The interplay of p38 MAPK signaling and mitochondrial metabolism, a dynamic target in cancer and pathological contexts.

Mitochondria play a crucial role in cellular metabolism and bioenergetics, orchestrating various cellular processes, including energy production, metabolism, adaptation to stress, and redox balance. Besides, mitochondria regulate cellular metabolic homeostasis through coordination with multiple signaling pathways. Importantly, the p38 mitogen-activated protein kinase (MAPK) signaling pathway is a key player in the intricate communication with mitochondria, influencing various functions. This review explores the multifaced interaction between the mitochondria and p38 MAPK signaling and the consequent impact on metabolic alterations. Overall, the p38 MAPK pathway governs the activities of key mitochondrial proteins, which are involved in mitochondrial biogenesis, oxidative phosphorylation, thermogenesis, and iron homeostasis. Additionally, p38 MAPK contributes to the regulation of mitochondrial responses to oxidative stress and apoptosis induced by cancer therapies or natural substances by coordinating with other pathways responsible for energy homeostasis. Therefore, dysregulation of these interconnected pathways can lead to various pathologies characterized by aberrant metabolism. Consequently, gaining a deeper understanding of the interaction between mitochondria and the p38 MAPK pathway and their implications presents exciting forecasts for novel therapeutic interventions in cancer and other disorders characterized by metabolic dysregulation.

The Prevalence of Shoulder Pain and Awareness of Frozen Shoulder Among the General Population in Taif City, Saudi Arabia.

Background The global prevalence of shoulder pain varies widely across countries. Additionally, shoulder pain and frozen shoulder can significantly affect patients' quality of life due to high levels of pain and disability. Objective This study aimed to investigate the prevalence of shoulder pain and its risk factors. It also aims to assess the level of knowledge regarding frozen shoulders and its related factors in Taif City, Saudi Arabia. Methods A cross-sectional observational study was conducted in Taif City in December 2023 using a validated questionnaire comprised of socio-demographic characteristics, the prevalence of shoulder pain, and the awareness of frozen shoulders. Results A total of 378 participants enrolled in the study, with 54.8% being male and 62.7% being graduates and having jobs equally distributed among office (24.9%) and in the field (24.9%). Most participants were smokers (75.9%) and did not engage in body-building activities (79.6%). Around 26.5% of them had diabetes. The prevalence of shoulder pain was 32.8%. Aging from 35 to 44 years (p<0.001), having a higher salary from 6000 to 10000 SAR (p<0.001), retirement (p<0.001), engaging in body-building activities (p=0.035), having diabetes (p<0.001), and having other comorbidities (p<0.001) are significantly impacted having shoulder pain. Increased knowledge about the frozen shoulder is correlated with aging from 25-34 (p=0.026), smoking (p=0.002), engaging in bodybuilding (p<0.001), having diabetes (p=0.010), and having other medical conditions (p=0.010). Conclusion The study has shown that shoulder pain is prevalent among Taif City's population. Nevertheless, a low level of knowledge was observed. Therefore, enhancing the national educational programs is needed to increase public awareness of frozen shoulders.

Airway Diseases Related to the Use of Cleaning Agents in Occupational Settings.

Exposure to disinfectants and cleaning products (DCPs) is now a well-established risk factor for work-related asthma (WRA). However, questions remain on the specific causal agents and pathophysiological mechanisms. Few studies have also reported an association between DCPs and rhinitis or chronic obstructive pulmonary disease. This review discusses the recent evidence pertaining to airway diseases attributable to occupational exposure to DCPs. In contrast to other agents, the incidence of WRA due to DCPs has increased over time. The use of DCPs in spray form has clearly been identified as an added risk factor. The mechanisms for WRA associated with DCPs remain poorly studied; however, both allergic and nonallergic responses have been described, with irritant mechanisms thought to play a major role. An early diagnostic workup based on clinical assessment accompanied by evaluation of lung function and immunological and airway inflammatory markers is important to guide optimal care and exposure avoidance to the implicated agent. Future research should focus on the effects of "green" products, pathophysiological mechanisms, and quantitative exposure assessment including the use of barcode-based methods to identify specific agents. There is an urgent need to strengthen preventive measures and interventions to reduce the burden of airway diseases associated with DCPs.

Postoperative infectious complications worsen oncologic outcomes following pancreaticoduodenectomy for pancreatic ductal adenocarcinoma.

BACKGROUND: Pancreaticoduodenectomy (PD) remains the only curative option for patients with pancreatic adenocarcinoma (PDAC). Infectious complications (IC) can negatively impact patient outcomes and delay adjuvant therapy in most patients. This study aims to determine IC effect on overall survival (OS) following PD for PDAC. STUDY DESIGN: Patients who underwent PD for PDAC between 2010 and 2020 were identified from a single institutional database. Patients were categorized into two groups based on whether they experienced IC or not. The relationship between postoperative IC and OS was investigated using Kaplan-Meier and Cox-regression multivariate analysis. RESULTS: Among 655 patients who underwent PD for PDAC, 197 (30%) experienced a postoperative IC. Superficial wound infection was the most common type of infectious complication (n = 125, 63.4%). Patients with IC had significantly more minor complications (Clavien-Dindo [CD] < 3; [59.4% vs. 40.2%, p < 0.001]), major complications (CD ≥ 3; [37.6% vs. 18.8%, p < 0.001]), prolonged LOS (47.2% vs 20.3%, p < 0.001), biochemical leak (6.1% vs. 2.8%, p = 0.046), postoperative bleeding (4.1% vs. 1.3%, p = 0.026) and reoperation (9.6% vs. 2.2%, p < 0.001). Time to adjuvant chemotherapy was delayed in patients with IC versus those without (10 vs. 8 weeks, p < 0.001). Median OS for patients who experienced no complication, noninfectious complication, and infectious complication was 33.3 months, 29.06 months, and 27.58 months respectively (p = 0.023). On multivariate analysis, postoperative IC were an independent predictor of worse OS (HR 1.32, p = 0.049). CONCLUSIONS: IC following PD for PDAC independently predict worse oncologic outcomes. Thus, efforts to prevent and manage IC should be a priority in the care of patients undergoing PD for PDAC.

The Antioxidant and anti-inflammatory Activity of Selenium and Lecithin Combination Against ethanol-induced Gastric Ulcer in mice via Modulating IGF-1/PTEN/Akt/FoxO3a Signaling.

Gastric ulcers are one of the most prevalent gastrointestinal disorders. The current study investigated the antioxidant and anti-inflammatory effects of selenium (Se) and lecithin (Lec) alone and in combination against ethanol-induced gastric ulcers in mice, and their ability to modulate insulin-like growth factor-1 (IGF-1)/ Phosphatase and tensin homologue deleted on chromosome 10 (PTEN)/ Protein kinase B (Akt)/ Forkhead box O3a (FoxO3a) signaling. The mice were divided into normal, ethanol, Se + ethanol, Lec + ethanol, Se + Lec + ethanol, and omeprazole + ethanol groups. Treatment with the selected doses was continued for 14 days before a single dose of absolute ethanol (5 ml/kg body weight) was administered to induce gastric ulcers in mice. The results showed that pretreatment with Se and Lec combination effectively decreased both the macro- and microscopic gastric lesions and increased the protection index compared to the ethanol group. Remarkably, the Se and Lec combination decreased the levels of reactive oxygen species, malondialdehyde, and cytochrome c and increased glutathione, glutathione peroxidase, and thioredoxin reductase activities in gastric tissues. The Se and Lec combination increased prostaglandin E2 and interleukin-10 levels but decreased tumor necrosis factor-α, interleukin-6 and interleukin-1ß levels compared to either treatment alone. Interestingly, this combination decreased the expression of IGF-1, p-Akt, and FoxO3a proteins and increased PTEN expression in gastric tissues. The gastric tissues examination by hematoxylin and eosin staining confirmed these results. Therefore, the Se and Lec combination showed superior protective effects against ethanol-induced gastric ulcers in mice, compared to either treatment alone, through antioxidant, and anti-inflammatory activities, in addition to modulating IGF-1/PTEN/Akt/FoxO3a pathway signaling.

Exploring marine-derived compounds for MET signalling pathway inhibition in cancer: integrating virtual screening, ADME profiling and molecular dynamics investigations.

The MET signalling pathway regulates fundamental cellular processes such as growth, division, and survival. While essential for normal cell function, dysregulation of this pathway can contribute to cancer by triggering uncontrolled proliferation and metastasis. Targeting MET activity holds promise as an effective strategy for cancer therapy. Among potential sources of anti-cancer agents, marine organisms have gained attention. In this study, we screened 47,450 natural compounds derived from marine sources within the CMNPD database against the Met crystal structure. By employing HTVS, SP, and XP docking modes, we identified three compounds (CMNPD17595, CMNPD14026, and CMNPD19696) that outperformed a reference molecule in binding affinity to the Met structure. These compounds demonstrated desirable ADME properties. Molecular Dynamics (MD) simulations for 200 ns confirmed the stability of their interactions with Met. Our findings highlight CMNPD17595, CMNPD14026, and CMNPD19696 as potential inhibitors against Met-dependent cancers. Additionally, these compounds offer new avenues for drug development, leveraging their inhibitory effects on Met to combat carcinogenesis.

Adenovirus type D and type E infection in broiler chickens: the effect on CD4 and CD8 T cell response, cytokines expression and their immunopathology.

1. A total of 150-day-old chicks were divided into three groups of 50 birds (G1-G3); G1 and G2 were orally inoculated at 1-day old with 0.5 ml of 107 TCID50/ml FAdV-D serotype 2 (MT386509.1) and FAdV-E serotype 8a (MW847902), respectively, and G3 was blank control group.2. Cell-mediated immune response was evaluated by detection of CD4, CD8 T lymphocytes and the mRNA expression of IL6 and IL8 in the chicken spleen using q-PCR. Additionally, immunopathology was performed at 3, 5 and 7 day post infection (dpi) and weekly until the end of the experiment.3. Results revealed that transcription of inflammatory cytokines (IL6, IL8) was up regulated in the spleen of FAdV type D and type E infected chickens at various time points relative to the control group. A marked decrease in the number of CD4 and CD8 T lymphocytes at 5 and 7 dpi in G1 of chickens infected with FAdV type D. Whereas, in chickens infected with FAdV type E, the CD4 and CD8 T lymphocytes were markedly decreased at 7 dpi.4. In contrast, there were no significant differences in humoral immune responses against NDV vaccine in (G1 and G2) at different intervals post-vaccination compared to the control group. The histopathology of the bursa, thymus, and spleen in the infected groups showed lymphocytolysis with severe reticular cells hyperplasia and lymphoid depletion.5. In conclusion, fowl adenovirus types D and E have an immunosuppressive effect in broilers which may be considered one of the main causes of the continuous co-infections with other viruses reported in the field during the last 10 years.

Awareness and knowledge of breast cancer rehabilitation among Saudi Arabia physical therapists.

OBJECTIVE: This study aimed to evaluate the physical therapists' knowledge and awareness of breast cancer, treatment modalities, contraindications, and clinical guidelines. SUBJECTS AND METHODS: A cross-sectional survey was conducted from December 2020 to May 2021 in Saudi Arabia. The sample size was determined using the Raosoft sample size calculator, which indicated the need for 67 participants. All physical therapists of both sex in private and public hospitals in Ha'il and non-Ha'il regions were included in the study. Data was collected by a structured Google form questionnaire, consisting of 4 main domains with a maximum score of 43. RESULTS: 57 physical therapists participated in the current study, out of which 31 were from the Ha'il region (42.1% male, 57.9% female) with a mean age of 29±7 years and a mean experience 6±7years. The referral of breast cancer patients was only 22.8%. Interestingly only 22.8% of the hospital has specific setups for oncology rehabilitation, and 12.3% have reported positive about continuing professional development (CPDs) workshops for breast cancer organized by their hospitals. 5.3% of patients with breast cancer are aware of the benefit of oncology rehabilitation, while 22.8% of patients come for follow-up sessions in the rehabilitation department. According to multiple regression, only gender was statistically significant for prediction, p<0.05. Females increased the mean score by 5.996 more than males. Female therapists are 38.2% more aware than males. CONCLUSIONS: Although physical therapists have a low level of knowledge and an average level of awareness, with a higher number of women than men, attitudes toward physical therapy are quite high, and the profession is practiced exceptionally well.

Occupational risk factors and exposure-response relationships for airway disease among health workers exposed to cleaning agents in tertiary hospitals.

OBJECTIVES: This study investigated occupational risk factors and exposure-response relationships for airway disease among health workers (HWs) exposed to cleaning agents in two tertiary hospitals in South Africa and Tanzania. METHODS: In this cross-sectional study, 697 participants completed questionnaire interviews while 654 underwent fractional exhaled nitric oxide (FeNO) testing. Asthma Symptom Score (ASS) was computed based on the sum of answers to five questions on asthma-related symptoms in the past 12 months. For exposure-response analyses, cleaning agent-related self-reported exposure variables were categorised into three levels (cleaning product not used; use of a cleaning product for up to 99 min per week and use of a cleaning product for ≥100 min per week). RESULTS: Asthma-related outcomes (ASS and FeNO) demonstrated positive associations with medical instrument cleaning agents (orthophthalaldehyde and enzymatic cleaners) and tasks (instruments precleaning and changing sterilisation solutions) as well as patient care activities (disinfection prior to procedures and disinfecting wounds). A particularly pronounced dose-response relationship was observed between work-related ocular-nasal symptoms and medical instrument cleaning agents (orthophthalaldehyde, glutaraldehyde, enzymatic cleaners, alcohols and bleach) (OR range: 2.37-4.56) and tasks (OR range: 2.92-4.44). A strong association was also observed between ASS and use of sprays for fixed surface cleaning (mean ratio 2.81; 95% CI 1.41 to 5.59). CONCLUSIONS: Specific agents for medical instrument disinfection for example, orthophthalaldehyde and enzymatic cleaners, patient care activities and use of sprays are important occupational risk factors for airway disease among HWs.

The use of angiotensin system inhibitors correlates with longer survival in resected pancreatic adenocarcinoma patients.

BACKGROUND: Activities and inhibition of the Renin-Angiotensin-Aldosterone System (RAAS) may affect the survival of resected pancreatic ductal adenocarcinoma (PDAC) patients METHOD: A single-institution retrospective analysis of resected PDAC patients between 2010 and 2019. To estimate the effect of angiotensin system inhibitors (ASIs) on patient survival, we performed Kaplan Meier analysis, Cox Proportional Hazards model, Propensity Score Matching (PSM), and inverse probability weighting (IPW) analysis. RESULTS: 742 patients were included in the analysis. The average age was 67.0 years, with a median follow-up of 24.1 months. The use of ASI was associated with significantly longer overall survival in univariate (p = 0.004) and multivariable (HR = 0.70 [0.56-0.88],p = 0.003) adjusted analysis. In a propensity score-matched cohort of 400 patients, ASI use was again associated with longer overall survival (p = 0.039). Lastly, inverse probability weighting (IPW) analysis suggested that the use of ASI was associated with an average treatment effect on the treated (ATT) of HR = 0.68 [0.53-0.86],p = 0.002) for overall survival. CONCLUSION: In this single-institution retrospective study focusing on resected PDAC patients, the use of ASI was associated with longer overall survival in multiple statistical models. Prospective clinical trials are needed before routine clinical implementation of ASI as an adjuvant to existing therapy can be recommended.

2-(Benzhydryl sulfinyl)-N-sec-butylacetamide) isolated from fig augmented trastuzumab-triggered phagocytic killing of cancer cells through interface with Fcγ receptor.

The objective of the current study was to extract 2-(benzhydryl sulfinyl)-N-sec-butylacetamide), a novel compound from fig, and then determine its role in enhancing trastuzumab-triggered phagocytic killing of SKOV-3 cancer cells. In this study, Soxhlet was used to extract the compound from the mature and air-dried fig fruits. The production of the isolated extracts was enhanced by using polar and non-polar solvents. Several solvents, such as methanol, ethyl acetate, chloroform, and n-hexane, were used to isolate the effective compound 2-(benzhydryl sulfinyl)-N-sec-butylacetamide) from the organic layer. UV-spectroscopy, FT-IR, 1H-NMR, and 13C-NMR were applied to identify the purified compound. The in vitro and in vivo assays demonstrated that the 2-(benzhydryl sulfinyl)-N-sec-butylacetamide) can increase the activity of the phagocytic cells, via the interaction with FcY receptors, along with trastuzumab, and the pathway can use a model for the therapeutic strategy for effective treatment of ovarian cancer cells.

Impact of Extended Antibiotic Use After Pancreaticoduodenectomy for Patients with Preoperative Metallic Biliary Stenting Treated with Neoadjuvant Chemotherapy.

INTRODUCTION: Pancreaticoduodenectomy (PD) remains a complex surgical procedure with infectious complications affecting nearly 50% of patients. Patients who undergo biliary drainage with stent placement prior to neoadjuvant treatment (NAT) reportedly have higher infection rates following PD. The aim of the current study is to evaluate the differences in postoperative infectious complication rates based on the duration of post operative prophylactic antibiotics in patients with indwelling metal biliary stent who had NAT. METHODS: A retrospective institutional pancreatic cancer database was queried for patients who had a metal biliary stent placed prior to NAT initiation, followed by subsequent PD between 2014 and 2021. Duration of postoperative prophylactic antibiotics was defined as short (SC: ≤ 24 h) or extended (EC: > 24 h-7 days). The primary outcome of interest was surgical site infection (SSI). RESULTS: Two hundred and ninety-five (n = 295) patients were identified of which the majority (n = 205, 69.5%) received a short course of antibiotics postoperatively. Baseline characteristics were similar between the two cohorts including age, sex, BMI, and comorbidity index. EC patients received more NAT cycles (4 vs. 3, p < 0.001) and underwent an open PD more frequently (61.8% vs. 41.0%, p < 0.001). SSI occurred in 64 (21.7%) patients; SC cohort: 54, 26.3% vs. EC cohort:10, 11.1%, (p = 0.003). Additionally, the SC cohort demonstrated a higher incidence of major complications (Clavien-Dindo ≥ 3: 51 [24.9%] vs. 13 [14.4%], p = 0.045). On the logistic regression model examining factors associated with SSI, higher BMI (continuous variable) was associated with increased odds of SSI (OR: 1.05 [95%CI: 1.00, 1.10, p = 0.040), while EC was protective (OR: 0.36 [95%CI: 0.17, 0.75], p = 0.007). CONCLUSIONS: These data suggest that an extended course of perioperative antibiotic correlates with reductions in SSI and major morbidity following PD in patients with a metallic biliary stent placed prior to NAT course. These results require validation in a future randomized clinical trial examining a larger cohort of patients with further emphasis on the types of perioperative antibiotics administered.

Obesity Is Associated With Increased Risk for Adverse Postoperative Outcomes After Distal Pancreatectomy for Pancreatic Ductal Adenocarcinoma.

INTRODUCTION: Conflicting reports exist about the effect obesity has on adverse postoperative surgical outcomes after distal pancreatectomy (DP). The aim of this study is to explore the role of obesity in terms of morbidity and pancreas-specific complications following DP for pancreatic ductal adenocarcinoma (PDAC). METHODS: All patients who underwent DP at a single institution over 10 y were analyzed (2009-2020). Patients were categorized as nonobese (body mass index [BMI] < 30 kg/m2) and obese (BMI ≥ 30 kg/m2). Independent predictors of adverse postoperative outcomes were calculated using multivariate logistic regression models. Overall survival was assessed using Kaplan-Meier survival analysis. RESULTS: Of the 178 patients included, 58 (32.5%) were obese. Clinically relevant postoperative pancreatic fistula (CR-POPF) formation rate was significantly higher in the obese group (20.6% versus 7.5%, P value = 0.011). We did not identify any significant difference between obese and nonobese patients in median overall survival (30.2 mon versus 28.9 mon, P value = 0.811). On multivariate binary logistic regression analysis, BMI ≥ 30 was an independent predictor of morbidity (any complication) and CR-POPF formation after DP for PDAC. CONCLUSIONS: Obesity is associated with a significantly increased risk for CR-POPF in patients undergoing DP for PDAC. Obesity should be considered as a variable in fistula risk calculators for DP.

Robotic Pancreaticoduodenectomy: Increased Adoption and Improved Outcomes: Is Laparoscopy Still Justified?

OBJECTIVE: To compare the rate of postoperative 30-day complications between laparoscopic pancreaticoduodenectomy (LPD) and robotic pancreaticoduodenectomy (RPD). BACKGROUND: Previous studies suggest that minimally invasive pancreaticoduodenectomy (MI-PD)-either LPD or RPD-is noninferior to open pancreaticoduodenectomy in terms of operative outcomes. However, a direct comparison of the two minimally invasive approaches has not been rigorously performed. METHODS: Patients who underwent MI-PD were abstracted from the 2014 to 2019 pancreas-targeted American College of Surgeons National Sample Quality Improvement Program (ACS NSQIP) dataset. Optimal outcome was defined as absence of postoperative mortality, serious complication, percutaneous drainage, reoperation, and prolonged length of stay (75th percentile, 11 days) with no readmission. Multivariable logistic regression models were used to compare optimal outcome of RPD and LPD. RESULTS: A total of 1540 MI-PDs were identified between 2014 and 2019, of which 885 (57%) were RPD and 655 (43%) were LPD. The rate of RPD cases/year significantly increased from 2.4% to 8.4% ( P =0.008) from 2014 to 2019, while LPD remained unchanged. Similarly, the rate of optimal outcome for RPD increased during the study period from 48.2% to 57.8% ( P <0.001) but significantly decreased for LPD (53.5% to 44.9%, P <0.001). During 2018-2019, RPD outcomes surpassed LPD for any complication [odds ratio (OR)=0.58, P =0.004], serious complications (OR=0.61, P =0.011), and optimal outcome (OR=1.78, P =0.001). CONCLUSIONS: RPD adoption increased compared with LPD and was associated with decreased overall complications, serious complications, and increased optimal outcome compared with LPD in 2018-2019.

Mycosynthesis of Silica Nanoparticles Using Aspergillus niger: Control of Alternaria solani Causing Early Blight Disease, Induction of Innate Immunity and Reducing of Oxidative Stress in Eggplant.

The threats to the life and production of crops are exacerbated by climate change and the misuse of chemical pesticides. This study was designed to evaluate the effectiveness of biosynthesized silica nanoparticles (SiO2-NPs) as an alternative to pesticides against early blight disease of eggplant. Antifungal activity, disease index, photosynthetic pigments, osmolytes, oxidative stress, antioxidant enzymes activities were tested for potential tolerance of eggplant infected with Alternaria solani. Silica nanoparticles were successfully biosynthesized using Aspergillus niger through green and ecofriendly method. Results revealed that SiO2-NPs exhibited promising antifungal activity against A. solani where MIC was 62.5 µg/mL, and inhibition growth at concentration 1000 µg/mL recorded 87.8%. The disease Index (DI) as a result of infection with A. solani reached 82.5%, and as a result, a severe decrease in stem and root length and number of leaves occurred, which led to a sharp decrease in the photosynthetic pigments. However, contents of free proline, total phenol and antioxidant enzymes activity were increased in infected plants. On the other hand, the treatment with SiO2-NPs 100 ppm led to a great reduction in the disease Index (DI) by 25% and a high protection rate by 69.69%. A clear improvement in growth characteristics and a high content of chlorophyll and total carotenoids was also observed in the plants as a result of treatment with silica nanoparticles in (healthy and infected) plants. Interestingly, the noticeable rise in the content of infected and healthy plants of proline and phenols and an increase in the activity of super oxide dismutase (SOD) and polyphenol oxidase (PPO). It could be suggested that foliar application of SiO2-NPs especially 100 ppm could be commercially used as antifungal and strong inducer of plant physiological immunity against early blight disease.

Pancreatic cyst fluid interleukin-1 beta (IL-1ß) level in predicting the risk of malignancy in pancreatic cysts.

Pancreatic cystic lesions (PCLs) may be accidentally discovered in up to 13.5% of cases. These PCLs are of multiple types, including mucinous cysts (intra-ductal papillary mucinous neoplasms [IPMN] and mucinous cystic neoplasms [MCN]) that have a risk of malignant transformation. The difficulty in differentiation between the various PCLs and their unpredictable risk of malignant transformation makes their management difficult. The new diagnostic tools of PCLs often include endoscopic ultrasound guided fine needle aspiration (EUS-FNA) for pancreatic cyst fluid analysis. This study aimed to determine if cystic fluid IL-1ß can predict the risk of malignancy and the degrees of dysplasia of pancreatic cysts. The study included 50 PCL patients. They were subjected to radiological, biochemical, serological, and histopathological examinations. Pancreatic cyst fluid IL-1ß was analyzed using an ELISA. Our data indicated that cyst fluid IL-1 ß can differentiate between benign and malignant cysts at cut-off value >150 pg/ml; with sensitivity and specificity of 84.00% and 56.00% respectively. Also, cyst fluid IL-1 ß can differentiate between mucinous and non- mucinous pancreatic cysts at cut-off value >150 pg/ml; with a sensitivity and specificity of 83.33% and 53.78%, respectively. However, cyst fluid IL-1 ß cannot differentiate between degrees of dysplasia of IPMN. In conclusion, our study suggested that pancreatic cyst fluid IL-1ß can differentiate between.

Design, Synthesis, Anticancer Activity and Molecular Docking of New 1,2,3-Triazole-Based Glycosides Bearing 1,3,4-Thiadiazolyl, Indolyl and Arylacetamide Scaffolds.

New 1,3,4-thiadiazole thioglycosides linked to a substituted arylidine system were synthesized via heterocyclization via click 1,3-dipolar cycloaddition. The click strategy was used for the synthesis of new 1,3,4-thiadiazole and 1,2,3-triazole hybrid glycoside-based indolyl systems as novel hybrid molecules by reacting azide derivatives with the corresponding acetylated glycosyl terminal acetylenes. The cytotoxic activities of the compounds were studied against HCT-116 (human colorectal carcinoma) and MCF-7 (human breast adenocarcinoma) cell lines using the MTT assay. The results showed that the key thiadiazolethione compounds, the triazole glycosides linked to p-methoxyarylidine derivatives and the free hydroxyl glycoside had potent activity comparable to the reference drug, doxorubicin, against MCF-7 human cancer cells. Docking simulation studies were performed to check the binding patterns of the synthesized compounds. Enzyme inhibition assay studies were also conducted for the epidermal growth factor receptor (EGFR), and the results explained the activity of a number of derivatives.

Cronkhite-Canada syndrome: First case report from Egypt and North Africa.

BACKGROUND: Gastrointestinal (GI) polyposis is a rare condition in GI diseases. To date about 500 cases of Cronkhite-Canada syndrome (CCS) have been reported worldwide. CASE SUMMARY: We report a 60-year-old female patient who presented with dyspepsia, abdominal pain, and weight loss of 1-year duration. Her physical examination showed alopecia and onychodystrophy. Upper endoscopy revealed diffuse markedly thickened gastric mucosa involving the whole stomach with thickened gastric rugae and numerous polypoidal lesions. Histopathological examination showed marked hyperplasia of the foveolar glands with inflammatory cell infiltration. Endoscopic ultrasound showed a significantly hypertrophic mucosa and muscularis mucosa, while the submucosa and the muscularis propria were spared, favouring its benign nature. Colonoscopy showed multiple sessile polyps scattered at different parts of the colon. Histopathological examination revealed tubular adenomatous polyps with low-grade dysplasia. Differential diagnoses included CCS, Menterier disease (MD), other polyposis syndromes, lymphoma, amyloidosis, and gastric malignancies. The presence of alopecia, nail dystrophy, GI polyposis, markedly thickened gastric mucosa and folds, abdominal pain, weight loss, and marked foveolar gland hyperplasia; all was in favour of CCS. Lymphoma was excluded due to sparing of the muscularis propria. The presence of colonic polyps and antral and duodenal infiltration, and the absence of hypoproteinaemia decreased the possibility for MD. CONCLUSION: The patient was diagnosed as having CCS.

Chitosan Based MicroRNA Nanocarriers.

Vectorization of microRNAs has shown to be a smart approach for their potential delivery to treat many diseases (i.e., cancer, osteopathy, vascular, and infectious diseases). However, there are barriers to genetic in vivo delivery regarding stability, targeting, specificity, and internalization. Polymeric nanoparticles can be very promising candidates to overcome these challenges. One of the most suitable polymers for this purpose is chitosan. Chitosan (CS), a biodegradable biocompatible natural polysaccharide, has always been of interest for drug and gene delivery. Being cationic, chitosan can easily form particles with anionic polymers to encapsulate microRNA or even complex readily forming polyplexes. However, fine tuning of chitosan characteristics is necessary for a successful formulation. In this review, we cover all chitosan miRNA formulations investigated in the last 10 years, to the best of our knowledge, so that we can distinguish their differences in terms of materials, formulation processes, and intended applications. The factors that make some optimized systems superior to their predecessors are also discussed to reach the highest potential of chitosan microRNA nanocarriers.

Clinical Trials in Hepatopancreatobiliary Surgery: Assessing Trial Characteristics, Early Discontinuation, Result Reporting, and Publication.

BACKGROUND: Hepatopancreaticobiliary (HPB) diseases carry high morbidity despite efforts aimed at their reduction. An assessment of their trial characteristics is paramount to determine trial design adequacy and highlight areas for improvement. As such, the aim of this study is to assess HPB surgery trial characteristics, summarize logistic, financial, and practical reasons behind early discontinuation, and propose potential interventions to prevent this in the future. METHODS: All clinical trials investigating HPB surgery registered on ClinicalTrials.gov from October 1st, 2007 (inclusive), to April 20th, 2021 (inclusive), were examined. Trial characteristics were collected including, but not limited to, study phase, duration, patient enrollment size, location, and study design. Peer-reviewed publications associated with the selected trials were also assessed to determine outcome reporting. RESULTS: A total of 1776 clinical trials conducted in 43 countries were identified, the majority of which were conducted in the USA. Of these trials, 32% were reported as "completed" whereas 12% were "discontinued." The most common cause of trial discontinuation was low accrual, which was reported in 37% of terminated studies. These resulted in 413 published studies. Most trials had multiple assignment, randomized, or open-label designs. Treatment was the most common study objective (73%) with pharmacological therapy being the most commonly studied intervention. CONCLUSIONS: The main reasons for early discontinuation of clinical trials in HPB surgery are poor patient recruitment and inadequate funding. Improved trial design, recruitment strategies and increased funding are needed to prevent trial discontinuation and increase publication rates of HPB surgery clinical trials.