Eating Like a Rainbow: The Development of a Visual Aid for Nutritional Treatment of CKD Patients. A South African Project.

Providing nutritional education for chronic kidney disease (CKD) patients in South Africa is complicated by several conditions: the population is composed of diverse ethnic groups, each with its own culture and food preferences; eleven languages are spoken and illiteracy is common in the lower socio-economic groups. Food preparation and storage are affected by the lack of electricity and refrigeration, and this contributes to a monotonous diet. In traditional African culture, two meals per day are often shared “from the pot”, making portion control difficult. There is both under- and over-nutrition; late referral of CKD is common. Good quality protein intake is often insufficient and there are several misconceptions about protein sources. There is a low intake of vegetables and fruit, while daily sodium intake is high, averaging 10 g/day, mostly from discretionary sources. On this background, we would like to describe the development of a simplified, visual approach to the “renal diet”, principally addressed to illiterate/non-English speaking CKD patients in Southern Africa, using illustrations to replace writing. This tool “Five steps to improve renal diet compliance”, also called “Eating like a Rainbow”, was developed to try to increase patients’ understanding, and has so far only been informally validated by feedback from users. The interest of this study is based on underlining the feasibility of dietary education even in difficult populations, focusing attention on this fundamental issue of CKD care in particular in countries with limited access to chronic dialysis

PD-L1, Galectin-9 and CD8+ tumor-infiltrating lymphocytes are associated with survival in hepatocellular carcinoma

Novel systemic treatments for hepatocellular carcinoma (HCC) are strongly needed. Immunotherapy is a promising strategy that can induce specific antitumor immune responses. Understanding the mechanisms of immune resistance by HCC is crucial for development of suitable immunotherapeutics. We used immunohistochemistry on tissue-microarrays to examine the co-expression of the immune inhibiting molecules PD-L1, Galectin-9, HVEM and IDO, as well as tumor CD8+ lymphocyte infiltration in HCC, in two independent cohorts of patients. We found that at least some expression in tumor cells was seen in 97% of cases for HVEM, 83% for PD-L1, 79% for Gal-9 and 66% for IDO. In the discovery cohort (n = 94), we found that lack of, or low, tumor expression of PD-L1 (p < 0.001), Galectin-9 (p < 0.001) and HVEM (p < 0.001), and low CD8+TIL count (p = 0.016), were associated with poor HCC-specific survival. PD-L1, Galectin-9 and CD8+TIL count were predictive of HCC-specific survival independent of baseline clinicopathologic characteristics and the combination of these markers was a powerful predictor of HCC-specific survival (HR 0.29; p <0.001). These results were confirmed in the validation cohort (n = 60). We show that low expression levels of PD-L1 and Gal-9 in combination with low CD8+TIL count predict extremely poor HCC-specific survival and it requires a change in two of these parameters to significantly improve prognosis. In conclusion, intra-tumoral expression of these immune inhibiting molecules was observed in the majority of HCC patients. Low expression of PD-L1 and Galectin-9 and low CD8+TIL count are associated with poor HCC-specific survival. Combining immune biomarkers leads to superior predictors of HCC mortality

A clustering of heterozygous missense variants in the crucial chromatin modifier WDR5 defines a new neurodevelopmental disorder

WDR5 is a broadly studied, highly conserved key protein involved in a wide array of biological functions. Among these functions, WDR5 is a part of several protein complexes that affect gene regulation via post-translational modification of histones. We collected data from 11 unrelated individuals with six different rare de novo germline missense variants in WDR5; one identical variant was found in five individuals, and another variant in two individuals. All individuals had neurodevelopmental disorders including speech/language delays (N=11), intellectual disability (N=9), epilepsy (N=7) and autism spectrum disorder (N=4). Additional phenotypic features included abnormal growth parameters (N=7), heart anomalies (N=2) and hearing loss (N=2). Three-dimensional protein structures indicate that all the residues affected by these variants are located at the surface of one side of the WDR5 protein. It is predicted that five out of the six amino acid substitutions disrupt interactions of WDR5 with RbBP5 and/or KMT2A/C, as part of the COMPASS (complex proteins associated with Set1) family complexes. Our experimental approaches in Drosophila melanogaster and human cell lines show normal protein expression, localization and protein-protein interactions for all tested variants. These results, together with the clustering of variants in a specific region of WDR5 and the absence of truncating variants so far, suggest that dominant-negative or gain-of-function mechanisms might be at play. All in all, we define a neurodevelopmental disorder associated with missense variants in WDR5 and a broad range of features. This finding highlights the important role of genes encoding COMPASS family proteins in neurodevelopmental disorders

Effects of angiotensin type 1 receptor blockade on arginine and ADMA synthesis and metabolic pathways in fawn-hooded hypertensive rats

Background. The fawn-hooded hypertensive (FHH) rat develops spontaneous glomerulosclerosis that is ameliorated by inhibition of the angiotensin II type 1 receptor (AT-1). Since kidney damage is associated with nitric oxide (NO) deficiency, we investigated how AT-1 antagonism influenced nitric oxide synthase (NOS), as well as NOS substrate [l-arginine (L-Arg)] and inhibitor [asymmetric dimethylarginine (ADMA)]. L-Arg is synthesized by renal argininosuccinate synthase/argininosuccinate lyase (ASS/ASL) and then either consumed within the kidney by arginase II or NOS or released into the circulation. L-Arg is then taken up from plasma into cells where it can be utilized by NOS and other pathways. The competitive inhibitor of NOS, ADMA, is degraded by dimethylarginine dimethylaminohydrolase (DDAH)

PD-L1, Galectin-9 and CD8(+) tumor-infiltrating lymphocytes are associated with survival in hepatocellular carcinoma

Novel systemic treatments for hepatocellular carcinoma (HCC) are strongly needed. Immunotherapy is a promising strategy that can induce specific antitumor immune responses. Understanding the mechanisms of immune resistance by HCC is crucial for development of suitable immunotherapeutics. We used immunohistochemistry on tissue-microarrays to examine the co-expression of the immune inhibiting molecules PD-L1, Galectin-9, HVEM and IDO, as well as tumor CD8(+) lymphocyte infiltration in HCC, in two independent cohorts of patients. We found that at least some expression in tumor cells was seen in 97% of cases for HVEM, 83% for PD-L1, 79% for Gal-9 and 66% for IDO. In the discovery cohort (n = 94), we found that lack of, or low, tumor expression of PD-L1 (p <0.001), Galectin-9 (p <0.001) and HVEM (p <0.001), and low CD8(+)TIL count (p = 0.016), were associated with poor HCC-specific survival. PD-L1, Galectin-9 and CD8CTIL count were predictive of HCC-specific survival independent of baseline clinicopathologic characteristics and the combination of these markers was a powerful predictor of HCCspecific survival (HR 0.29; p P <0.001). These results were confirmed in the validation cohort (n D 60). We show that low expression levels of PD-L1 and Gal-9 in combination with low CD8CTIL count predict extremely poor HCC-specific survival and it requires a change in two of these parameters to significantly improve prognosis. In conclusion, intra-tumoral expression of these immune inhibiting molecules was observed in the majority of HCC patients. Low expression of PD-L1 and Galectin-9 and low CD8(+)TIL count are associated with poor HCC-specific survival. Combining immune biomarkers leads to superior predictors of HCC mortalit

Sincerely James: Reconsidering Frederick Francis’s Proposed Health Wish Formula

This article interacts with Frederick Francis’s well-known suggestion that Jas 5 contains a health wish formula. Based on more recent findings of epistolography, this article argues that the references to healing in Jas 5 contrast sharply with the first-century CE health wish formula(s). In addition to current research on Hellenistic epistolography, this article offers three further pieces of evidence which suggest that the letter of James does not conclude with a health wish formula, but rather with a promise of restoration from spiritual sickness

Tacrolimus-induced hypertension and nephrotoxicity in Fawn-Hooded rats are attenuated by dual inhibition of renin-angiotensin system

Chronic immunosuppressive therapy is often complicated by the development of both arterial hypertension and renal dysfunction. The principal aim of this study was to assess the effects of dual inhibition of renin-angiotensin system (RAS) and other antihypertensive treatment on blood pressure and renal function in normotensive and hypertensive Fawn-Hooded (FH) strains during chronic calcineurin inhibitor (CNI) administration. Combinations of perindopril (5 mg kg(-1) per day) and losartan (50 mg kg(-1) per day) or amlodipine (6 mg kg(-1) per day) and metoprolol (80 mg kg(-1) per day) were administered to normotensive (FHL) and hypertensive (FHH) rats, fed with diet containing tacrolimus (Tac; 12 mg kg(-1) per day). Tac-induced arterial hypertension in both animal strains (FHL: 151 +/- 4; FHH: 198 +/- 6 mm Hg) was prevented by dual RAS inhibition (FHL: 132 +/- 3 mm Hg,