An international cohort study of autosomal dominant tubulointerstitial kidney disease due to REN mutations identifies distinct clinical subtypes

There have been few clinical or scientific reports of autosomal dominant tubulointerstitial kidney disease due to REN mutations (ADTKD-REN), limiting characterization. To further study this, we formed an international cohort characterizing 111 individuals from 30 families with both clinical and laboratory findings. Sixty-nine individuals had a REN mutation in the signal peptide region (signal group), 27 in the prosegment (prosegment group), and 15 in the mature renin peptide (mature group). Signal group patients were most severely affected, presenting at a mean age of 19.7 years, with the prosegment group presenting at 22.4 years, and the mature group at 37 years. Anemia was present in childhood in 91% in the signal group, 69% prosegment, and none of the mature group. REN signal peptide mutations reduced hydrophobicity of the signal peptide, which is necessary for recognition and translocation across the endoplasmic reticulum, leading to aberrant delivery of preprorenin into the cytoplasm. REN mutations in the prosegment led to deposition of prorenin and renin in the endoplasmic reticulum-Golgi intermediate compartment and decreased prorenin secretion. Mutations in mature renin led to deposition of the mutant prorenin in the endoplasmic reticulum, similar to patients with ADTKD-UMOD, with a rate of progression to end stage kidney disease (63.6 years) that was significantly slower vs. the signal (53.1 years) and prosegment groups (50.8 years) (significant hazard ratio 0.367). Thus, clinical and laboratory studies revealed subtypes of ADTKD-REN that are pathophysiologically, diagnostically, and clinically distinct

An international cohort study of autosomal dominant tubulointerstitial kidney disease due to REN mutations identifies distinct clinical subtypes

There have been few clinical or scientific reports of autosomal dominant tubulointerstitial kidney disease due to REN mutations (ADTKD-REN), limiting characterization. To further study this, we formed an international cohort characterizing 111 individuals from 30 families with both clinical and laboratory findings. Sixty-nine individuals had a REN mutation in the signal peptide region (signal group), 27 in the prosegment (prosegment group), and 15 in the mature renin peptide (mature group). Signal group patients were most severely affected, presenting at a mean age of 19.7 years, with the prosegment group presenting at 22.4 years, and the mature group at 37 years. Anemia was present in childhood in 91% in the signal group, 69% prosegment, and none of the mature group. REN signal peptide mutations reduced hydrophobicity of the signal peptide, which is necessary for recognition and translocation across the endoplasmic reticulum, leading to aberrant delivery of preprorenin into the cytoplasm. REN mutations in the prosegment led to deposition of prorenin and renin in the endoplasmic reticulum-Golgi intermediate compartment and decreased prorenin secretion. Mutations in mature renin led to deposition of the mutant prorenin in the endoplasmic reticulum, similar to patients with ADTKD-UMOD, with a rate of progression to end stage kidney disease (63.6 years) that was significantly slower vs. the signal (53.1 years) and prosegment groups (50.8 years) (significant hazard ratio 0.367). Thus, clinical and laboratory studies revealed subtypes of ADTKD-REN that are pathophysiologically, diagnostically, and clinically distinct

Multilevel Modelling with Spatial Interaction Effects with Application to an Emerging Land Market in Beijing, China

This paper develops a methodology for extending multilevel modelling to incorporate spatial interaction effects. The motivation is that classic multilevel models are not specifically spatial. Lower level units may be nested into higher level ones based on a geographical hierarchy (or a membership structure—for example, census zones into regions) but the actual locations of the units and the distances between them are not directly considered: what matters is the groupings but not how close together any two units are within those groupings. As a consequence, spatial interaction effects are neither modelled nor measured, confounding group effects (understood as some sort of contextual effect that acts ‘top down’ upon members of a group) with proximity effects (some sort of joint dependency that emerges between neighbours). To deal with this, we incorporate spatial simultaneous autoregressive processes into both the outcome variable and the higher level residuals. To assess the performance of the proposed method and the classic multilevel model, a series of Monte Carlo simulations are conducted. The results show that the proposed method performs well in retrieving the true model parameters whereas the classic multilevel model provides biased and inefficient parameter estimation in the presence of spatial interactions. An important implication of the study is to be cautious of an apparent neighbourhood effect in terms of both its magnitude and statistical significance if spatial interaction effects at a lower level are suspected. Applying the new approach to a two-level land price data set for Beijing, China, we find significant spatial interactions at both the land parcel and district levels

Effect of selected lactic acid bacteria on physicochemical characteristics and microbiological quality of mechanically separated poultry meat

Celem pracy była ocena wpływu wybranych szczepów bakterii kwasu mlekowego na przydatność technologiczną i trwałość mikrobiologiczną mięsa drobiowego oddzielonego mechanicznie (MDOM). Materiał doświadczalny stanowiło mięso drobiowe MDOM, do którego dodano trzy szczepy bakterii kwasu mlekowego na poziomie 10 7 jtk/g – Lactobacillus plantarum SCH1 i Lactobacillus brevis KL5 wyizolowane z surowych wędlin dojrzewających oraz Lactobacillus plantarum S21 wyizolowany z ser- watki kwasowej. Wariant kontrolny nie zawierał dodatku bakterii. Farsze z MDOM przechowywano w warunkach chłodniczych i badano po 1, 4 i 7 dniach przechowywania. Zakres badań obejmował ozna- czenie: ogólnej liczby drobnoustrojów, liczby mezofilnych bakterii fermentacji mlekowej, liczby Escheri- chia coli, liczby Enterobacteriaceae, obecności Salmonella spp., obecności Campylobacter spp. i liczby gronkowców koagulazododatnich oraz oznaczenie cech fizykochemicznych, tj. pH i potencjału oksyda- cyjno-redukcyjnego, zawartości azotanów (III) i (V) oraz ocenę barwy w systemie CIE L*a*b*. Zastoso- wanie szczepów bakterii kwasu mlekowego w farszach z mięsa drobiowego oddzielonego mechanicznie nie wpłynęło negatywnie na ich przydatność technologiczną. Zaobserwowano pozytywny wpływ Lacto- bacillus brevis KL5 na kształtowanie barwy surowych farszów z MDOM. Wykazano hamujący wpływ Lactobacillus plantarum SCH1 na bakterie Escherichia coli oraz Enterobacteriaceae w surowych farszach z MDOM po 4 dniach chłodniczego przechowywania. Przeprowadzone badania umożliwiają stwierdzenie, że wybrane szczepy LAB wyizolowane z produktów pochodzenia zwierzęcego wpływają hamująco na wzrost drobnoustrojów w MDOM