Search

Thoracic trauma continues to cause at least 25% of traumatic deaths in the USA, and many of these injuries cause death within the first minutes to hours following trauma. Mortality of thoracic injuries is second only to head injuries. Many deaths are preventable by prompt diagnosis and treatment given the vital structures that reside within the thoracic cavity. Injuries from chest trauma range from rib fractures requiring only pain control to cardiac lacerations with tamponade or exsanguinating hemorrhage. Given the range of injuries, acuity and clinical presentation, multiple diagnostic modalities, and treatment options exist for thoracic trauma. Thoracoscopic techniques have evolved from simple cavity washout through an existing chest tube site with evaluation of diaphragmatic injury to the currently used video-assisted thoracic surgery (VATS). Management of critical injuries by means of sternotomy or thoracotomy remains valuable procedures.

Biofouling causes major problems and economic losses to marine and shipping industries. In the search for new antifouling agents, marine bacteria with biosurfactants production capability can be an excellent option, due to the amphipathic surface-active characteristic that confers antimicrobial and antibiofilm activities. The aim of this study was to evaluate the antifouling activity of biosurfactants producing marine bacteria from the Gulf of California. The cell free culture supernatant (CFCS) of Bacillus niabensis (S-69), Ralstonia sp. (S-74) (isolated from marine sediment) and of B. niabensis (My-30) (bacteria associated to the sponge Mycale ramulosa) were screened for production of biosurfactants (using hemolysis and drop collapse test, oil displacement and emulsifying activity). The toxicity and antifouling activity were evaluated against biofoulers (bacteria forming biofilm and macrofoulers) both in laboratory and field assays. The results indicate that all bacteria were biosurfactant producers, but the higher capability was shown by B. niabensis (My-30) with high emulsifying properties (E24) of 71%. The CFCS showed moderate toxicity but were considered non-toxic against Artemia franciscana at low concentrations. In the antifouling assay, the CFCS of both strains of B. niabensis showed the best results for the reduction of the biofilm formation (up 50%) against all Gram-positive bacteria and most Gram-negative bacteria with low concentrations. In the field assay, the CFCS of B. niabensis (My-30) led to the reduction of 30% of biofouling compared to the control. The results indicate that the biosurfactant produced by B. niabensis (My-30) has promising antifouling activity.

Background Trauma centers are receiving increasing numbers of older trauma patients. There is a lack of literature on the outcomes for elderly trauma patients who undergo damage control laparotomy (DCL). We hypothesized that trauma centers with geriatric protocols would have better outcomes in elderly patients after DCL. Methods A retrospective chart review of consecutive adult trauma patients with DCL at 8 level 1 trauma centers was conducted from 2012 to 2018. Patients aged 40 or older were included. Age ≥ 55 years was defined as elderly. Demographics, injury information, clinical outcomes, including mortality, and complications were recorded. Univariate and multivariate analyses were performed. Results A total of 379 patients with DCLs were identified with an average age of 54.8 ± 0.4 years with 39.3% (n = 149/379) of patients aged ≥ 55. Geriatric protocols or a consulting geriatric service was present at 37.5% (n = 3/8) of institutions. Age ≥ 55 was a significant risk factor for in-hospital mortality (OR 2, 95% CI 1.0-4.0, P = .04). Institutions without dedicated geriatric trauma protocols/services had higher overall in-hospital mortality on both univariate (57.9% vs 34.3%, P = .02) and multivariate analyses (OR 2.1, 95% CI 1.3-3.4, P < .001). Conclusions Surgical management of older trauma patients remains a challenge. Geriatric protocols or dedicated services were found to be associated with improved outcomes. Future efforts should focus on standardizing the availability of these resources at trauma centers.

Rationale The contractile dysfunction that underlies heart failure involves perturbations in multiple biological processes ranging from metabolism to electrophysiology. Yet the epigenetic mechanisms that are altered in this disease state have not been elucidated. SWI/SNF chromatin-remodeling complexes are plausible candidates based on mouse knockout studies demonstrating a combined requirement for the BRG1 and BRM catalytic subunits in adult cardiomyocytes. Brg1 / Brm double mutants exhibit metabolic and mitochondrial defects and are not viable although their cause of death has not been ascertained. Objective To determine the cause of death of Brg1 / Brm double-mutant mice, to test the hypothesis that BRG1 and BRM are required for cardiac contractility, and to identify relevant downstream target genes. Methods and results A tamoxifen-inducible gene-targeting strategy utilizing αMHC-Cre-ERT was implemented to delete both SWI/SNF catalytic subunits in adult cardiomyocytes. Brg1 / Brm double-mutant mice were monitored by echocardiography and electrocardiography, and they underwent rapidly progressive ventricular dysfunction including conduction defects and arrhythmias that culminated in heart failure and death within 3 weeks. Mechanistically, BRG1/BRM repressed c - Myc expression, and enforced expression of a DOX-inducible c - MYC trangene in mouse cardiomyocytes phenocopied the ventricular conduction defects observed in Brg1 / Brm double mutants. BRG1/BRM and c-MYC had opposite effects on the expression of cardiac conduction genes, and the directionality was consistent with their respective loss- and gain-of-function phenotypes. To support the clinical relevance of this mechanism, BRG1/BRM occupancy was diminished at the same target genes in human heart failure cases compared to controls, and this correlated with increased c - MYC expression and decreased CX43 and SCN5A expression. Conclusion BRG1/BRM and c-MYC have an antagonistic relationship regulating the expression of cardiac conduction genes that maintain contractility, which is reminiscent of their antagonistic roles as a tumor suppressor and oncogene in cancer.

Objectives: To determine the presence of post-needling induced pain in subjects who had suffered a stroke and received trigger point (TrP) dry needling (DN), and to investigate the effects of including TrP-DN into a rehabilitation program for shoulder pain in this population. Methods: A randomized clinical trial was conducted. Sixteen patients who had suffered a stroke and presented with shoulder pain were randomly assigned to receive rehabilitation alone or rehabilitation combined with DN. Both groups received a neurorehabilitation session including modulatory interventions targeting the central nervous system. Patients in the DN group also received a single session of DN over active TrPs in the shoulder musculature. A numerical pain rating scale (NPRS, 0–10) was used to asses post-needling induced pain at 1 min, 24 h, and 72 h after needling. Shoulder pain (NPRS, 0–10) was assessed at baseline, and 3 and 7 days after DN in both groups. Results: Five (62%) patients receiving TrP-DN reported post-needling induced pain. Post hoc analysis found that post-needling induced pain decreased significantly at 24 and 72 h (both p Conclusion: This trial found that 50% of stroke patients receiving DN experienced post-needling induced pain, a side effect that almost disappeared 72 h after the intervention without any additional therapeutic action. In addition, the inclusion of TrP-DN into a rehabilitation session was effective at decreasing shoulder pain in these patients.

Healthcare-associated infections (HAIs) in critically ill patients are a serious public health problem. Extracorporeal membrane oxygenation (ECMO) has been used increasingly for patients with severe cardiac or respiratory failure, but it may increase HAI risk. The goal of our study was to characterize HAIs in ECMO patients at an ECMO referral center.This institutional review board-approved study identified all consecutive adult ECMO patients admitted to the cardiac surgery intensive care unit (CSICU) between January 1, 2015, and December 31, 2017. Demographic data, diagnosis, ECMO cannulation technique, and survival were collected. Urinary tract infection, pneumonia, and bacteremia incidence during ECMO and within 3 months of decannulation were collected. Outcomes of patients with HAIs were compared with noninfected patients, the CSICU infection incidence, and overall Extracorporeal Life Support Organization survival data.There were 288 ECMO patients and 3396 CSICU admissions during this period. Survival was 72.3% for venoarterial ECMO, 85.3% for venovenous ECMO, and 57.1% for multimodality or veno-arteriovenous ECMO, with discharge survival of 60.2%, 72.0%, and 28.6%, respectively. Bacteremia incidence while cannulated was 6.8% for venoarterial ECMO and 9.3% for venovenous ECMO. Bacteremia occurred in 22 of 288 (7.6%) ECMO patients, compared with 48 of 3109 (1.5%) in non-ECMO CSICU patients, which was statistically significant (P.002). Bacteremia and pneumonia were associated with decreased VA-ECMO survival, with prolonged overall requirements for ECMO support.Nosocomial ECMO infections are significantly higher than in other CSICU patients. Infection risk remains significant even after decannulation. Infection is associated with increased mortality and longer duration of ECMO support. Further efforts are needed to determine HAI reduction strategies in this high-risk patient population.

BACKGROUND Primary ovarian insufficiency (POI) and diminished ovarian reserve are two conditions that affect women’s fertility. Oocyte donation remains an option for these patients; however, the development of certain novel technologies, such as in vitro activation of ovarian cortex (IVA), enables the possibility of activating the pool of resting primordial follicles, increasing the chance of pregnancy. OBJECTIVE AND RATIONALE Here, we review the main pathways (PI3K and Hippo signaling) that govern the activation of primordial follicles and its application through the development of culture systems that support ovarian cortex for autologous transplantation. We also review the available data from case reports regarding outcomes of pregnancy and live birth rates with IVA. SEARCH METHODS A PubMed search was conducted using the PubMed-NCBI database to identify literature pertinent to the pathways involved in the activation of primordial follicles and the outcomes of IVA techniques from 2013 to the present. OUTCOMES Women with POI have around a 5% chance of spontaneous pregnancy. Recently, novel techniques involving the activation of primordial follicles through molecular pathways have been developed, thus increasing the odds of these patients. More recently, the introduction of a drug-free IVA technique has shown to increase the number of antral follicles with successful oocyte maturation after gonadotropin treatment, reaching pregnancy rates over 30%, either through spontaneous conception or by the implementation of assisted reproductive technology. LIMITATIONS The evidence of this review is based on a few small series, so data should be interpreted with caution, and only randomized controlled trials could estimate the real magnitude and success of the procedure. REASONS FOR CAUTION IVA technique remains an experimental strategy, with limited available data and the requirement of invasive procedures. Moreover, possible carcinogenic effects not yet determined after transplantation require special caution. WIDER IMPLICATIONS In view of the results achieved, IVA could provide a promising option for the preservation of fertility in some cancer patients and prepuberal girls where the only alternative is tissue cryopreservation. STUDY FUNDING/COMPETING INTERESTS The authors received no specific funding for this work and declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Acute myocardial infarction (AMI) results in systolic dysfunction, myocarditis and fibrotic remodeling, which causes irreversible pathological remodeling of the heart. Associated cell death and inflammation cause cytokine release, which activates the p38 MAPK signaling pathway to propagate damaging signals via MAPKAP kinase 2 (MK2). Previously we showed that intraperitoneal injection of a cell permeable peptide inhibitor of MK2, MMI-0100, protects against fibrosis, apoptosis and systolic dysfunction in a mouse model of AMI induced by left-anterior descending coronary artery (LAD) ligation. Here we tested a new route of administration of MMI-0100: inhalation of nebulized peptide. When given within 30 min of AMI and daily for 2 weeks thereafter, both inhaled and injected MMI-0100 improved cardiac function as measured by conscious echocardiography. Limited fibrosis was observed after 2 weeks by Massons trichrome staining, suggesting that MMI-0100 protects the heart prior to the formation of significant fibrosis. These results support a nebulized route of administration of MMI-0100 can protect the myocardium from ischemic damage.

Background Congenital diaphragmatic hernia (CDH) is a structural birth defect associated with pulmonary hypoplasia and pulmonary arterial hypertension (PAH). We hypothesize that echocardiography provides a method to assess real-time right ventricle (RV) function, remodeling, and pulmonary artery (PA) flow. Materials and methods Slit3 wild-type (WT) (n = 6) and knockout (KO) (n = 5) mice were analyzed at 2-3 months of age. Mice were anesthetized using isoflurane. Echocardiography was performed to analyze left and right ventricular wall thickness, internal diameter (ID), and function. Color Doppler was used to analyze flow in the PA and across the tricuspid valve. Results There was significant RV dilation in the KO mice versus WT, with an average RVID of 1.99 mm versus 1.26 mm, respectively (P = 0.007). Flow in the PA of KO mice was altered compared to WT, with elevated PA velocity time indices, 30.68 mm versus 22.13 mm (P = 0.012), elevated PA peak velocities, 952.61 mm/s versus 628.73 mm/s (P = 0.003), and decreased pulmonary acceleration times, 8.94 ms versus 16.18 ms (P = 0.002), respectively. Pulmonary vascular resistance, calculated by measuring tricuspid regurgitation peak velocity and right ventricular outflow tract velocity time index, was increased in KO versus WT mice, 17.61 mm2/s versus 8.91 mm2/s (P = 0.003), respectively. Conclusions Slit3 KO mice with CDH show evidence of PAH and resultant RV dilation. Using direct cardiac puncture, elevated RV systolic pressures have been demonstrated in KO mice as evidence of PAH. Echocardiography allows direct analysis of the PA and real-time RV function without sacrifice of the mouse. This mode of evaluation allows longitudinal study in mice with PAH and CDH.

Studies of skeletal muscle disuse, either in patients on bed rest or experimentally in animals (immobilization), have demonstrated that decreased protein synthesis is common, with transient parallel increases in protein degradation. Muscle disuse atrophy involves a process of transition from slow to fast myosin fiber types. A shift toward glycolysis, decreased capacity for fat oxidation, and substrate accumulation in atrophied muscles have been reported, as has accommodation of the liver with an increased gluconeogenic capacity. Recent studies have modeled skeletal muscle disuse by using cyclic stretch of differentiated myotubes (C2C12), which mimics the loading pattern of mature skeletal muscle, followed by cessation of stretch. We utilized this model to determine the metabolic changes using non-targeted metabolomics analysis of the media. We identified increases in amino acids resulting from protein degradation (largely sarcomere) that occurs with muscle atrophy that are involved in feeding the Kreb’s cycle through anaplerosis. Specifically, we identified increased alanine/proline metabolism (significantly elevated proline, alanine, glutamine, and asparagine) and increased α-ketoglutaric acid, the proposed Kreb’s cycle intermediate being fed by the alanine/proline metabolic anaplerotic mechanism. Additionally, several unique pathways not clearly delineated in previous studies of muscle unloading were seen, including: 1) elevated keto-acids derived from branched chain amino aicds (i.e. 2-ketoleucine and 2-keovaline), which feed into a metabolic pathway supplying acetyl-CoA and 2-hydroxybutyrate (also significantly increased); and 2) elevated guanine, an intermediate of purine metabolism, was seen at 12 hours unloading. Given the interest in targeting different aspects of the ubiquitin proteasome system to inhibit protein degradation, this C2C12 system may allow the identification of direct and indirect alterations in metabolism due to anaplerosis or through other yet to be identified mechanisms using a non-targeted metabolomics approach.

The concentration of biological particles in the atmosphere is widely variable because it depends on several meteorological and geographical factors. Meteorological conditions in tropical coastal cities are unique due to both marine and terrestrial influences that can strongly modify the concentration and diversity of airborne microorganisms. Nevertheless, very few studies have been conducted in tropical coastal cities. This study presents the comparative results from four field campaigns carried out between 2017 and 2018 in two tropical cities located in the Yucatan Peninsula (Mexico): Sisal (a village right on the coast) and Merida (the State capital, 48 km from the coastline). The concentration of bacteria and fungal propagules, in colony-forming units or CFU per m3, sampled in Merida and Sisal are not comparable despite their proximity (i.e., 48 km away); however, both show similar seasonality and inter-annual trends. The results indicate that terrestrial microbiota dominates over that of marine origin, and show that fungal propagules are the dominant microorganism present at both sites. Also, these results indicate that meteorological conditions in the rainy season are more favorable for the growth of microorganisms than dry cold conditions. The predominant culturable bacterial phylum sampled during the four field campaigns carried out in 2017 and 2018 in the Yucatan Peninsula were Actinobacteria, Firmicutes, and Proteobacteria. The fraction of bacteria that reacted to a Gram positive stain was 62% and to Gram negative 38%. The fungal propagules genera relative concentration varied between both sampling sites, with Cladosporium and Penicillium being the most common at the coast in Sisal and Aspergillus in Merida.

Supplemental Data Supplemental Table S1 Download Supplemental Table S2 Download Supplemental Table S3 Download Supplemental Table S4 Download Supplemental Data Supplemental material for this article can be found at . The Bcl2-associated anthanogene (BAG) 3 protein is a member of the BAG family of cochaperones, which supports multiple critical cellular processes, including critical structural roles supporting desmin and interactions with heat shock proteins and ubiquitin ligases intimately involved in protein quality control. The missense mutation P209L in exon 3 results in a primarily cardiac phenotype leading to skeletal muscle and cardiac complications. At least 10 other Bag3 mutations have been reported, nine resulting in a dilated cardiomyopathy for which no specific therapy is available. We generated αMHC-human Bag3 P209L transgenic mice and characterized the progressive cardiac phenotype in vivo to investigate its utility in modeling human disease, understand the underlying molecular mechanisms, and identify potential therapeutic targets. We identified a progressive heart failure by echocardiography and Doppler analysis and the presence of pre-amyloid oligomers at 1 year. Paralleling the pathogenesis of neurodegenerative diseases (eg, Parkinson disease), pre-amyloid oligomers–associated alterations in cardiac mitochondrial dynamics, haploinsufficiency of wild-type BAG3, and activation of p38 signaling were identified. Unexpectedly, increased numbers of activated cardiac fibroblasts were identified in Bag3 P209L Tg+ hearts without increased fibrosis. Together, these findings point to a previously undescribed therapeutic target that may have application to mutation-induced myofibrillar myopathies as well as other common causes of heart failure that commonly harbor misfolded proteins.

Diabetic cardiomyopathy is characterized by structural and functional alterations leading to cardiac hypertrophy and heart failure. These changes are regulated in part by PPAR signaling and subsequ...

Metabolic changes of diabetic cardiomyopathy are regulated by PPAR family nuclear receptors. Mice lacking the Muscle Ring Finger-2 (MuRF2-/-) E3 have increased cardiac PPAR-α PPARβ/δ, and PPAR-γ ac...

An 87 year-old white female presented with a two-year history of intermittent discomfort in her left foot. PET-CT identified intense18F-fluorodeoxyglucose (FDG) uptake corresponding to the lesion. Histology of a fine needle aspiration and open biopsy were consistent with a benign giant cell tumor (GCT) of the bone. GCT of bone is an uncommon primary tumor typically presenting as a benign solitary lesion that arises in the end of the long bones. While GCT can occur throughout the axial and appendicular skeleton, it is exceedingly uncommon in the bone of the foot. While 18F-FDG has been established in detecting several malignant bone tumors, benign disease processes may also be identified. The degree of 18F-FDG activity in a benign GCT may be of an intensity that can be mistakenly interpreted as a malignant lesion. Therefore, GCT of the bone can be included in the differential diagnosis of an intensely 18F-FDG-avid neoplasm located within the tarsal bones.

addition of PKA inhibitors before IEC-6 infection with CS prevents CS-induced apoptosis (p

Background The pathogenesis of diabetic cardiomyopathy (DCM) involves the enhanced activation of peroxisome proliferator activating receptor (PPAR) transcription factors, including the most prominent isoform in the heart, PPARα. In cancer cells and adipocytes, post-translational modification of PPARs have been identified, including ligand-dependent degradation of PPARs by specific ubiquitin ligases. However, the regulation of PPARs in cardiomyocytes and heart have not previously been identified. We recently identified that muscle ring finger-1 (MuRF1) and MuRF2 differentially inhibit PPAR activities by mono-ubiquitination, leading to the hypothesis that MuRF3 may regulate PPAR activity in vivo to regulate DCM. Methods MuRF3−/− mice were challenged with 26 weeks 60 % high fat diet to induce insulin resistance and DCM. Conscious echocardiography, blood glucose, tissue triglyceride, glycogen levels, immunoblot analysis of intracellular signaling, heart and skeletal muscle morphometrics, and PPARα, PPARβ, and PPARγ1 activities were assayed. Results MuRF3−/− mice exhibited a premature systolic heart failure by 6 weeks high fat diet (vs. 12 weeks in MuRF3+/+). MuRF3−/− mice weighed significantly less than sibling-matched wildtype mice after 26 weeks HFD. These differences may be largely due to resistance to fat accumulation, as MRI analysis revealed MuRF3−/− mice had significantly less fat mass, but not lean body mass. In vitro ubiquitination assays identified MuRF3 mono-ubiquitinated PPARα and PPARγ1, but not PPARβ. Conclusions These findings suggest that MuRF3 helps stabilize cardiac PPARα and PPARγ1 in vivo to support resistance to the development of DCM. MuRF3 also plays an unexpected role in regulating fat storage despite being found only in striated muscle. Electronic supplementary material The online version of this article (doi:10.1186/s12902-015-0028-z) contains supplementary material, which is available to authorized users.