•The NMJ becomes unstable with age.•Many NMJ aging phenotypes are shared between rodents and humans, but key differences are observed.•MuSK participates in three signaling pathways: Agrin-LRP4, Wnt ...and MuSK-BMP, via distinct domains.•Determining the roles of these three pathways in synapse stability could open new pathways for therapeutic intervention.
The neuromuscular junction (NMJ) is the vehicle for fast, reliable and robust communication between motor neuron and muscle. The unparalleled accessibility of this synapse to morphological, electrophysiological and genetic analysis has yielded an in depth understanding of many molecular components mediating its formation, maturation and stability. However, key questions surrounding the signaling pathways mediating these events and how they play out across the lifetime of the synapse remain unanswered. Such information is critical since the NMJ is necessary for normal movement and is compromised in several settings including myasthenia gravis, amyotrophic lateral sclerosis (ALS), spinal muscular atrophy (SMA), muscular dystrophy, sarcopenia and aging. Muscle specific kinase (MuSK) is a central player in most if not all contexts of NMJ formation and stability. However, elucidating the function of this receptor in this range of settings is challenging since MuSK participates in at least three signaling pathways: as a tyrosine kinase-dependent receptor for agrin-LRP4 and Wnts; and, as a kinase-independent BMP co-receptor. Here we focus on NMJ stability during aging and discuss open questions regarding the molecular mechanisms that govern active maintenance of the NMJ, with emphasis on MuSK and the potential role of its multiple signaling contexts.
Background
It remains unclear whether abnormal systolic function and relaxation are essential for developing heart failure in pathophysiology of severe aortic stenosis.
Methods and Results
Yorkshire ...pigs underwent surgical banding of the ascending aorta. The animals were followed for up to 5 months after surgery, and cardiac function was assessed comprehensively by invasive pressure–volume measurements, 3‐dimensional echocardiography, echocardiographic speckle‐tracking strain, and postmortem molecular and histological analyses. Pigs with aortic banding (n=6) exhibited significant left ventricular hypertrophy with increased stiffness compared with the control pigs (n=7) (end‐diastolic pressure–volume relationship β: 0.053±0.017 versus 0.028±0.009 mm Hg/mL, P=0.007); however, all other parameters corresponding to systolic function, including ejection fraction, end‐systolic pressure–volume relationship, preload recruitable stroke work, echocardiographic circumferential strain, and longitudinal strain, were not impaired in pigs with aortic banding. Relaxation parameters were also similar between groups. Sarcoplasmic reticulum calcium (Ca2+) ATPase protein levels in the left ventricle were similar. There were significant increases in 3‐dimensional echocardiographic left atrial volumes, suggesting the usefulness of these indexes to detect increased stiffness. Right atrial pacing with a heart rate of 120 beats per minute induced increased end‐diastolic pressure in pigs with aortic banding in contrast to decreased end‐diastolic pressure in the control pigs. Histological evaluation revealed that increased stiffness was accompanied by cardiomyocyte hypertrophy and increased perimysial and perivascular fibrosis.
Conclusion
Increased stiffness is the major early pathological process that predisposes to congestive heart failure without abnormalities in systolic function and relaxation in a clinically relevant animal model of aortic stenosis.
Myofiber size regulation is critical in health, disease, and aging. MuSK (muscle-specific kinase) is a BMP (bone morphogenetic protein) co-receptor that promotes and shapes BMP signaling. MuSK is ...expressed at all neuromuscular junctions and is also present extrasynaptically in the mouse soleus, whose predominantly oxidative fiber composition is akin to that of human muscle. To investigate the role of the MuSK-BMP pathway in vivo, we generated mice lacking the BMP-binding MuSK Ig3 domain. These ∆Ig3-MuSK mice are viable and fertile with innervation levels comparable to wild type. In 3-month-old mice, myofibers are smaller in the slow soleus, but not in the fast tibialis anterior (TA). Transcriptomic analysis revealed soleus-selective decreases in RNA metabolism and protein synthesis pathways as well as dysregulation of IGF1-Akt-mTOR pathway components. Biochemical analysis showed that Akt-mTOR signaling is reduced in soleus but not TA. We propose that the MuSK-BMP pathway acts extrasynaptically to maintain myofiber size in slow muscle by promoting protein synthetic pathways including IGF1-Akt-mTOR signaling. These results reveal a novel mechanism for regulating myofiber size in slow muscle and introduce the MuSK-BMP pathway as a target for promoting muscle growth and combatting atrophy.
Individuals with autism may engage in sexual behavior at inappropriate times and/or in inappropriate places. The current study investigated the effects of response interruption and redirection (RIRD) ...and response interruption (RI) on public masturbation (PM) of children and adolescents with autism. Initial assessments showed that PM was maintained by automatic reinforcement. During the treatment evaluation phase, we compared RIRD and RI to determine whether either procedure was successful in decreasing the duration of PM. In the RIRD condition, contingent on the occurrence of any PM the participant completed physical activities involving both hands (e.g., moving chairs, touching toes). In the RI condition, the therapist interrupted all instances of PM using physical and verbal prompts (e.g., saying in a neutral tone, “Stop that” and moving hands away from genitals). Both procedures were effective in decreasing the duration of PM but RI required fewer resources and less time. Clinical implications and suggestions for future research are reviewed.
Background We describe an investigation and improvement project designed to provide comfortable, affordable, fluid-resistant isolation gowns in response to inadequate compliance with gown use. ...Methods Infection control and purchasing departments determined number of gowns used, cost/gown, and contract information for our laundry service. We investigated disposable gown options. During a conference call for a multihospital project, we learned that 4 local hospitals all used the same laundry service and that all were dissatisfied with the quality of the reusable gowns. The 4 hospitals resolved to meet with the hospital laundry service to negotiate as a group. In preparation, we both investigated laundry services in neighboring cities and reviewed Centers for Disease Control and Prevention and Occupational Safety and Health Administration isolation gown requirements. Results Confronted with its major customers acting collectively, the laundry service agreed to identify gowns by age, bring gowns to Occupational Safety and Health Administration compliance, mark grids so gowns could be removed after 75 washes, add 6,000 new gowns, and remove 6,000 old gowns. The cost increase was 3.75¢/gown. After the changeover was complete, reports of fluid leaking through gowns stopped. We saved $187,000 by keeping reusable gowns. Conclusion When we tried to provide comfortable, affordable, fluid-resistant isolation gowns, we encountered 2 barriers: our city had only 1 hospital laundry service, and disposable gown were costly. We solved the problem through unusual collaboration: internal (Infection Control and Purchasing) and external (with otherwise competing hospitals). Collaboration and knowledge sharing led to accountability: the hospital to its staff and budget and the laundry service to the hospitals.
Catheter-associated urinary tract infections (CAUTI) are a significant cause of morbidity and financial burden to healthcare systems. The aim of this study was to develop and implement a program ...designed to reduce Foley catheter use days and associated CAUTI rates.
A retrospective evaluation of a multi-modal program aimed toward reducing Foley catheter use days and associated CAUTI rates across the Indiana University Health (IUH) system was conducted. IUH is comprised of 16 hospitals and 2,703 available beds. The program included the adoption of new technologies with evidence-based clinical training materials based on change management and feedback from clinicians. National Healthcare Safety Network Standardized Infection Ratio (SIR), Standardized Utilization Ratio (SUR), and Incidence Density Ratio (IDR) rates were assessed.
Implementation of the multi-modal program resulted in a significant reduction in SIR, SUR, and IDR in the post-implementation compared to the baseline periods.
Through CAUTI bundle workflow assessments, education, and interventions designed to standardize practice variation, the program was successfully implemented and resulted in a significant decrease in Foley Catheter use days, and associated CAUTI rates.
OBJECTIVESCatheter-associated urinary tract infections (CAUTI) are a significant cause of morbidity and financial burden to healthcare systems. The aim of this study was to develop and implement a ...program designed to reduce Foley catheter use days and associated CAUTI rates.METHODSA retrospective evaluation of a multi-modal program aimed toward reducing Foley catheter use days and associated CAUTI rates across the Indiana University Health (IUH) system was conducted. IUH is comprised of 16 hospitals and 2,703 available beds. The program included the adoption of new technologies with evidence-based clinical training materials based on change management and feedback from clinicians. National Healthcare Safety Network Standardized Infection Ratio (SIR), Standardized Utilization Ratio (SUR), and Incidence Density Ratio (IDR) rates were assessed.RESULTSImplementation of the multi-modal program resulted in a significant reduction in SIR, SUR, and IDR in the post-implementation compared to the baseline periods.CONCLUSIONSThrough CAUTI bundle workflow assessments, education, and interventions designed to standardize practice variation, the program was successfully implemented and resulted in a significant decrease in Foley Catheter use days, and associated CAUTI rates.
Hand hygiene feedback impacts compliance Fish, Lauren; Bopp, Donna; Gregory, Debbie ...
American journal of infection control,
07/2021, Letnik:
49, Številka:
7
Journal Article
Recenzirano
Health care-acquired infections are one of the top causes of mortality in the United States (Stone, 2009; Scott, 2009). Hand hygiene (HH) can reduce the incidence of such infections. Adherence to HH ...practices remains challenging for health care workers (World Health Organization, 2014). This investigation compared results of private and public HH feedback at the team and individual level.
A quality improvement study was conducted in 2 units utilizing HH radiofrequency identification (RFID) technology. Each unit was assigned either private or public feedback mechanisms. The study was divided into 3 phases; baseline, team, and individual. Time series analysis compared HH compliance by health care workers' role and feedback mechanisms.
Individual HH compliance were the highest in both groups. The private group compliance was 63.3% (P ≤ .0001) and the public group compliance was 55.4% (P = .0001). During the team feedback phase, HH compliance decreased in the private group to 42.79% (P = .006); however, compliance increased in the public feedback group to 42.5% (P = .2661). The physician role in the private group decreased by 12% (P = .1804) during the individual phase.
HH data provided at the individual level and posted publicly could improve HH compliance. Use of RFID measurement technology can provide organizations with tools to measure HH compliance.
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