Disruptions to circadian rhythm may be implicated in the pathogenesis of metabolic syndrome (Met‐S). For example, eating during an extended period of the day may negatively impact the circadian ...rhythms governing metabolic control, contributing, therefore, to Met‐S and associated end‐organ damage. Accordingly, time‐restricted eating (TRE)/feeding (TRF) is gaining popularity as a dietary intervention for the treatment and prevention of Met‐S. To date, no studies have specifically examined the impact of TRE/TRF on the renal consequences of Met‐S. The proposed study seeks to use a model of experimental Met‐S‐associated kidney disease to address this knowledge gap, disambiguating therein the effects of calorie restriction from the timing of food intake. Spontaneously hypertensive rats will consume a high‐fat diet (HFD) for 8 weeks and then be allocated by stratified randomisation according to albuminuria to one of three groups. Rats will have free 24‐h access to HFD (Group A), access to HFD during the scheduled hours of darkness (Group B) or access to HFD provided in the form of two rations, one provided during the light phase and one provided during the dark phase, equivalent overall in quantity to that consumed by rats in Group B (Group C). The primary outcome measure will be a change in albuminuria. Changes in food intake, body weight, blood pressure, glucose tolerance, fasting plasma insulin, urinary excretion of C‐peptide and renal injury biomarkers, liver and kidney histopathology and inflammation, and fibrosis‐related renal gene expression will be assessed as secondary outcomes.
Introduce Shimming Toolbox ( https://shimming-toolbox.org), an open-source software package for prototyping new methods and performing static, dynamic, and real-time B0 shimming as well as B1 ...shimming experiments.
Shimming Toolbox features various field mapping techniques, manual and automatic masking for the brain and spinal cord, B0 and B1 shimming capabilities accessible through a user-friendly graphical user interface. Validation of Shimming Toolbox was demonstrated in three scenarios: (i) B0 dynamic shimming in the brain at 7T using custom AC/DC coils, (ii) B0 real-time shimming in the spinal cord at 3T, and (iii) B1 static shimming in the spinal cord at 7T.
The B0 dynamic shimming of the brain at 7T took about 10 min to perform. It showed a 47% reduction in the standard deviation of the B0 field, associated with noticeable improvements in geometric distortions in EPI images. Real-time dynamic xyz-shimming in the spinal cord took about 5 min and showed a 30% reduction in the standard deviation of the signal distribution. B1 static shimming experiments in the spinal cord took about 10 min to perform and showed a 40% reduction in the coefficient of variation of the B1 field.
Shimming Toolbox provides an open-source platform where researchers can collaborate, prototype and conveniently test B0 and B1 shimming experiments. Future versions will include additional field map preprocessing techniques, optimization algorithms, and compatibility across multiple MRI manufacturers.
We are grateful our case has aroused such interest from our Turkish colleagues, and we thank them for their kind reply. Sigmoid volvulus (SV) is the third leading cause of colonic obstruction in the ...world. Is it widely known there is a progressive aging of the population. Prevention with lifestyle habits and early treatment of cardiovascular risk factors has led to an increase of pluripatologic chronic conditions. A higher incidence of neurodegenerative diseases is also a proven fact. Their intestinalinvolvementcan be ina direct form, withneuronal destruction in myenteric plexus leading to chronic constipation, and alsodue to secondary drug effects (laxatives causing fecal overloading, increased intracolonic pressure, dolichocolon…), all favouringweakness in colonic wall, and therefore the appearance of sigmoid volvulus. We don´t have specific data about SV incidence and recurrence in our centre.However, literature reviews show recurrence is the norm in the majority of cases after colonic decompression. Data reported from our colleagues in Turkey represents a single centre cohort and a broad spectrum over time (from 1960s until now), so recurrence rate should not be generalized to global population. The continuous improvement in endoscopic procedures since their beginning might have despair results of colonic decompression and need of surgery among years. Nowadays we have more sophisticated and high-resolution endoscopes, as well as better trained endoscopists with more advanced therapeutic techniques. This might overlap with surgical development of less invasive techniques, lower rates of complication and shorter postoperative recovery. We suggest the authors to examin in their database the different outcomes through decades in their cohort since we believe medical/endoscopic/surgical approach has changed from 1960s until now. Finally, we agree elective surgery must be the final treatment in SV cases with American Society of Anesthesiologists (ASA) scores 1-3. Endoscopic or laparoscopic colopexychoice for ASA > 3 patients should be made based on each centre´s experience. We believe endoscopic approach with endoscopic colostomy or sigmoidopexy might be the first approach for fragile patients since it is an easily performed technique, with low rate of complications and acceptable long-term results preventing a recurrence of SV. Further studies are needed to compare minimally invasive surgery to endoscopic approach.
Common genetic variation at human 8q23.3 is significantly associated with colorectal cancer (CRC) risk. To elucidate the basis of this association we compared the frequency of common variants at ...8q23.3 in 1,964 CRC cases and 2,081 healthy controls. Reporter gene studies showed that the single nucleotide polymorphism rs16888589 acts as an allele-specific transcriptional repressor. Chromosome conformation capture (3C) analysis demonstrated that the genomic region harboring rs16888589 interacts with the promoter of gene for eukaryotic translation initiation factor 3, subunit H (EIF3H). We show that increased expression of EIF3H gene increases CRC growth and invasiveness thereby providing a biological mechanism for the 8q23.3 association. These data provide evidence for a functional basis for the non-coding risk variant rs16888589 at 8q23.3 and provides novel insight into the etiological basis of CRC.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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Hypertension is a complex disorder ensuing necessarily from alterations in the pressure-natriuresis relationship, the main determinant of long-term control of blood pressure. This ...mechanism sets natriuresis to the level of blood pressure, so that increasing pressure translates into higher osmotically driven diuresis to reduce volemia and control blood pressure. External factors affecting the renal handling of sodium regulate the pressure-natriuresis relationship so that more or less natriuresis is attained for each level of blood pressure. Hypertension can thus only develop following primary alterations in the pressure to natriuresis balance, or by abnormal activity of the regulation network. On the other hand, increased sympathetic tone is a very frequent finding in most forms of hypertension, long regarded as a key element in the pathophysiological scenario. In this article, we critically analyze the interplay of the renal component of the sympathetic nervous system and the pressure-natriuresis mechanism in the development of hypertension. A special focus is placed on discussing recent findings supporting a role of baroreceptors as a component, along with the afference of reno-renal reflex, of the input to the nucleus tractus solitarius, the central structure governing the long-term regulation of renal sympathetic efferent tone.
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Five new laxaphycins were isolated and fully characterised from the bloom forming cyanobacteria Anabaena torulosa sampled from Moorea, French Polynesia: three acyclic laxaphycin ...A-type peptides, acyclolaxaphycin A (1), des-Gly11acyclolaxaphycin A (2) and des-(Leu10-Gly11)acyclolaxaphycin A (3), as well as two cyclic ones, l-Val8laxaphycin A (4) and d-Val9laxaphycin A (5). The absolute configuration of the amino acids, established using advanced Marfey’s analysis for compounds 2–5, highlights a conserved stereochemistry at the Cα carbons of the peptide ring that is characteristic of this family. To the best of our knowledge, this is the first report of acyclic analogues within the laxaphycin A-type peptides. Whether these linear laxaphycins with the aliphatic β-amino acid on the N-terminal are biosynthetic precursors or compounds obtained after enzymatic hydrolysis of the macrocycle is discussed. Biological evaluation of the new compounds together with the already known laxaphycin A shows that l-Val8laxaphycin A, d-Val9laxaphycin A and des-Gly11acyclolaxaphycin induce cellular toxicity whereas laxaphycin A and des-(Leu10-Gly11)acyclolaxaphycin A do not affect the cellular viability. An analysis of cellular death shows that the active peptides do not induce apoptosis or necrosis but instead, involve the autophagy pathway.
Cyclophilins (Cyps) are a group of peptidyl-prolyl
isomerases that play crucial roles in regulatory mechanisms of cellular physiology and pathology in several inflammatory conditions. Their receptor, ...CD147, also participates in the development and progression of the inflammatory response. Nevertheless, the main function of Cyps and their receptor are yet to be deciphered. The release of CypA and the expression of the CD147 receptor in activated T lymphocytes were already described, however, no data are available about other Cyps in these cells. Therefore, in the present work intra and extracellular CypA, B and C levels were measured followed by induced inflammatory conditions. After activation of T lymphocytes by incubation with concanavalin A, both intra and extracellular Cyps levels and the CD147 membrane receptor expression were increased leading to cell migration towards circulating CypA and CypB as chemoattractants. When CypA was modulated by natural and synthetic compounds, the inflammatory cascade was avoided including T cell migration. Our results strengthen the relationship between CypA, B, and C, their receptor, and the inflammatory process in human T lymphocytes, associating CypC with these cells for the first time.
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