Src Dependent Pancreatic Acinar Injury Can Be Initiated Independent of an Increase in Cytosolic Calcium

Several deleterious intra-acinar phenomena are simultaneously triggered on initiating acute pancreatitis. These culminate in acinar injury or inflammatory mediator generation in vitro and parenchymal damage in vivo. Supraphysiologic caerulein is one such initiator which simultaneously activates numerous signaling pathways including non-receptor tyrosine kinases such as of the Src family. It also causes a sustained increase in cytosolic calcium- a player thought to be crucial in regulating deleterious phenomena. We have shown Src to be involved in caerulein induced actin remodeling, and caerulein induced changes in the Golgi and post-Golgi trafficking to be involved in trypsinogen activation, which initiates acinar cell injury. However, it remains unclear whether an increase in cytosolic calcium is necessary to initiate acinar injury or if injury can be initiated at basal cytosolic calcium levels by an alternate pathway. To study the interplay between tyrosine kinase signaling and calcium, we treated mouse pancreatic acinar cells with the tyrosine phosphatase inhibitor pervanadate. We studied the effect of the clinically used Src inhibitor Dasatinib (BMS-354825) on pervanadate or caerulein induced changes in Src activation, trypsinogen activation, cell injury, upstream cytosolic calcium, actin and Golgi morphology. Pervanadate, like supraphysiologic caerulein, induced Src activation, redistribution of the F-actin from its normal location in the sub-apical area to the basolateral areas, and caused antegrade fragmentation of the Golgi. These changes, like those induced by supraphysiologic caerulein, were associated with trypsinogen activation and acinar injury, all of which were prevented by Dasatinib. Interestingly, however, pervanadate did not cause an increase in cytosolic calcium, and the caerulein induced increase in cytosolic calcium was not affected by Dasatinib. These findings suggest that intra-acinar deleterious phenomena may be initiated independent of an increase in cytosolic calcium. Other players resulting in acinar injury along with the Src family of tyrosine kinases remain to be explored. © 2013 Mishra et al

Consensus Statement Immunonutrition and Exercise.

In this consensus statement on immunonutrition and exercise, a panel of knowledgeable contributors from across the globe provides a consensus of updated science, including the background, the aspects for which a consensus actually exists, the controversies and, when possible, suggested directions for future research

Characterization of Power Induced Heating and Damage in Fiber Optic Probes for Near-Field Scanning Optical Microscopy

Tip-induced sample heating in near-field scanning optical microscopy (NSOM) is studied for fiber optic probes fabricated using the chemical etching technique. To characterize sample heating from etched NSOM probes, the spectra of a thermochromic polymer sample are measured as a function of probe output power, as was previously reported for pulled NSOM probes. The results reveal that sample heating increases rapidly to ~55–60°C as output powers reach ~50 nW. At higher output powers, the sample heating remains approximately constant up to the maximum power studied of ~450 nW. The sample heating profiles measured for etched NSOM probes are consistent with those previously measured for NSOM probes fabricated using the pulling method. At high powers, both pulled and etched NSOM probes fail as the aluminum coating is damaged. For probes fabricated in our laboratory we find failure occurring at input powers of 3.4 ± 1.7 and 20.7 ± 6.9 mW for pulled and etched probes, respectively. The larger half-cone angle for etched probes (∼15° for etched and ~6° for pulled probes) enables more light delivery and also apparently leads to a different failure mechanism. For pulled NSOM probes, high resolution images of NSOM probes as power is increased reveal the development of stress fractures in the coating at a taper diameter of ~6μm. These stress fractures, arising from the differential heating expansion of the dielectric and the metal coating, eventually lead to coating removal and probe failure. For etched tips, the absence of clear stress fractures and the pooled morphology of the damaged aluminum coating following failure suggest that thermal damage may cause coating failure, although other mechanisms cannot be ruled out

Characterization of power induced heating and damage in fiber optic probes for near-field scanning optical microscopy

This is the published version, also available here: http://dx.doi.org/10.1063/1.2740133.Tip-induced sample heating in near-field scanning optical microscopy (NSOM) is studied for fiber optic probes fabricated using the chemical etching technique. To characterize sample heating from etched NSOM probes, the spectra of a thermochromic polymer sample are measured as a function of probe output power, as was previously reported for pulled NSOM probes. The results reveal that sample heating increases rapidly to ∼55–60°C as output powers reach ∼50nW. At higher output powers, the sample heating remains approximately constant up to the maximum power studied of ∼450nW. The sample heating profiles measured for etched NSOM probes are consistent with those previously measured for NSOM probes fabricated using the pulling method. At high powers, both pulled and etched NSOM probes fail as the aluminumcoating is damaged. For probes fabricated in our laboratory we find failure occurring at input powers of 3.4±1.7 and 20.7±6.9mW for pulled and etched probes, respectively. The larger half-cone angle for etched probes (∼15° for etched and ∼6° for pulled probes) enables more light delivery and also apparently leads to a different failure mechanism. For pulled NSOM probes, high resolution images of NSOM probes as power is increased reveal the development of stress fractures in the coating at a taper diameter of ∼6μm. These stress fractures, arising from the differential heating expansion of the dielectric and the metalcoating, eventually lead to coating removal and probe failure. For etched tips, the absence of clear stress fractures and the pooled morphology of the damaged aluminumcoating following failure suggest that thermal damage may cause coating failure, although other mechanisms cannot be ruled out

The effect on mental health of a large scale psychosocial intervention for survivors of mass violence: A quasi-experimental study in Rwanda

Background: War has serious and prolonged mental health consequences. It is argued that post-emergency mental health interventions should not only focus on psychological factors but also address the social environment. No controlled trials of such interventions exist. We studied the effect on mental health of a large scale p

Predicting transitions between longitudinal classes of post-traumatic stress disorder, adjustment disorder and well-being during the COVID-19 pandemic:protocol of a latent transition model in a general Dutch sample

BACKGROUND: A growing body of literature shows profound effects of the COVID-19 pandemic on mental health, among which increased rates of post-traumatic stress disorder (PTSD) and adjustment disorder (AD). However, current research efforts have largely been unilateral, focusing on psychopathology and not including well-being, and are dominated by examining average psychopathology levels or on disorder absence/presence, thereby ignoring individual differences in mental health. Knowledge on individual differences, as depicted by latent subgroups, in the full spectrum of mental health may provide valuable insights in how individuals transition between health states and factors that predict transitioning from resilient to symptomatic classes. Our aim is to (1) identify longitudinal classes (ie, subgroups of individuals) based on indicators of PTSD, AD and well-being in response to the pandemic and (2) examine predictors of transitioning between these subgroups. METHODS AND ANALYSIS: We will conduct a three-wave longitudinal online survey study of n≥2000 adults from the general Dutch population. The first measurement occasion takes place 6 months after the start of the pandemic, followed by two follow-up measurements with 6 months of intervals. Latent transition analysis will be used for data analysis. ETHICS AND DISSEMINATION: Ethical approval has been obtained from four Dutch universities. Longitudinal study designs are vital to monitor mental health (and predictors thereof) in the pandemic to develop preventive and curative mental health interventions. This study is carried out by researchers who are board members of the Dutch Society for Traumatic Stress Studies and is part of a pan-European study (initiated by the European Society for Traumatic Stress Studies) examining the impact of the pandemic in 11 countries. Results will be published in peer-reviewed journals and disseminated at conferences, via newsletters, and media appearance among (psychotrauma) professionals and the general public

Trajectories of prolonged grief disorder severity after loss during the COVID-19 pandemic

Due to the presumed high risk for prolonged grief disorder (PGD) in people bereaved during the COVID-19 pandemic, it is crucial to examine how grief develops over time in this population. This is the first study examining longitudinal symptom-profiles of PGD severity in people bereaved during the pandemic. We aimed to identify latent trajectories of DSM-5-TR PGD severity and predictors thereof in Dutch adults bereaved during the pandemic. Latent class growth modeling was employed to identify differential trajectories of PGD severity in 266 people bereaved on average 115 days prior when entering the study. Participants completed a PGD measure online (using the Traumatic Grief Inventory-Self Report-Plus) at three time-intervals six months apart. Associations between class-membership and socio-demographic, loss-related, health-related, and trauma-related characteristics were examined using multinomial logistic regression. Three trajectories were identified: Low/decreasing PGD symptoms (74%), Mild/stable PGD symptoms (18%), and High/decreasing PGD trajectory (8%). Closer kinship to the deceased, poorer self-rated health status, and having a mental disorder increased the likelihood of belonging to the Mild/stable PGD symptoms and High/decreasing PGD trajectories. This study provides insights in longitudinal PGD symptom-profiles in people bereaved during the pandemic. We found that PGD severity either remained low/mild or eventually decreased over time.</p

Older mothers and increased impact of prenatal screening: stable livebirth prevalence of trisomy 21 in the Netherlands for the period 2000-2013

Research into fetal development and medicin

Predicting transitions between longitudinal classes of post-traumatic stress disorder, adjustment disorder and well-being during the COVID-19 pandemic: protocol of a latent transition model in a general Dutch sample

Stress and Psychopatholog