Protein and energy intake, nitrogen balance and nitrogen losses in patients treated with continuous ambulatory peritoneal dialysis

Protein and energy intake, nitrogen balance and nitrogen losses in patients treated with continuous ambulatory peritoneal dialysis. The aim of this investigation was to analyze factors which influence the dietary protein intake (DPI), the energy intake and the utilization of ingested protein, and to determine the relationship between various types of nitrogen losses in stable continuous ambulatory peritoneal dialysis (CAPD) patients. We performed 23 nitrogen balance (NB) studies of 6 to 11 days duration in 12 CAPD patients. One study was performed in all patients 3.4 ± 1.2 months after starting CAPD (early studies). The study was then repeated in nine patients after 12.1 ± 2.6 months, and two of these patients were studied again after 16 and 24 months, respectively (late studies). Before each NB study, the dietary intakes prior to the study were assessed in diaries and interviews. During a few days preceding the NB periods and during the NB periods each patient received an individualized diet composed so as to resemble the patients' spontaneously chosen diet regarding DPI and dietary energy intake (DEI). Total nitrogen, protein, urea and creatinine were analyzed in the dialysate and urine collected daily. Total nitrogen was also analyzed in the feces, collected over the whole NB period. Total nitrogen appearance (TNA), non-protein nitrogen appearance (NPNA) and urea nitrogen appearance (UNA) were calculated by correcting total nitrogen output, non-protein nitrogen output, that is, TNA minus the total protein losses (PL) and urea nitrogen output for changes in total body urea nitrogen. Glucose was determined in the collected dialysate and the daily glucose absorption was calculated. DPI varied between 0.62 and 2.09 g/kg/day, DEI between 21 and 42 kcal/kg/day and the peritoneal energy (glucose) intake (PEI) between 4 and 13 kcal/kg/day. DPI (but not DEI) correlated with Kt/Vurea and Kt/VCr and with total and renal clearances for urea and creatinine. NB (not corrected for “unmeasured” nitrogen losses) was positive in most studies, and it correlated with DPI and the total energy intake (TEI) in the early studies, but only with TEI in the late studies. DPI correlated with TNA, NPNA, UNA, non-protein-non-urea nitrogen loss and fecal nitrogen loss. UNA was highly correlated with TNA and NPNA (r = 0.95). We used data from 33 NB studies in CAPD patients (our present data combined with data from the literature) to calculate regression equations describing the relationship between TNA and NPNA, respectively, and UNA. Equations were derived by which the protein equivalent of TNA (PNA), that is, 6.25 TNA, and the protein equivalent of NPNA (PNPNA), that is, 6.25 NPNA, may be calculated from UNA which is directly measured. In stable CAPD patients, who are not strongly catabolic or anabolic, PNA may be used to estimate DPI and PNPNA may be used to estimate the net protein intake (DPI – PL)

A kinetic model explains why shorter and less affine enzyme-recruiting oligonucleotides can be more potent

Antisense oligonucleotides complementary to RNA targets promise generality and ease of drug design. The first systemically administered antisense drug was recently approved for treatment and others are in clinical development. Chemical modifications that increase the hybridization affinity of oligonucleotides are reasoned to confer higher potency, i.e., modified oligonucleotides can be dosed at lower concentrations to achieve the same effect. Surprisingly, shorter and less affine oligonucleotides sometimes display increased potency. To explain this apparent contradiction, increased uptake or decreased propensity to form structures have been suggested as possible mechanisms. Here, we provide an alternative explanation that invokes only the kinetics behind oligonucleotide-mediated cleavage of RNA targets. A model based on the law of mass action predicts, and experiments support, the existence of an optimal binding affinity. Exaggerated affinity, and not length per se, is detrimental to potency. This finding clarifies how to optimally apply high-affinity modifications in the discovery of potent antisense oligonucleotide drugs

Early vascular ageing and cellular senescence in chronic kidney disease

Chronic kidney disease (CKD) is a clinical model of premature ageing characterized by progressive vascular dis- ease, systemic inflammation, muscle wasting and frailty. The predominant early vascular ageing (EVA) process mediated by medial vascular calcification (VC) results in a marked discrepancy between chronological and bio- logical vascular age in CKD. Though the exact underlying mechanisms of VC and EVA are not fully elucidated, ac- cumulating evidence indicates that cellular senescence - and subsequent chronic inflammation through the senescence-associated secretary phenotype (SASP) - plays a fundamental role in its initiation and progression. In this review, we discuss the pathophysiological links between senescence and the EVA process in CKD, with focus on cellular senescence and media VC, and potential anti-ageing therapeutic strategies of senolytic drugs targeting cellular senescence and EVA in CKD.Swedish Research Council (grant no 2009-1068)European Union‘s Horizon 2020 research and innovation Program, Marie Skłodowska-Curie (grant agreement No 722609)International Network for Training on Risks of Vascular Intimal Calcification and roads to Regression of Cardiovascular Disease (INTRICARE)Baxter HealthcarePublishe

Medical examination of divers after COVID-19 infection: a prospective, observational study using published (original and revised) guidelines for evaluation.

IntroductionThe COVID-19 pandemic raised significant concerns about fitness to dive due to potential damage to the pulmonary and cardiovascular systems. Our group previously published guidelines (original and revised) for assessment of these divers. Here, we report a prospective, observational study to evaluate the utility of these guidelines.MethodsRecreational, commercial, and scientific divers with a history of COVID-19 were consented and enrolled. Subjects were evaluated according to the aforementioned guidelines and followed for any additional complications or diving related injuries.ResultsOne-hundred and twelve divers (56 male, 56 female, ages 19-68) were enrolled: 59 commercial, 30 scientific, 20 recreational, two unknown (not documented), one military. Cases were categorised according to two previous guidelines ('original' n = 23 and 'revised' n = 89): category 0 (n = 6), category 0.5 (n = 64), category 1 (n = 38), category 2 (n = 2), category 3 (n = 1), uncategorisable due to persistent symptoms (n = 1). One hundred divers (89.3%) were cleared to return to diving, four (3.6%) were unable to return to diving, four (3.6%) were able to return to diving with restrictions, and four (3.6%) did not complete testing. Regarding diving related complications, one diver had an episode of immersion pulmonary oedema one year later and one diver presented with decompression sickness and tested positive for COVID-19.ConclusionsMost divers who presented for evaluation were able to return to diving safely. Abnormalities were detected in a small percentage of divers that precluded them from being cleared to dive. Guidelines were easily implemented by a variety of clinicians

Three Styles in the Study of Violence

This is a postprint (accepted manuscript) version of the article published in Reviews in Anthropology 37:1-19. The final version of the article can be found at http://dx.doi.org/10.1080/00938150701829525 (login required to access content). The version made available in Digital Common was supplied by the author.Accepted Manuscripttru

QKI-7 Regulates Expression of Interferon-Related Genes in Human Astrocyte Glioma Cells

The human QKI gene, called quaking homolog, KH domain RNA binding (mouse), is a candidate gene for schizophrenia encoding an RNA-binding protein. This gene was shown to be essential for myelination in oligodendrocytes. QKI is also highly expressed in astrocytes, but its function in these cells is not known.We studied the effect of small interference RNA (siRNA)-mediated QKI depletion on global gene expression in human astrocyte glioma cells. Microarray measurements were confirmed with real-time quantitative polymerase chain reaction (qPCR). The presence of QKI binding sites (QRE) was assessed by a bioinformatic approach. Viability and cell morphology were also studied. The most significant alteration after QKI silencing was the decreased expression of genes involved in interferon (IFN) induction (P = 6.3E-10), including IFIT1, IFIT2, MX1, MX2, G1P2, G1P3, GBP1 and IFIH1. All eight genes were down-regulated after silencing of the splice variant QKI-7, but were not affected by QKI-5 silencing. Interestingly, four of them were up-regulated after treatment with the antipsychotic agent haloperidol that also resulted in increased QKI-7 mRNA levels.The coordinated expression of QKI-7 splice variant and IFN-related genes supports the idea that this particular splice variant has specific functions in astrocytes. Furthermore, a role of QKI-7 as a regulator of an inflammatory gene pathway in astrocytes is suggested. This hypothesis is well in line with growing experimental evidence on the role of inflammatory components in schizophrenia

Polymorphism in the MHC2TA Gene Is Associated with Features of the Metabolic Syndrome and Cardiovascular Mortality

BACKGROUND: Recently, a -168A→G polymorphism in the MHC class II transactivator gene (MHC2TA) was shown to be associated with increased susceptibility to myocardial infarction (MI). AIM: To confirm the association between the MHC2TA -168A→G polymorphism and MI and to study its putative role for microalbuminuria, the metabolic syndrome (MetS) and cardiovascular mortality. MATERIALS AND METHODS: Using an allelic discrimination method we genotyped 11,064 individuals from three study populations: 1) 4,432 individuals from the Botnia type 2 diabetes (T2D) study, 2) 1,222 patients with MI and 2,345 control subjects participating in the Malmö Diet and Cancer study and comprising an MI case-control sample, and 3) 3,065 T2D patients from the Local Swedish Diabetes registry. RESULTS: No association between the -168A→G polymorphism in MHC2TA and MI was observed. However, in the Botnia cohort the AG/GG genotypes were associated with cardiovascular mortality after MI (1.78 [1.09–2.92], p = 0.02). In addition, the AG/GG genotypes were more common in subjects with MetS (40.1% vs. 36.9%, p = 0.03) and in non-diabetic subjects with microalbuminuria (45.4% vs. 36.5%, p = 0.003) compared to control subjects. CONCLUSIONS: A polymorphism in MHC2TA was associated with cardiovascular mortality and predictors of cardiovascular mortality, microalbuminuria and MetS

Seismicity and Sources of Stress in Fennoscandia

This chapter investigates the Fennoscandian uplift area since the latest Ice Age and addresses the question if glacial isostatic adjustment may influence current seismicity. The region is in an intraplate area, with stresses caused by the lithospheric relative plate motions. Discussions on whether uplift and plate tectonics are the only causes of stress have been going on for many years in the scientific community. This review considers the improved sensitivity of the seismograph networks, and at the same time attempts to omit man-made explosions and mining events in the pattern, to present the best possible earthquake pattern. Stress orientations and their connection to the uplift pattern and known tectonics are evaluated. Besides plate motion and uplift, one finds that some regions are affected stress-wise by differences in geographical sediment loading as well as by topography variations. The stress release in the present-day earthquakes shows a pattern that deviates from that of the time right after the Ice Age. This chapter treats the stress pattern generalized for Fennoscandia and guides the interested reader to more details in the national chapters.Peer reviewe