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Complete dentures offer the replacement of all missing teeth and surrounding tissues. Replacing the entire arch of missing teeth, the prosthesis is exclusively tissue-supported. Adapting a spacer during removable complete denture impression-making is one of the important steps. The success and failure of complete denture therapy are largely dependent upon the method by which the clinician records impressions. Many theories of impression have been proposed and the selective-pressure technique is one of the most widely used theories and has been used successfully. During the selective pressure technique, custom trays with different designs and materials spacers are used so that vulnerable tissues are relieved of undue stresses while stress-bearing areas are utilized properly. The current paper mainly describes some of the conventional wax spacers that may be used during impression making of removable complete denture prostheses.

Background Spinal cord injury is a life changing threatening neurological condition that completely changes subject’s life. In medical management recent advances has significantly improved diagnosis, stabilization, survival rate and well being of SCI patients, but there has been very small progression in its treatment, and some such as Stem cell transplantation etc. is very costly that is not possible for everyone to afford.So now a days major focus is on nutraceutical supplementation as they are easy to administer and easy to afford. Omega 3 fatty acid are important polyunsaturated fatty acids with some roles in normal cellular metabolism, they have Anti inflammatory and antioxidant properties. Studies have proved its beneficial role in ameliorating inflammation in different diseases and thus plays role in improving neurological outcomes after neuronal injury.Fish are the best source of omega 3 fatty acid,EPA & DHA are two main types of omega 3 fatty acid and both the sources are found in fish, salmon, tuna, mackerel, and sardines fatty fish are good source of EPA & DHA,and high in protein content and low in saturated fat.In SCI,inflammatory events results in activating various inflammatory markers so PUFA 3 helps in suppressing their activity, for healthy adults, the daily recommended level of omega?3 fatty acid is 300 mg.Leukotriene?5, thromboxane?3, and prostaglandin?3 are derived from essential fatty acids, and are known to be therapeutically important in inflammatory conditions as well as for mental health. A marine crustacean Antarctic krill, Euphausia superba, has not been a traditional food in the human diet, its a rich source of high-quality protein, with the advantage over other animal proteins of being low in fat and a rich source of EPA and DHA. Antioxidant levels in krill are higher than in fish, suggesting benefits against oxidative damage. Finally, the waste generated by the processing of krill into edible products can be developed into value added products. Material and method Online literature search was undertaken in PUBMED library and PLOS ONE library ,Scopus with the key word Spinal cord injury & its prevalence, Epidemology of Spinal Cord Injury,Role of omega 3 fatty acid and its role in spinal cord inury,Potential health benefits of Omega 3 fatty acid etc.A systematic Literature Search was made upto 2023.Using the above mentioned database we selected 100 articles. Result and Conclusion Omega 3 fatty acid plays a role in regulating several pathways associated with the damage resulting from secondary SCI . Given the considerable health advantages, the consumption of EPA and DHA is encouraged, with fatty fishes such as salmon, mullet, and mackerel identified as prime sources of these beneficial acids. This emphasis on aquaculture industries is leading to increased attention. Consequently, this review aims to comprehensively explore the potential benefits of PUFA.

Rationale & Objective: We sought to compare outcomes of patients receiving dialysis after cardiothoracic surgery on the basis of dialysis modality (intermittent hemodialysis [HD] vs peritoneal dialysis [PD]). Study Design: This was a retrospective analysis. Setting & Participants: In total, 590 patients with kidney failure receiving intermittent HD or PD undergoing coronary artery bypass graft and/or valvular cardiac surgery at Cleveland Clinic were included. Exposure: The patients received PD versus HD (intermittent or continuous). Outcomes: Our primary outcomes were in-hospital and 30-day mortality. Secondary outcomes were length of stay, days in the intensive care unit, the number of intraoperative blood transfusions, postsurgical pericardial effusion, and sternal wound infection, and a composite of the following 4 in-hospital events: death, cardiac arrest, effusion, and sternal wound infection. Analytical Approach: We used χ2, Fisher exact, Wilcoxon rank sum, and t tests, Kaplan-Meier survival, and plots for analysis. Results: Among the 590 patients undergoing cardiac surgery, 62 (11%) were receiving PD, and 528 (89%) were receiving intermittent HD. Notably, 30-day Kaplan-Meier survival was 95.7% (95% CI: 93.9-97.5) for HD and 98.2% (95% CI: 94.7-100) for PD (P = 0.30). In total, 75 patients receiving HD (14.2%) and 1 patient receiving PD (1.6%) had a composite of 4 in-hospital events (death, cardiac arrest, effusion, and sternal wound infection) (P = 0.005). Out of 62 patients receiving PD, 16 (26%) were converted to HD. Limitations: Retrospective analyses are prone to residual confounding. We lacked details about nutritional data. Intensive care unit length of stay was used as a surrogate for volume status control. Patients have been followed in a single health care system. The HD cohort outnumbered the PD cohort significantly. Conclusions: When compared with PD, HD does not appear to improve outcomes of patients with kidney failure undergoing cardiothoracic surgery. Patients receiving PD had a lower incidence of a composite outcome of 4 in-hospital events (death, cardiac arrest, pericardial effusion, and sternal wound infections). Plain-Language Summary: Patients receiving peritoneal dialysis (PD) are frequently switched to hemodialysis (HD) around the time of an open-heart surgery. More times than not, this is driven by the preference of nonkidney doctors, because HD is perceived to control toxins and fluids better. PD is, however, more advantageous and can achieve similar results while being gentler. In an effort to keep patients on their home PD, we analyzed how they fared when compared with their HD counterparts. Patients maintained on PD did just as well if not better around and after their open-heart surgery. Given the expected increase in patients treated with PD, efforts should be made to maintain them on their home modality even around major surgeries.

Diabetic kidney disease (DKD) is a complication of diabetes that can lead to kidney failure. Over the years, several drugs have been developed to combat this disease. In the early 90s, angiotensin blockade (ACEi and ARBs) was introduced, which revolutionized the treatment of DKD. In recent years, newer drugs such as sodium-glucose co-transporter 2 (SGLT2) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists, endothelin antagonists, and mineralocorticoid receptor antagonists (MRA) have shown great promise in reducing albuminuria and protecting the kidneys. These drugs are being used in combination with lifestyle modifications, patient education, and risk factor modification to effectively manage DKD. In this review, we will explore the latest pharmacological options, their efficacy, and their potential to revolutionize the management of this debilitating disease.

Objective: To compare and observe the differences of 18F-FDG produced using FDG citrate and FDG duo citrate cassette on the GE Healthcare FASTlab2 Synthesizer system following standard operating parameters. Study Design: Quasi-experimental study. Place and Duration of Study: Armed Forces Institute of Radiology and Imaging, Rawalpindi Pakistan, from Sep 2020 to Aug 2021. Methodology: Comparison of 18F-FDG produced using FDG citrate and FDG duo citrate cassette on FASTlab2 consists of evaluating the estimated yield uncorrected (EYUC), estimated yield decay corrected (EYDC), radiochemical purity (RCP), synthesis duration and tracer volume in both cassettes. Sixty Batches of each FDG citrate and duo citrate cassettes were utilized to obtain the required results. Results: Results acquired by comparing the mean yield of FDG citrate and FDG duo citrate cassette were 74.98±8.92% for EYUC and 86.35±10.26% for EYDC for the FDG citrate cassette. At the same time, the mean RCP turned out to be 99.58±1.06% for the citrate cassette and 99.9±0.35 for the duo citrate cassette. The mean synthesis duration of FDG was 24.21±0.76min and 24.75±0.43min for the citrate cassette and duo citrate cassette correspondingly, and the volume of the tracer was 3.5ml for both cassettes. Conclusion: The results obtained by comparing these two cassettes were within the range of acceptable limits as claimed by the manufacturer, with a single cassette offering more yield as compared to a duo cassette, while the radiochemical purity, pH and volume of the tracer were found to be identical in both cassettes.

Background: LINC00092 and MCM3AP-AS1 long non-coding RNAs (LncRNAs) play significant roles in the development and pathogenesis of many cancers. However, their expression levels and prognostic values were not evaluated in human gastric adenocarcinoma (GAC). Therefore, the present study aimed to investigate the clinico-pathological correlations of LINC00092 and MCM3AP-AS1, LncRNAs expression in GAC, and evaluate their prognostic values. Materials and Methods: The expression of LINC00092 and MCM3AP-AS1 was detected in 89 GAC tissues by quantitative real-time reverse-transcription PCR (qRT-PCR). Results: Our results showed that LINC00092 and MCM3AP-AS1 are overexpressed in GAC patients and positively correlated with GAC invasion and vascular, peritoneal, and lymph node metastasis (P < 0.05). Furthermore, the results indicated that MCM3AP-AS1 (P = 0.0225) and LINC00092 (P < 0.001) have positive correlations with GAC patients’ overall survival. Conclusion: Altogether, the present results indicated that LINC00092 and MCM3AP-AS1 overexpression is associated with clinico-pathological characteristic of GAC patients. In addition, both of these LncRNAs may have prognostic value for estimation of patients’ overall survival.

Abstract Background Bluetongue (BT), a vector‐borne disease of wild and domestic ruminants, is responsible for severe economic losses in flocks. To reduce this impact, a surveillance and control plan was implemented in Tunisia. However, the epidemiological situation of BT remains incompletely understood, especially for the circulating serotypes. Objective The aim of this survey was to determine the seroprevalence, to identify the circulating serotypes and to identify the associated risk factors for bluetongue virus (BTV) circulation in Tunisia using risk‐based sampling (RBS). Methods A total of 3314 blood samples were randomly collected from 67 sectors using risk‐based sampling and screened by competitive enzyme‐linked immunosorbent assays (c‐ELISAs). Out of the 1330 positive samples, 200 samples were analysed by serum neutralization test (SNT) to identify circulating BTV serotypes. Results Of 3314 sera, 1330 were c‐ELISA‐positive (40.1%) for antibodies against the BTV structural protein VP7. The result of SNT showed the presence of BTV‐1, BTV‐2, BTV‐3, BTV‐4 and, for the first time in Tunisia, BTV‐26. The logistic regression model revealed that older animals had nearly two times the odds of being infected with BTV compared to younger animals. Flocks with a history of BT were almost 1.5 times more likely to be at risk for contracting BTV infection. The flock size, housing indoors and intensive production system were significant protective factors. Conclusions High seroprevalence of BTV among sheep was highlighted in Tunisia. The neutralization test showed the presence of the following BTV serotypes: BTV‐1, BTV‐2, BTV‐3, BTV‐4 and, for the first time in Tunisia, BTV‐26. Age, production system and flock size were important variables associated with BTV infection in sheep. This finding is crucial, as it will allow the adjustment of the BT control programme in Tunisia.

Sodium–glucose co-transporter inhibitors (SGLT2i) have recently gained a lot of emphasis in their role in preventing progression of chronic kidney disease and helping with cardiac mortality. Various studies have proven the benefit of these medications in the management of patients with kidney and heart disease. SGLT2i exert their effect in the proximal convoluted tubule with various downstream effects noted in the kidney also. With spreading use of these medications, it is imperative to understand the effects they have on various electrolytes and the pathways involved in bringing about these changes in the kidney. Here, the authors review the current knowledge of SGLT2i with their effects on the kidney, electrolytes, and water balance.

Background: Since 2012, the northeast region of Tunisia has witnessed an increase in dog rabies cases, indicating a concerning emergence of the disease. Previous studies have indicated the widespread nature of rabies in northern Tunisia. However, there remains a lack of comprehensive understanding regarding the associated risk factors. Aim: This study aimed to identify potential risk factors associated with the occurrence of dog rabies in northeast Tunisia through a case-control approach. Methods: A case-control study was conducted, involving a case group (n = 77) consisting of dogs confirmed positive for rabies at the referral laboratory using the Fluorescent Antibody Test between 2013 and 2019. The control group (n = 77) comprised both negative cases received at the laboratory and dogs that underwent a 15-day quarantine period and received a certificate of absence of rabies after observation. Univariate and multivariate logistic regression analyses were performed to explore various potential risk factors, including age, sex, breed, confinement, vaccination status, presence of bites, ownership status, origin of dogs, geographic sector, presence of rabies cases, and proximity to slaughterhouses. Results: The final logistic regression model revealed several significant findings. The odds of an unconfined dog being affected by rabies were nearly twice as high as for confined dogs odds ratio [OR = 1.9; 95% confidence intervals (CI): 1.17-3.27]. Furthermore, the odds of rabies occurrence were 25 times higher in areas where rabies cases had been reported within the previous 3 months to 1 year compared to uninfected areas (OR = 25.7; 95% CI: 3.02-219.14). Dogs born at home to the owner's bitch were also found to be at significantly higher risk of rabies (OR = 2.41; 95% CI: 1.14-5.13). Additionally, residing in areas with reported rabies cases in the last 3 months was found to increase the risk of rabies by 2.8 times (OR = 2.8; 95% CI: 1.16-6.77). However, vaccination was associated with a 1.6-fold reduction in the risk of contracting rabies (OR = 0.6; 95% CI: 0.38-0.97). Conclusion: This study provides valuable insights into the risk factors associated with dog rabies in northeast Tunisia. The findings underscore the importance of implementing targeted control measures, such as increased vaccination coverage and enhanced confinement measures, to mitigate the spread of rabies in the region. These findings can inform decision-making processes aimed at improving the effectiveness of national rabies control programs. [ABSTRACT FROM AUTHOR]

Rationale & Objective: There has been an increasing demand for the expertise provided by a renal genetics clinic. Such programs are limited in the United States and typically operate in a genomics research setting. Here we report a 3-year, real-world, single-center renal genetics clinic experience. Study Design: Retrospective cohort. Setting & Participants: Outpatient cases referred to the renal genetics clinic of the Cleveland Clinic between January 2019 and March 2022 were reviewed. Analytical Approach: Clinical and laboratory characteristics were analyzed. All genetic testing was performed in clinical labs. Results: 309 new patients referred from 15 specialties were evaluated, including 118 males and 191 females aged 35.1 ± 20.3 years. Glomerular diseases were the leading presentation followed by cystic kidney diseases, electrolyte disorders, congenital anomalies of kidneys and urinary tract, nephrolithiasis, and tubulointerstitial kidney diseases. Dysmorphic features were noted in 27 (8.7%) patients. Genetic testing was recommended in 292 (94.5%) patients including chromosomal microarray (8.9%), single-gene tests (19.5%), multigene panels (77.3%), and exome sequencing (17.5%). 80.5% of patients received insurance coverage for genetic testing. 45% (115/256) of patients had positive results, 25% (64/256) had variants of unknown significance, and 22.3% (57/256) had negative results. 43 distinct monogenic disorders were diagnosed. Family history of kidney disease was present in 52.8% of patients and associated with positive genetic findings (OR, 2.28; 95% CI, 1.40-3.74). 69% of patients with positive results received a new diagnosis and/or a change in the diagnosis. Among these, 39.7% (31/78) of patients received a significant change in disease management. Limitations: Retrospective and single-center study. Conclusions: The renal genetics clinic plays important roles in the diagnosis and management of patients with genetic kidney diseases. Multigene panels are the most frequently used testing modality with a high diagnostic yield. Family history of kidney disease is a strong indication for renal genetics clinic referral.

Study objective: Data is scarce regarding which dialysis modality portends more severe cardiac valvular calcification (CVC). Our aim was to compare the degree of CVC in hemodialysis (HD) and peritoneal dialysis (PD) patient cohorts prior to open heart surgery (OHS) using a CT calcium score. Design, setting, and participants: Dialysis patients who underwent OHS at our institution from 2009 to 2019 and who had pre-surgical cardiac CT were included in our study. We obtained duration of dialysis modality prior to their surgical date. There were two study cohorts to evaluate outcomes of interest: mitral and aortic calcification. CVC was assessed using the Agatston score. Logistic regression was performed to test for the association of PD and HD cumulative dialysis duration with presence of CVC. Results: A total of 214 and 166 patients met inclusion for the mitral and aortic strata, respectively. Age, female sex, and BMI were associated with higher odds of presence of mitral calcification. Age and BMI were associated with higher odds of presence of aortic calcification, while female sex was associated with lower odds in the aortic strata. Cumulative years on PD and cumulative years on HD were not significantly associated with presence of CVC in either cohort. Conclusion: Presence of mitral and aortic calcification for patients undergoing OHS was not significantly associated with cumulative length of PD or HD after adjusting for age, gender, and BMI suggesting that there may be more factors at play in the progression of CVC in end stage renal disease patients than what was previously established.

Rationale & Objective: Dysnatremias have been associated with an increased risk of mortality in the chronic kidney disease (CKD) population. Our objective is to identify the prevalence of and risk factors associated with dysnatremias in a CKD population and assess the association of dysnatremias with kidney failure and mortality among patients with CKD enrolled in the Chronic Renal Insufficiency Cohort Study. Study Design: Analysis of prospective cohort study. Setting & Participants: Adult patients aged 21-74 years with CKD from the Chronic Renal Insufficiency Cohort study. Predictors: Baseline and time-dependent hyponatremia and hypernatremia. Outcomes: All-cause mortality and kidney failure. Analytical Approach: Baseline characteristics were compared using χ2 tests for categorical variables, analysis of variance for age, and Kruskal-Wallis tests for laboratory variables. Cox proportional hazards models and competing risk models were used to evaluate the association between baseline sodium level and overall mortality. Results: Of a total of 5,444 patients with CKD, 486 (9%) had hyponatremia and 53 (1%) had hypernatremia. Altogether, 1,508 patients died and 1,206 reached kidney failure. In adjusted Cox models, time-dependent dysnatremias were strongly associated with mortality for both hyponatremia (HR, 1.38; 95% CI, 1.16-1.64) and hypernatremia (HR, 1.54; 95% CI, 1.04-2.29). Factors associated with hyponatremia included female sex, diabetes, and hypertension. Regardless of age, time-dependent hypernatremia was associated with an increased risk of kidney failure (HR, 1.64; 95% CI, 1.06-2.53). Baseline and time-dependent hyponatremia were associated with an increased risk of kidney failure in patients younger than 65 (baseline hyponatremia HR, 1.30; 95% CI, 1.03-1.64 and time-dependent hyponatremia HR, 1.36; 95% CI, 1.09-1.70) but not among patients aged >65 years. Limitations: Inability to establish causality and lack of generalizability to hospitalized patients. Conclusions: Dysnatremias are prevalent among ambulatory CKD patients and are associated with mortality and kidney failure. Time-dependent dysnatremias were significantly associated with mortality in patients with CKD. Time-dependent hypernatremia was associated with progression to kidney failure. Baseline and time-dependent hyponatremia were associated with an increased risk of progression to kidney failure in those younger than 65 years.

Objective: To evaluate the patients' feedback for potential improvements in the patient management of PET-CT Department. Study Design: Cross-sectional survey. Place and Duration of Study: Armed Forces Institute of Radiology and Imaging, Rawalpindi Pakistan, from Sep to Dec 2020. Methodology: A total of 350 participants were investigated in the study. Structured proforma was utilized for collecting patient feedback, and the ages ranged from 4 to 89 years. The collected data were arranged systematically to apply statistical tests using Microsoft excel. Results: Explicitly, 14(4%) patients communicated their reservations about further development in PET-CT scan practice. In this regard, 4(1.14%) patients suggested overall improvement in the department. Further, 4(1.14%) and 3(0.86%) patientss’ suggestions were towards staff behaviour and building of the department, respectively. Additionally, 2(0.57%) patients were not contented with the available prerequisite equipment, and 1(0.29%) patient suggested a reduction in scanning charges. Conclusion: More than 95% patients were satisfied with their experience. The studied data can be utilized to establish patient management protocols for similar PET-CT departments.

Rationale and Objective: Chronic kidney disease is a risk enhancing factor for cardiovascular disease (CVD) and mortality, and the role of aspirin use is unclear in this population. We investigated the risk and benefits of aspirin use in primary and secondary prevention of CVD in the Chronic Renal Insufficiency Cohort Study. Study Design: Prospective observational cohort. Setting & Participants: 3,664 Chronic Renal Insufficiency Cohort participants. Exposure: Aspirin use in patients with and without preexisting CVD. Outcomes: Mortality, composite and individual CVD events (myocardial infarction, stroke, and peripheral arterial disease), kidney failure (dialysis and transplant), and major bleeding. Analytical Approach: Intention-to-treat analysis and multivariable Cox proportional hazards model to examine associations of time varying aspirin use. Results: The primary prevention group was composed of 2,578 (70.3%) individuals. Mean age was 57 ± 11 years, 46% women, 42% Black, and 47% had diabetes. The mean estimated glomerular filtration rate was 45 mL/min/1.73 m2. Median follow-up was 11.5 (IQR, 7.4-13) years. Aspirin was not associated with all-cause mortality in those without preexisting cardiovascular disease (CVD) (HR, 0.84; 95% CI, 0.7-1.01; P = 0.06) or those with CVD (HR, 0.88; 95% CI, 0.77-1.02, P = 0.08). Aspirin was not associated with a reduction of the CVD composite in primary prevention (HR, 0.97; 95% CI, 0.77-1.23; P = 0.79) and in secondary prevention because the original study design was not meant to study the effects of aspirin. Limitations: This is not a randomized controlled trial, and therefore, causality cannot be determined. Conclusions: Aspirin use in chronic kidney disease patients was not associated with reduction in primary or secondary CVD events, progression to kidney failure, or major bleeding.

Objective: To find out the optimal timeline for the safe disposal of radioactive wastes generated at the end of normal and anomalous productions of 18F-Fluorodeoxyglucose for positron emission tomography-computed tomography scans. Study Design: Quasi-experimental study. Place and Duration of Study: Armed Forces Institute of Radiology and Imaging, Rawalpindi Pakistan, from Aug to Dec 2020. Methodology: Wastes generated at the end of 18F-Fluorodeoxyglucose production were tested for residual radioactivity at 2, 12 and 24 hours after synthesis to ascertain the optimal timeline for discarding. The radiation dose at 5 cm from the surface of the container was also assessed. Results: Fifty productions were included in the study, of which 46(92%) were normal, and 4(8%) were anomalous productions. The mean activity at 2 and 24 hours after the end of synthesis was 4.102±0.831mCi and 0.0047±0.00116mCi, respectively, in normal productions and 45.125±2.332mCi and 0.005±0.00026mCi respectively in anomalous productions. The mean radiation dose at 5cm from the surface of the container at 2 and 24 hours after the end of synthesis was 8.2107±1.665mSv/h and 0.00000966±0.00000212mSv/h in normal productions and 90.32±4.66mSv/h and 0.00975±0.0005-mSv/h respectively in anomalous productions. Conclusion: The residual radioactivity in wastes was negligible 24 hours after the end of synthesis in both normal and anomalous productions. Radioactive wastes from 18F-Fluorodeoxyglucose production should, therefore, be conserved for at least 24 hours before their disposal to the environment.

Abstract Background The relationship between proton-pump inhibitor (PPI) use and chronic kidney disease (CKD) progression remains controversial. Specifically, there is a lack of data evaluating renal outcomes in established CKD patients. The aim of our study is to determine the risk of progression to end-stage kidney disease (ESKD) or death amongst CKD patients on PPI, histamine-2 receptor blocker (H2B), or no anti-acid therapy. Methods Using our CKD registry, we evaluated the relationship between PPI and H2B use and outcomes amongst patients with CKD (eGFR

Abstract Background Interest in nephrology has been declining among internal medicine residents but the reasons behind this observation are not well characterized. Our objective was to evaluate factors influencing residents’ choice of subspecialty. Methods This is a mixed-method QUAL-QUAN design study that used the results of our previously published qualitative analysis on residents’ perception of nephrology to create and pilot a questionnaire of 60 questions. The final questionnaire was distributed to 26 programs across the United States and a total of 1992 residents. We calculated response rates and tabulated participant characteristics and percentage of participant responses. We categorized choice of fellowship into 2 medical categories (Highly Sought After vs. Less Sought After) and fitted a logistic regression model of choosing a highly vs. less sought after fellowship. Results Four hundred fifteen out of 1992 (21%) US residents responded to the survey. Of the 268 residents planning to pursue fellowship training, 67 (25%) selected a less sought after fellowship. Female sex was associated with significantly higher odds of selecting a less sought after fellowship (OR = 2.64, 95% CI: 1.47, 4.74). Major factors deterring residents from pursuing nephrology were perception of inadequate financial compensation, broad scope of clinical practice and complexity of patient population. We observed a decline in exposure to nephrology during the clinical years of medical school with only 35.4% of respondents rotating in nephrology versus 76.8% in residency. The quality of nephrology education was rated less positively during clinical medical school years (median of 50 on a 0–100 point scale) compared to the pre-clinical years (median 60) and residency (median 75). Conclusion Our study attempts to explain the declining interest in nephrology. Results suggest potential targets for improvement: diversified trainee exposure, sub-specialization of nephrology, and increased involvement of nephrologists in the education of trainees.

Abstract Background Prostate Cancer (PCa) is the second most common cancer in men where advancements have been made for early detection using imaging techniques, however these are limited by lesion size. Immune surveillance has emerged as an effective approach for early detection and to monitor disease progression. In recent studies, we have shown that host peripheral blood immune cells undergo changes in DNA methylation in liver and breast cancer. Methods In the current study, we examined the DNA methylation status of peripheral blood T cells of men with positive biopsy for PCa versus men with negative biopsy having benign prostate tissue, defined as controls. T cells DNA was isolated and subjected to Illumina Infinium methylation EPIC array and validated using Illumina amplicon sequencing and pyrosequencing platforms. Results Differential methylation of 449 CG sites between control and PCa T cell DNA showed a correlation with Gleason score (p

Healthcare providers as well as medical technologists lay a strong focus on clinical conditions for patient centric care delivery. Currently, the challenges are to (1) obtain a consolidated view of various stakeholders and pain points for the entire disease lifecycle, (2) identify interdependencies between different stages of the disease, and (3) prioritize solutions based on customer needs. A structured approach is required to address clinical needs across disease care plans tailored to different geographies and ethnicities. Innovation Think Tank (ITT) teams across multiple locations formed focus groups to elaborate the pathways of 22 global diseases, selected based on ranking of associated economic burden and threat to life. Ideation sessions were held to identify pain points and find innovative solutions. Additionally, inputs were taken from co-creation sessions at universities worldwide. The optimization and design of infographics and care plan was done based on the key information gathered—facts and figures, stakeholders, pain points and solutions. Finally, validation was obtained from clinical and technology experts globally. A disease pathway framework was created to develop pathways for 22 global diseases. Over 1,500 pain points were collected and about 1,900 ideas were proposed. The approach was applied to optimize its application to 30 product and portfolio definition projects over 2 years at Siemens Healthineers, as well as co-creation programs with universities and hospitals. The disease pathway framework provides a unique foundation for extensive collaboration among multiple stakeholders, through information sharing and delivering high-quality solutions based on the identified problems and customer needs.

Immune checkpoint inhibitors (ICPi) targeting the PD-1/PD-L1 pathway have shown marked success in patients with advanced melanoma. However, 60–70% of patients fail to respond, warranting a therapeutic intervention that could increase response rates. We and others have shown that S-adenosylmethionine (SAM), a universal methyl donor, has significant anticancer effects in numerous cancers previously; however, its effect on melanoma progression has not been evaluated. Interestingly, SAM was reported to be essential for T cell activation and proliferation and, thus, could potentially cooperate with ICPi and block melanoma progression. In this study, we examined the antitumor effects of SAM and ICPi alone and in combination in a well-established melanoma mouse model wherein syngeneic C57BL/6 mouse were subcutaneously (orthotopic) injected with B16-F1 cells. Treatment of mice with either SAM or anti-PD-1 antibody alone resulted in significant reduction in tumor volumes and weights; effects that were highest in mice treated with a combination of SAM+anti-PD-1. RNA-sequencing analysis of the primary tumors showed numerous differentially expressed genes (DEGs) following treatment with SAM+anti-PD-1, which was shown to downregulate cancer, MAPK, and tyrosine kinase pathways. Indeed, SAM+anti-PD-1 reversed the aberrant expression of some known melanoma genes. Tumor immunophenotyping revealed the SAM+anti-PD-1 combination was significantly more effective than either SAM or anti-PD-1 as the CD8+ T cells had higher activation, proliferation, and cytokine production compared to all other groups. This study shows that the combination of currently approved agents SAM and ICPi can effectively block melanoma via alteration of key genes/pathways implicated in cancer and immune response pathways, providing the rationale for the initiation of clinical trials with SAM and ICPi.