Background
Rates of parastomal hernia following stoma formation remain high. Previous systematic reviews suggested that prophylactic mesh reduces the rate of parastomal hernia; however, a larger ...trial has recently called this into question. The aim was to determine whether mesh placed at the time of primary stoma creation prevents parastomal hernia.
Methods
The Cochrane Central Register of Controlled Trials, MEDLINE, Embase and CINAHL were searched using medical subject headings for parastomal hernia, mesh and prevention. Reference lists of identified studies, clinicaltrials.gov and the WHO International Clinical Trials Registry were also searched. All randomized clinical trials were included. Two authors extracted data from each study independently using a purpose‐designed sheet. Risk of bias was assessed by a tool based on that developed by Cochrane.
Results
Ten randomized trials were identified among 150 studies screened. In total 649 patients were included in the analysis (324 received mesh). Overall the rates of parastomal hernia were 53 of 324 (16·4 per cent) in the mesh group and 119 of 325 (36·6 per cent) in the non‐mesh group (odds ratio 0·24, 95 per cent c.i. 0·12 to 0·50; P < 0·001). Mesh reduced the rate of parastomal hernia repair by 65 (95 per cent c.i. 28 to 85) per cent (P = 0·02). There were no differences in rates of parastomal infection, stomal stenosis or necrosis. Mesh type and position, and study quality did not have an independent effect on this relationship.
Conclusion
Mesh placed prophylactically at the time of stoma creation reduced the rate of parastomal hernia, without an increase in mesh‐related complications.
Should be used
Human motor skills can be acquired by observation without the benefit of immediate physical practice. The current study tested if physical rehearsal and observational learning share common neural ...substrates within an action observation network (AON) including premotor and inferior parietal regions, that is, areas activated both for execution and observation of similar actions. Participants trained for 5 days on dance sequences set to music videos. Each day they physically rehearsed one set of dance sequences (“danced”), and passively watched a different set of sequences (“watched”). Functional magnetic resonance imaging was obtained prior to and immediately following the 5 days of training. After training, a subset of the AON showed a degree of common activity for observational and physical learning. Activity in these premotor and parietal regions was sustained during observation of sequences that were danced or watched, but declined for unfamiliar sequences relative to the pretraining scan session. These imaging data demonstrate the emergence of action resonance processes in the human brain based on observational learning without physical practice and identify commonalities in the neural substrates for physical and observational learning.
A
bstract
Neutrinoless double-beta decay is a key process in particle physics. Its experimental investigation is the only viable method that can establish the Majorana nature of neutrinos, providing ...at the same time a sensitive inclusive test of lepton number violation. CROSS (Cryogenic Rare-event Observatory with Surface Sensitivity) aims at developing and testing a new bolometric technology to be applied to future large-scale experiments searching for neutrinoless double-beta decay of the promising nuclei
100
Mo and
130
Te. The limiting factor in large-scale bolometric searches for this rare process is the background induced by surface radioactive contamination, as shown by the results of the CUORE experiment. The basic concept of CROSS consists of rejecting this challenging background component by pulse-shape discrimination, assisted by a proper coating of the faces of the crystal containing the isotope of interest and serving as energy absorber of the bolometric detector. In this paper, we demonstrate that ultra-pure superconductive Al films deposited on the crystal surfaces act successfully as pulse-shape modifiers, both with fast and slow phonon sensors. Rejection factors higher than 99.9% of
α
surface radioactivity have been demonstrated in a series of prototypes based on crystals of Li
2
MoO
4
and TeO
2
. We have also shown that point-like energy depositions can be identified up to a distance of
∼
1 mm from the coated surface. The present program envisions an intermediate experiment to be installed underground in the Canfranc laboratory (Spain) in a CROSS-dedicated facility. This experiment, comprising
∼
3
×
10
25
nuclei of
100
Mo, will be a general test of the CROSS technology as well as a worldwide competitive search for neutrinoless double-beta decay, with sensitivity to the effective Majorana mass down to 70 meV in the most favorable conditions.
The transcription factor Nrf2 regulates the basal and inducible expression of a battery of cytoprotective genes. Whereas numerous Nrf2-inducing small molecules have been reported, very few chemical ...inhibitors of Nrf2 have been identified to date. The quassinoid brusatol has recently been shown to inhibit Nrf2 and ameliorate chemoresistance in vitro and in vivo. Here, we show that brusatol provokes a rapid and transient depletion of Nrf2 protein, through a posttranscriptional mechanism, in mouse Hepa-1c1c7 hepatoma cells. Importantly, brusatol also inhibits Nrf2 in freshly isolated primary human hepatocytes. In keeping with its ability to inhibit Nrf2 signaling, brusatol sensitizes Hepa-1c1c7 cells to chemical stress provoked by 2,4-dinitrochlorobenzene, iodoacetamide, and N-acetyl-p-benzoquinone imine, the hepatotoxic metabolite of acetaminophen. The inhibitory effect of brusatol toward Nrf2 is shown to be independent of its repressor Keap1, the proteasomal and autophagic protein degradation systems, and protein kinase signaling pathways that are known to modulate Nrf2 activity, implying the involvement of a novel means of Nrf2 regulation. These findings substantiate brusatol as a useful experimental tool for the inhibition of Nrf2 signaling and highlight the potential for therapeutic inhibition of Nrf2 to alter the risk of adverse events by reducing the capacity of nontarget cells to buffer against chemical and oxidative insults. These data will inform a rational assessment of the risk:benefit ratio of inhibiting Nrf2 in relevant therapeutic contexts, which is essential if compounds such as brusatol are to be developed into efficacious and safe drugs.
•Nrf2 regulates the expression of numerous cytoprotective genes.•We show that the quassinoid brusatol rapidly and transiently inhibits Nrf2 signaling.•Brusatol sensitizes mammalian cells to chemical stress provoked by electrophiles.•Brusatol inhibits Nrf2 independent of its key regulatory mechanisms.•Therapeutic inhibition of Nrf2 could enhance drug-induced adverse effects.
Inhalation injury is predictive of dysphagia post burns; however, the nature of dysphagia associated with inhalation burns is not well understood. This study describes the clinical profile and ...recovery pattern of swallowing following inhalation burn injury. All patients admitted 2008–2017 with confirmed inhalation burns on laryngoscopy and managed by speech-language pathology (SLP) were included. Initial dysphagia presentation and dysphagia recovery pattern were documented using the FOIS. Co-presence of dysphonia was determined clinically and rated present/absent. Persistent laryngeal/pharyngeal injury at 6 months was documented using laryngoscopy. Data were compared to published data from a large adult burn cohort. All patients with confirmed inhalation burns during the study period received SLP input, enabling review of 38 patients (68% male;
m
= 40.8 years). Percent Total Body Surface Area burn ranged 1–90%, 100% had head and neck burns, 97% required mechanical ventilation (mean 9.4 days), 18% required tracheostomy and 100% had dysphonia. Comparing to non-inhalation burn patients, the inhalation cohort had significantly (
p
< 0.01) higher dysphagia incidence (89.47% vs 5.6%); more with severe dysphagia at presentation (78.9% vs 1.7%); increased duration to initiate oral intake (
m
= 24.69 vs 0.089 days); longer duration of enteral feeding (
m
= 45.03 vs 1.96 days); and longer duration to resolution of dysphagia (
m
= 29.79 vs 1.67 days). Persistent laryngeal pathology was present in 47.37% at 6 months. This study shows dysphagia incidence in burn patients with inhalation injury is 16 times greater than for those without inhalation injury. Laryngeal pathology due to inhalation injury increases dysphagia severity and duration to dysphagia recovery.
Natural resource managers are seeking tools to help them address current and future effects of climate change. We present a model for collaborative planning aimed at identifying ways to adapt ...management actions to address the effects of climate change in landscapes that cross public and private jurisdictional boundaries. The Southwest Climate Change Initiative (SWCCI) piloted the Adaptation for Conservation Targets (ACT) planning approach at workshops in 4 southwestern U.S. landscapes. This planning approach successfully increased participants' self-reported capacity to address climate change by providing them with a better understanding of potential effects and guiding the identification of solutions. The workshops fostered cross-jurisdictional and multidisciplinary dialogue on climate change through active participation of scientists and managers in assessing climate change effects, discussing the implications of those effects for determining management goals and activities, and cultivating opportunities for regional coordination on adaptation of management plans. Facilitated application of the ACT framework advanced group discussions beyond assessing effects to devising options to mitigate the effects of climate change on specific species, ecological functions, and ecosystems. Participants addressed uncertainty about future conditions by considering more than one climate-change scenario. They outlined opportunities and identified next steps for implementing several actions, and local partnerships have begun implementing actions and conducting additional planning. Continued investment in adaptation of management plans and actions to address the effects of climate change in the southwestern United States and extension of the approaches used in this project to additional landscapes are needed if biological diversity and ecosystem services are to be maintained in a rapidly changing world. Los manejadores de recursos naturales están buscando herramientas para ayudarles a atender los efectos actuales y futuros del cambio climático. Presentamos un modelo para la planificación colaborativa enfocada a identificar formas para adaptar las acciones de manejo para atender los efectos del cambio climático en paisajes que cruzan límites jurisdiccionales públicos y privados. La Iniciativa Sudoccidental de Cambio Climático (ISCC) puso a prueba el método de planificación de Adaptación para Metas de Conservación (AMC) en talleres en cuatro paisajes del suroeste de E. U. A. Este método de planificación incrementó exitosamente la capacidad de los participantes para atender el cambio climático al proporcionarles un mejor entendimiento de los efectos potenciales y guiar la identificación de soluciones. Los talleres promovieron el diálogo trans-jurisdiccional y multidisciplinario sobre cambio climático mediante la participación activa de científicos y manejadores en la evaluación de efectos del cambio climático, la discusión de implicaciones de esos efectos para determinar las metas y actividades de manejo y desarrollar oportunidades para la coordinación regional de la adaptación de planes de manejo. La aplicación simplificada del marco AMC llevó las discusiones de grupo más allá de la evaluación de los efectos a la concepción de opciones para mitigar los efectos del cambio climático sobres determinadas especies, funciones ecológicas y ecosistemas. Los participantes abordaron la incertidumbre de las condiciones futuras al considerar más de un escenario de cambio climático. Delinearon oportunidades e identificaron los siguientes pasos para la implementación de varias acciones, y asociaciones locales han comenzado a implementar acciones y realizar planificación adicional. Se requiere inversión continua en la adaptación de planes y acciones de manejo para atender los efectos del cambio climático en el suroeste de Estados Unidos y la extensión de los métodos utilizados en este proyecto en paisajes adicionales si se quiere mantener la diversidad biológica y los servicios de los ecosistemas en un mundo que cambia rápidamente.
As natural resource management agencies and conservation organizations seek guidance on responding to climate change, myriad potential actions and strategies have been proposed for increasing the ...long-term viability of some attributes of natural systems. Managers need practical tools for selecting among these actions and strategies to develop a tailored management approach for specific targets at a given location. We developed and present one such tool, the participatory Adaptation for Conservation Targets (ACT) framework, which considers the effects of climate change in the development of management actions for particular species, ecosystems and ecological functions. Our framework is based on the premise that effective adaptation of management to climate change can rely on local knowledge of an ecosystem and does not necessarily require detailed projections of climate change or its effects. We illustrate the ACT framework by applying it to an ecological function in the Greater Yellowstone Ecosystem (Montana, Wyoming, and Idaho, USA)—water flows in the upper Yellowstone River. We suggest that the ACT framework is a practical tool for initiating adaptation planning, and for generating and communicating specific management interventions given an increasingly altered, yet uncertain, climate.
Mercury in seafood is a neurotoxicant that threatens human health. Dynamic rates of mercury emission, re-emission, and atmospheric deposition warrant studies into mercury concentrations in fish ...because many are consumed by humans and can serve as sentinels of mercury levels in the environment. We modeled trends in total mercury content in an apex marine fish predator, Atlantic blue marlin Makaira nigricans, whose muscle tissues were opportunistically sampled from North Carolina (USA) sportfishing tournaments over a discontinuous time period: between 1975 and 77 and 1998–2021 (n = 148). The model-estimated influence of marlin weight on total mercury concentration was constant across years (shared slope) allowing for comparisons of weight-corrected mercury concentrations among years. Weight-corrected total mercury concentrations revealed an inter-decadal decline of approximately 45 % between the 1970s and late 1990s and then variable but relatively stable concentrations through 2021. The mean (SD) wet weight concentration of total mercury was 9.47 (4.11) from 1975 to 77 and 4.17 (2.61) from 2020 to 2021. Methylmercury and selenium were measured on a subset of fish to address questions related to human health and consumption. Methylmercury levels (mean = 0.72 μg/g) were much lower than total mercury (mean = 4.69 μg/g) indicating that total mercury is not a good proxy for methylmercury in Atlantic blue marlin. Selenium, examined as a Se:Hg molar ratio and as a selenium health benefit value (HBVSe), showed high protective value against mercury toxicity. Long-term trends in the concentration of mercury in blue marlin should continue to be monitored to determine whether policies to mitigate anthropogenic contributions to global mercury are achieving their intended goals and to provide information to inform safe human consumption.
Display omitted
•Long-term studies of offshore marine apex predators are valuable for indexing ambient heavy metal concentrations.•Atlantic blue marlin muscle collected from 1975 to 2021 was analyzed for total mercury, methylmercury, and selenium.•Total mercury concentrations declined from the 1970s to late 1990s, but remained approximately constant during this century.•Methylmercury is a small percentage of total mercury in Atlantic blue marlin, which is not typically observed in fish.•High selenium concentrations in Atlantic blue marlin tissue may substantially offset mercury toxicity in human consumers.
Identifying the underlying genetic drivers of the heritability of breast cancer prognosis remains elusive. We adapt a network-based approach to handle underpowered complex datasets to provide new ...insights into the potential function of germline variants in breast cancer prognosis. This network-based analysis studies ~7.3 million variants in 84,457 breast cancer patients in relation to breast cancer survival and confirms the results on 12,381 independent patients. Aggregating the prognostic effects of genetic variants across multiple genes, we identify four gene modules associated with survival in estrogen receptor (ER)-negative and one in ER-positive disease. The modules show biological enrichment for cancer-related processes such as G-alpha signaling, circadian clock, angiogenesis, and Rho-GTPases in apoptosis.
Multiple sclerosis (MS) is an autoimmune demyelinating disease characterized by complex genetics and multifaceted gene-environment interactions. Compared to whites, African Americans have a lower ...risk for developing MS, but African Americans with MS have a greater risk of disability. These differences between African Americans and whites may represent differences in genetic susceptibility and/or environmental factors. SNPs from 12 candidate genes have recently been identified and validated with MS risk in white populations. We performed a replication study using 918 cases and 656 unrelated controls to test whether these candidate genes are also associated with MS risk in African Americans. CD6, CLEC16a, EVI5, GPC5, and TYK2 contained SNPs that are associated with MS risk in the African American data set. EVI5 showed the strongest association outside the major histocompatibility complex (rs10735781, OR=1.233, 95% CI=1.06-1.43, P-value=0.006). In addition, RGS1 seems to affect age of onset whereas TNFRSF1A seems to be associated with disease progression. None of the tested variants showed results that were statistically inconsistent with the effects established in whites. The results are consistent with shared disease genetic mechanisms among individuals of European and African ancestry.
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