Optokinetic stimulation rehabilitation in preventing seasickness

SummaryObjectivesSeasickness occurs when traveling on a boat: symptoms such as vomiting are very disturbing and may be responsible for discontinuing travel or occupation and can become life-threatening. The failure of classical treatment to prevent seasickness has motivated this retrospective study exploring optokinetic stimulation in reducing these symptoms.Patients and methodsExperimental training of 75 sailors with optokinetic stimulation attempted to reduce seasickness manifestations and determine the factors that could predict accommodation problems.ResultsEighty percent of the trained subjects were able to return on board. No predictive factors such as sex, occupation, degree of illness, number of treatment sessions, time to follow-up, and age were found to influence training efficacy.ConclusionOptokinetic stimulation appears to be promising in the treatment of seasickness. Nevertheless, statistically significant results have yet to demonstrate its efficacy

Long term outcomes in diabetic patients treated with atherectomy for peripheral artery disease

Background: The prevalence of diabetes has increased significantly in well-developed countries during the last decade and it continues to grow. Diabetes increases the risk of restenosis in patients treated percutaneously for peripheral artery disease. The present study sought to compare outcomes of atherectomy treatment in diabetic (DM) vs. non-diabetic (nDM) patients suffering from peripheral artery disease.Method: Between 2008 and 2012, 204 revascularization atherectomy procedures were performed on arteries of the lower extremities. The endpoints included target lesion revascularization (TLR), amputation and death. The type of atherectomy (excisional-soft plaque, orbital-calcified plaque, with active aspiration — with a thrombus) was left to operator discretion.Results: This study contains 132 DM (66% male, age 68 ± 11.2 years) and 72 nDM (63% male, age 75 ± 11.3 years) subjects. DM were younger but had a higher prevalence of coronary artery disease (DM: 91% vs. nDM: 62%, p < 0.0001) and end-stage renal disease (DM: 22% vs. nDM: 2.5%, p < 0.0001). There were no differences in critical limb ischemia between the groups (DM: 21% vs. nDM: 12%, p = = 0.13). Mean time of follow-up was 384 and 411 days in DM and nDM, respectively (p = 0.43). There were no significant differences in TLR (DM: 15.2% vs. nDM: 22.2%, p = 0.249), amputations (DM: 3.0% vs. nDM: 1.5%, p = NS) or death rates (DM: 2.2% vs. nDM: 2.7%, p = NS). Kaplan-Mayer analysis showed no significant differences between the groups in the time to TLR, amputation or death.Conclusions: Plaque modification with adjusted atherectomy appears to have similar outcomes indiabetic as well as in non-diabetic patients. Nonetheless, a randomized study would be warranted toconfirm the findings of the current study

CRISPR-assisted detection of RNA-protein interactions in living cells.

We have developed CRISPR-assisted RNA-protein interaction detection method (CARPID), which leverages CRISPR-CasRx-based RNA targeting and proximity labeling to identify binding proteins of specific long non-coding RNAs (lncRNAs) in the native cellular context. We applied CARPID to the nuclear lncRNA XIST, and it captured a list of known interacting proteins and multiple previously uncharacterized binding proteins. We generalized CARPID to explore binders of the lncRNAs DANCR and MALAT1, revealing the method's wide applicability in identifying RNA-binding proteins

Exceptional preservation of palaeozoic steroids in a diagenetic continuum

The occurrence of intact sterols has been restricted to immature Cretaceous (~125 Ma) sediments with one report from the Late Jurassic (~165 Ma). Here we report the oldest occurrence of intact sterols in a Crustacean fossil preserved for ca. 380 Ma within a Devonian concretion. The exceptional preservation of the biomass is attributed to microbially induced carbonate encapsulation, preventing full decomposition and transformation thus extending sterol occurrences in the geosphere by 250 Ma. A suite of diagenetic transformation products of sterols was also identified in the concretion, demonstrating the remarkable coexistence of biomolecules and geomolecules in the same sample. Most importantly the original biolipids were found to be the most abundant steroids in the sample. We attribute the coexistence of steroids in a diagenetic continuum-ranging from stenols to triaromatic steroids-to microbially mediated eogenetic processes

The last forests on Antarctica: Reconstructing flora and temperature from the Neogene Sirius Group, Transantarctic Mountains

Fossil-bearing deposits in the Transantarctic Mountains, Antarctica indicate that, despite the cold nature of the continent’s climate, a tundra ecosystem grew during periods of ice sheet retreat in the mid to late Neogene (17–2.5 Ma), 480 km from the South Pole. To date, palaeotemperature reconstruction has been based only on biological ranges, thereby calling for a geochemical approach to understanding continental climate and environment. There is contradictory evidence in the fossil record as to whether this flora was mixed angiosperm-conifer vegetation, or whether by this point conifers had disappeared from the continent. In order to address these questions, we have analysed, for the first time in sediments of this age, plant and bacterial biomarkers in terrestrial sediments from the Transantarctic Mountains to reconstruct past temperature and vegetation during a period of East Antarctic Ice Sheet retreat. From tetraether lipids (MBT’/CBT palaeothermometer), we conclude that the mean continental summer temperature was ca. 5 °C, in agreement with previous reconstructions. This was warm enough to have allowed woody vegetation to survive and reproduce even during the austral winter. Biomarkers from vascular plants indicate a low diversity and spatially variable flora consisting of higher plants, moss and algal mats growing in microenvironments in a glacial outwash system. Abietane-type compounds were abundant in some samples, indicating that conifers, most likely Podocarpaceae, grew on the Antarctic continent well into the Neogene. This is supported by the palynological record, but not the macrofossil record for the continent, and has implications for the evolution of vegetation on Antarctica

Dental Health and Mortality in People With End-Stage Kidney Disease Treated With Hemodialysis: A Multinational Cohort Study

Background Dental disease is more extensive in adults with chronic kidney disease, but whether dental health and behaviors are associated with survival in the setting of hemodialysis is unknown. Study Design Prospective multinational cohort. Setting & Participants 4,205 adults treated with long-term hemodialysis, 2010 to 2012 (Oral Diseases in Hemodialysis [ORAL-D] Study). Predictors Dental health as assessed by a standardized dental examination using World Health Organization guidelines and personal oral care, including edentulousness; decayed, missing, and filled teeth index; teeth brushing and flossing; and dental health consultation. Outcomes All-cause and cardiovascular mortality at 12 months after dental assessment. Measurements Multivariable-adjusted Cox proportional hazards regression models fitted with shared frailty to account for clustering of mortality risk within countries. Results During a mean follow-up of 22.1 months, 942 deaths occurred, including 477 cardiovascular deaths. Edentulousness (adjusted HR, 1.29; 95% CI, 1.10-1.51) and decayed, missing, or filled teeth score ≥ 14 (adjusted HR, 1.70; 95% CI, 1.33-2.17) were associated with early all-cause mortality, while dental flossing, using mouthwash, brushing teeth daily, spending at least 2 minutes on oral hygiene daily, changing a toothbrush at least every 3 months, and visiting a dentist within the past 6 months (adjusted HRs of 0.52 [95% CI, 0.32-0.85], 0.79 [95% CI, 0.64-0.97], 0.76 [95% CI, 0.58-0.99], 0.84 [95% CI, 0.71-0.99], 0.79 [95% CI, 0.65-0.95], and 0.79 [95% CI, 0.65-0.96], respectively) were associated with better survival. Results for cardiovascular mortality were similar. Limitations Convenience sample of clinics. Conclusions In adults treated with hemodialysis, poorer dental health was associated with early death, whereas preventive dental health practices were associated with longer survival

Purification of cross-linked RNA-protein complexes by phenol-toluol extraction

Recent methodological advances allowed the identification of an increasing number of RNA-binding proteins (RBPs) and their RNA-binding sites. Most of those methods rely, however, on capturing proteins associated to polyadenylated RNAs which neglects RBPs bound to non-adenylate RNA classes (tRNA, rRNA, pre-mRNA) as well as the vast majority of species that lack poly-A tails in their mRNAs (including all archea and bacteria). We have developed the Phenol Toluol extraction (PTex) protocol that does not rely on a specific RNA sequence or motif for isolation of cross-linked ribonucleoproteins (RNPs), but rather purifies them based entirely on their physicochemical properties. PTex captures RBPs that bind to RNA as short as 30 nt, RNPs directly from animal tissue and can be used to simplify complex workflows such as PAR-CLIP. Finally, we provide a global RNA-bound proteome of human HEK293 cells and the bacterium Salmonella Typhimurium

THE ESTABLISHMENT OF CRITERIA FOR THE APPLICATION OF GENERAL SYSTEMS THEORY TO ADMINISTRATION

The system approach in the area of reference to man\u27s work is considered to be a rather recent phenomenon. This belief is not only untrue, but has led to many misconceptions about the term, systems. Science has used this approach since before the birth of Christ, and its origin can be traced approximately to the third century B.C. The general systems concept has a long and involved history, although the term itself was not introduced until after the Second World War, when von Bertalanffy discussed general systems theory in relation to Biology. Since that time, the concept of systems has prolifereated so that each discipline has used the term in its unique way..

Perfect adaptation of CD8+ T cell responses to constant antigen input over a wide range of affinity is overcome by costimulation

Maintaining and limiting T cell responses to constant antigen stimulation is critical to eliminate pathogens and maintain self-tolerance, respectively. Antigen recognition by the T cell receptor (TCR) induces signalling that can activate T cells to produce cytokines and downregulation of the TCR. Precisely how TCR downregulation controls T cell responses to constant antigen stimulation is controversial. In other systems, receptor downregulation can induce perfect adaptation to constant stimulation by a mechanism known as state-dependent inactivation but this relies on complete downregulation of the receptor or the ligand, which is not the case for the TCR. Here, we observed that primary human effector T cells exhibit perfect adaptation in cytokine production to constant antigen stimulation. Perfect adaptation was observed across a wide variation in antigen concentration (2,000-fold) and affinity (100,000-fold) even with partial TCR downregulation. A mechanistic model showed that TCR downregulation produces imperfect adaptation, but when coupled to digital signalling led to perfect adaptation in cytokine production. A prediction of the model is that pMHC-induced TCR signalling continues after adaptation and this is confirmed by showing that, while costimulation cannot prevent adaptation, CD28 and 4-1BB signalling reactivated adapted T cells to produce cytokines in a pMHC-dependent manner. We show that adaptation also applied to 1st generation chimeric antigen receptor (CAR)-T cells but is partially avoided in 2nd generation CARs. These findings highlight the role of even partial TCR downregulation in generating perfect adaptation with implications for costimulation and adoptive T cell therapies

Perfect adaptation of CD8(+) T cell responses to constant antigen input over a wide range of affinities is overcome by costimulation

Maintaining and limiting T cell responses to constant stimulation with antigen are critical to control pathogens and maintain self-tolerance, respectively. Antigen recognition by T cell receptors (TCRs) activates signaling that stimulates T cells to produce cytokines and also leads to the down-regulation of cell surface TCRs. In other systems, receptor down-regulation can induce perfect adaptation to constant stimulation by a mechanism known as state-dependent inactivation, which requires complete down-regulation of the receptor or the ligand; however, this is not the case for the TCR. Here, we observed that in vitro–expanded primary human T cells exhibited perfect adaptation with respect to cytokine production to constant antigen stimulation across a 100,000-fold variation in affinity with partial TCR down-regulation. By directly fitting a mechanistic model to these data, we showed that TCR down-regulation produced imperfect adaptation, but, when coupled to a switch, produced perfect adaptation in terms of cytokine production. A prediction of this model was that TCR signaling induced by peptide-bound major histocompatibility complex (pMHC) continues after adaptation, which we confirmed by showing that, whereas costimulation could not prevent adaptation, signaling by the costimulatory receptors CD28 and 4-1BB reactivated adapted T cells to produce cytokines in a pMHC-dependent manner. We showed that adaptation also applied to first-generation chimeric antigen receptor (CAR) T cells but was partially avoided with second-generation CARs. These findings highlight that perfect adaptation limits the responses of T cells, rendering them dependent on costimulation for sustained responses