TRPS1 function beyond breast: A retrospective immunohistochemical study on non-breast cytology specimens.

INTRODUCTION: Trichorhinophalangeal syndrome type 1 (TRPS1) has emerged as a reliable immunohistochemistry (IHC) marker for identifying breast origin in metastatic carcinomas. This study investigates the utility of TRPS1 IHC in non-breast cytology specimens. MATERIALS AND METHODS: A retrospective search of our pathology database for the year 2021 identified fluids (pleural and peritoneal) and liver, lung and bone fine needle aspirations (FNAs) with surgical follow-up confirming non-breast metastatic carcinomas. Cell blocks from cases with sufficient neoplastic cells underwent immunostaining using a rabbit polyclonal antibody against human TRPS1. Cases lacking tumor on deeper levels after the original work-up were excluded from the study. Two pathologists independently interpreted the TRPS1 staining. RESULTS: Of 136 cases assessed, 31 (22.79%) exhibited positive TRPS1 staining, while 105 (77.21%) were nonreactive. Positivity rates were observed in tumors of Mullerian cell origin, gastrointestinal tract (GIT), and lung origin at 28.85%, 25%, and 21.57%, respectively. Of the tumors of Mullerian cell origin 10 (66.67%) were serous carcinomas, 4 (26.67%) were endometrioid carcinomas, and one (6.67%) was a clear cell carcinoma. Lung tumors comprised seven (63.64%) squamous cell carcinomas and four (36.36%) adenocarcinomas, while the gastrointestinal tumors consisted of 14 (80%) adenocarcinomas and one (20%) squamous cell carcinoma. CONCLUSIONS: Although recognized as a sensitive marker for mammary carcinomas, TRPS1 immunostaining was also detected in Mullerian, lung, and GIT carcinomas. This highlights the significance of being cautious when depending solely on TRPS1 immunostaining to distinguish metastatic breast tumors.

Free Vascularized Proximal Fibular Epiphyseal Transfer For Hip Reconstruction Following Septic Necrosis In Children.

BACKGROUND: Septic necrosis of the femoral head and neck in children represents a challenging problem. Several reconstructive techniques have been described but with disappointing long-term results. Vascularized epiphyseal transfer utilizing the proximal fibula have been successfully used for reconstruction of the proximal humerus and distal radius and only scarcely used for hip reconstruction. This cohort represents the largest reported series of epiphyseal transfer for hip reconstruction following septic necrosis in children. METHODS: A total of 18 patients with an average age at surgery of 5.4 years were included. The average follow-up was 3.6 years (range 2.3 to 6.8 y). RESULTS: Transient postoperative foot drop was observed in 4 patients. Radiographic resorption of the transferred fibula occurred in 2 cases. Longitudinal growth averaged 7.3 mm/year, and the physis width increased by an average of 2.7 mm/year. The rate of longitudinal growth was fastest after the age of 10 years (18.5 mm/y), which coincides with the pubertal growth spurt. All successful transfers had an open growth plate on final follow-up radiographs. Ten patients had limb length discrepancy of an average 2.8 cm (range 1 to 8 cm). Thirteen patients had satisfactory functional according to the criteria of Hunka et al. Three patients had unsatisfactory results; one had painful nonunion at the fibula-femur junction, and the other two had limited flexion range of 45 degrees. The average postoperative neck-shaft angle was 96.4 degrees which decreased by an average of 8 degrees at the final follow-up. Three patients underwent a valgus subtrochanteric osteotomy to correct a severe varus deformity. The final neck-shaft angle correlated significantly with the functional results where it averaged 96 degrees in the satisfactory group and 57 degrees in the unsatisfactory group. CONCLUSION: Vascularized epiphyseal transfer presents a promising treatment for children with septic necrosis of the femoral head and neck in whom other methods have failed to provide satisfactory long-term results. We recommend the procedure be done before the age of 5 years for optimum results. LEVEL OF EVIDENCE: Level-IV.

Efficient photocatalytic remediation of lerui acid brilliant blue dye using radiation- prepared carboxymethyl cellulose/acrylic acid hydrogel supported by ZnO@Ag.

Organic dye pollution from textiles and other industries presents a substantial risk to people and aquatic life. The use of photocatalysis to decolorize water using the strength of UV light is one of the most important remediation techniques. In the present study, a novel nanocomposites hydrogel including carboxymethyl cellulose (CMC), acrylic acid (AAc), Zinc oxide (ZnO), and silver (Ag) nanoparticles was produced using an eco-friendly γ-irradiation technique for photocatalytic decolorization applications. ZnO and Ag nanoparticles were distributed in the CMC/AAc hydrogel matrix without significant aggregation. SEM, XRD, EDX, TEM, and FTIR analyses were used to assess the physicochemical characteristics of the nanocomposite samples. Carboxymethyl cellulose/acrylic acid/Zinc oxide doped silver (CMC/PAAc/ZnO@Ag) nanocomposite hydrogels were developed and utilized in the photocatalytic decolorization of the lerui acid brilliant blue dye (LABB) when exposed to ultraviolet (UV) radiation. UV- Vis spectrophotometry was utilized to analyze the optical properties of the produced nanostructure. Regarding the decolorization of the LABB, the impacts of operational variables were investigated. The optimum conditions for decolorization (93 %) were an initial concentration of 50 mg/L, pH = 4, catalyst dosage of 50 g/L, and exposure time of 90 min. The results illustrated that the LABB acidic dye from wastewater was remarkably decolored.

Randomized Controlled Trial to Compare Stapled Hemorrhoidopexy Plus Ligation Anopexy With Stapled Hemorrhoidopexy for Managing Grade III and IV Hemorrhoidal Disease.

BACKGROUND: Despite the benefits of the stapled hemorrhoidopexy in the short term, management of prolapsing hemorrhoids, the long-term results are still insufficient regarding recurrent prolapse and patient satisfaction. The current study investigates the addition of ligation anopexy to stapled hemorrhoidopexy. OBJECTIVE: Valuation of adding ligation anopexy to stapled hemorrhoidopexy in improving short-term and long-term results in the treatment of grade III and IV hemorrhoids. DATA SOURCES: Between January 2018 and January 2020, we recruited 124 patients with grade III and IV hemorrhoids at Alexandria Main University Hospital. STUDY SELECTION: Randomized controlled trial. INTERVENTIONS: One hundred twenty-four patients were blindly randomly assigned to 2 equal groups: stapled hemorrhoidopexy (group I) and stapled hemorrhoidopexy plus ligation anopexy (group II). MAIN OUTCOME MEASURES: Recurrence of hemorrhoids and patient satisfaction after a follow-up period of at least 2 years. RESULTS: The average operating time was noticeably less in the stapled hemorrhoidopexy group. Postoperative pain, analgesia requirement, hemorrhoid symptoms score, return to work, complications rate, and quality of life 1 month after surgery were similar between groups. Following a mean follow-up of 36 months (interval, 24-47), in group I, 10 patients (16%) reported recurrent external swelling and/or prolapse compared to 3 patients (5%) in group II ( p = 0.0368). Five patients in group I required redo surgery, whereas no patients required redo surgery in group II. Long-term patient satisfaction was significantly better in group II. LIMITATIONS: It was a single-center experience, so longer follow-up was needed. CONCLUSIONS: Stapled hemorrhoidopexy and stapled hemorrhoidopexy plus ligation anopexy were similar in short-term results with regard to complications rate, hemorrhoids symptoms score, return to work, and quality of life. Long-term results were significantly better with regard to recurrence of external swelling and/or prolapse and patient satisfaction after stapled hemorrhoidopexy plus ligation anopexy. See Video Abstract . TRIAL REGISTRATION NUMBER: Pan African Clinical Trials Registry identifier PACTR20180100293130. ECA PARA COMPARAR LA HEMORROIDOPEXIA CON GRAPAS MS ANOPEXIA POR LIGADURA CON LA HEMORROIDOPEXIA CON GRAPAS PARA EL TRATAMIENTO DE LA ENFERMEDAD HEMORROIDAL DE GRADO III Y IV: ANTECEDENTES:A pesar de los beneficios de la hemorroidopexia con grapas a corto plazo, el manejo de las hemorroides prolapsadas, los resultados a largo plazo aún son insuficientes en cuanto al prolapso recurrente y la satisfacción del paciente, por lo que en nuestro estudio actual agregamos anopexia por ligadura a la hemorroidopexia con grapas.OBJETIVO:Valoración de añadir anopexia por ligadura a la hemorroidopexia con grapas para mejorar los resultados a corto y largo plazo en el tratamiento de las hemorroides grado III-IV.FUENTES DE DATOS:Entre enero de 2018 y enero de 2020 reclutamos a 124 pacientes con hemorroides de grado III-IV en el hospital universitario principal de Alexandria.SELECCIÓN DEL ESTUDIO:Ensayo controlado aleatorio PACTR201801002931307.INTERVENCIÓN(S):124 pacientes fueron asignados al azar de forma ciega a dos grupos iguales, hemorroidopexia con grapas (grupo I) y hemorroidopexia con grapas más anopexia por ligadura (grupo II).PRINCIPALES MEDIDAS DE RESULTADO:Recurrencia de hemorroides y satisfacción del paciente después de un período de seguimiento de al menos dos años.RESULTADOS:El tiempo operatorio promedio fue notablemente menor en el grupo de hemorroidopexia con grapas. Mientras tanto, el dolor posoperatorio, la necesidad de analgesia, la puntuación de los síntomas de hemorroides, el regreso al trabajo, la tasa de complicaciones y la calidad de vida un mes después de la cirugía fueron similares. Después de un seguimiento medio de 36 meses (intervalo: 24-47), el Grupo I, 10 pacientes (16%) se quejaron de inflamación externa recurrente y/o prolapso en comparación con 3 pacientes (5%) en el Grupo II ( p = 0,0368) que requiere rehacer la cirugía. No fue necesaria una nueva cirugía en el grupo II; además, la satisfacción del paciente a largo plazo fue significativamente mejor en el grupo II.LIMITACIONES:Se necesita un seguimiento más prolongado y experiencia en un solo centro.CONCLUSIONES:La hemorroidopexia con grapas comparada con la hemorroidopexia con grapas más anopexia por ligadura fue similar en resultados a corto plazo en cuanto a tasa de complicaciones, puntuación de síntomas de hemorroides, regreso al trabajo y calidad de vida. Los resultados a largo plazo fueron significativamente mejores en cuanto a la recurrencia de la inflamación externa y/o el prolapso y la satisfacción del paciente después de la hemorroidopexia con grapas más anopexia por ligadura. (Traducción-Dr. Mauricio Santamaria ).

Association between non-alcoholic fatty liver disease and coronary artery disease outcomes: A systematic review and meta-analysis.

OBJECTIVES: To evaluate the association between non-alcoholic fatty liver disease (NAFLD) and cardiovascular outcomes, including angina, coronary artery disease (CAD), coronary artery calcification (CAC), myocardial infarction (MI), and calcified coronary plaques. METHODS: A comprehensive search of databases, including PubMed, EMBASE, and Cochrane Library, was conducted up to January 2023. Studies were included investigating the relationship between NAFLD and cardiovascular outcomes in adult populations. Exclusion criteria were studies on animals, pediatric populations, and those not published in English. Two reviewers assessed the risk of bias in the included studies using the Newcastle-Ottawa Scale. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using random-effects models. RESULTS: The meta-analysis included 32 studies with a total of 5,610,990 participants. NAFLD demonstrated significant associations with increased risks of angina (Relative Risk (RR): 1.45, 95% CI: 1.17, 1.79), CAD (RR: 1.21, 95% CI: 1.07, 1.38), CAC >0 (RR: 1.39, 95% CI: 1.15, 1.69), and calcified coronary plaques (RR: 1.55, 95% CI: 1.05, 2.27). However, no significant association was found between NAFLD and CAC >100 (RR: 1.16, 95% CI: 0.97, 1.38) or MI (RR: 1.70, 95% CI: 0.16, 18.32). CONCLUSION: The meta-analysis demonstrated a significant association between NAFLD and cardiovascular outcomes independent of conventional cardiovascular disease (CVD) risk factors. These findings emphasize the importance of prevention, early detection, and proper management of NAFLD.

Pericardiectomy for Successful Treatment of Constrictive Pericarditis in a Pediatric Patient.

A 15-year-old girl with history of asthma and obesity presented with recurrent anasarca without systolic heart failure or significant renal disease. She was diagnosed with constrictive pericarditis and successfully underwent pericardiectomy with pericardial stripping and a waffle procedure. (Level of Difficulty: Advanced.).

Preparing ethical review systems for emergencies: next steps.

Ethical review systems need to build on their experiences of COVID-19 research to enhance their preparedness for future pandemics. Recommendations from representatives from over twenty countries include: improving relationships across the research ecosystem; demonstrating willingness to reform and adapt systems and processes; and making the case robustly for better resourcing.

The SGLT2 inhibitor canagliflozin suppresses growth and enhances prostate cancer response to radiotherapy.

Radiotherapy is a non-invasive standard treatment for prostate cancer (PC). However, PC develops radio-resistance, highlighting a need for agents to improve radiotherapy response. Canagliflozin, an inhibitor of sodium-glucose co-transporter-2, is approved for use in diabetes and heart failure, but is also shown to inhibit PC growth. However, whether canagliflozin can improve radiotherapy response in PC remains unknown. Here, we show that well-tolerated doses of canagliflozin suppress proliferation and survival of androgen-sensitive and insensitive human PC cells and tumors and sensitize them to radiotherapy. Canagliflozin blocks mitochondrial respiration, promotes AMPK activity, inhibits the MAPK and mTOR-p70S6k/4EBP1 pathways, activates cell cycle checkpoints, and inhibits proliferation in part through HIF-1α suppression. Canagliflozin mediates transcriptional reprogramming of several metabolic and survival pathways known to be regulated by ETS and E2F family transcription factors. Genes downregulated by canagliflozin are associated with poor PC prognosis. This study lays the groundwork for clinical investigation of canagliflozin in PC prevention and treatment in combination with radiotherapy.

Canagliflozin mediates tumor suppression alone and in combination with radiotherapy in non-small cell lung cancer (NSCLC) through inhibition of HIF-1α.

Non-small cell lung cancer (NSCLC) has a poor prognosis, and effective therapeutic strategies are lacking. The diabetes drug canagliflozin inhibits NSCLC cell proliferation and the mammalian target of rapamycin (mTOR) pathway, which mediates cell growth and survival, but it is unclear whether this drug can enhance response rates when combined with cytotoxic therapy. Here, we evaluated the effects of canagliflozin on human NSCLC response to cytotoxic therapy in tissue cultures and xenografts. Ribonucleic acid sequencing (RNA-seq), real-time quantitative PCR (RT-qPCR), metabolic function, small interfering ribonucleic acid (siRNA) knockdown, and protein expression assays were used in mechanistic analyses. We found that canagliflozin inhibited proliferation and clonogenic survival of NSCLC cells and augmented the efficacy of radiotherapy to mediate these effects and inhibit NSCLC xenograft growth. Canagliflozin treatment alone moderately inhibited mitochondrial oxidative phosphorylation and exhibited greater antiproliferative capacity than specific mitochondrial complex-I inhibitors. The treatment downregulated genes mediating hypoxia-inducible factor (HIF)-1α stability, metabolism and survival, activated adenosine monophosphate-activated protein kinase (AMPK) and inhibited mTOR, a critical activator of hypoxia-inducible factor-1α (HIF-1α) signaling. HIF-1α knockdown and stabilization experiments suggested that canagliflozin mediates antiproliferative effects, in part, through suppression of HIF-1α. Transcriptional regulatory network analysis pinpointed histone deacetylase 2 (HDAC2), a gene suppressed by canagliflozin, as a key mediator of canagliflozin's transcriptional reprogramming. HDAC2 knockdown eliminated HIF-1α levels and enhanced the antiproliferative effects of canagliflozin. HDAC2-regulated genes suppressed by canagliflozin are associated with poor prognosis in several clinical NSCLC datasets. In addition, we include evidence that canagliflozin also improves NSCLC response to chemotherapy. In summary, canagliflozin may be a promising therapy to develop in combination with cytotoxic therapy in NSCLC.

Prevalence and Associated Factors of Vitamin D Deficiency in High Altitude Region in Saudi Arabia: Three-Year Retrospective Study.

Background: Vitamin D has many functions in the human body, and its deficiency is associated with skeletal and non-skeletal diseases. Vitamin D deficiency (blood level of 25 (OH) vitamin D < 20 ng/mL) has been reported worldwide, including Kingdom of Saudi Arabia (KSA). Its prevalence and associated factors vary according to KSA region. Therefore, this study aimed to explore the prevalence and risk factors of vitamin D deficiency in the Taif region of KSA. Methods: This retrospective study included patients who attended outpatient clinics at the Alameen General Hospital from 2019 to 2021. Demographic, clinical, and laboratory data were collected using a hospital software system. Results: The study included 2153 patients and vitamin D deficiency was diagnosed in 900 (41.8%) of whom were diagnosed with vitamin D deficiency. It was more common in males (P=0.021), younger age (<0.001), and in patients without comorbidities. There was a positive correlation between 25 (OH) vitamin D levels and blood cholesterol, high-density lipoprotein, calcium, and vitamin B12 levels. In the binary logistic regression analysis, age was the most significant predictor (P<0.001), followed by the absence of thyroid disease (P=0.012) and asthma (P=0.030). Conclusion: Vitamin D deficiency is common in the Saudi population despite sunny weather in KSA. It is more prevalent among males, younger individuals, and those without comorbidities such as thyroid diseases and asthma.

Treatment of Concomitant Congenital Pseudarthrosis of the Fibula With Propeller Periosteal Flap.

INTRODUCTION: Congenital pseudarthrosis of the fibula is not an uncommon condition to accompany congenital pseudarthrosis of the tibia. Persistence of the fibular pseudarthrosis has been linked to inferior outcomes including tibial union and alignment, refractures, and ankle alignment. In this report, we present the results of a pedicled periosteal propeller flap technique for the treatment of fibular pseudarthrosis. METHODS: Ten children with an average age at surgery of 5.3 years who had congenital pseudarthrosis of both tibia and fibula were studied. The tibia was treated with free vascularized fibular grafting, and the ipsilateral fibula was treated with a technique after resection of the pseudarthrosis. A periosteal flap from the proximal healthy part of the fibula is harvested off the bone, rotated 180° based on a branch from the peroneal vessels to cover the fibular defect and fashioned in the form of a tube filled with bone fragments. RESULTS: The periosteal flap size ranged from 5 to 7 cm. Follow-up averaged 37.2 months. The tibia was united in all cases; in 2 of them, refractures occurred and healed with conservative management. The fibula was united in 8 cases. At final follow-up, 5 cases showed residual tibial deformity, and 5 showed residual ankle deformity. Average leg-length discrepancy was 1.4 cm (0-3 cm). CONCLUSION: The pedicled periosteal propeller flap presents a useful new technique for managing concomitant congenital fibular pseudarthrosis.

Radiation synthesis and photocatalytic performance of floated graphene oxide decorated ZnO/ alginate-based beads for methylene blue degradation under visible light irradiation.

Organic dye contamination, emanating from pharmaceutical, paper, and textile industries into water resources, severely threatens marine and human life even at low concentrations. Photocatalysis is one of the most important remediation techniques that decolorize water by employing the power of light. In this work, the development of floated beads of Sodium Alginate/hydroxyethyl methacrylate (Alg-g-HEMA) encompass graphene oxide (GO) decorated Zinc oxide (ZnO) utilizing ionizing radiation was designed to function as a photocatalyst when exposed to visible light. Floatability was induced using calcium carbonate. GO was sonochemically decorated with ZnO nanoparticles and the yield was characterized using XRD, FTIR, TEM, SEM, and EDX techniques. Optical characteristics of the developed nanostructure were performed using UV-Vis spectrophotometry. The photocatalytic activity of the floated (Alg-g-HEMA)-ZnO@GO beads was assessed for the photo decolorization of methylene blue dye (MB) under visible light. The upshot of operational factors such as photocatalyst dose, pH, initial dye concentration, and irradiation time on the decolorization of MB was examined. It was observed that 1 g of the developed (Alg-g-HEMA)-ZnO@GO photocatalyst was able to decolorize 1000 ml of 20 ppm of MB within 150 min at pH 9. In terms of kinetics, photo-decolorization follows Langmuir Hinshelwood pseudo-first order.

A Case of Diabetic Ketoacidosis Presented With Severe Rhabdomyolysis-Induced Acute Kidney Injury.

We present a patient who presented with diabetic ketoacidosis and severe rhabdomyolysis-induced acute kidney injury. The patient developed generalized edema, nausea, and vomiting, and his kidney function deteriorated, necessitating renal replacement therapy, despite the successful treatment of his initial conditions. A comprehensive evaluation was conducted to determine the underlying cause of the severe rhabdomyolysis, including autoimmune myopathies, viral infections, and metabolic disorders. A muscle biopsy revealed necrosis and myophagocytosis but no significant inflammation or myositis. The patient's clinical and laboratory results improved with appropriate treatment, including temporary dialysis and erythropoietin therapy, and he was discharged to continue his rehabilitation with home health care.

Congenital Pseudarthrosis of the Tibia: Long-term Outcome of Treatment With Intramedullary Vascularized Fibular Graft Combined With Ilizarov Distraction.

BACKGROUND: Late presenting cases of congenital pseudarthrosis of the tibia, are further complicated with severe shortening. Limb length discrepancy (LLD) cannot be corrected by vascularized fibular grafting and the use of Ilizarov distraction is associated with a high rate of complications. The aim of this study was to report the long-term follow-up of a combined technique previously published under the name "telescoping vascularized fibular graft". MATERIALS AND METHODS: Eleven patients operated at an average age of 10.2±3.2 years were reviewed. All cases were Crawford type IV affected by neurofibromatosis 1. Nine patients had an average of 4.3 previous operations. Preoperative LLD averaged 7.9±2.5 cm. RESULTS: Follow-up averaged 10±5.4 years. Seven cases (63.6%) reached skeletal maturity before final follow-up. Primary union was achieved in all cases after an average of 7.2±1.3 months. Full weightbearing was possible after an average of 10.6±2.2 months. Recurrent stress fractures occurred in 9 cases (81.8%) and healed with casting in 6 cases and required internal fixation in 3 cases. Eight cases (72.8%) developed tibial shaft deformities, mainly procurvatum that required corrective osteotomy in 2 cases. Final LLD averaged 2.7±1.3 cm. Complete tibialization of the graft was achieved after an average of 17.0 ± 3.6 months. Valgus deformity of the ipsilateral ankle averaged 12.4 degrees±7.5. CONCLUSION: The presented technique avoids osteotomy of the diseased bone and allows simultaneous treatment of the pseudarthrosis and correction of shortening. Compared with conventional bone transport, it requires shorter time of frame application and therefore better patient tolerability because there is no waiting for consolidation of the regenerate. The dis-impaction of the doweled fibula occurs proximally, allowing the less active site located at the distal aspect of the pseudarthrosis to heal without displacement. A shortcoming of the presented technique is the more propensity for axial deviation and refractures that seldom require surgery. LEVEL OF EVIDENCE: Level-IV.

Zirconium preconcentration from zircon raffinate using gamma radiation-induced polymerization of reduced graphene oxide composite.

Zirconium is commonly used as a cladding material for nuclear reactors. The purity of the zirconium material seeks to control reactor efficiency. A novel composite of reduced graphene oxide-grafted polyacrylic acid, malic acid, and trioctylamine (rGO-g-PAA-MA/TOA) was prepared using in situ radical polymerization with gamma radiation at a dose of 25 KGy from a 60Co cell to preconcentrate zirconium Zr(IV) from zircon raffinate. Five distinct rGO-g-PAA-MA/TOA composite compositions were created and evaluated. The best composite composition was 62.95% acrylic acid, 15.8% malic acid, and 15.8% trioctylamine. After 60 min, the sorption reaction reached equilibrium at pH 0.35 and 20 °C. The pseudo nth order indicated that the order of the sorption reaction was 1.8476. The Elovich model and Dubinin-Radushkevich model controlled the kinetic mechanism and adsorption isotherm of the sorption reaction, respectively; based on estimated regression plots and quantitatively with three different error functions: coefficient of determination (R2), chi-square statistic (χ2), and corrected Akaike information (AICc). The adsorption capacity of rGO-g-PAA-MA/TOA was 75.06 mg g-1. Exothermic reaction and spontaneous sorption took place. Using 2 M H2SO4, 98% of the zirconium was efficiently desorbed. The separation of contaminated Ti(IV) from desorbed Zr(IV) by raising pH to 2.5 through hydrolysis and ZrO2 formation.

18F-DCFPyL (PSMA) PET as a radiotherapy response assessment tool in metastatic prostate cancer.

Background: Prostate Specific Membrane Antigen (PSMA) - positron emission tomography (PET) guides metastasis-directed radiotherapy (MDRT) in prostate cancer (PrCa). However, its value as a treatment response assessment tool after MDRT remains unclear. Importantly, there is limited understanding of the potential of radiotherapy (RT) to alter PSMA gene (folate hydrolase 1; FOLH1) expression. Methodology: We reviewed a series of 11 men with oligo-metastatic PrCa (25 metastasis sites) treated with MDRT before re-staging with 18F-DCFPyL (PSMA) PET upon secondary recurrence. Acute effects of RT on PSMA protein and mRNA levels were examined with qPCR and immunoblotting in human wild-type androgen-sensitive (LNCap), castrate-resistant (22RV1) and castrate-resistant neuroendocrine (PC3 and DU145) PrCa cell lines. Xenograft tumors were analyzed with immunohistochemistry. Further, we examined PSMA expression in untreated and irradiated radio-resistant (RR) 22RV1 (22RV1-RR) and DU145 (DU145-RR) cells and xenografts selected for survival after high-dose RT. Results: The majority of MDRT-treated lesions showed lack of PSMA-PET/CT avidity, suggesting treatment response even after low biological effective dose (BED) MDRT. We observed similar high degree of heterogeneity of PSMA expression in both human specimens and in xenograft tumors. PSMA was highly expressed in LNCap and 22RV1 cells and tumors but not in the neuroendocrine PC3 and DU145 models. Single fraction RT caused detectable reduction in PSMA protein but not in mRNA levels in LNCap cells and did not significantly alter PSMA protein or mRNA levels in tissue culture or xenografts of the other cell lines. However, radio-resistant 22RV1-RR cells and tumors demonstrated marked decrease of PSMA transcript and protein expression over their parental counterparts. Conclusions: PSMA-PET may be a promising tool to assess RT response in oligo-metastatic PrCa. However, future systematic investigation of this concept should recognize the high degree of heterogeneity of PSMA expression within prostate tumors and the risk for loss of PSMA expression in tumor surviving curative courses of RT.

Policies of biomedical preprint servers on conflicts of interest, authorship, and research integrity lacked important details.

OBJECTIVES: To assess the policies of biomedical preprint servers on the reporting of funding, conflict of interest (COI), author contributions, and research integrity. STUDY DESIGN AND SETTING: We generated a list of potentially eligible preprint servers then judged their eligibility in duplicate and independently. Between July and September 2021, we extracted information from the websites of these servers in duplicate and independently and through a simulated submission. RESULTS: We included 37 preprint servers. A variable percentage of these servers had policies for reporting of funding (43%), disclosure of COI (78%), specification of authors' contributions (54%), and research integrity (76%). While 97% of the COI policies required authors to disclose their own interests, only 7% addressed interests related to family members. About a third of authors' contribution policies (30%) did not specify the types of contributions to report. While a majority of research integrity polices described screening checks for plagiarism (71%), a minority described screening checks for fabrication (39%), falsification (36%), and image manipulation (32%). CONCLUSION: Less than half of biomedical preprint servers have policies on reporting on funding. Policies related to COI disclosure, reporting of author contributions, and research integrity lack important details.

Performance evaluation of microbial fuel cell using a radiation synthesized low density polyethylene-grafted-poly (glycidyl methacrylate-co-vinyl acetate) as a proton exchange membrane.

ABSTRACTThe present work focuses on the synthesis of a proton exchange membrane to be assembled in a microbial fuel cell (MFC) for simultaneous bioelectricity production and domestic wastewater treatment. The indigenous membrane was prepared by ionizing irradiation-induced graft copolymerization of glycidyl methacrylate (GMA) and vinyl acetate (VAc) onto low-density polyethylene and subsequently, the prepared grafted sheets were sulfonated via epoxy ring-opening of PGMA moieties. Parameters affecting the grafting degree were investigated and the prepared membranes were characterized by investigating their structural, thermal, mechanical, and electrical properties. Some physicochemical characteristics including ion exchange capacity, sulfonation density, and proton conductivity were also evaluated. The data confirmed the success of the preparation protocol to obtain a suitable membrane for the proposed application. Moreover, the performance of the assembled MFC was thoroughly investigated through the evaluation of its electrochemical behaviour including cyclic voltammetry, electrochemical impedance spectroscopy, columbic efficiency, and wastewater treatment capability. The sulfonated LDPE-g-P(GMA-co-VAc) membrane of 80% grafting degree shows substantial removal of chemical oxygen demand up to about 90% with columbic efficiency of 10.1%, columbic recovery of 8.7%, rate of energy harvest of 2.1 C/h and power density of 2.72 W m-2. However, the use of 10 mM of KMnO4 as electron acceptor drastically increase the harvested power density to reach 356.4 W m-2.

Pernicious Anemia and Vitamin B12 Deficiency Presenting As Pseudothrombotic Microangiopathy and Developing Secondary Thrombocytopenia After Treatment: A Case Report.

Pernicious anemia (PA) is an autoimmune disease secondary to chronic atrophic gastritis leading to vitamin B12 deficiency. Rarely, some patients may develop advanced hematological complications that mimic those of thrombotic thrombocytopenic purpura (TTP). Differentiating these conditions is crucial because they require different management. We present a case of a 68-year-old male who presented with generalized weakness, fatigue, and shortness of breath. This patient had anemia, thrombocytopenia, and a markedly deficient serum level of vitamin B12. The symptoms initially mimicked those associated with TTP, but the activity of ADAMTS 13 was normal. A diagnosis of pseudo-TTP has been made due to vitamin B12 deficiency resulting from PA with reactive thrombocytosis. Ultimately, vitamin B12 deficiency pseudo-TTP should be considered a differential diagnosis for therapy refractory TTP because of its different management strategies ranging from parenteral Vitamin B12 in PA patients with highly favorable outcomes to more advanced treatment with less favorable outcomes in TTP patients.

Combined metformin-salicylate treatment provides improved anti-tumor activity and enhanced radiotherapy response in prostate cancer; drug synergy at clinically relevant doses.

BACKGROUND: There is need for well-tolerated therapies for prostate cancer (PrCa) secondary prevention and to improve response to radiotherapy (RT). The anti-diabetic agent metformin (MET) and the aspirin metabolite salicylate (SAL) are shown to activate AMP-activated protein kinase (AMPK), suppress de novo lipogenesis (DNL), the mammalian target of rapamycin (mTOR) pathway and reduce PrCa proliferation in-vitro. The purpose of this study was to examine whether combined MET+SAL treatment could provide enhanced PrCa tumor suppression and improve response to RT. METHODS: Androgen-sensitive (22RV1) and resistant (PC3, DU-145) PrCa cells and PC3 xenografts were used to examine whether combined treatment with MET+SAL can provide improved anti-tumor activity compared to each agent alone in non-irradiated and irradiated PrCa cells and tumors. Mechanisms of action were investigated with analysis of signaling events, mitochondria respiration and DNL activity assays. RESULTS: We observed that PrCa cells are resistant to clinically relevant doses of MET. Combined MET + SAL treatment provides synergistic anti-proliferative activity at clinically relevant doses and enhances the anti-proliferative effects of RT. This was associated with suppression of oxygen consumption rate (OCR), activation of AMPK, suppression of acetyl-CoA carboxylase (ACC)-DNL and mTOR-p70s6k/4EBP1 and HIF1α pathways. MET + SAL reduced tumor growth in non-irradiated tumors and enhanced the effects of RT. CONCLUSION: MET+SAL treatment suppresses PrCa cell proliferation and tumor growth and enhances responses to RT at clinically relevant doses. Since MET and SAL are safe, widely-used and inexpensive agents, these data support the investigation of MET+SAL in PrCa clinical trials alone and in combination with RT.