Nursing Students' Resilience and Intent to Work at the Bedside.

AIM: The primary purpose of this study was to explore relationships between self-efficacy, peer support, coping style, intent to work at the bedside, and resilience in nursing students. BACKGROUND: Resilience correlates with one-year retention at the bedside. Retention of bedside nurses improves patient outcomes. METHOD: A quantitative, correlational design determined relationships between variables. Surveys were completed by 205 participants. Surveys included a program type list, intent to work at the bedside items, the Brief Cope Scale, the General Self-Efficacy Scale, the Peer Group Caring Interaction Scale. RESULTS: Significant relationships were found between resilience and self-efficacy, resilience and coping style, and peer support and approach coping style. Half of the respondents intended to work at the bedside for two years after graduation. Self-efficacy and avoidance coping were resilience predictors. CONCLUSION: To support resilience, educators should facilitate students' development of self-efficacy and approach coping style.

Association of Locus Xq26.1-27.3 with Erosive Tooth Wear Phenotypes in a Group of Adolescents.

Erosive tooth wear is a multifactorial condition of an increasing prevalence. There is a need for discovering individual genetic predisposition for the development of this condition. Considering that the chromosome X locus was previously shown to be associated with dental caries, the aim of the present study was to look for the association between this locus and erosive tooth wear when dietary habits are considered as a co-factor. Saliva samples, erosive wear experience data, and dietary information from 16- to 18-year-old dental patients (n = 705) were used. Genotyping analyses were performed, and thereafter, analyses considering diet and oral hygiene data, using logistic regression, with the assumption that erosive tooth wear is a complex gene-environment model. Genotypic analyses revealed an association between chromosome X marker rs1324156 and erosive tooth wear phenotype. Logistic regression analysis showed that, in the presence of less common allele of rs12687601 and rs1324156, erosive tooth wear more likely develops when associated with numerous dietary variables from the questionnaire. These results indicate that erosive tooth wear may be the result of gene-environment interactions.

Who Engaged in Home-Based Arts Activities During the COVID-19 Pandemic? A Cross-Sectional Analysis of Data From 4,731 Adults in the United States.

Arts engagement is a health-related behavior that may be influenced by social inequalities. While the COVID-19 pandemic provided new opportunities for some people to engage in the arts, it might have created barriers for others. We aimed to examine whether there was social patterning in home-based arts engagement during the pandemic in the United States, and whether predictors of engagement differed according to the type of arts activity. We included 4,731 adults who participated in the United States COVID-19 Social Study between April and July 2020. Three types of home-based arts engagement were considered: reading for pleasure, arts or crafts activities, and digital arts activities. Using logistic regression models, we tested cross-sectional associations between a broad range of demographic, socioeconomic, psychosocial, and health-related factors as well as adverse events and worries during lockdown and each type of arts engagement. The factors most strongly associated with all three types of arts engagement were social support, social network size, age, race/ethnicity, keyworker status, and experiencing physical or psychological abuse during the pandemic. However, most socioeconomic and health-related factors were not associated with arts engagement, including household income and mental and physical health problems. Overall, our findings indicate that the social gradient in arts engagement was reduced in the first 4 months of the COVID-19 pandemic in the United States. Given the health benefits of arts engagement, the potential diversification of arts audiences during the pandemic is promising for both population-level health and wellbeing and the future of the arts and cultural sector.

Assessment of ecosystem health of a micro-level Ramsar coastal zone in the Vembanad Lake, Kerala, India.

Health of an ecosystem is very much important as we depend on its goods and services for our existence. Because of this, we need to continuously monitor its health for human benefit and for identifying areas for improvement of our natural systems. The present study tries to assess the condition of a coastal ecosystem within the Vembanad Lake, Kerala, India, using key water quality parameters at micro-level. Principal component analysis identified the minimum required water quality dataset for further analysis and was scored using linear scoring functions. The weighted additive method was used to integrate the individual scores to arrive at a final score representing the ecosystem health. Spline interpolation was applied to develop the ecosystem health map of the study area. Using this method, 35.8% area of the aquatic ecosystem studied was characterized as good, 32.2% as moderate, 26.2% as fair and 5.8% as poor. The assessment results can help the policymakers/managers to make appropriate decisions for the better management of the coastal ecosystems studied. Moreover, this methodology can be replicated for the assessment of coastal regions with similar ecosystem characteristics.

A mixed-methods feasibility study of an arts-based intervention for patients receiving maintenance haemodialysis.

BACKGROUND: Haemodialysis can negatively impact quality of life and mental health. Arts-based interventions used successfully in other settings to improve health and well-being, could help address the impact of haemodialysis. This study aimed to evaluate the feasibility and acceptability of conducting a randomised controlled trial (RCT) of an arts-based intervention for patients receiving haemodialysis. METHODS: A parallel convergent mixed-methods design was used, including a pilot cluster RCT and qualitative process evaluation. Phase 1 evaluated recruitment and retention rates through a pilot cluster RCT at a single haemodialysis unit in Northern Ireland. Participants included patients who received haemodialysis for ESKD, were over the age of 18 and had the capacity to consent. These participants were randomised to the intervention or control group according to their haemodialysis shift. The intervention involved six one-hour, one-to-one facilitated arts sessions during haemodialysis. Phase 2 explored intervention and trial acceptability through a qualitative process evaluation using semi-structured interviews based on the RE-AIM framework. Participants included 13 patients who participated in phase 1 of the study, including 9 participants from the experimental group and four participants from the control group, and nine healthcare professionals who were present on the unit during implementation. RESULTS: Out of 122 outpatient haemodialysis patients, 94 were assessed as eligible for participation. Twenty-four participants were randomised, meaning 80% of the target sample size was recruited and the attrition rate at 3 months was 12.5% (n = 3). Participants viewed the arts as more accessible and enjoyable than anticipated following implementation. All participants who started the intervention (n = 11) completed the full six sessions. Qualitative benefits of the intervention suggest improvements in mental well-being. Patient choice and facilitation were important factors for successful implementation. CONCLUSION: An arts-based intervention for patients receiving haemodialysis is acceptable for both patients and healthcare professionals, and a definitive trial is feasible. The intervention may help improve mental-wellbeing in patients receiving haemodialysis, but this requires further investigation in a definitive trial. TRIAL REGISTRATION: The trial was prospectively registered on clinicaltrials.gov on 14/8/2018, registration number NCT03629496 .

What to do in failed hemispherotomy? Our clinical series and review of the literature.

Hemispherotomy is an established surgical technique to cure or palliate selected, mostly young patients suffering from refractory epilepsy. However, a few patients continue to have seizures despite the surgical hemispherical disconnection. We present a case series of patients who underwent redo hemispherotomy after a first unsuccessful hemispherical disconnection and provide a roadmap for subsequent workup and treatment. The institutional database of epilepsy surgery was reviewed. Twenty-four patients who underwent hemispherotomies for refractory epilepsy were identified between 2007 and 2016. Patients' notes were checked for demographics, history, clinical presentation, preoperative workup, medical treatment, age at first hemispherotomy, and surgical technique. Complications, histopathology, postoperative antiepileptic drug, and postoperative neurological follow-up were documented. Engel class was used to determine the outcome after surgery. Three patients (one hemimegalencephaly, one perinatal stroke, and one Rasmussen's disease) underwent redo hemispherotomy after electroencephalography and MRI studies with particular importance given to diffusion tensor imaging (DTI) to demonstrate residual connection between hemispheres. In one case, redo disconnection followed by a frontal lobectomy rendered the patient seizure-free (Engel class I). In one case, the seizure frequency remained the same but generalized seizures disappeared (Engel class III), and in one case, seizure frequency was considerably reduced after the redo disconnection (Engel class II), with a minimum follow-up of 2 years. Surgical aspects, possible reasons of failure of first hemispherotomy, and rationale that led to second-look surgery are presented. Reasons for failure can be related to patient's selection and/or surgical aspects. Hemispherotomy is a technically demanding procedure and requires accurate preoperative workup. Redo hemispherotomy is a valid option on the basis of further epileptological and radiological workup to demonstrate residual interhemispheric connections and/or rule out bi-hemispheric epileptic activity.

[Effect of herd health management on the prevalence of Postpartum Dysgalaktie Syndrome (PPDS) and the treatment incidence]. / Auswirkungen einer Bestandesbetreuung auf das Vorkommen des Postpartalen Dysgalaktie Syndroms (PPDS) und die Tierbehandlungsinzidenz.

INTRODUCTION: The Postpartum Dysgalaktie Syndrome (PPDS) also known as metritis agalactia mastitis (MMA), is considered the most common disease of the sow after farrowing. The reasons for PPDS are multifactorial and are to be found in the areas of management and hygiene, feeding, water supply and animal specific factors such as body condition and age of the sows. In this study a veterinary herd health management was carried out in 28 pig farms with PPDS, with the aim to reduce the PPDS prevalence and animal treatment incidence (TI). In 20 of 28 problem farms the PPDS-prevalence could be decreased from 37.4% (± 21.8%) to 24.5% (± 14.1%). The TI was not significantly reduced. The most effective procedures to reduce the PPDS-prevalence were the use of a prepartal transition feed, optimizing the PPDSdiagnostic and the use of nonsteroidal antiinflammatory drugs (NSAID) and oxytocin in the PPDS-treatment.

Le syndrome de dysgalactie postpartum (PPDS), aussi appelé mammite, métrite, agalactie (MMA) est considéré comme la pathologie des truies la plus fréquente en période post partum. Ses causes sont multifactorielles et doivent être recherchées aussi bien dans le domaine de la gestion, de l'hygiène, de l'alimentation et de l'abreuvement que dans des facteurs propres aux animaux, comme la condition et l'âge. Dans le cadre de cette étude, on a effectué un suivi d'exploitation dans 28 exploitations d'élevage porcin avec une problématique de PPDS, dans le but de réduire la prévalence de cette affection et l'index des traitements. La prévalence de la PPDS s'est réduite dans 20 des 28 exploitations de 37.4% (± 21.8%) à 24.5% (± 14.1%). L'index des traitements n'a pas pu être abaissé significativement. Les mesures les plus efficaces pour abaisser la prévalence de la PPDS ont été l'utilisation d'un aliment de préparation à la mise-bas, l'optimisation du diagnostic de PPDS et l'utilisation d'antiinflammatoires non-stéroïdiens (AINS) et d'ocytocine pour traiter les cas de PPDS.

A Conserved Residue Cluster That Governs Kinetics of ATP-dependent Gating of Kir6.2 Potassium Channels.

ATP-sensitive potassium (KATP) channels are heteromultimeric complexes of an inwardly rectifying Kir channel (Kir6.x) and sulfonylurea receptors. Their regulation by intracellular ATP and ADP generates electrical signals in response to changes in cellular metabolism. We investigated channel elements that control the kinetics of ATP-dependent regulation of KATP (Kir6.2 + SUR1) channels using rapid concentration jumps. WT Kir6.2 channels re-open after rapid washout of ATP with a time constant of ∼60 ms. Extending similar kinetic measurements to numerous mutants revealed fairly modest effects on gating kinetics despite significant changes in ATP sensitivity and open probability. However, we identified a pair of highly conserved neighboring amino acids (Trp-68 and Lys-170) that control the rate of channel opening and inhibition in response to ATP. Paradoxically, mutations of Trp-68 or Lys-170 markedly slow the kinetics of channel opening (500 and 700 ms for W68L and K170N, respectively), while increasing channel open probability. Examining the functional effects of these residues using φ value analysis revealed a steep negative slope. This finding implies that these residues play a role in lowering the transition state energy barrier between open and closed channel states. Using unnatural amino acid incorporation, we demonstrate the requirement for a planar amino acid at Kir6.2 position 68 for normal channel gating, which is potentially necessary to localize the ϵ-amine of Lys-170 in the phosphatidylinositol 4,5-bisphosphate-binding site. Overall, our findings identify a discrete pair of highly conserved residues with an essential role for controlling gating kinetics of Kir channels.

Controlled release of anti-inflammatory peptides from reducible thermosensitive nanoparticles suppresses cartilage inflammation.

Characterized by pain, cartilage degradation, and inflammation, osteoarthritis is often treated with anti-inflammatory therapies that provide short-term relief but can have adverse side effects; intra-articular drug delivery systems with controlled release of anti-inflammatory peptides using degradable poly(N-isopropylacrylamide) (pNIPAM) nanoparticles could prolong relief and minimize these side effects. Nanoparticles provide a biocompatible drug carrier that can protect encapsulated therapeutics from enzymatic degradation and increase payload delivery upon encountering a degradation stimulus. Here we demonstrate passive targeting of inflamed cartilage ex vivo by uptake of PEGylated pNIPAM nanoparticles with degradable disulfide crosslinks (abbreviated as NGPEGSS) into chondrocytes and subsequent intracellular release of an anti-inflammatory peptide KAFAKLAARLYRKALARQLGVAA (KAFAK). The KAFAK-loaded NGPEGSS treatment reduced ex vivo inflammation to a greater extent compared to its non-degradable counterparts. This study highlights a nanoparticle system that delivers therapeutics intracellularly with improved efficacy by triggered degradation and suppresses inflammation in multiple cell types within an inflamed joint.

The effects of a heat acclimation protocol in persons with spinal cord injury.

Persons without spinal cord injury (SCI) physiologically acclimate between seven to fourteen consecutive days of exercise in the heat. Decreased resting and exercise core temperature, decreased heart rate, increased plasma volume and increased thermal comfort during exercise are changes consistent with heat acclimation. Autonomic dysfunction after SCI impairs heat dissipation through sweating and vasodilation. The purpose of this study is to determine if seven consecutive days of exercise in the heat would result in physiologic changes consistent with heat acclimation in persons with SCI. Ten persons with SCI divided into two groups: tetraplegia (n=5) and paraplegia (n=5) exercised in 35°C using an arm ergometer at 50% Wpeak for 30min followed by 15min rest. This protocol was repeated over seven consecutive days. Heart rate (HR), skin temperature, aural temperature (Taur), rate of perceived exertion (RPE), rate of perceived thermal strain (RPTS), and plasma volume (PV) were measured throughout the protocol. There were no significant differences in resting Taur exercise Taur, mean skin temperature, HR, PV, RPE or RPTS over the 7 days for either the tetraplegic or paraplegic group. Participants with SCI did not demonstrate the ability to dissipate heat more efficiently over 7 days of exercise at 35°C. The lack of heat acclimation seen in persons with SCI has implications for the athlete and non-athlete alike. For the SCI athlete, inability to acclimate will impair performance and endurance especially in warm environments, compared to the person without SCI. For the SCI non-athlete, there is a greater risk of heat-related illness in warm environments that can negatively affect participation in outdoor activities and thus quality of life.

Using Innovative Teaching Strategies to Improve Outcomes in a Pharmacology Course.

It is often difficult to engage nursing students and keep their interest when teaching pharmacology. This article reports on an effective change from a lecture-only approach to teaching with the use of games and case studies in a baccalaureate nursing education program. Improvements have been noted in standardized test scores and student evaluations, and students are more engaged in the learning process. Learning has been shifted from the instructor, as in the traditional classroom, and is now student focused.

Release of anti-inflammatory peptides from thermosensitive nanoparticles with degradable cross-links suppresses pro-inflammatory cytokine production.

Pro-inflammatory cytokines tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6) are mediators in the development of many inflammatory diseases. To demonstrate that macrophages take up and respond to thermosensitive nanoparticle drug carriers, we synthesized PEGylated poly(N-isopropylacrylamide-2-acrylamido-2-methyl-1-propanesulfonate) particles cross-linked with degradable disulfide (N,N'-bis(acryloyl)cystamine) (NGPEGSS). An anti-inflammatory peptide (KAFAK) was loaded and released from the thermosensitive nanoparticles and shown to suppress levels of TNF-α and IL-6 production in macrophages. Cellular uptake of fluorescent, thermosensitive, and degradable nanoparticles and therapeutic efficacy of free KAFAK peptide compared to that of KAFAK loaded in PEGylated degradable thermosensitive nanoparticles were examined. The data suggests that the degradable, thermosensitive nanoparticles loaded with KAFAK may be an effective tool to treat inflammatory diseases.

Enamel formation genes associated with dental erosive wear.

Dental erosive wear is a multifactorial condition that is greatly affected by environmental factors. So far, no study has investigated how dental erosive wear is influenced by variations in enamel formation genes. The aim of the present study was to investigate polymorphisms in genes involved in enamel formation and their influence on enamel susceptibility to dental erosion. DNA samples were collected from 795 Norwegian adolescents aged 16-18 years. Five single-nucleotide polymorphism markers were genotyped in selected candidate genes (ameloblastin, amelogenin, enamelin, tuftelin 1 and tuftelin interacting protein 11), reported to influence enamel formation. Allele and genotype frequencies were compared within two patient groups with dental erosions; all participants with dental erosion and only those with severe dental erosion (erosion extending into dentine). Overrepresentation of the G allele of the enamelin marker was seen in the erosion group compared to the unaffected group (p = 0.047). When erosion severity was considered, statistical significant difference in allele frequency was observed for amelogenin, with the C allele suggesting a protective role (p = 0.02). A suggestive overrepresentation of the TT genotype of the amelogenin marker was also seen in cases with severe erosion (p = 0.049) when compared to cases with no dentine erosion. Amelogenin was also associated with severe erosion in the recessive model; the TT genotype was significantly more frequent in the affected group than in the unaffected group (p = 0.01). The present study suggests that polymorphisms in enamel formation genes are statistically associated with an individual's susceptibility to dental erosive wear.

Short communication: Substituting dry distillers grains with solubles and rumen-protected amino acids for soybean meal in late-lactation cows' diets based on corn silage or ryegrass silage.

Excess protein in dairy cattle diets increases production costs and contributes to environmental pollution. The objective of the present study was to evaluate the effect of feeding dry distillers grains with solubles (DDGS) supplemented with rumen-protected Lys and Met in place of solvent-extracted soybean meal on the performance of late-lactation cows. Two experiments were carried out, with each using 24 late-lactating dairy cows distributed among 4 pens. In trial 1, corn silage was the main forage source. Control (HP1) total mixed ration (TMR) contained 16.3% crude protein (CP) with soybean meal as the main protein source. Treatment TMR (LP1) had 13.7% CP when soybean meal was replaced with DDGS and rumen-protected Lys and Met. Forage in trial 2 was ryegrass silage; control TMR (HP2; 15.4% CP) contained soybean meal and rumen-protected Met, whereas treatment TMR (LP2; 13.8% CP) contained DDGS and rumen-protected Lys and Met. Trials were analyzed as crossover design using the MIXED procedure of SAS (SAS Institute Inc., Cary NC) with cow as sampling unit and pen as the experimental unit. Treatments were similar in dry matter intake (21.0 and 20.4 kg/cow per day for HP1 and LP1, respectively) and milk yield (20.7 and 20.5 kg/cow per day for HP1 and LP1, respectively) during trial 1. Milk composition was similar between treatments, averaging 4.22, 3.73, 4.54, and 9.15, respectively, for fat, protein, lactose, and solids nonfat. Milk urea nitrogen decreased from 17.2 mg/dL for HP1 to 9.93 mg/dL for LP1. In trial 2, no significant differences were observed for dry matter intake (21.4 and 20.9 kg/cow per day for HP2 and LP2, respectively), milk yield (28.1 and 26.6 kg/d for HP2 and LP2, respectively), fat yield (0.99 vs. 0.92 kg/d for HP2 and LP2, respectively), protein yield (0.94 vs. 0.86 kg/d for HP2 and LP2, respectively) and lactose yield (1.37 vs. 1.28 for HP2 and LP2, respectively). Milk urea nitrogen decreased from 9.88 mg/dL with HP2 to 6.39 mg/dL with the LP2 treatment. Milk N efficiency tended to be higher for LP treatments in trial 1, but not in trial 2. Low milk urea N suggested nitrogen losses to the environment may be lower when cows were fed diets based on DDGS in both trials. The studies indicated that DDGS with rumen-protected Lys and Met could substitute solvent-extracted soybean meal in low-protein corn silage- and ryegrass silage-based diets for late-lactation dairy cows averaging 20.6 or 27.4 kg of milk/d, respectively.

Imaging of small animal peripheral artery disease models: recent advancements and translational potential.

Peripheral artery disease (PAD) is a broad disorder encompassing multiple forms of arterial disease outside of the heart. As such, PAD development is a multifactorial process with a variety of manifestations. For example, aneurysms are pathological expansions of an artery that can lead to rupture, while ischemic atherosclerosis reduces blood flow, increasing the risk of claudication, poor wound healing, limb amputation, and stroke. Current PAD treatment is often ineffective or associated with serious risks, largely because these disorders are commonly undiagnosed or misdiagnosed. Active areas of research are focused on detecting and characterizing deleterious arterial changes at early stages using non-invasive imaging strategies, such as ultrasound, as well as emerging technologies like photoacoustic imaging. Earlier disease detection and characterization could improve interventional strategies, leading to better prognosis in PAD patients. While rodents are being used to investigate PAD pathophysiology, imaging of these animal models has been underutilized. This review focuses on structural and molecular information and disease progression revealed by recent imaging efforts of aortic, cerebral, and peripheral vascular disease models in mice, rats, and rabbits. Effective translation to humans involves better understanding of underlying PAD pathophysiology to develop novel therapeutics and apply non-invasive imaging techniques in the clinic.

[Evaluation of risk factors for Mastitis-Metritis-Agalactia in pig farms in Switzerland]. / Erhebung von Risikofaktoren für Mastitis-Metritis-Agalaktie in Schweine- betrieben in der Schweiz.

Mastitis-Metritis-Agalactia (MMA), also known as postpartum dysgalactia syndrome (PPDS) is the most important disease complex in sows after birth. The present study compared 30 MMA problem herds (over 12% of farrowing sows affected) with 30 control farms (less than 10% of farrowing sows affected) to identify risk factors and treatment incidence. Important risk factors identified were in gilts the integration into the herd after the first farrowing, in gestating sows firm fecal consistency as well as in lactating sows soiled troughs, a low flow rate (<2 liters per minute) in drinking nipples and a high prevalence of lameness. The treatment incidence was also significantly different between the two groups. The MMA prevalence could be reduced through optimization of husbandry, feeding and management, which could essentially diminish the use of antibiotics.

Scanning the topography of polyamine blocker binding in an inwardly rectifying potassium channel.

Steeply voltage-dependent inward rectification of Kir (inwardly rectifying potassium) channels arises from blockade by cytoplasmic polyamines. These polycationic blockers traverse a long (>70 Å) pore, displacing multiple permeant ions, en route to a high affinity binding site that remains loosely defined. We have scanned the effects of cysteine modification at multiple pore-lining positions on the blocking properties of a library of polyamine analogs, demonstrating that the effects of cysteine modification are position- and blocker-dependent. Specifically, introduction of positively charged adducts results in two distinct phenotypes: either disruption of blocker binding or generation of a barrier to blocker migration, in a consistent pattern that depends on both the length of the polyamine blocker and the position of the modified cysteine. These findings reveal important details about the chemical basis and specific location of high affinity polyamine binding.

Decomposition of slide helix contributions to ATP-dependent inhibition of Kir6.2 channels.

Regulation of inwardly rectifying potassium channels by intracellular ligands couples cell membrane excitability to important signaling cascades and metabolic pathways. We investigated the molecular mechanisms that link ligand binding to the channel gate in ATP-sensitive Kir6.2 channels. In these channels, the "slide helix" forms an interface between the cytoplasmic (ligand-binding) domain and the transmembrane pore, and many slide helix mutations cause loss of function. Using a novel approach to rescue electrically silent channels, we decomposed the contribution of each interface residue to ATP-dependent gating. We demonstrate that effective inhibition by ATP relies on an essential aspartate at residue 58. Characterization of the functional importance of this conserved aspartate, relative to other residues in the slide helix, has been impossible because of loss-of-function of Asp-58 mutant channels. The Asp-58 position exhibits an extremely stringent requirement for aspartate because even a highly conservative mutation to glutamate is insufficient to restore normal channel function. These findings reveal unrecognized slide helix elements that are required for functional channel expression and control of Kir6.2 gating by intracellular ATP.

Direct role for smooth muscle cell mineralocorticoid receptors in vascular remodeling: novel mechanisms and clinical implications.

The mineralocorticoid receptor (MR) is a key regulator of blood pressure. MR antagonist drugs are used to treat hypertension and heart failure, resulting in decreased mortality by mechanisms that are not completely understood. In addition to the kidney, MR is also expressed in the smooth muscle cells (SMCs) of the vasculature, where it is activated by the hormone aldosterone and affects the expression of genes involved in vascular function at the cellular and systemic levels. Following vascular injury due to mechanical or physiological stresses, vessels undergo remodeling resulting in SMC hypertrophy, migration, and proliferation, as well as vessel fibrosis. Exuberant vascular remodeling is associated with poor outcomes in cardiovascular patients. This review compiles recent findings on the specific role of SMC-MR in the vascular remodeling process. The development and characterization of a SMC-specific MR-knockout mouse has demonstrated a direct role for SMC-MR in vascular remodeling. Additionally, several novel mechanisms contributing to SMC-MR-mediated vascular remodeling have been identified and are reviewed here, including Rho-kinase signaling, placental growth factor signaling through vascular endothelial growth factor type 1 receptor, and galectin signaling.

Levodopa-based device-aided therapies for the treatment of advanced Parkinson's disease: a social return on investment analysis.

Introduction: Parkinson's disease (PD) is an incurable, progressive, neurodegenerative disorder. As PD advances and symptoms progress, patients become increasingly dependent on family and carers. Traditional cost-effectiveness analyses (CEA) only consider patient and payer-related outcomes, failing to acknowledge impacts on families, carers, and broader society. This novel Social Return on Investment (SROI) analysis aimed to evaluate the broader impact created by improving access to levodopa (LD) device-aided therapies (DATs) for people living with advanced PD (aPD) in Australia. Methods: A forecast SROI analysis over a three-year time horizon was conducted. People living with aPD and their families were recruited for qualitative interviews or a quantitative survey. Secondary research and clinical trial data was used to supplement the primary research. Outcomes were valued and assessed in a SROI value map in Microsoft Excel™. Financial proxies were assigned to each final outcome based on willingness-to-pay, economic valuation, and replacement value. Treatment cost inputs were sourced from Pharmaceutical Benefits Schedule (PBS) and Medicare Benefits Scheme (MBS) published prices. Results: Twenty-four interviews were conducted, and 55 survey responses were received. For every $1 invested in access to LD-based DATs in Australia, an estimated $1.79 of social value is created. Over 3 years, it was estimated $277.16 million will be invested and $406.77 million of social return will be created. This value is shared between people living with aPD (27%), their partners (22%), children (36%), and the Australian Government (15%). Most of the value created is social and emotional in nature, including reduced worry, increased connection to family and friends, and increased hope for the future. Discussion: Investment in LD-based DATs is expected to generate a positive social return. Over 50% of the value is created for the partners and children of people living with aPD. This value would not be captured in traditional CEA. The SROI methodology highlights the importance of investing in aPD treatment, capturing the social value created by improved access to LD-based DATs.