A bulky glycocalyx fosters metastasis formation by promoting G1 cell cycle progression.

Metastasis depends upon cancer cell growth and survival within the metastatic niche. Tumors which remodel their glycocalyces, by overexpressing bulky glycoproteins like mucins, exhibit a higher predisposition to metastasize, but the role of mucins in oncogenesis remains poorly understood. Here we report that a bulky glycocalyx promotes the expansion of disseminated tumor cells in vivo by fostering integrin adhesion assembly to permit G1 cell cycle progression. We engineered tumor cells to display glycocalyces of various thicknesses by coating them with synthetic mucin-mimetic glycopolymers. Cells adorned with longer glycopolymers showed increased metastatic potential, enhanced cell cycle progression, and greater levels of integrin-FAK mechanosignaling and Akt signaling in a syngeneic mouse model of metastasis. These effects were mirrored by expression of the ectodomain of cancer-associated mucin MUC1. These findings functionally link mucinous proteins with tumor aggression, and offer a new view of the cancer glycocalyx as a major driver of disease progression

An In Vivo Platform for Tumor Biomarker Assessment

Tumor biomarkers provide a quantitative tool for following tumor progression and response to therapy. However, investigations of clinically useful tumor biomarkers are time-consuming, costly, and limited by patient and tumor heterogeneity. In addition, assessment of biomarkers as indicators of therapy response is confounded by the concomitant use of multiple therapeutic interventions. Herein we report our use of a clinically relevant orthotopic animal model of malignant pleural mesothelioma for investigating tumor biomarkers. Utilizing multi-modality imaging with correlative histopathology, we demonstrate the utility and accuracy of the mouse model in investigating tumor biomarkers – serum soluble mesothelin-related peptide (SMRP) and osteopontin (OPN). This model revealed percentage change in SMRP level to be an accurate biomarker of tumor progression and therapeutic response – a finding consistent with recent clinical studies. This in vivo platform demonstrates the advantages of a validated mouse model for the timely and cost-effective acceleration of human biomarker translational research

Genetic effects on alcohol dependence risk : Re-evaluating the importance of psychiatric and other heritable risk factors

Background. Genetic influences have been shown to play a major role in determining the risk of alcohol dependence (AD) in both women and men; however, little attention has been directed to identifying the major sources of genetic variation in AD risk. Method. Diagnostic telephone interview data from young adult Australian twin pairs born between 1964 and 1971 were analyzed. Cox regression models were fitted to interview data from a total of 2708 complete twin pairs (690 MZ female, 485 MZ male, 500 DZ female, 384 DZ male, and 649 DZ female/male pairs). Structural equation models were fitted to determine the extent of residual genetic and environmental influences on AD risk while controlling for effects of sociodemographic and psychiatric predictors on risk. Results. Risk of AD was increased in males, in Roman Catholics, in those reporting a history of major depression, social anxiety problems, and conduct disorder, or (in females only) a history of suicide attempt and childhood sexual abuse; but was decreased in those reporting Baptist, Methodist, or Orthodox religion, in those who reported weekly church attendance, and in university-educated males. After allowing for the effects of sociodemographic and psychiatric predictors, 47% (95% CI 28–55) of the residual variance in alcoholism risk was attributable to additive genetic effects, 0% (95% CI 0–14) to shared environmental factors, and 53% (95% CI 45–63) to non-shared environmental influences. Conclusions. Controlling for other risk factors, substantial residual heritability of AD was observed, suggesting that psychiatric and other risk factors play a minor role in the inheritance of AD

Fifty years of hemodialysis in Ghana-current status, utilization and cost of dialysis services

BACKGROUND Kidney failure is common in Ghana. Haemodialysis (HD) is the most common treatment modality for survival. Although, HD has been available in Ghana for 50 years, the majority of patients who develop kidney failure cannot access it. We describe the state of HD, dialysis prevalence, its utilization and cost of HD after fifty years of dialysis initiation in Ghana. METHODS A situational assessment of HDs centres in Ghana was conducted by surveying nephrologists, doctors, nurses and other health care professionals in HD centres from August to October 2022. We assessed the density of HD centres, number of HD machines, prevalence of nephrologists, number of patients receiving HD treatment and the cost of dialysis in private and government facilities in Ghana. RESULTS There are 51 HD centres located in 9 of the 16 regions of Ghana. Of these, only 40 centres are functioning, as 11 had shut down or are yet to operate. Of the functioning centres most (n = 26, 65%) are in the Greater Accra region serving 17.7% of the population and 7(17.5%) in the Ashanti region serving 17.5% of the population in Ghana. The rest of the seven regions have one centre each. The private sector has twice as many HD centers (n = 27, 67.5%) as the public sector (n = 13,32.5%). There are 299 HD machines yielding 9.7 HD machines per million population (pmp) with a median of 6 (IQR 4-10) machines per centre. Ghana has 0.44 nephrologists pmp. Currently, 1195 patients receive HD, giving a prevalence of 38.8 patients pmp with 609(50.9%) in the private sector. The mean cost of HD session is US $53.9 ± 8.8 in Ghana. CONCLUSION There are gross inequities in the regional distribution of HD centres in Ghana, with a low HD prevalence and nephrology workforce despite a high burden of CKD. The cost of haemodialysis remains prohibitive and mainly paid out-of-pocket limiting its utilization

Inequities in kidney health and kidney care

Acknowledgements The European Kidney Health Alliance (EKHA) is a not-for-profit organization defending the case of the kidney patients and the nephrological community at the level of the European Commission. The EKHA network has five full members (the European Renal Association, the International Society of Nephrology, the European Kidney Patients Federation, the European Dialysis and Transplant Nurses Association-European Renal Care Association and the Dutch Kidney Foundation) next to 27 National or Regional Societies as affiliated members. European Kidney Health Alliance is the recipient of support by the European Union in the context of the Annual Work Program 2022 on prevention of non communicable diseases of EU4Health, topic ID EU4H-2022-PJ02, project #Peer reviewedPostprin

Inequities in kidney health and kidney care

Health inequity refers to the existence of unnecessary and unfair differences in the ability of an individual or community to achieve optimal health and access appropriate care. Kidney diseases, including acute kidney injury and chronic kidney disease, are the epitome of health inequity. Kidney disease risk and outcomes are strongly associated with inequities that occur across the entire clinical course of disease. Insufficient investment across the spectrum of kidney health and kidney care is a fundamental source of inequity. In addition, social and structural inequities, including inequities in access to primary health care, education and preventative strategies, are major risk factors for, and contribute to, poorer outcomes for individuals living with kidney diseases. Access to affordable kidney care is also highly inequitable, resulting in financial hardship and catastrophic health expenditure for the most vulnerable. Solutions to these injustices require leadership and political will. The nephrology community has an important role in advocacy and in identifying and implementing solutions to dismantle inequities that affect kidney health