Fabrication and Enhanced Performance Evaluation of TiO2@Zn/Al-LDH for DSSC Application: The Influence of Post-Processing Temperature.

A sequence of dye-sensitized solar cells is proposed, utilizing TiO2@Zn/Al-layered double hydroxide (LDH) as their starting materials, in which Ruthenizer N719 was used as a photon absorber. The anticipated system was turned into sheet-like TiO2@mixed metal oxide (MMO) via post-processing treatment. The crystal quality indicated a relation to power conversion efficiency (PCE); this was combined with a comparable morphology profile. In detail, the optimum DSSC device exhibited average sheet-like thickness and a dye loading amount of 43.11 nm and 4.28 ×10-3 mM/cm-2, respectively. Concurrently, a considerable PCE enhancement of the optimum DSSC device (TiO2@MMO-550°) was attained compared to pristine MMO (0.91%), which could be due to boosted electron transfer efficiency. Of the fabricated devices, DSSC fabricated at 550° exhibited the highest PCE (1.91%), with a 35.6% enhancement compared to that obtained at 450°, as a result of its increased open-circuit voltage (3.29 mA/cm2) and short-circuit current (0.81 V). The proposed work delivers an enhanced efficiency as compared to similar geometries.

Low dose insulin infusion versus the standard dose in children with diabetic ketoacidosis: a meta-analysis.

Aim: This systematic review aims to consolidate findings from current clinical trials that compare the effectiveness of insulin infusion at 0.05 IU/kg/h versus 0.1 IU/kg/h in managing pediatric diabetic ketoacidosis. Methods: We searched several databases, including PubMed, Embase, Scopus, Cochrane Central and Web of Science. Our primary outcomes were time to reach blood glucose ≤250 mg/dl and time to resolution of acidosis. Secondary outcomes included rate of blood glucose decrease per hour, incidence of hypoglycemia, hypokalemia, treatment failure, and cerebral edema. Results & conclusion: The present study establishes that a low insulin dose exhibits comparable efficacy to the standard dosage for managing pediatric patients suffering from diabetic ketoacidosis, with a lower incidence of complications.

When kids with type 1 Diabetes (T1DM) face a serious complication called Diabetic Ketoacidosis (DKA), it becomes a life-threatening situation. This condition, responsible for significant mortality, involves high blood sugar, ketone buildup and acidity. Our study delves into a critical aspect of DKA treatment-finding the right insulin dose. By pooling the studies on this point, we discovered that using a lower insulin dose is just as effective as the standard dose in managing DKA in children, with fewer complications. This insight is crucial for improving the care and outcomes for young patients dealing with this challenging condition.

Immune Checkpoints Receptors Expression of Macrophage/Monocytes in Response to Acute Viral Respiratory Infection.

Background: We aimed to monitor the phenotypic changes in macrophages and their polarization in patients with acute viral respiratory diseases, including coronavirus disease diagnosis, focusing on the variations in the percentages of macrophages and monocytes and their sub-populations in those patients compared to healthy control. Moreover, we defined the correlation between macrophage subtypes and some inflammatory indices. Methods: Twenty-seven patients with clinical and radiologic diagnosis of acute viral respiratory infection admitted in Al-Azhar and Assiut University hospitals were recruited. Fresh peripheral blood samples were collected from all patients and healthy controls for flow cytometric analysis using BD FACSCanto II analyzer equipped with three lasers. Results: Compared to healthy controls, accumulation of cluster of differentiation (CD)11B+CD68+ macrophages (M) (P = 0.018), CD274+ M1 (P = 0.01), CD274+ M2 (P < 0.001), and CD80-CD206+ M2 (P = 0.001) was more evident in patients. Moreover, CD273+ M2 (P = 0.03), CD80+CD206- M1 (P = 0.002), and CD80+CD86+ M1 (P = 0.002) were highly expressed in controls compared with patients. Conclusion: The examination of clinical specimens obtained from patients with signs of acute respiratory viral infection showed the role of the macrophage in the immune response. Dysfunction in macrophages results in heightened immune activity and inflammation, which plays a role in the progression of viral diseases and the emergence of accompanying health issues. This malfunction in macrophages is a common characteristic seen in various viruses, making it a promising focus for antiviral therapies with broad applicability. The immune checkpoint could be a target for immune modulation in patients with severe symptoms.

Evaluating knowledge, attitude, and physical activity levels related to cardiovascular disease in Egyptian adults with and without cardiovascular disease: a community-based cross-sectional study.

BACKGROUND: Cardiovascular disease (CVD) represents a significant health challenge in Egypt, yet there exists limited understanding regarding the knowledge, attitudes, and physical activity levels associated with CVD. These factors play a pivotal role in developing effective prevention and management strategies. Hence, this cross-sectional study aimed to evaluate Egyptian adults' knowledge, attitudes, and physical activity (KAP) levels. METHODS: Data were collected using a previously validated questionnaire encompassing demographic characteristics, CVD knowledge (including risk factors and symptoms), attitudes toward CVD, and self-reported physical activity levels. The survey was distributed among social media channels, and trained researchers administered the questionnaire via face-to-face interviews with adult patients with and without CVD admitted to Cairo University Hospital clinics. RESULTS: The study involved 591 participants, of whom 21.7% had CVD. Overall, participants exhibited poor knowledge regarding CVD, with a mean score of 21 ± 7 out of 40, equivalent to 52.5%. Attitudes toward CVD were moderate, with a mean score of 66.38 ± 8.7 out of 85, approximately 78%. Physical activity levels per week were also moderate, averaging 1188 MET-min with a range of 1121-18,761. Subgroup analysis revealed that individuals with CVD had lower average knowledge, attitude, and physical activity levels than those without CVD. Working in the healthcare field was a predictor of higher knowledge score (standard error (SE) 5.89, 95% confidence interval (CI) 4.61 to 7.17, P < 0.001), while those with CVD and smokers were predictors of lower attitude score (SE -4.08, 95% CI -6.43 to -1.73, P < 0.001) and (SE -2.54, 95% CI -4.69 to -0.40, P = 0.02), respectively. CONCLUSION: The study findings highlight a significant disparity in knowledge, attitudes, and physical activity levels related to CVD in Egypt. Targeted interventions aimed at improving awareness, fostering positive attitudes, and promoting physical activity among individuals at risk for CVD are crucial for effective prevention and management.

Time to Move Beyond a Binary Criterion for Gestational Diabetes?

Over the years, several international guidelines have been developed by specialist organizations for the diagnosis of gestational diabetes mellitus (GDM). However, these guidelines vary and lack consensus on what level of glycemia defines GDM and worryingly, there is now evidence of over- or- under-diagnosis of women with GDM by current criteria. Towards this end, the National Priorities Research Program (NPRP) funded a program of research aimed at elucidating the problem with GDM diagnosis. It was determined, on completion of the project, that the solution required diagnosis of graded levels of dysglycemia in pregnancy and not just a diagnosis of presence or absence of GDM. A new diagnostic criterion (called the NPRP criterion) was created based on a single numerical summary of the three readings from the oral glucose tolerance test (GTT) that diagnosed women in pregnancy into four levels: normal, impaired, GDM and high risk GDM. This paper now examines existing GDM criteria vis-à-vis the NPRP criterion. It is noted that no significant change has happened over the years for existing criteria except for a gradual reduction in the threshold values of individual time-points or the number of time points, bringing us towards over-diagnosis of GDM in pregnancy. The new criterion unifies all readings from the GTT into one numerical value and, because it results in four levels of glycemia, represents a new way forwards for GDM diagnosis and can potentially reduce the rates of under diagnosis and over diagnosis of GDM.

Improving Thoracic Surgery Ward Round Quality and Enhancing Patient Safety in a Referral Centre.

Introduction Ward rounds are vital clinical processes that facilitate an opportunity for daily review and management of thoracic surgery inpatients. The aim of this study was to compare thoracic surgery ward round documentation against locally agreed standards and design a template to improve the detail and uniformity of this process to enhance patient care. Materials and methods Data for this audit was collected retrospectively and prospectively. Data was collected during three auditing periods and managed on Microsoft Excel. Descriptive statistics were used for its analysis. Chi-square and Fisher's Exact tests were used to test for differences in reporting rates. Results and discussion Initially, a total of 199 ward round notes were reviewed. Imaging results (19%) and discharge planning (23%) were not reported. eCARE (electronic Clinical Assessment for Round Evaluation) was developed to ensure that all aspects of patient evaluation recommended by the guidelines were included. Reporting rates significantly improved after such changes. We analysed the effect of the new ward round note on discharge planning (23.3 vs 41%, p<0.001), complication rates (32.6 vs 21.9%, p=0.03), post-surgical length of stay (LOS) (7.0 vs 5.0, p<0.001). Conclusion Over a year, we audited the Thoracic Surgery Department's ward round documentation against locally agreed standards in line with national recommendations. Several important items were not regularly reported. Using closed-ended questions improved reporting rates, and patient care was optimised. Further research should explore the impact of this new documentation method on patient care and postoperative outcomes in our Trust as well as other cardiothoracic centres.

Epithelioid haemangioendothelioma-a rare cause of right pleural effusion and multiple primary nodules: Case report & review of the literature.

Pulmonary epithelioid haemangioendothelioma (PEH) is a rare vascular neoplasm. The thoracic manifestation of this disorder is identified via three major imaging patterns, namely multiple primary nodules, diffuse infiltrative pleural thickening, and multiple pulmonary reticulonodular opacities. The commonest pattern of presentation is bilateral multiple nodules. Diagnosis is based on histopathological findings and verified by positive immunochemistry staining. Patients with PEH are usually asymptomatic. We report the case of a 51-year-old female who presented to our facility with a five-month history of cough, pleural nodularity, and pleural effusion. She underwent surgical washout with right pleural biopsies that showed a malignant epithelioid tumor with features of epithelioid haemangioendothelioma (EH). A CXR after treatment did not demonstrate a residual pleural effusion.

Looking Beyond What You See: A Rare Cause of Dysphagia.

Hypothyroidism is a common endocrine condition with typical symptoms such as cold intolerance, weight gain, fatigue, constipation, and coarse skin, as well as less common symptoms such as depression, difficulty in concentration, and hair thinning. It is usually diagnosed by combining clinical features and applying clinical judgment; however, the wide spectrum of presenting symptoms can sometimes lead to a diagnostic dilemma. Dysphagia secondary to hypothyroidism is a rarely reported symptom in the literature and is believed to be associated with a hormonal effect on esophageal and gastric motility with neuromuscular incoordination; however, the underlying mechanism remains unknown. The most common cause of hypothyroidism is Hashimoto's disease, which can rarely manifest as heartburn, possibly due to esophageal dysmotility. Herein, we describe an unusual presentation of severe hypothyroidism with dysphagia, for which we could not identify any obstructive cause despite extensive investigations This condition was resolved successfully with levothyroxine treatment. Through this report, we aimed to communicate to the audience the important learning message that hypothyroidism may cause symptoms of dysphagia and to inform practitioners regarding this possibility, which should be considered after ruling out any obstructive pathology.

Sel1-like proteins and peptides are the major Oxalobacter formigenes-derived factors stimulating oxalate transport by human intestinal epithelial cells.

Kidney stones (KSs) are very common, excruciating, and associated with tremendous healthcare cost, chronic kidney disease (CKD), and kidney failure (KF). Most KSs are composed of calcium oxalate and small increases in urinary oxalate concentration significantly enhance the stone risk. Oxalate also potentially contributes to CKD progression, kidney disease-associated cardiovascular diseases, and poor renal allograft survival. This emphasizes the urgent need for plasma and urinary oxalate lowering therapies, which can be achieved by enhancing enteric oxalate secretion. We previously identified Oxalobacter formigenes (O. formigenes)-derived factors secreted in its culture-conditioned medium (CM), which stimulate oxalate transport by human intestinal Caco2-BBE (C2) cells and reduce urinary oxalate excretion in hyperoxaluric mice by enhancing colonic oxalate secretion. Given their remarkable therapeutic potential, we now identified Sel1-like proteins as the major O. formigenes-derived secreted factors using mass spectrometry and functional assays. Crystal structures for six proteins were determined to confirm structures and better understand functions. OxBSel1-14-derived small peptides P8 and P9 were identified as the major factors, with P8 + 9 closely recapitulating the CM's effects, acting through the oxalate transporters SLC26A2 and SLC26A6 and PKA activation. Besides C2 cells, P8 + 9 also stimulate oxalate transport by human ileal and colonic organoids, confirming that they work in human tissues. In conclusion, P8 and P9 peptides are identified as the major O. formigenes-derived secreted factors and they have significant therapeutic potential for hyperoxalemia, hyperoxaluria, and related disorders, impacting the outcomes of patients suffering from KSs, enteric hyperoxaluria, primary hyperoxaluria, CKD, KF, and renal transplant recipients.NEW & NOTEWORTHY We previously identified Oxalobacter formigenes-derived secreted factors stimulating oxalate transport by human intestinal epithelial cells in vitro and reducing urinary oxalate excretion in hyperoxaluric mice by enhancing colonic oxalate secretion. We now identified Sel1-like proteins and small peptides as the major secreted factors and they have significant therapeutic potential for hyperoxalemia and hyperoxaluria, impacting the outcomes of patients suffering from kidney stones, primary and secondary hyperoxaluria, chronic kidney disease, kidney failure, and renal transplant recipients.

Preparation and Photovoltaic Evaluation of CuO@Zn(Al)O-Mixed Metal Oxides for Dye Sensitized Solar Cell.

In this manuscript, a series of dye-sensitized solar cells (DSSCs) were fabricated as a function of post-processing temperature based on mesoporous CuO@Zn(Al)O-mixed metal oxides (MMO) in conjunction with dye N719 as the main light absorber; the proposed CuO@Zn(Al)O geometry was, in turn, attained using Zn/Al-layered double hydroxide (LDH) as a precursor via combination of co-precipitation and hydrothermal techniques. In particular, the dye loading amount onto the deposited mesoporous materials was anticipated via regression equation-based UV-Vis technique analysis, which evidently demonstrated a robust correlation along with the fabricated DSSCs power conversion efficiency. In detail, of the DSSCs assembled, CuO@MMO-550 exhibited short-circuit current (JSC) and open-circuit voltage (VOC) of 3.42 (mA/cm2) and 0.67 (V) which result in significant fill factor and power conversion efficiency of 0.55% and 1.24%, respectively. This could mainly be due to the relatively high surface area of 51.27 (m2/g) which in turn validates considerable dye loading amount of 0.246 (mM/cm-2).

Treatment of peanut allergy and colitis in mice via the intestinal release of butyrate from polymeric micelles.

The microbiome modulates host immunity and aids the maintenance of tolerance in the gut, where microbial and food-derived antigens are abundant. Yet modern dietary factors and the excessive use of antibiotics have contributed to the rising incidence of food allergies, inflammatory bowel disease and other non-communicable chronic diseases associated with the depletion of beneficial taxa, including butyrate-producing Clostridia. Here we show that intragastrically delivered neutral and negatively charged polymeric micelles releasing butyrate in different regions of the intestinal tract restore barrier-protective responses in mouse models of colitis and of peanut allergy. Treatment with the butyrate-releasing micelles increased the abundance of butyrate-producing taxa in Clostridium cluster XIVa, protected mice from an anaphylactic reaction to a peanut challenge and reduced disease severity in a T-cell-transfer model of colitis. By restoring microbial and mucosal homoeostasis, butyrate-releasing micelles may function as an antigen-agnostic approach for the treatment of allergic and inflammatory diseases.

Principle Parameters and Environmental Impacts that Affect the Performance of Wind Turbine: An Overview.

The share of wind-based electricity generation is gradually increasing in the world energy market. Wind energy can reduce dependency on fossil fuels, as the result being attributed to a decrease in global warming. This paper discusses and reviews the basic principle parameters that affect the performance of wind turbines. An overview presents the introduction and the background of energy consumption, following the order of the elaboration of wind turbines, including mathematical models, categories of wind turbines were critically discussed. Moreover, it also focuses on materials that are commonly considered for wind turbine manufacturing, and the process used to recycle them. The scale of recycling methods for fiberglass and thermoplastic is presented in the respective section. Various parameters that reduce the function of wind turbines are explained in depth. This review also discusses various environmental impacts of wind turbines. Future research studies are suggested in the conclusion section.

Investigating the Dimensional Accuracy of the Cavity Produced by ABS P400 Polymer-Based Novel EDM Electrode.

In the present study, cylindrical ABS P400 polymer parts (diameter 6.5 mm) to be used as die-sinking EDM (electric discharge machining) novel electrodes were fabricated using a fused deposition modeling (FDM) process. To meet the conductivity requirement in EDM, ABS parts were metallized using an innovative method that comprised putting aluminum-charcoal (Al-C) on them followed by their copper electroplating. Real-time EDM of the mild steel workpiece was performed using novel electrodes, and machining performance of the electrodes, measured in terms of dimensional accuracy, i.e., change in diameter (ΔD) and change in depth (ΔH) of the cavity, under varying levels of three EDM factors, i.e., current (I), pulse on time (Ton), and pulse off time (Toff), was investigated. Machining results were analyzed using analysis of variance (ANOVA), perturbation graphs, and 3D surface plots. The optimal setting of the EDM parameters for minimizing ΔD and ΔH was determined using the desirability function approach. The suitability of the novel electrodes for EDM was ascertained by comparing their machining results with those of solid copper (SC) electrodes and electrodes fabricated by FDM and metallized using the electro-deposition method (FDM-EM), already reported in the literature, under similar machining conditions. From the results, it was found that ΔD and ΔH were less when EDM was performed using novel electrodes.

Mitigation of hypoglycemia during Ramadan using the flash glucose monitoring system following dose adjustment of insulin and sulphonylurea in patients taking multiple glucose-lowering therapies (The PROFAST-IT Study).

BACKGROUND AND HYPOTHESIS: Patients with type-2 diabetes mellitus (T2DM) on multiple glucose-lowering therapies who fast during Ramadan are at increased risk of hypoglycemia. We have assessed the utility of the flash glucose monitoring system after adjusting the dose of insulin and sulphonylureas to mitigate the risk of hypoglycemia in patients with T2DM who fast during Ramadan. PATIENTS AND METHODS: Patients with T2DM on either basal insulin or a sulphonylurea and at least 2 other glucose-lowering agents received structured education and adjustment of insulin or sulphonylurea dose according to the PROFAST Ramadan protocol. Glucose variability and episodes of hypoglycemia were assessed using the flash glucose monitoring system (Free Style Libre) before and during Ramadan. RESULTS: A total of 33 patients with T2DM (on sulphonylurea (SU+) (n = 21), on basal insulin (BI+) (n = 12) aged 50.8 ± 1.6 years with a diabetes duration of 13.1 ± 6.5 years were studied. The average sensor glucose was 154 ± 34 mg/dl (8.5 ± 1.88 mmol/l) with 65.2% in the target range before Ramadan and the average sensor glucose was 156 ± 36 mg/dl (8.6 ± 2.0 mmol/l) with 67.1% in the target range during Ramadan. The incidence of hypoglycemia in the whole group (2.9 v 2.9) and in the SU+ (3.7 vs 3.0) and BI+ (1.7 vs 2.9) groups and eHbA1c (P = 0.56, P = 0.93), average glucose (P = 0.56, P = 0.92) and time within range (P = 0.63, P = 0.73) did not change in the SU+ and BI+ groups, respectively, before and during Ramadan. CONCLUSION: Structured education with adjustment of the dose of glucose lowering medication alongside use of the FGMS can effectively mitigate the increased risk of hypoglycemia in patients with T2DM on multiple glucose-lowering therapies who fast during Ramadan.

Patterns of Mycobacterium avium-intracellulare complex infection in duodenal endoscopic biopsies in HIV/AIDS patients.

Mycobacterium avium-intracellulare complex (MAIC) is a nontuberculous opportunistic infection in immunocompromised patients. Involvement of the gastrointestinal tract (GIT) is usually part of a disseminated disease in AIDS patients with a low CD4 count, however with standard antiretroviral therapy (ART), a localized presentation is more likely. It can affect any part of the GIT, mostly the duodenum and typically as patches. Incomplete or refractory ART for HIV-strains, therapy-related side effects, noncompliant or incomplete treatment to previous MAIC infections, superimposed complications and comorbid opportunistic infections may result in atypical clinical, endoscopic and histopathologic manifestations. We performed a retrospective review study retrieving cases of MAIC in duodenal endoscopic biopsy. We found five cases of MAIC in HIV/AIDS patients. They were males with an average age of 40-years. They showed different histopathologic features, variable patterns of MAIC-histiocytic infiltrates, and varying intensity of intracellular acid-fast positive bacilli. Enterocytes vacuolization and transepithelial elimination were also observed. Three cases were associated with cytomegalovirus and cryptococcal infections. A case was complicated by lymphangiectasia-associated protein-losing enteropathy. Initially, three cases were morphologically missed. Ziehl-Neelsen stain helped reach the correct diagnosis. Pathologists have an important role in patients' management by guiding clinicians to the correct diagnosis. Pathologists should be aware of these different histopathologic manifestations, their potential pitfalls, look for certain helpful clues complemented with multiple levels and special stains. In particular, AFB stains are mandatory in all mucosal biopsy specimens from HIV/AIDS patients regardless of their appearances.

Activation of the PKA signaling pathway stimulates oxalate transport by human intestinal Caco2-BBE cells.

Most kidney stones are composed of calcium oxalate, and small increases in urine oxalate enhance the stone risk. The mammalian intestine plays a crucial role in oxalate homeostasis, and we had recently reported that Oxalobacter-derived factors stimulate oxalate transport by human intestinal Caco2-BBE (C2) cells through PKA activation. We therefore evaluated whether intestinal oxalate transport is directly regulated by activation of the PKA signaling pathway. To this end, PKA was activated with forskolin and IBMX (F/I). F/I significantly stimulated (3.7-fold) [14C]oxalate transport by C2 cells [≥49% of which is mediated by the oxalate transporter SLC26A6 (A6)], an effect completely blocked by the PKA inhibitor H89, indicating that it is PKA dependent. PKA stimulation of intestinal oxalate transport is not cell line specific, since F/I similarly stimulated oxalate transport by the human intestinal T84 cells. F/I significantly increased (2.5-fold) A6 surface protein expression by use of immunocytochemistry. Assessing [14C]oxalate transport as a function of increasing [14C]oxalate concentration in the flux medium showed that the observed stimulation is due to a F/I-induced increase (1.8-fold) in Vmax and reduction (2-fold) in Km. siRNA knockdown studies showed that significant components of the observed stimulation are mediated by A6 and SLC26A2 (A2). Besides enhancing A6 surface protein expression, it is also possible that the observed stimulation is due to PKA-induced enhanced A6 and/or A2 transport activity in view of the reduced Km. We conclude that PKA activation positively regulates oxalate transport by intestinal epithelial cells and that PKA agonists might therapeutically impact hyperoxalemia, hyperoxaluria, and related kidney stones.

The impact of anastomotic leakage on recurrence and long-term survival in patients with colonic cancer: A systematic review and meta-analysis.

BACKGROUND/OBJECTIVE: Anastomotic leakage (AL) is one of the most severe complications following colorectal cancer surgery and is associated with increased short and long term mortality. The literature is conflicting regarding increased risk of recurrence after AL. The aim of this study was to systematically review the impact of anastomotic leakage on the risk of local or distant recurrence and overall survival, cancer specific survival, and disease-free survival. METHODS: A systematic review and meta-analysis was conducted in accordance with the PRISMA guidelines. A systematic search in PubMed, EMBASE, CINHAL, and The Cochrane Library was performed and meta-analyses were performed on all outcomes including analysis based on time-to-event data. RESULTS: A total of eighteen cohort studies, including 69,047 patients whereof 2,555 patients had anastomotic leakage, were included. Meta-analysis demonstrated no significant effects of anastomotic leakage on local recurrence (RR 1.16, 95% CI 0.84-1.59) or distant recurrence (RR 1.44, 95% CI 0.52-3.96). Anastomotic leakage decreased overall survival (RR 0.85, 95% CI 0.77-0.94), disease free survival (RR 0.80, 95% CI 0.72-0.89), and cancer specific survival (RR 0.90, 95% CI 0.83-0.97). A time-to-event analysis was conducted on available data and the results were congruent with the frequency analyses. CONCLUSION: Anastomotic leakage following colonic resections is significantly associated with impaired overall survival, disease free survival and cancer specific survival. The study did not show any statistically significant association between anastomotic leakage and recurrence.

Trefoil factors peptide-3 is associated with residual invasive breast carcinoma following neoadjuvant chemotherapy.

BACKGROUND: Breast carcinoma is the commonest cancer among UAE population and the most common cancer among females. Examination of the 5' promoter regions of trefoil factor 3 (TFF3) gene has identified putative estrogen and progesterone receptor-DNA binding domains as direct response elements to estrogen and progesterone that are linked to breast functions or steroid regulation. The study was designed to determine the role of TFF3 in breast cancer chemoresistance with the aim of establishing TFF3 expression as a biomarker for drug resistance. METHODS: In total, 133 cases of breast carcinoma treated with neo-adjuvant therapy were collected. Tissue samples from pre-neoadjuvant therapy as well as tissues from post-neo-adjuvant therapy of those cases were collected and stained with immunohistochemistry for TFF3, Bcl2, BAX, cleaved caspase-3, AKT-1, NF kappa B and Ki-67. RESULTS: There was increased expression of TFF3 in residual invasive carcinoma cells. There was a significant correlation between the expression of TFF3 in breast carcinoma cells and response to neoadjuvant chemotherapy (p = 0.0165). There was significant co-expression of TFF3 with AKT1 (p = 0.0365), BCl2 (p = 0.0152), and NF Kappa-B (p = 0.0243) in breast carcinoma cases with residual carcinoma following neoadjuvant therapy which support the role of TFF3 in chemoresistance. CONCLUSION: The expression of TFF3 is significantly associated with residual breast carcinoma following neoadjuvant chemotherapy suggesting its expression is associated with increased resistance to chemotherapy. This is supported by its co-expression with antiapoptotic proteins; BCl2, AKT1 and NF Kappa-B in residual breast carcinoma cells and very low proliferating index and apoptotic bodies in residual tumors.

Enhanced gastrointestinal passive paracellular permeability contributes to the obesity-associated hyperoxaluria.

Most kidney stones (KS) are composed of calcium oxalate and small increases in urine oxalate enhance the stone risk. Obesity is a risk factor for KS, and urinary oxalate excretion increases with increased body size. We previously established the obese ob/ob ( ob) mice as a model (3.3-fold higher urine oxalate) to define the pathogenesis of obesity-associated hyperoxaluria (OAH). The purpose of this study was to test the hypothesis that the obesity-associated enhanced small intestinal paracellular permeability contributes to OAH by increasing passive paracellular intestinal oxalate absorption. ob Mice have significantly higher jejunal (1.6-fold) and ileal (1.4-fold) paracellular oxalate absorption ex vivo and significantly higher (5-fold) urine [13C]oxalate following oral gavage with [13C]oxalate, indicating increased intestinal oxalate absorption in vivo. The observation of higher oxalate absorption in vivo compared with ex vivo suggests the possibility of increased paracellular permeability along the entire gut. Indeed, ob mice have significantly higher fractions of the administered sucrose (1.7-fold), lactulose (4.4-fold), and sucralose (3.1-fold) excreted in the urine, reflecting increased gastric, small intestinal, and colonic paracellular permeability, respectively. The ob mice have significantly reduced gastrointestinal occludin, zonula occludens-1, and claudins-1 and -3 mRNA and total protein expression. Proinflammatory cytokines and oxidative stress, which are elevated in obesity, significantly enhanced paracellular intestinal oxalate absorption in vitro and ex vivo. We conclude that obese mice have significantly higher intestinal oxalate absorption and enhanced gastrointestinal paracellular permeability in vivo, which would likely contribute to the pathogenesis of OAH, since there is a transepithelial oxalate concentration gradient to drive paracellular intestinal oxalate absorption. NEW & NOTEWORTHY This study shows that the obese ob/ob mice have significantly increased gastrointestinal paracellular oxalate absorption and remarkably enhanced paracellular permeability along the entire gut in vivo, which are likely mediated by the obesity-associated increased systemic and intestinal inflammation and oxidative stress. A transepithelial oxalate concentration gradient driving gastrointestinal paracellular oxalate absorption exists, and therefore, our novel findings likely contribute to the hyperoxaluria observed in the ob/ob mice and hence to the pathogenesis of obesity-associated hyperoxaluria.