them, such as anti-cancer antibiotics and many toxins like diphtheria are widely being used in the treatment of cancer. In contrast, the remaining bacterial peptides are either in clinical trials or under research in vitro studies. This study includes the most recent information on the characteristics and mechanism of action of the bacterial peptides that have anti-cancer activities, some of which are now being employed in cancer therapy while some are still undergoing research.

Unraveling IL-17 and IL-22 role in occult hepatitis C versus chronic hepatitis C virus infection.

BACKGROUND: Cytokines play a crucial role in regulating the function of the immune system by controlling the production, differentiation, and activity of immune cells. Occult hepatitis C virus (OHCV) infection can lead to liver damage, including cirrhosis and hepatocellular carcinoma. This study investigates the immunopathogenic impact of the cytokines IL-17 and IL-22 in OHCV infection compared to chronic hepatitis C (CHC) infection. METHODS: We studied three groups of patients: 35 with OHCV, 100 untreated patients with CHC, and 30 healthy control subjects. All subjects underwent physical examination and biochemical testing. We used the sandwich enzyme-linked immunosorbent assay method to measure serum IL-17 and IL-22 levels in all groups. RESULTS: Compared to the occult and control groups, the CHC group had significantly higher serum IL-17 levels (p < 0.001). The occult group also had higher serum IL-17 levels compared to the control group (p < 0.0001). There were no significant differences in IL-22 levels across the research groups. In the OHCV group, individuals with moderate inflammation (A2-A3) had significantly higher serum IL-17 levels than those with minimal inflammation (A0-A1), while in the CHC group, this difference was not statistically significant (p = 0.601). Neither the occult nor the CHC groups showed a correlation between serum IL-22 and inflammatory activity. There was no significant correlation between the levels of IL-17 or IL-22 and the stage of fibrosis/cirrhosis in either group. ROC curves were calculated for serum IL-17 and IL-22 levels and occult HCV infection, with cut-off values set at ≤ 32.1 pg/ml and < 14.3 pg/ml for IL-17 and IL-22, respectively. The AUROC (95%CI) was significantly higher for IL-17 than IL-22 (0.829 (0.732-0.902) vs. 0.504 (0.393-0.614), p < 0.001), suggesting that IL-17 has a stronger correlation with infection risk than IL-22. CONCLUSION: This study suggests that IL-17 may be involved in the immunopathogenesis of OHCV infection, especially in patients with moderate inflammation.

Cold atmospheric plasma induces the curing mechanism of diabetic wounds by regulating the oxidative stress mediators iNOS and NO, the pyroptotic mediators NLRP-3, Caspase-1 and IL-1ß and the angiogenesis mediators VEGF and Ang-1.

It has been demonstrated that cold atmospheric plasma (CAP) accelerates the wound healing process, however the underlying molecular pathways behind this effect remain unclear. Thus, the goal of the proposed investigation is to elucidate the therapeutic advantages of CAP on angiogenesis, pyroptotic, oxidative stress, and inflammatory mediators during the wound-healing mechanisms associated with diabetes. Intraperitoneal administration of streptozotocin (STZ, 60 mg/Kg) of body weight was used to induce type-1 diabetes. Seventy-five male mice were randomized into 3 groups: the control non-diabetic group, the diabetic group that was not treated, and the diabetic group that was treated with CAP. The key mediators of pyroptosis and its impact on the slow healing process of diabetic wounds were examined using histological investigations employing H&E staining, immunohistochemistry, ELISA, and Western blotting analysis. Angiogenesis proteins (VEGF, Ang-1, and HO-1) showed a significant decline in expression concentrations in the diabetic wounds, indicating that diabetic animals' wounds were less likely to heal. Furthermore, compared to the controls, the major mediators of pyroptosis (NLRP-3, IL-1ß, and caspase-1), oxidative stress (iNOS and NO), and inflammation (TNF-α and IL-6) have higher expression levels in the diabetic wounds. These factors substantially impede the healing mechanism of diabetic wounds. Interestingly, our results disclosed the therapeutic impacts of CAP treatment in the healing process of diabetic wounds via significantly regulating the expression levels of angiogenesis, pyroptosis, oxidative stress and pro-inflammatory mediators. Our findings demonstrated the curative likelihood of CAP and the underlying mechanisms for enhancing the healing process of diabetic wounds.

Therapeutic benefits of prophetic medicine remedies in treating hematological diseases (A review article).

Hematological disorders are common medical ailments constituting an important cause of morbidity and mortality worldwide, which may be managed efficiently using different prophetic medicine remedies as adjuvants to current therapeutics. Prophetic medicine includes the body of knowledge about medicine that has been derived from the deeds, customs (sunnah), ahadith (sayings), actions, and agreements of Prophet Muhammad, peace be upon him. This review article aims at exploring the magnitude of therapeutic benefits of prophetic medicine remedies as adjuvant treatments to many different types of hematological disorders. Herein, we reviewed many published research studies throughout the literature to delineate the potential therapeutic benefits of prophetic remedies on hematological disorders. Several types of hematological disorders may benefit from prophetic medicine remedies that are rich in natural antioxidants that combat oxidative stress-induced harm e.g. nigella sativa, oral honey, camel milk and urine, Ajwa date fruits, olive oil, Zamzam water and figs. Many prophetic medicine remedies were reported to decrease the hematological cytotoxicity effects induced by different chemicals and are beneficial in treating anemias e.g. iron deficiency anemia, sickle cell anemia, thalassemia, coagulopathies and hematological malignancies as leukemia and myeloma. These remedies treat or alleviate the different hematological disorders using different mechanisms e.g. modulating the immune function, treating deficiencies of different substances, protecting against toxins-induced cytotoxicity, decreasing platelets aggregation, suppressing clotting factors activation, exerting antineoplastic effects (enhancing cancer cells cytotoxicity) and inhibiting angiogenesis. Prophetic medicine remedies exert clinically significant therapeutic benefits for treating COVID-19 pandemic, anemia, thrombosis, thalassemia and blood cancers without inducing toxicity or side effects.

Al-Hijamah (Prophetic Wet Cupping Therapy) is a Novel Adjuvant Treatment for Viral Hepatitis That Excretes Viral Particles and Excess Ferritin Percutaneously, Synergizes Pharmacotherapy, Enhances Antiviral Immunity and Helps Better HCC Prevention and Treatment: A Novel Evidence-Based Combination with Prophetic Medicine Remedies.

Viral hepatitis progresses to liver cirrhosis and HCC. Several challenges are facing Sovaldi treatment to viral C hepatitis, eg, viral resistance, difficulty to treat all genotypes, and inability to access treatments in low-income countries. Also, current treatments to Hepatitis B are still challenging. Ideal treatments to viral hepatitis should decrease the viral load, enhance antiviral immunity and repair the viruses-induced tissue damage. That is still beyond reach. High serum ferritin in viral hepatitis correlates with chronicity, increased necro-inflammation, hepatotoxicity, progression to cirrhosis, progression to HCC, unresponsiveness to treatments and viremia. Previously, Al-hijamah (wet cupping therapy of prophetic medicine) significantly cleared thalassemic children of causative pathological substances (CPS), eg, excess ferritin, free radicals and serum lipids. Moreover, Al-hijamah significantly increased the antioxidant power and potentiated the natural antiviral immunity, eg, increasing CD4 count, CD8 count and CD4/CD8 ratio. Prophet Muhammad peace be upon him said: "If there is a benenvolence (benefit) in any of your medicines, benefit will be in shrtat mihjam (Al-hijamah), honey drink, and a stinge of fire compatible with disease and I do not like to cauterize". Likewise, the author suggests Al-hijamah as a novel promising adjuvant treatment for viral hepatitis (B and C) for percutaneous excretion of CPS as hepatitis viral particles, excess ferritin, inflammatory mediators, free radicals, and antigen-antibody complexes. Published reports proved that Al-hijamah exerted tissue-protective effects, and cleared blood through the fenestrated skin capillaries in a pressure-dependent and size-dependent manner (a kidney-like manner). That collectively may decrease the viral load for better HCC prevention and supports the evidence-based Taibah theory (Taibah mechanism). Same therapeutic benefits apply to other viral illnesses as AIDS. Even after HCC development, Al-hijamah is quite mandatory for excretion and clearance of CPS that favor malignancy, eg, lactate (Warburg effect), growth factors, metalloproteinases, and others. Al-hijamah-induced immune potentiation benefits HCC patients. Combining Al-hijamah with other natural antioxidant remedies of prophetic medicine, eg, nigella sativa, costus, natural honey, Zamzam water and others will maximize the therapeutic benefits. In conclusion, Al-hijamah and other prophetic medicine remedies are recommended adjuvants to current pharmacological treatments to viral hepatitis and HCC.

Potent Dual Inhibitors of Steroid Sulfatase and 17ß-Hydroxysteroid Dehydrogenase Type 1 with a Suitable Pharmacokinetic Profile for In Vivo Proof-of-Principle Studies in an Endometriosis Mouse Model.

Treating estrogen-dependent diseases like endometriosis with drugs suppressing local estrogen activation may be superior to existing endocrine therapies. Steroid sulfatase (STS) and 17ß-hydroxysteroid dehydrogenase type 1 (17ß-HSD1) are key enzymes of local estrogen activation. We describe the rational design, synthesis, and biological profilation of furan-based compounds as a novel class of dual STS/17ß-HSD1 inhibitors (DSHIs). In T47D cells, compound 5 showed irreversible inhibition of STS and potent, reversible inhibition of 17ß-HSD1. It was selective over 17ß-HSD2 and displayed high metabolic stabilities in human and mouse liver S9 fractions. No effect on cell viability was detected up to 31 µM (HEK293) and 23 µM (HepG2), respectively, and there was no activation of the aryl hydrocarbon receptor (AhR) up to 3.16 µM. Single daily application to mice revealed steady-state plasma levels high enough to make this compound eligible for an in vivo proof-of-principle study in a mouse endometriosis model.

Computed tomography-guided stereotactic surgery in the management of brain lesions: A single-center experience.

Background: The present study presents our experience with computed tomography (CT)-guided stereotactic surgery in managing deep-seated brain lesions and provides a background in the expanding fields of morphological stereotactic neurosurgery. Methods: We conducted this retrospective cohort study on 80 patients managed at the Department of Neurosurgery, Zagazig University Hospitals, Zagazig, Egypt, between January 2019 to January 2021. We targeted patients with morphological stereotactic surgeries performed as the primary management modality of their treatment. Results: A total of 80 patients, with a mean age of 44.3 years, were included in the study. The stereotactic targets were supratentorial in 71 patients (88.75%), infratentorial in seven patients (8.75%), and both supraand infratentorial in two patients (2.5%). The lesions showed enhancements with IV contrast in 55 patients (68.75%). Stereotactic procedures were performed under local anesthesia in 64 patients and general anesthesia in 16 patients. Of the 80 stereotactic procedures, 52 were biopsies (65%). We observed a significant improvement in the postoperative Karnofsky performance score compared to the postoperative score (63.4 ± 19.8 vs. 56.7 ± 15.4, P = 0.001). The level of agreement between clinical, radiological, and final pathological diagnosis was assessed; it was complete in 47.5% of the patients. The postprocedural CT scan demonstrated intracranial hemorrhage in five patients (6.25%); four (5%) were silent with no neurological complications. Conclusion: This study provided evidence that the stereotactic procedure is easy to perform, accurate in targeting the lesion, and spares patients from undergoing major surgical procedures. Stereotactic applications of spontaneous intracerebral hemorrhage, deep-seated abscesses, encysted tumors, or medically refractory benign intracranial hypertension can improve the outcome even in medically high-risk patients.

Biochemical Origin of the Warburg Effect in Light of 15 Years of Research Experience: A Novel Evidence-Based View (An Expert Opinion Article).

Cancer cells strongly upregulate glucose uptake and glycolysis to produce vital biomolecules for cancer cell survival, proliferation, and metastasis as ATP, lipids, proteins, nucleotides, and lactate. The Warburg effect is tumours' unique glucose oxidation to give lactate (not pyruvate) even in the presence of oxygen. Nicotinamide adenine dinucleotide (NAD/NADH.H) is used in glycolysis via glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and lactate dehydrogenase (LDH). Both catalyse reversible biochemical reactions to produce 1,3-diphosphoglycerate and lactate, respectively. In this expert opinion and based on published evidence, the author suggests that: "In transformed cells and hyperglycolytic cancer cells, the Warburg effect (permanent conversion of pyruvate to lactate) occurs secondary to a vicious cycle and a closed circuit between GAPDH and LDH (reaction of carcinogenesis) causing increased endogenous oxidative stress and subsequent carcinogenesis. Mitochondrial defects in cancer cells cause hyperglycolysis resulting in NADH.H accumulation (produced during GAPDH step) that obligatorily drives LDH to become an irreversible reaction in the direction of lactate formation (Warburg effect) but not pyruvate formation. Likewise, LDH oxidizes NADH.H producing excessive NAD+ that secondarily drives GAPDH reaction to be irreversible to produce NADH.H and so on. Pyruvate is an antioxidant while lactate is pro-oxidant, causing increased endogenous oxidative stress in cancer cells, tumour's hypoxia and obligatory hyperglycolysis with NADH.H overproduction (GAPDH step) to be consumed in the LDH step for lactate production and NAD+ generation (utilized by GAPDH) and so on". This confirms Warburg's origin of cancer cells. Best anticancer applications based on this hypothesis are: breaking this closed vicious circle using siRNA to target GAPDH and LDH, avoiding strong oxidants (as many cancer chemotherapeutics), and using strong antioxidants for causing antioxidant-oxidant antagonism or antioxidant-lactate antagonism to inhibit the Warburg effect. Strong natural antioxidants of prophetic medicine (related to Prophet Muhammad peace be upon him) such as Zamzam water, Nigella sativa, costus, Ajwa date fruit, olive oil, Al-hijamah and natural honey are strongly recommended to prevent and antagonize the Warburg effect.

Synovial Chondromatosis of the Shoulder in Rheumatoid Arthritis: A Case Report and Brief Review of the Literature.

BACKGROUND: Synovial chondromatosis is an uncommon benign condition characterized by synovial membrane proliferation and metaplasia. Synovial chondromatosis cases in patients with rheumatoid arthritis have been reported. However, involvement of the glenohumeral joint is rare. CASE PRESENTATION: We herein report a case of a rare association of synovial chondromatosis involving the shoulder in a rheumatoid arthritis patient. The symptoms have improved with anti-tumor necrosis factor drugs. Consequently, there was no need for invasive therapy to treat synovial chondromatosis. CONCLUSION: Synovial chondromatosis can be aggressive and destructive. More trials are needed to establish a better clinical diagnostic strategy and pharmacological management.

Modeling and Solution of Reaction-Diffusion Equations by Using the Quadrature and Singular Convolution Methods.

In the present work, polynomial, discrete singular convolution and sinc quadrature techniques are employed as the new techniques to derive accurate and efficient numerical solutions for the reaction-diffusion equations. Three models, Fitzhugh-Nagumo, Newell-Whitehead-Segel, and tumor growth models, were presented. The equations of three models are reduced to nonlinear ordinary differential equations by using different quadrature schemes. Then, Runge-Kutta fourth-order method is employed to solve nonlinear ordinary differential equations. In addition, the MATLAB program is used to solve these problems. Comparisons between the new methods and the existing ones are included, demonstrating the ease of implementation and efficiency. Also, the calculated results are supported by four various statistical errors. It is found that the rate of error reaches ≤ 10-6 in discrete singular convolution depending on regularized Shannon kernel which is better than others. Further, a parametric analysis is presented to discuss the influence of diffusion and reaction parameters on the solution.

Insoluble dietary fibers: structure, metabolism, interactions with human microbiome, and role in gut homeostasis.

Consumption of food rich in dietary fibers (DFs) has been long recognized to exert an overall beneficial effect on human health. This review aims to provide a holistic overview on how IDFs impact human gut health either directly, or through modulation of the gut microbiome. Several databases were searched for collecting papers such as PubMed, Google Scholar, Web of Science, Scopus and Reaxys from 2000 till 2022. Firstly, an overview of the chemical structure of the various IDFs and the pathways employed by gut microbiota for their degradation is provided. The impact of IDFs on microbial community structure and pathogens colonization inside the human gut was discussed. Finally, the impact of IDFs on gut homeostasis and systemic effects at the cellular level, as well as the overall immunological benefits of IDFs consumption were analyzed. IDFs viz., cellulose, hemicellulose, resistant starch, and lignin found enriched in food are discussed for these effects. IDFs were found to induce gut immunity, improve intestinal integrity and mucosal proliferation, and favor adhesion of probiotics and hence improve human health. Also, IDFs were concluded to improve the bioavailability of plant polyphenols and improve their health-related functional roles. Ultimately, dietary fibers processing by modification shows potential to enhance fibers-based functional food production, in addition to increase the economic value and usage of food-rich fibers and their by-products.

The durability of thin superficial circumflex iliac artery perforator flap in sole reconstruction: Clinical experience with 18 cases.

BACKGROUND: The superficial circumflex iliac artery perforator flap's overall success in the reconstruction of the lower limb has been acceptable, but the sole of the foot remains more challenging. The purpose of this article is to report our experience employing the SCIP flap and evaluate its durability in reconstructing different units of the foot's sole, heel, middle, and forefoot. PATIENTS AND METHODS: This retrospective study reviewed 18 patients with sole defect reconstructed with free SCIP flap from 2017 to 2019. 18 free SCIP flaps were harvested depending on the superficial branch of SCIA (n = 16) or deep branch (n = 2). All flaps were thin and elevated above the scrapa's fascia. The heel (n = 10), middle foot sole (n = 5), forefoot sole (n = 2), and combined heel and midfoot in one patient were among the defect locations. Sole defects were caused by trauma in 10 patients (55.5%), while the rest of the causes were melanoma (three patients, 16.7%), diabetic ulcer (three patients, 16.7%), and unstable scar (one patient), and calcaneal osteomyelitis (one patient). The defect size ranged from 24 to 230 cm2 . RESULTS: The flap dimensions ranged from 6 × 4 to 18 × 11 cm. Mean follow-up observations were 42.5 months. 72.2% of our patients developed protective sensation between 12-18 months. No ulcerations were observed, and all of the patients had successful functional recoveries with satisfying cosmetic outcomes. CONCLUSION: The SCIP flap can be an optimal durable skin flap for weight-bearing sole reconstruction. SCIP flap has the advantage of being thin minimizing the problem of shearing, the need for secondary procedures, and the faster recovery of protective sensation that could prevent ulceration.

Traumatic Floating Neural Arch of the Subaxial Cervical Spine: Case Report.

Bilateral traumatic pedicle fracture in the lower cervical spine is a very unusual lesion. Its association with bilateral facet dislocation has been reported once in the literature. We report a unique traumatic lesion considered as subaxial cervical floating neural arch with special emphasize on reduction maneuvers and surgical management. It was a case of bilateral C7 pedicle fracture with bilateral C6/C7 facet dislocation in a neurologically intact 70-year-old patient. Open posterior reduction with fixation followed by anterior fusion was performed with good functional and radiological outcomes at last follow up. The floating neural arch lesion is the combination of bilateral pedicle fracture and facet dislocation. The detection of such lesions imposes a two-stage surgery with open posterior reduction and anterior fusion.

The Preventive and Therapeutic Effects of Ajwa Date Fruit Extract Against Acute Diclofenac Toxicity-Induced Colopathy: An Experimental Study.

Background: Studies regarding treatment of acute toxicity with diclofenac (ATD) are quite few. Diclofenac is commonly prescribed in neurology, psychiatry, and general medicine practice. This study investigated possible colon-protective effects exerted by Ajwa date fruit extract (ADFE), a prophetic medicine remedy native to Al-Madinah, Saudi Arabia against ATD. Phytochemicals in ADFE as gallic acid and quercetin have reported protective effects against ATD. Methods: Total phenols and flavonoids in ADFE were estimated as equivalents to gallic acid and quercetin. Four experimental groups were allocated each of six rats: control group, ATD group received a single dose of 150 mg diclofenac intraperitoneally, toxicity prevention group received a single dose of ADFE orally followed 4 hours later by diclofenac injection, and toxicity treatment group received a similar diclofenac dose followed 4 hours later by a single dose of ADFE. Four days later, animals were sacrificed. Histological and biochemical examinations were done. Results: ADFE has a total phenolic content of 331.7 gallic acid equivalent/gram extract and a total flavonoid content of 70.23 quercetin equivalent/gram. ATD significantly increased oxidative stress markers as serum malondialdehyde (MDA) and hydrogen peroxide (H2O2). Serum MDA and H2O2 were significantly scavenged by ADFE. ATD significantly (p<0.001) decreased antioxidant power as serum total antioxidant capacity and catalase activity. That was reversed by ADFE in both prevention and treatment groups. Histologically, ATD caused complete destruction of colonic crypts architecture, patchy loss of the crypts, loss of the surface epithelium, absent goblet cells and submucosal exudate, heavy infiltration of the lamina propria and submucosa with inflammatory cells, mainly lymphocytes and eosinophils. There were mucosal haemorrhages and submucosal dilated congested blood vessels. All that was prevented and treated using ADFE. Conclusion: ADFE is rich in quercetin and gallic acid equivalents that exert potent antitoxic effects. ADFE is strongly recommended for preventive and therapeutic colon effects against ATD.

Dual Targeting of Steroid Sulfatase and 17ß-Hydroxysteroid Dehydrogenase Type 1 by a Novel Drug-Prodrug Approach: A Potential Therapeutic Option for the Treatment of Endometriosis.

A novel approach for the dual inhibition of steroid sulfatase (STS) and 17ß-hydroxysteroid dehydrogenase type 1(17ß HSD1) by a single drug was explored, starting from in-house 17ß HSD1 inhibitors via masking their phenolic OH group with a sulfamate ester. The sulfamates were intentionally designed as drugs for the inhibition of STS and, at the same time, prodrugs for 17ß-HSD1 inhibition ("drug-prodrug approach"). The most promising sulfamates 13, 16, 18-20, 22-24, 36, and 37 showed nanomolar IC50 values for STS inhibition in a cellular assay and their corresponding phenols displayed potent 17ß-HSD1 inhibition in cell-free and cellular assays, high selectivity over 17ß-HSD2, reasonable metabolic stability, and low estrogen receptor α affinity. A close relationship was found between the liberation of the phenolic compound by sulfamate hydrolysis and 17ß-HSD1 inactivation. These results showed that the envisaged drug-prodrug concept was successfully implemented. The novel compounds constitute a promising class of therapeutics for the treatment of endometriosis and other estrogen-dependent diseases.

Gain-of-function mutations in ALPK1 cause an NF-κB-mediated autoinflammatory disease: functional assessment, clinical phenotyping and disease course of patients with ROSAH syndrome.

OBJECTIVES: To test the hypothesis that ROSAH (retinal dystrophy, optic nerve oedema, splenomegaly, anhidrosis and headache) syndrome, caused by dominant mutation in ALPK1, is an autoinflammatory disease. METHODS: This cohort study systematically evaluated 27 patients with ROSAH syndrome for inflammatory features and investigated the effect of ALPK1 mutations on immune signalling. Clinical, immunologic and radiographical examinations were performed, and 10 patients were empirically initiated on anticytokine therapy and monitored. Exome sequencing was used to identify a new pathogenic variant. Cytokine profiling, transcriptomics, immunoblotting and knock-in mice were used to assess the impact of ALPK1 mutations on protein function and immune signalling. RESULTS: The majority of the cohort carried the p.Thr237Met mutation but we also identified a new ROSAH-associated mutation, p.Tyr254Cys.Nearly all patients exhibited at least one feature consistent with inflammation including recurrent fever, headaches with meningeal enhancement and premature basal ganglia/brainstem mineralisation on MRI, deforming arthritis and AA amyloidosis. However, there was significant phenotypic variation, even within families and some adults lacked functional visual deficits. While anti-TNF and anti-IL-1 therapies suppressed systemic inflammation and improved quality of life, anti-IL-6 (tocilizumab) was the only anticytokine therapy that improved intraocular inflammation (two of two patients).Patients' primary samples and in vitro assays with mutated ALPK1 constructs showed immune activation with increased NF-κB signalling, STAT1 phosphorylation and interferon gene expression signature. Knock-in mice with the Alpk1 T237M mutation exhibited subclinical inflammation.Clinical features not conventionally attributed to inflammation were also common in the cohort and included short dental roots, enamel defects and decreased salivary flow. CONCLUSION: ROSAH syndrome is an autoinflammatory disease caused by gain-of-function mutations in ALPK1 and some features of disease are amenable to immunomodulatory therapy.