Summary
Imbalances in the gut microbiota, the bacteria that inhabit the intestines, are central to the pathogenesis of obesity. This systematic review assesses the association between the gut ...microbiota and weight loss in overweight/obese adults and its potential manipulation as a target for treating obesity. This review identified 43 studies using the keywords ‘overweight’ or ‘obesity’ and ‘microbiota’ and related terms; among these studies, 17 used dietary interventions, 11 used bariatric surgery and 15 used microbiota manipulation. The studies differed in their methodologies as well as their intervention lengths. Restrictive diets decreased the microbiota abundance, correlated with nutrient deficiency rather than weight loss and generally reduced the butyrate producers Firmicutes, Lactobacillus sp. and Bifidobacterium sp. The impact of surgical intervention depended on the given technique and showed a similar effect on butyrate producers, in addition to increasing the presence of the Proteobacteria phylum, which is related to changes in the intestinal absorptive surface, pH and digestion time. Probiotics differed in strain and duration with diverse effects on the microbiota, and they tended to reduce body fat. Prebiotics had a bifidogenic effect and increased butyrate producers, likely due to cross‐feeding interactions, contributing to the gut barrier and improving metabolic outcomes. All of the interventions under consideration had impacts on the gut microbiota, although they did not always correlate with weight loss. These results show that restrictive diets and bariatric surgery reduce microbial abundance and promote changes in microbial composition that could have long‐term detrimental effects on the colon. In contrast, prebiotics might restore a healthy microbiome and reduce body fat.
Summary
Asthma was previously defined as an allergic Th2‐mediated inflammatory immune disorder. Recently, this paradigm has been challenged because not all pathological changes observed in the ...asthmatic airways are adequately explained simply as a result of Th2‐mediated processes. Contemporary thought holds that asthma is a complex immune disorder involving innate as well as adaptive immune responses, with the clinical heterogeneity of asthma perhaps a result of the different relative contribution of these two systems to the disease. Epidemiological studies show that exposure to certain environmental substances is strongly associated with the risk of developing asthma. The airway epithelium is first barrier to interact with, and respond to, environmental agents (pollution, viral infection, allergens), suggesting that it is a key player in the pathology of asthma. Epithelial cells play a key role in the regulation of tissue homeostasis by the modulation of numerous molecules, from antioxidants and lipid mediators to growth factors, cytokines, and chemokines. Additionally, the epithelium is also able to suppress mechanisms involved in, for example, inflammation in order to maintain homeostasis. An intrinsic alteration or defect in these regulation mechanisms compromises the epithelial barrier, and therefore, the barrier may be more prone to environmental substances and thus more likely to exhibit an asthmatic phenotype. In support of this, polymorphisms in a number of genes that are expressed in the bronchial epithelium have been linked to asthma susceptibility, while environmental factors may affect epigenetic mechanisms that can alter epithelial function and response to environmental insults. A detailed understanding of the regulatory role of the airway epithelium is required to develop new therapeutic strategies for asthma that not only address the symptoms but also the underlining pathogenic mechanism(s) and prevent airway remodelling.
Abstract Recent observations of Rossby waves and other more exotic forms of inertial oscillations in the Sun’s convection zone have kindled the hope that such waves might be used as a seismic probe ...of the Sun's interior. Here, we present a 3D numerical simulation in spherical geometry that models the Sun’s convection zone and upper radiative interior. This model features a wide variety of inertial oscillations, including both sectoral and tesseral equatorial Rossby waves, retrograde mixed inertial modes, prograde thermal Rossby waves, the recently observed high-frequency retrograde (HFR) vorticity modes, and what may be latitudinal overtones of these HFR modes. With this model, we demonstrate that sectoral and tesseral Rossby waves are ubiquitous within the radiative interior as well as within the convection zone. We suggest that there are two different Rossby-wave families in this simulation that live in different wave cavities: one in the radiative interior and one in the convection zone. Finally, we suggest that many of the retrograde inertial waves that appear in the convection zone, including the HFR modes, are in fact all related, being latitudinal overtones that are mixed modes with the prograde thermal Rossby waves.
Strange particles have been a very important observable in the search for a deconfined state of strongly interacting matter, the quark–gluon plasma (QGP), which is expected to be formed in ...ultra-relativistic heavy ion collisions. We review the main experimental observations made at the Super Proton Synchrotron (SPS) at CERN, Geneva, and at the Relativistic Heavy Ion Collider (RHIC) at Brookhaven National Laboratory (BNL). The large amount of recently collected data allows for a comprehensive study of strangeness production as a function of energy and system size. We review results on yields, transverse mass and rapidity spectra, as well as elliptic flow. The measurements are interpreted in the context of various theoretical concepts and their implications are discussed. Of particular interest is the question whether strange particles are in any way sensitive to a partonic phase. Finally, a compilation of experimental data is provided.
Mutations of the tumor suppressor p53 lead to chemotherapy resistance and a dismal prognosis in chronic lymphocytic leukemia (CLL). Whereas p53 targets are used to identify patient subgroups with ...impaired p53 function, a comprehensive assessment of non-coding RNA targets of p53 in CLL is missing. We exploited the impaired transcriptional activity of mutant p53 to map out p53 targets in CLL by small RNA sequencing. We describe the landscape of p53-dependent microRNA/non-coding RNA induced in response to DNA damage in CLL. Besides the key p53 target miR-34a, we identify a set of p53-dependent microRNAs (miRNAs; miR-182-5p, miR-7-5p and miR-320c/d). In addition to miRNAs, the long non-coding RNAs (lncRNAs) nuclear enriched abundant transcript 1 (NEAT1) and long intergenic non-coding RNA p21 (lincRNA-p21) are induced in response to DNA damage in the presence of functional p53 but not in CLL with p53 mutation. Induction of NEAT1 and lincRNA-p21 are closely correlated to the induction of cell death after DNA damage. We used isogenic lymphoma cell line models to prove p53 dependence of NEAT1 and lincRNA-p21. The current work describes the p53-dependent miRNome and identifies lncRNAs NEAT1 and lincRNA-p21 as novel elements of the p53-dependent DNA damage response machinery in CLL and lymphoma.
Abstract
Meridional circulation regulates the Sun’s interior dynamics and magnetism. While it is well accepted that meridional flows are poleward at the Sun’s surface, helioseismic observations have ...yet to provide a definitive answer for the depth at which those flows return to the equator, or the number of circulation cells in depth. Here, we explore the observability of multiple circulation cells stacked in radius. Specifically, we examine the seismic signature of several meridional flow profiles by convolving time–distance averaging kernels with mean flows obtained from a suite of 3D hydrodynamic simulations. At mid and high latitudes, we find that weak flow structures in the deep convection zone can be obscured by signals from the much stronger surface flows. This contamination of 1–2 m s
−1
is caused by extended side lobes in the averaging kernels, which produce a spurious equatorward signal with flow speeds that are 1 order of magnitude stronger than the original flow speeds in the simulations. At low latitudes, the flows in the deep layers of the simulations are stronger (>2 m s
−1
) and multiple cells across the convection zone can produce a sufficiently strong signal to survive the convolution process. Now that meridional flows can be measured over two decades of data, the uncertainties arising from convective noise have fallen to a level where they are comparable in magnitude to the systematic biases caused by nonlocal features in the averaging kernels. Hence, these systematic errors are beginning to influence current helioseismic deductions and need broader consideration.
Abstract Background Early identification of patients with chronic kidney disease (CKD) and advancing kidney insufficiency, followed by specialist care, can decelerate the progression of the disease. ...However, awareness of the importance and possible consequences of kidney insufficiency is low among doctors and patients. Since kidney insufficiency can be asymptomatic even in higher stages, it is often not even known to those belonging to risk groups. This study aims to clarify whether, for hospitalised patients with advanced chronic kidney disease, a risk-based appointment with a nephrology specialist reduces disease progression. Methods The target population of the study is hospitalised CKD patients with an increased risk of end-stage renal disease (ESRD), more specifically with an ESRD risk of at least 9% in the next 5 years. This risk is estimated by the internationally validated Kidney Failure Risk Equation (KFRE). The intervention consists of a specific appointment with a nephrology specialist after the hospital stay, while control patients are discharged from the hospital as usual. Eight medical centres include participants according to a stepped-wedge design, with randomised sequential centre-wise crossover from recruiting patients into the control group to recruitment to the intervention. The estimated glomerular filtration rate (eGFR) is measured for each patient during the hospital stay and after 12 months within the regular care by the general practitioner. The difference in the change of the eGFR over this period is compared between the intervention and control groups and considered the primary endpoint. Discussion This study is designed to evaluate the effect of risk-based appointments with nephrology specialists for hospitalised CKD patients with an increased risk of end-stage renal disease. If the intervention is proven to be beneficial, it may be implemented in routine care. Limitations will be examined and discussed. The evaluation will include further endpoints such as non-guideline-compliant medication, economic considerations and interviews with contributing physicians to assess the acceptance and feasibility of the intervention. Trial registration German Clinical Trials Register DRKS00029691 . Registered on 12 September 2022.
Background
Healthy circadian rhythmicity has been suggested to relate to a better state of brain‐injured patients and to support the emergence of consciousness in patient groups characterized by a ...relative instability thereof such as patients with disorders of consciousness (DOC).
Methods
Going beyond earlier studies, a systems‐level perspective was adopted and, using multilevel modelling, the joint predictive value of three indices of circadian rhythm integrity derived from skin temperature variations, melatoninsulfate secretion, and physical activity (wrist actigraphy) patterns was evaluated for the behaviourally assessed state Coma Recovery Scale ‐ Revised (CRS‐R) score of DOC patients 13 unresponsive wakefulness syndrome; seven minimally conscious (exit) state. Additionally, it was assessed in a subset of 16 patients whether patients’ behavioural repertoire (CRS‐R score) varied (i) with time of day or (ii) offset from the body temperature maximum (BTmax), i.e. when cognitive performance is expected to peak.
Results
The results reveal that better integrity of circadian melatoninsulfate and temperature rhythms relate to a richer behavioural repertoire. Moreover, higher CRS‐R scores are, by trend, related to assessments taking place at a later daytime or deviating less from the pre‐specified time of occurrence of BTmax.
Conclusions
In conclusion, the results suggest that therapeutic approaches aimed at improving circadian rhythms in brain‐injured patients are promising and should be implemented in hospitals or nursing homes. Beyond this, it might be helpful to schedule diagnostic procedures and therapies around the (pre‐assessed) BTmax (≈4 pm in healthy individuals) as this is when patients should be most responsive.