Cross-fellowship Inter-institutional Exchange: Answering the Call for Hepatopancreatobiliary Training Standardization.

OBJECTIVE: General surgery trainees interested in performing hepatopancreatobiliary (HPB) surgery can choose from multiple fellowship pathways, namely HPB, surgical oncology (SO), and abdominal transplant-HPB (TXP-HPB). Although focused on similar operations, each program offers distinct clinical and technical emphases. DESIGN: An annual inter-institutional exchange between TXP-HPB and SO fellowships, starting in 2014. SETTING AND PARTICIPANTS: TXP-HPB fellows from Washington University in St. Louis (WUSTL) and SO fellows from Memorial Sloan Kettering Cancer Center (MSKCC). RESULTS: About 14 fellows have participated in the exchange so far, 13 of whom responded to our survey. At MSKCC, TXP-HPB fellows performed a median of 24 cases, including 6 major pancreatic resections, 3 major hepatectomies, 4 hepatic artery infusion pump insertions, and 1 major biliary case. At WUSTL, SO fellows performed a median of 16 cases, including 5 liver transplants, 2 major pancreatic resections, 2 major hepatectomies, and 2 major biliary cases. About 92.3% of respondents stated they would repeat the rotation, with SO fellows emphasizing the exposure to vascular anastomoses and transplant-HPB fellows appreciating the oncologic focus. CONCLUSIONS: A monthlong inter-institutional exchange offers a unique opportunity to standardize and improve HPB education.

Unveiling Immune Infiltration Characterizing Genes in Hypertrophic Cardiomyopathy Through Transcriptomics and Bioinformatics.

Background: Hypertrophic cardiomyopathy (HCM) is a dominantly inherited disease associated with sudden immune cell associations that remain unclear. The aim of this study was to comprehensively screen candidate markers associated with HCM and immune cells and explore potential pathogenic pathways. Methods: First, download the GSE32453 dataset to identify differentially expressed genes (DEGs) and perform Gene Ontology and pathway enrichment analysis using DAVID and GSEA. Next, construct protein-protein interaction (PPI) networks using String and Cytoscape to identify hub genes. Afterward, use CIBERSORT to determine the proportion of immune cells attributed to key genes in HCM and conduct ROC analysis based on the external dataset GSE36961 to evaluate their diagnostic value. Finally, validate the expression of key genes in the hypertrophic cardiomyocyte model through qRT-PCR using data from the HPA database. Results: Comprehensive analysis revealed that there were 254 upregulated genes and 181 downregulated genes in HCM. The enrichment study underscored pathways of inflammatory signaling, including MAPK and PI3K-Akt pathways. Pathways abundant in genes associated with HCM encompassed myocardial contraction and NADH dehydrogenase activity. Additionally, the analysis of immune infiltration revealed a notable increase in macrophages, NK cells, and monocytes in the HCM group, showing statistically significant variances in CD4 memory resting T cell infiltration when compared to the healthy control group. Within the validation dataset GSE36961, the Area Under the Curve (AUC) scores for eight crucial genes (FOS, CD86, CD68, BDNF, PIK3R1, PLEK, RAC2, CCL2) each exceeded 0.8. The HPA database revealed the positioning traits and paths of these eight crucial genes in smooth muscle cells, myocardial cells, and fibroblasts. The outcomes of the qRT-PCR were aligned with the sequencing findings. Conclusion: Bioinformatics analysis unveiled pivotal genes, pathways, and immune involvement, illuminating the molecular underpinnings of HCM. These findings suggest promising therapeutic targets for clinical applications.

Robotic living donor nephrectomy is associated with reduced post-operative opioid use compared to hand-assisted laparoscopic approach.

BACKGROUND: Robotic donor nephrectomy (RDN) has emerged as a safe alternative to laparoscopic donor nephrectomy (LDN). Having previously demonstrated comparable efficacy, this study aims to examine postoperative analgesia use (opioid and non-opioid) in the two groups. METHODS: We conducted a retrospective review of 300 living donor nephrectomies performed at our center, comparing 150 RDN's with a contemporary cohort of 150 hand-assisted LDN's. In addition to clinical and demographic information, data on postoperative inpatient opioid and non-opioid analgesia (from patient's arrival to the surgical floor after surgery till the time of discharge) was collected. Opioid dosages were standardized by conversion to morphine milligram equivalents (MME). All patients were managed post-operatively under a standardized ERAS pathway for living donor nephrectomy patients. RESULTS: There were no significant differences in donor age, gender, and BMI between RDN and LDN groups. Total post-operative opioid use (MME's) was significantly lower in RDN patients (RDN 27.1 vs. LDN 46.3; P < 0.0001). Breakdown of opioid use with post-operative (POD) day demonstrated significantly lower use in RDN group on POD1 (RDN 8.6 vs. LDN 17.0; P < 0.05), and POD2 (RDN 3.9 vs LDN 10; P < 0.05). RDN patients had a shorter post-operative length of stay (LOS) (RDN 1.69 days vs. LDN 1.98; P = 0.0003). There were no differences between groups in non-opioid medication use, complications, and readmission rates. CONCLUSION: RDN has comparable safety to hand-assist LDN and offers additional benefits of lower postoperative opioid requirement and a shorter hospital LOS.

A retrospective study comparing the results of continuous glucose monitoring to self-blood glucose monitoring for pregnant women with type 1 diabetes mellitus.

BACKGROUND: Type 1 diabetes mellitus (T1DM) is associated with adverse maternal and fetal outcomes. Continuous glucose monitoring (CGM) during pregnancy is associated with better glycemic control in women with T1DM. However, no clear benefits have been demonstrated in reducing adverse feto-maternal outcomes in pregnant women with T1DM. DESIGN AND METHODS: This is a retrospective, single-center study of pregnant women with T1DM to evaluate the impact of CGM use on glycemic control and feto-maternal outcomes in pregnant women with T1DM. RESULTS: Of 265 women with T1DM, 92 (34.7%) used CGM, and 173 (65.3%) were managed with capillary blood glucose (CBG) monitoring. The mean (SD) age and BMI at the first visit were 29.4 (4.7) years and 27.2 (5.2) kg/m2, respectively. The mean (SD) HbA1c at the first-trimester visit was 63 (1) mmol/mol, and in the last trimester was 51 (1%). There was no difference in the mean changes in HbA1c between the two groups. Women using CGM had lower insulin requirements (1.02 + 0.37 vs. 0.87 + 0.04 units/kg, p = 0.01). The two groups had no significant differences in maternal or fetal outcomes. CONCLUSION: CGM use in pregnant T1DM women is not associated with improved fetomaternal outcomes.

Functional characterisation of Dof gene family and expression analysis under abiotic stresses and melatonin-mediated tolerance in pitaya (Selenicereus undatus).

DNA binding proteins with one finger (Dof ) transcription factors are essential for seed development and defence against various biotic and abiotic stresses in plants. Genomic analysis of Dof has not been determined yet in pitaya (Selenicereus undatus ). In this study, we have identified 26 Dof gene family members, renamed as HuDof-1 to HuDof-26 , and clustered them into seven subfamilies based on conserved motifs, domains, and phylogenetic analysis. The gene pairs of Dof family members were duplicated by segmental duplications that faced purifying selection, as indicated by the K a /K s ratio values. Promoter regions of HuDof genes contain many cis -acting elements related to phytohormones including abscisic acid, jasmonic acid, gibberellin, temperature, and light. We exposed pitaya plants to different environmental stresses and examined melatonin's influence on Dof gene expression levels. Signifcant expression of HuDof -2 and HuDof -6 were observed in different developmental stages of flower buds, flowers, pericarp, and pulp. Pitaya plants were subjected to abiotic stresses, and transcriptome analysis was carried out to identify the role of Dof gene family members. RNA-sequencing data and reverse transcription quantitative PCR-based expression analysis revealed three putative candidate genes (HuDof -1, HuDof -2, and HuDof -8), which might have diverse roles against the abiotic stresses. Our study provides a theoretical foundation for functional analysis through traditional and modern biotechnological tools for pitaya trait improvement.

Oxidative stress, inflammation, and steatosis elucidate the complex dynamics of HgCl2 induced liver damage in Channa punctata.

Water bodies are highly pollution-prone areas in which mercury (Hg) is considered as a major menace to aquatic organisms. However, the information about the toxicity of mercuric chloride (HgCl2) in a vital organ such as the liver of fish is still inadequate. This study aimed to assess the impact of mercuric chloride (HgCl2) exposure on the liver of Channa punctata fish over 15, 30, and 45 days, at two different concentrations (0.039 mg/L and 0.078 mg/L). Mercury is known to be a significant threat to aquatic life, and yet, information regarding its effects on fish liver remains limited. The results of this study demonstrate that exposure to HgCl2 significantly increases oxidative stress markers, such as lipid peroxidation (LPO) and protein carbonyls (PC), as well as the levels of serum glutamic-oxaloacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT) in the fish. Additionally, the transcriptional and protein analysis of specific genes and molecules associated with necroptosis and inflammation, such as ABCG2, TNF α, Caspase 3, RIPK 3, IL-1ß, Caspase-1, IL-18, and RIPK1, confirm the occurrence of necroptosis and inflammation in the liver. Histopathological and ultrastructural examinations of the liver tissue further reveal a significant presence of liver steatosis. Interestingly, the upregulation of PPARα suggests that the fish's body is actively responding to counteract the effects of liver steatosis. This study provides a comprehensive analysis of oxidative stress, biochemical changes, gene expression, protein profiles, and histological findings in the liver tissue of fish exposed to mercury pollution in freshwater environments.

Intracranial Efficacy of Atezolizumab, Bevacizumab, Carboplatin, and Paclitaxel in Real-World Patients with Non-Small-Cell Lung Cancer and EGFR or ALK Alterations.

Contrary to Pemetrexed-containing chemo-immunotherapy studies, Atezolizumab, Bevacizumab, Carboplatin, and Paclitaxel (ABCP) treatment has consistently shown clinical benefit in prospective studies in patients with lung cancer and actionable mutations, where intracranial metastases are common. Here, we aimed to describe the real-life population of patients fit to receive ABCP after targeted therapy and quantify its clinical effect in patients with brain metastases. Patients treated in Cheshire and Merseyside between 2019 and 2022 were identified. Data were collected retrospectively. A total of 34 patients with actionable EGFR or ALK alterations had treatment with a median age of 59 years (range 32-77). The disease control rate was 100% in patients with PDL1 ≥ 1% (n = 10). In total, 19 patients (56%) had brain metastases before starting ABCP, 17 (50%) had untreated CNS disease, and 4 (22%) had PDL1 ≥ 1%. The median time to symptom improvement was 12.5 days (range 4-21 days), with 74% intracranial disease control rates and 89.5% synchronous intracranial (IC) and extracranial (EC) responses. IC median Progression Free Survival (mPFS) was 6.48 months, EC mPFS was 10.75 months, and median Overall Survival 11.47 months. ABCP in real-life patients with brain metastases (treated or untreated) was feasible and showed similar efficacy to that described in patients without actionable mutations treated with upfront chemo-immunotherapy.

Utilization of older deceased donors for pediatric liver transplant may negatively impact long-term survival.

BACKGROUND: Multiple adult studies have investigated the role of older donors (ODs) in expanding the donor pool. However, the impact of donor age on pediatric liver transplantation (LT) has not been fully elucidated. METHODS: UNOS database was used to identify pediatric (≤18 years) LTs performed in the United States during 2002-22. Donors ≥40 years at donation were classified as older donors (ODs). Propensity analysis was performed with 1:1 matching for potentially confounding variables. RESULTS: A total of 10,024 pediatric liver transplantation (PLT) patients met inclusion criteria; 669 received liver grafts from ODs. Candidates receiving OD liver grafts were more likely to be transplanted for acute liver failure, have higher Model End-Stage Liver Disease/Pediatric End-Stage Liver Disease (MELD/PELD) scores at LT, listed as Status 1/1A at LT, and be in the intensive care unit (ICU) at time of LT (all p < 0.001). Kaplan-Meier (KM) analyses showed that recipients of OD grafts had worse patient and graft survival (p < 0.001) compared to recipients of younger donor (YD) grafts. KM analyses performed on candidates matched for acuity at LT revealed inferior patient and graft survival in recipients of deceased donor grafts (p < 0.001), but not living donor grafts (p > 0.1) from ODs. Cox regression analysis demonstrated that living donor LT, diagnosis of biliary atresia and first liver transplant were favorable predictors of recipient outcomes, whereas ICU stay before LT and transplantation during 2002-12 were unfavorable. CONCLUSION: Livers from ODs were used for candidates with higher acuity. Pediatric recipients of livers from ODs had worse outcome compared to YDs; however, living donor LT from ODs had the least negative impact on recipient outcomes.

Knowledge, Attitude and Practice Toward Artificial Intelligence Among Healthcare Workers in Private Polyclinics in Jeddah, Saudi Arabia.

Purpose: The objective of our study was to assess awareness, attitudes, and practices regarding artificial intelligence (AI) among healthcare workers in private polyclinics in Jeddah, Saudi Arabia. Methods: We conducted cross-sectional study among healthcare workers in private clinics in Jeddah. Data was collected using a structured, validated questionnaire in Arabic and English on awareness, attitudes, and behaviors regarding AI. Cronbach's alpha for the questionnaire ranged from 0.6 to 0.8. Descriptive and bivariate analysis was done to assess the scores and their association of various sociodemographic variables with awareness, attitudes, and behaviors regarding AI. Multiple linear regression was performed to predict the scores of awareness, attitudes, and behaviors based on the sociodemographic variables. Results: We recruited 361 participants for this study. Approximately, 62% of the healthcare workers were female. The majority (36%) of healthcare workers were nurses, while 25% were physicians. The median awareness, attitude, and behavioral scores were 5/6 (IQR 3-6), 5/8 (IQR 4-7), and 0/3 (IQR 0), respectively. Approximately three-fourths (74%) of the healthcare workers believed that they understood the basic computational principles of AI. Only half of the participants were willing to use AI when making future medical decisions. We found that male healthcare workers had better knowledge scores regarding AI as compared to female healthcare workers (Beta = 0.555, 95%, p value = 0.010), while for attitude scores, being administrative employee as compared to other employees was found to have negative attitude towards AI (Beta = 0.049, 95%, p value = 0.03). Conclusion: We found that healthcare workers had an overall good awareness and optimistic attitude toward AI. Despite this, the majority is worried about the potential consequences of replacing their jobs with AI in the future. There is a dire need to educate and sensitize healthcare workers regarding the potential impact of AI on healthcare.

Successful medical management of a pituitary macroadenoma with features of resistant acromegaly and hyperprolactinemia using pasireotide.

BACKGROUND: The somatostatin analog, pasireotide, is used for the treatment of acromegaly after the failure of surgery and/or first-line medical treatment. CASE PRESENTATION: A 48-year-old male reported that during a workup for obesity in his home country, hyperprolactinemia was diagnosed and a 3.5 × 3.5 cm pituitary macroadenoma was identified on pituitary MRI. He received cabergoline for 6 months; then he was lost to follow-up. He presented at our Endocrine clinic 2 years later for treatment of obesity (BMI 49.5 kg/m2). Biochemical workup revealed that in addition to hyperprolactinemia (7,237 [normal: 85-323 mIU/L), he had acromegaly, evident by elevated insulin-like growth factor 1 (IGF-1) level (450 [normal: 88-210 µg/L]), and a positive growth hormone suppression test, secondary hypothyroidism, and secondary hypogonadism. Pituitary MRI showed that the adenoma encased parts of the left and right internal carotid arteries and encroached on the optic chiasm. Surgical excision was therefore not feasible. He was treated with cabergoline and later, long-acting release (LAR) octreotide. Prolactin levels were reduced with cabergoline, but IGF-1 levels did not respond to octreotide, and it was discontinued. The patient abandoned radiotherapy after two sessions. He was started on LAR pasireotide 40 mg every 4 weeks and continued on cabergoline 0.5 mg per week. His biochemical response was dramatic, with a near normalization of IGF-1 levels in 3 months. After 6 months from starting pasireotide, we increased cabergoline dose from 0.5 mg/week to 3 mg/week. Three months later, IGF-1 level was normalized. The patient developed type 2 diabetes as a side effect of pasireotide; however, this was well-controlled with medications. CONCLUSIONS: The case suggests that pasireotide can provide marked biochemical improvement in acromegaly after the failure of both cabergoline monotherapy and cabergoline plus octreotide. This further confirms a potentially efficacious treatment regimen in treatment-resistant acromegaly with hyperprolactinemia.

Total robotic liver transplant: the final frontier of minimally invasive surgery.

The use of robotic surgery in transplantation is increasing; however, robotic liver transplantation (RLT) remains a challenging undertaking. To our knowledge, this is a report of the first RLT in North America and the first RLT using a whole graft from a deceased donor in the world. This paper describes the preparation leading to the RLT and the surgical technique of the operation. The operation was performed in a 62-year-old man with hepatitis C cirrhosis and hepatocellular carcinoma with a native Model for End-Stage Liver Disease score of 10. The total console time for the operation was 8 hours 30 minutes, and the transplant hepatectomy took 3 hours 30 minutes. Warm ischemia time was 77 minutes. Biliary reconstruction was performed in a primary end-to-end fashion and took 19 minutes to complete. The patient had an uneventful recovery without early allograft dysfunction or surgical complications and continues to do well after 6-months follow-up. This paper demonstrates the feasibility of this operation in highly selected patients with chronic liver disease. Additional experience is required to fully understand the role of RLT in the future of transplant surgery. Narrated video is available at https://youtu.be/TkjDwLryd3I.

Once-weekly versus twice-weekly bortezomib in newly diagnosed multiple myeloma: a real-world analysis.

Induction regimens for multiple myeloma (MM) commonly include bortezomib, which has typically been administered twice weekly despite studies demonstrating comparable efficacy and less peripheral neuropathy (PN) with once-weekly bortezomib. We aimed to analyze the real-world prevalence and efficacy of once-weekly versus twice-weekly bortezomib regimens in newly diagnosed MM. We analyzed 2497 US patients aged 18-70 years treated with commercial first-line bortezomib using nationwide Flatiron Health electronic health record-derived data, including 910 (36.4%) patients who received twice-weekly and 1522 (63.2%) who received once-weekly bortezomib. Once-weekly bortezomib use increased over time, from 57.7% in 2017 to 73.1% in 2022. Multivariate analysis identified worsened performance status and more recent year of diagnosis with higher odds of receiving once-weekly bortezomib. Real-world progression-free survival (median 37.2 months with once-weekly versus 39.6 months with twice-weekly, p = 0.906) and overall survival (medians not reached in either cohort, p = 0.800) were comparable. PN rates were higher in patients receiving twice-weekly bortezomib (34.7% versus 18.5%, p < 0.001). In conclusion, once-weekly bortezomib is clearly associated with similar efficacy and fewer toxicities compared to twice-weekly bortezomib. Our findings support once-weekly bortezomib as a standard-of-care regimen for newly diagnosed patients with MM.

Prevalence and prognosis of fulminant type 1 diabetes mellitus in The Middle East: a comparative analysis in a 5-year nationwide cohort.

PURPOSE: To analyze the prevalence and progression of fulminant type 1 diabetes (FT1D) in Qatar. METHODS: This retrospective study analyzed consecutive index- diabetic ketoacidosis (DKA) admissions (2015-2020) among patients with new-onset T1D (NT1D) in Qatar. RESULTS: Of the 242 patients, 2.5% fulfilled the FT1D diagnostic criteria. FT1D patients were younger (median-age 4-years vs.15-years in classic-T1D). Gender distribution in FT1D was equal, whereas the classic-T1D group showed a female predominance at 57.6% (n = 136). FT1D patients had a mean C-peptide of 0.11 ± 0.09 ng/ml, compared to 0.53 ± 0.45 ng/ml in classic-T1D. FT1D patients had a median length of stay (LOS) of 1 day (1-2.2) and a DKA duration of 11.25 h (11-15). The median (length of stay) LOS and DKA duration in classic-T1D patients were 2.5 days (1-3.9) and 15.4 h (11-23), respectively. The FT1D subset primarily consisted of moderate (83.3%) and severe 916.7%) DKA, whereas classic T1D had 25.4% mild, 60.6% moderate, and 14% severe DKA cases. FT1D was associated with a higher median white cell count (22.3 × 103/uL) at admission compared to classic T1D (10.6 × 103/uL). ICU admission was needed for 66.6% of FT1D patients, compared to 38.1% of classic-T1D patients. None of the patients in the FT1D group had mortality, while two died in the classic-T1D group. CONCLUSION: This is the first study establishing the existence of FT1D in ME, which presented distinctively from classic-T1D, exhibiting earlier age onset and higher critical care requirements. However, the clinical outcomes in patients with FT1D seem similar to classic T1D.

Clinical characteristics and outcomes of patients with TSH-secreting pituitary adenoma and Graves' disease - a case report and systematic review.

BACKGROUND: Coexistence of TSH-secreting pituitary adenoma (TSHoma) and Graves' disease (GD) is rare and complicates the management decision. METHODS: We present a case of the co-existence of TSHoma and GD. In addition, we systematically searched articles describing TSHoma and GD in the same patient published until 20th March 2023, using Pubmed, Scopus and Embase. CASE PRESENTATION: A 46-year-old man presented with symptoms of thyrotoxicosis. His thyroid function tests showed serum TSH 3.35 (reference range 0.3-4.2) mIU/L, FT3 19.7 (3.7-6.4) pmol/L, and FT4 68.9 (11-23.3) pmol/L. The serum TSH receptor antibody was 11.5 mIU/L (positive at ≥ 1.75 mIU/L). Pituitary magnetic resonance imaging showed macroadenoma compressing the optic chiasm. The patient underwent trans-sphenoidal resection of pituitary adenoma. Postoperatively, he remained on maintenance carbimazole and octreotide. RESULTS: Fourteen articles comprising 15 patients were identified from the systemic search. A total of 16 patients (including the current case) were included in the systematic review. The mean (± SD) age at diagnosis was 41 ± 13.6 years. The majority were females (75%). The median (IQR) TSH was 1.95 (0.12-5.5) mIU/L, the median (IQR) free T3 was 11.7 (7.6-19.7) pmol/L and the median (IQR) free T4 level was 47.6 (33.3-64.4) pmol/L. Ten (76.9%) patients had positive TSH receptor antibody levels. 84.6% had pituitary macroadenoma. Pituitary surgery was performed in 12 (75%) patients. At the last follow-up, 4 (25%) patients had complete resolution of symptoms after pituitary surgery, 3 (18.7%) were on maintenance treatment with thionamides for GD, 1 (6.25%) on beta-blockers and 1 (6.25%) on somatostatin analog. CONCLUSION: TSHoma and GD can co-exist, and it is essential to identify this rare association as it can significantly impact treatment strategies.

A systematic review of literature on Insulin-like growth factor-2-mediated hypoglycaemia in non-islet cell tumours.

INTRODUCTION: Insulin-like growth factor-2 (IGF-2)-mediated hypoglycemia is a rare yet clinically significant entity with considerable morbidity and mortality. Existing literature is limited and fails to offer a comprehensive understanding of its clinical trajectory, management and prognostication. METHODS: Systematic review of English-language articles reporting primary patient data on IMH was searched using electronic databases (PubMed, Scopus and Embase) from any date up to 21 December 2022. Data were analysed in STATA-16. RESULTS: The systematic review contains 172 studies, including 1 Randomised controlled trial, 1 prospective observational study, 5 retrospective observational studies, 150 case reports, 11 case series and 4 conference abstracts. A total of 233 patients were analysed, averaging 60.6 ± 17.1 years in age, with comparable proportions of males and females. The commonest tumours associated with Insulin-like Growth Factor-2-mediated hypoglycaemia were fibrous tumours (N = 124, 53.2%), followed by non-fibrous tumours originating from the liver (N = 21, 9%), hemangiopericytomas (N = 20, 8.5%) and mesotheliomas (N = 11, 4.7%). Hypoglycaemia was the presenting feature of NICT in 42% of cases. Predominant clinical features included loss of consciousness (26.7%) and confusion (21%). The mean IGF-2 and IGF-1 levels were 882.3 ± 630.6 ng/dL and 41.8 ± 47.8, respectively, with no significant correlation between these levels and patient outcomes. Surgical removal was the most employed treatment modality (47.2%), followed by medication therapy. The recovery rate was 77%, with chronic liver disease (CLD) significantly associated with a poor outcome (OR: 7.23, P: 0.03). Tumours originating from fibrous tissues were significantly associated with recovery (p < .001). In the logistic regression model, CLD remained a significant predictor of poor outcomes. CONCLUSION: This systematic review highlights that most non-islet-cell tumour-hypoglycaemia (NICTH) is due to fibrous tumours. NICTs demonstrate a variable prognosis, which is fair if originating from fibrous tissue. Management such as octreotide, corticosteroids, diazoxide, embolization, radiotherapy and surgical resection have disparate success rates.

Identification of serum exosomal miRNA biomarkers for diagnosis of Rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis (RA) is an autoimmune disorder characterized by inflammation-induced joint damage, which can cause lasting disability. Therefore, early diagnosis and treatment of RA are crucial. Herein, we evaluated whether exosomal microRNAs (miRNAs) could be served as promising biomarkers that can accelerate the diagnosis of RA and development of therapies for RA. METHODS: First, we performed small RNA sequencing to determine the miRNA profiles of serum exosomes within a screening cohort comprised of 18 untreated active RA patients, along with 18 age and gender-matched healthy controls (HCs). Subsequently, the miRNA profiles were then validated in a training cohort consisting of 24 RA patients and 24 HCs by RT-qPCR. Finally, the selected exosomal miRNAs were validated in a larger cohort comprising 108 RA patients and 103 HCs. The diagnostic efficacy of the exosomal miRNAs was evaluated by receiver operating characteristic (ROC) curve analysis. Biological functions of the miRNAs were determined by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. RESULTS: Our results first demonstrated a noteworthy upregulation of three candidate miRNAs (miR-885-5p, miR-6894-3p, and miR-1268a) in the RA patients' serum exosomes compared to HCs. The combination of three miRNAs along with anti- citrullinated peptide antibodies (ACPA) exhibited excellent diagnostic accuracy, yielding an area under the curve (AUC) of 0.963 (95 % CI : 0.941-0.984), sensitivity of 87.96 %, and specificity of 93.20 %. Notably, miR-885-5p exhibited remarkable discriminatory capacity by itself in indistinguishing ACPA- negative RA patients from HCs, with an AUC of 0.993 (95 % CI : 0.978-1.000), sensitivity of 96.67 %, and specificity of 100 %. Moreover, the expression of miR-1268a in the assessment of therapeutic effectiveness displayed significant reduction on 29th day of Methotrexate (MTX) treatment in RA patients. This decreased expression paralleled with trends observed in tender 28-joint count (TJC28), swollen 28-joint count (SJC28), and disease activity score with 28-joint count using C-reactive protein (DAS28-CRP), all of which are indicative of RA disease activity. Finally, predictive analysis indicated that, these three exosomal miRNAs target pivotal signaling molecules involved in inflammatory pathways, thereby demonstrating effective modulation of the immune system. CONCLUSIONS: In this study, we successfully demonstrated the promising potential for serum exosomal miRNAs, particularly miR-885-5p, miR-6894-3p and miR-1268a as biomarkers for early diagnosis and prediction of RA for the first time.

Dietary inclusion of Withania somnifera and Asparagus racemosus induces growth, activities of digestive enzymes, and transcriptional modulation of MyoD, MyoG, Myf5, and MRF4 genes in fish, Channa punctatus.

The present study explores growth potential of two medicinal herbs, Withania somnifera (Ashwagandha or 'A') and Asparagus racemosus (Shatavari or 'S') after their dietary inclusion in fish, Channa punctatus (13.5 ± 2 g; 11.5 ± 1 cm). Three hundred well-acclimatized fish were distributed into 10 groups- C (Control), S1 (1% S), S2 (2% S), S3 (3% S), A1 (1% A), A2 (2% A), A3 (3% A), AS1 (1% A and S), AS2 (2% A and S), and AS3 (3% A and S), each having 10 specimens. Fish were fed with these diets for 60 days. The study was performed in triplicate. Growth indices- weight gain (WG), specific growth rate percentage (SGR%), feed intake (FI), and condition factor (CF), after 30 and 60 days, were found significantly (p < 0.05) up-regulated in all the groups, except S1, when compared to the C. A significant (p < 0.05) increase in final body weight (FBW) was noticed in all the groups, except S1, after 60 days. Relative to the control group, activities of lipase and amylase in the gut tissue were elevated in all groups, at both sampling times, with the exception of lipase in S1 at 60 days, and amylase in S1 at day 30 and day 60 and S2 at day 60. The mRNA expression of myogenic regulatory factors (MRFs) was also found to be significantly (p < 0.05) up-regulated with the highest fold changes recorded in AS3 for myoD (3.93 ± 0.91); myoG (6.71 ± 0.30); myf5 (4.40 ± 0.33); MRF4 (4.94 ± 0.21) in comparison to the C.

Development of a Magnetically-Assisted SERS Biosensor for Rapid Bacterial Detection.

Introduction: Ultrasensitive bacterial detection methods are crucial to ensuring accurate diagnosis and effective clinical monitoring, given the significant threat bacterial infections pose to human health. The aim of this study is to develop a biosensor with capabilities for broad-spectrum bacterial detection, rapid processing, and cost-effectiveness. Methods: A magnetically-assisted SERS biosensor was designed, employing wheat germ agglutinin (WGA) for broad-spectrum recognition and antibodies for specific capture. Gold nanostars (AuNSs) were sequentially modified with the Raman reporter molecules and WGA, creating a versatile SERS tag with high affinity for a diverse range of bacteria. Staphylococcus aureus (S. aureus) and Pseudomonas aeruginosa (P. aeruginosa) antibody-modified Fe3O4 magnetic gold nanoparticles (MGNPs) served as the capture probes. Target bacteria were captured by MGNPs and combined with SERS tags, forming a "sandwich" composite structure for bacterial detection. Results: AuNSs, with a core size of 65 nm, exhibited excellent storage stability (RSD=5.6%) and demonstrated superior SERS enhancement compared to colloidal gold nanoparticles. Efficient binding of S. aureus and P. aeruginosa to MGNPs resulted in capture efficiencies of 89.13% and 85.31%, respectively. Under optimized conditions, the developed assay achieved a limit of detection (LOD) of 7 CFU/mL for S. aureus and 5 CFU/mL for P. aeruginosa. The bacterial concentration (10-106 CFU/mL) showed a strong linear correlation with the SERS intensity at 1331 cm-1. Additionally, high recoveries (84.8% - 118.0%) and low RSD (6.21% - 11.42%) were observed in spiked human urine samples. Conclusion: This study introduces a simple and innovative magnetically-assisted SERS biosensor for the sensitive and quantitative detection of S. aureus or P. aeruginosa, utilizing WGA and antibodies. The developed biosensor enhances the capabilities of the "sandwich" type SERS biosensor, offering a novel and effective platform for accurate and timely clinical diagnosis of bacterial infections.