Optogenetic induction of mechanical muscle stress identifies myosin regulatory ubiquitin ligase NHL-1 in C. elegans.

Mechanical stress during muscle contraction is a constant threat to proteome integrity. However, there is a lack of experimental systems to identify critical proteostasis regulators under mechanical stress conditions. Here, we present the transgenic Caenorhabditis elegans model OptIMMuS (Optogenetic Induction of Mechanical Muscle Stress) to study changes in the proteostasis network associated with mechanical forces. Repeated blue light exposure of a muscle-expressed Chlamydomonas rheinhardii channelrhodopsin-2 variant results in sustained muscle contraction and mechanical stress. Using OptIMMuS, combined with proximity labeling and mass spectrometry, we identify regulators that cooperate with the myosin-directed chaperone UNC-45 in muscle proteostasis. One of these is the TRIM E3 ligase NHL-1, which interacts with UNC-45 and muscle myosin in genetic epistasis and co-immunoprecipitation experiments. We provide evidence that the ubiquitylation activity of NHL-1 regulates myosin levels and functionality under mechanical stress. In the future, OptIMMuS will help to identify muscle-specific proteostasis regulators of therapeutic relevance.

A ubiquitin fusion reporter to monitor muscle proteostasis in C. elegans.

Muscle is a highly dynamic tissue in which a variety of folding and degradation processes are active to maintain protein homeostasis (proteostasis) and functionality. The muscle-specific chaperone UNC-45 folds the motor protein myosin and assembles it into myofilaments. Malfunction of this chaperone leads to misfolding of myosin, disorganization of myofilaments, and degradation of misfolded myosin molecules by the proteasome. Here, we present a new muscle-specific ubiquitin fusion degradation (UFD) model substrate in C. elegans that helps clarify how UNC-45 dysfunction affects muscle proteostasis.

Differentiation of Lower Extremity Skin Changes in the Intensive Care Setting.

Digital and lower extremity skin changes often signify critical underlying disorders. Patients in the intensive care unit also frequently have hemodynamic instability requiring the use of vasoactive medications, which may lead to various presentations of limb ischemia; preexisting conditions increase these patients' risk for arterial embolization. Most arterial emboli are clots that originate in the heart and travel to distant vascular beds, where they cause arterial occlusion, ischemia, and, potentially, infarction; the 2 most common sequelae are stroke and lower limb ischemia. Emboli also arise from atherosclerotic plaques. Other conditions can also cause skin color changes in this vulnerable population. Prompt recognition and differentiation of lower extremity skin changes can result in improved patient outcomes. A thorough literature search was conducted to differentiate the primary causes of lower extremity and digital skin changes in the critically ill patient and outline diagnostic and management techniques.

Nonhealing venous ulcer in a patient with dystrophic soft tissue calcification.

Venous leg ulcers (VLUs) are lesions of the skin found in regions of venous hypertension. VLUs that fail to heal can become chronic, especially because of calcified deposits in the bed of the ulcer. The unclear mechanism behind the cause of calcification poses a challenge when approaching diagnosis and management. In the present report, we discuss the case of a 58-year-old woman who had presented with a chronic VLU that was resistant to healing despite numerous interventions. During a 3-year period, a multidisciplinary team was involved to provide medical and surgical care. Eventually, she was found to have dystrophic calcification of the VLU.

Evaluation of Current Pressure Ulcer Staging.

BACKGROUND: We sought to assess health professionals' satisfaction with the National Pressure Injury Advisory Panel staging system (NPUAP). METHODS: A paper survey assessing the satisfaction with the NPUAP was distributed to participants of a national wound care meeting. A total of 88 surveys were completed. Results were tabulated using SPSS. RESULTS: The survey response rate was 50%. Nearly all respondents (95.0%) used NPAUP for documentation. 75.3% indicated that a better staging system was needed. When participants were asked to evaluate their current staging system, 63.5% stated that the system does not adequately reflect patient's clinical condition, 61.6% felt that the current staging system was not easily reproducible, 58.0% believed that the current staging system was generally easy-to-use, and 43.9% indicated that it is unable to suggest management recommendations. When asked about an ideal classification system, the respondents proposed incorporating tissue necrosis (97.6%), depth of tissue involvement (96.3%), discharge documentation (92.5%), presence of osteomyelitis (90%), local infection (88.8%), and systemic infection (80.0%). Overall, 67.0% of the participants wanted to use a classification system that would reflect the progress of injury healing and could be used to indicate the need for intervention. DISCUSSION: Health care workers caring for pressure injury patients indicated dissatisfaction with the NPAUP.

Practice Dilemmas: Conditions That Mimic Pressure Ulcers/Injuries- To Be or Not To Be?

BACKGROUND: Pressure ulcers/injuries (PU/Is) negatively affect patients by causing pain and increasing morbidity and mortality risks. Care teams have a heightened sense of awareness of the condition and may feel confident in their ability to appropriately identify and manage PU/Is, but the potential for, and consequences of, a misdiagnosis always should be considered. PURPOSE: The purpose of this compendium is to describe and illustrate conditions that may mimic PU/Is. METHODS: Advanced practice wound care nurses were asked to identify and describe conditions that may mimic PU/Is. Permission was obtained from all patients to use their cases and photos in this article. RESULTS: Sixteen (16) different skin and wound presentations resulting from vascular diseases, systemic infections, trauma, cancer, autoimmune disorders, coagulopathies, and multisystem organ dysfunction were identified and described. CONCLUSION: A complete patient history and assessment will help prevent misidentification of the etiology of a skin lesion or wound and misdiagnosis of these lesions as PU/Is.

Principles of Best Diagnostic Practice in Tissue Repair and Wound Healing: An Expert Consensus.

Chronic wound treatment currently relies heavily on visual assessment by clinicians; however, the clinical signs and symptoms of infection and inflammation are unreliable in chronic wounds. The specialty of wound care has witnessed the advent of advanced interventions, such as cellular and/or tissue based products (CTP). The success of advanced therapies relies on preparing the wound bed by reducing bacterial burden and inflammation. The lack of diagnostics in chronic wound care leads to uncertainty in the adequacy of wound bed preparation. Recent research suggests that two novel point-of-care diagnostic tests can assist in the detection of chronic inflammation known as elevated neutrophil derived protease activity (EPA) and bacterial pathogenesis known as bacterial protease activity(BPA) in chronic wounds. Despite the evidence, however, clinicians report that incorporating diagnostics into every day practice is challenging and across the globe, they have requested guidance on their use. Methods and Recommendations: A panel of wound care experts, experienced with these tests, met to develop guidelines on their use in wound care practice. The consensus panel concluded that the clinician should test for BPA first. The panel maintained that the risk of invasive infection resulting from the presence of pathogenic bacteria was the greatest threat to the patient's health. If the BPA test is negative, the panel recommended testing for EPA. In addition, it was suggested that if the wound failed to progress after the elevated BPA was treated and subsequent testing was negative for BPA, the clinician should consider testing for EPA. Conclusions: In this manuscript, the consensus panel suggests pathways for testing, treating, and retesting for EPA and BPA. The panel expects that following the algorithm has the potential to improve healing outcomes, result in more cost-effective use of advanced therapies, and improve antimicrobial stewardship by guiding antimicrobial use.

Pressure Ulcers in the United States' Inpatient Population From 2008 to 2012: Results of a Retrospective Nationwide Study.

Pressure ulcers are common, increase patient morbidity and mortality, and costly for patients, their families, and the health care system. A retrospective study was conducted to evaluate the impact of pressure ulcers on short-term outcomes in United States inpatient populations and to identify patient characteristics associated with having 1 or more pressure ulcers. The US Nationwide Inpatient Sample (NIS) database was analyzed using the International Classification of Disease, 9th Revision, Clinical Modification (ICD-9 CM) diagnosis codes as the screening tool for all inpatient pressure ulcers recorded from 2008 to 2012. Patient demographics and comorbid conditions, as identified by ICD-9 code, were extracted, along with primary outcomes of length of stay (LOS), total hospital charge (TC), inhospital mortality, and discharge disposition. Continuous variables with normal distribution were expressed in terms of mean and standard deviation. Group comparisons were performed using t-test or ANOVA test. Continuous nonnormal distributed variables such as LOS and TC were expressed in terms of median, and nonparametric tests were used to compare the differences between groups. Categorical data were presented in terms of percentages of the number of cases within each group. Chi-squared tests were used to compare categorical data in different groups. For multivariate analysis, linear regressions (for continuous variable) and logistic regression (for categorical variables) were used to analyze the possible risk factors for the investigated outcomes of LOS, TC, inhospital mortality, and patient disposition. Coefficients were calculated with multivariate regression with all included patients versus patients with pressure ulcers alone. The 5-year average number of admitted patients with at least 1 pressure ulcer was determined to be 670 767 (average overall rate: 1.8%). Statistically significant differences between patients with and without pressure ulcers were observed for median LOS (7 days [mean 11.1 ± 15] compared to 3 days [mean 4.6 ± 6.8]) and median TC ($36 500 [mean $72 000 ± $122 900] compared to $17 200 [mean $32 200 ± $57 500]). The mortality rate in patients with a pressure ulcer was significantly higher than in patients without a pressure ulcer (9.1% versus 1.8%, OR = 5.08, CI: 5.03-5.1, P <0.001). Pressure ulcers were significantly more common in patients who were older or had malnutrition. The results of this study confirm the importance of prevention initiatives to help reduce the negative impact of pressure ulcers on patient outcomes and costs of care.

The mean green popsicle: using cryotherapy to remove aspirated foreign bodies.

Foreign body (FB) aspiration can be a life-threatening event. Although more common in children, FB aspiration can occur at any age. Symptoms related to FB aspiration range from coughing and shortness of breath to asphyxiation. Chest imaging can be nonspecific and infrequently identifies an FB. Herein, we describe a case of a 54-year-old male patient who aspirated an FB and experienced respiratory arrest. He failed to improve with conservative measures and required emergent bronchoscopy. He was found to have an FB in his proximal left mainstem bronchus that could not be removed using standard bronchoscopy and he was referred to our center for definitive care. We used a cryotherapy probe to remove the FB. We propose that cryotherapy is a useful tool to remove FBs that are soft and amenable to freezing.

Are newborns morally different from older children?

Policies and position statements regarding decision-making for extremely premature babies exist in many countries and are often directive, focusing on parental choice and expected outcomes. These recommendations often state survival and handicap as reasons for optional intervention. The fact that such outcome statistics would not justify such approaches in other populations suggests that some other powerful factors are at work. The value of neonatal intensive care has been scrutinized far more than intensive care for older patients and suggests that neonatal care is held to a higher standard of justification. The relative value placed on the life of newborns, in particular the preterm, is less than expected by any objective medical data or any prevailing moral frameworks about the value of individual lives. Why do we feel less obligated to treat the premature baby? Do we put newborns in a special and lesser moral category? We explore this question from a legal and ethical perspective and offer several hypotheses pertaining to personhood, reproductive choices, "precious children," and probable evolutionary and anthropological factors.