Purpose in life as a resilience factor for brain health: diffusion MRI findings from the Midlife in the U.S. study.

Introduction: A greater sense of purpose in life is associated with several health benefits relevant for active aging, but the mechanisms remain unclear. We evaluated if purpose in life was associated with indices of brain health. Methods: We examined data from the Midlife in the United States (MIDUS) Neuroscience Project. Diffusion weighted magnetic resonance imaging data (n=138; mean age 65.2 years, age range 48-95; 80 females; 37 black, indigenous, and people of color) were used to estimate microstructural indices of brain health such as axonal density, and axonal orientation. The seven-item purpose in life scale was used. Permutation analysis of linear models was used to examine associations between purpose in life scores and the diffusion metrics in white matter and in the bilateral hippocampus, adjusting for age, sex, education, and race. Results and discussion: Greater sense of purpose in life was associated with brain microstructural features consistent with better brain health. Positive associations were found in both white matter and the right hippocampus, where multiple convergent associations were detected. The hippocampus is a brain structure involved in learning and memory that is vulnerable to stress but retains the capacity to grow and adapt through old age. Our findings suggest pathways through which an enhanced sense of purpose in life may contribute to better brain health and promote healthy aging. Since purpose in life is known to decline with age, interventions and policy changes that facilitate a greater sense of purpose may extend and improve the brain health of individuals and thus improve public health.

Two-Pole Nature of the Λ(1405) Resonance from Lattice QCD.

This Letter presents the first lattice QCD computation of the coupled channel πΣ-K[over ¯]N scattering amplitudes at energies near 1405 MeV. These amplitudes contain the resonance Λ(1405) with strangeness S=-1 and isospin, spin, and parity quantum numbers I(J^{P})=0(1/2^{-}). However, whether there is a single resonance or two nearby resonance poles in this region is controversial theoretically and experimentally. Using single-baryon and meson-baryon operators to extract the finite-volume stationary-state energies to obtain the scattering amplitudes at slightly unphysical quark masses corresponding to m_{π}≈200 MeV and m_{K}≈487 MeV, this study finds the amplitudes exhibit a virtual bound state below the πΣ threshold in addition to the established resonance pole just below the K[over ¯]N threshold. Several parametrizations of the two-channel K matrix are employed to fit the lattice QCD results, all of which support the two-pole picture suggested by SU(3) chiral symmetry and unitarity.

Operating room organization and surgical performance: a systematic review.

BACKGROUND: Organizational factors may influence surgical outcomes, regardless of extensively studied factors such as patient preoperative risk and surgical complexity. This study was designed to explore how operating room organization determines surgical performance and to identify gaps in the literature that necessitate further investigation. METHODS: We conducted a systematic review according to PRISMA guidelines to identify original studies in Pubmed and Scopus from January 1, 2000 to December 31, 2019. Studies evaluating the association between five determinants (team composition, stability, teamwork, work scheduling, disturbing elements) and three outcomes (operative time, patient safety, costs) were included. Methodology was assessed based on criteria such as multicentric investigation, accurate population description, and study design. RESULTS: Out of 2625 studies, 76 met inclusion criteria. Of these, 34 (44.7%) investigated surgical team composition, 15 (19.7%) team stability, 11 (14.5%) teamwork, 9 (11.8%) scheduling, and 7 (9.2%) examined the occurrence of disturbing elements in the operating room. The participation of surgical residents appeared to impact patient outcomes. Employing specialized and stable teams in dedicated operating rooms showed improvements in outcomes. Optimization of teamwork reduced operative time, while poor teamwork increased morbidity and costs. Disturbances and communication failures in the operating room negatively affected operative time and surgical safety. CONCLUSION: While limited, existing scientific evidence suggests that operating room staffing and environment significantly influences patient outcomes. Prioritizing further research on these organizational drivers is key to enhancing surgical performance.

Acute Care Advanced Practice Providers' Use of Telehealth During the COVID-19 Pandemic.

Advanced practice registered nurses and physician assistants, collectively termed advanced practice providers (APPs), have been part of telehealth for many years. During the COVID-19 pandemic, APPs experienced the growth in roles, responsibilities, and tools used for telehealth care delivery. This article uses examples from 3 health systems to highlight the ways in which telehealth use was expanded due to the pandemic, how APP roles were altered across the United States during and after the pandemic, and implications for future practice.

Economic analysis of surgical outcome monitoring using control charts: the SHEWHART cluster randomised trial.

IMPORTANCE: Surgical complications represent a considerable proportion of hospital expenses. Therefore, interventions that improve surgical outcomes could reduce healthcare costs. OBJECTIVE: Evaluate the effects of implementing surgical outcome monitoring using control charts to reduce hospital bed-days within 30 days following surgery, and hospital costs reimbursed for this care by the insurer. DESIGN: National, parallel, cluster-randomised SHEWHART trial using a difference-in-difference approach. SETTING: 40 surgical departments from distinct hospitals across France. PARTICIPANTS: 155 362 patients over the age of 18 years, who underwent hernia repair, cholecystectomy, appendectomy, bariatric, colorectal, hepatopancreatic or oesophageal and gastric surgery were included in analyses. INTERVENTION: After the baseline assessment period (2014-2015), hospitals were randomly allocated to the intervention or control groups. In 2017-2018, the 20 hospitals assigned to the intervention were provided quarterly with control charts for monitoring their surgical outcomes (inpatient death, intensive care stay, reoperation and severe complications). At each site, pairs, consisting of one surgeon and a collaborator (surgeon, anaesthesiologist or nurse), were trained to conduct control chart team meetings, display posters in operating rooms, maintain logbooks and design improvement plans. MAIN OUTCOMES: Number of hospital bed-days per patient within 30 days following surgery, including the index stay and any acute care readmissions related to the occurrence of major adverse events, and hospital costs reimbursed for this care per patient by the insurer. RESULTS: Postintervention, hospital bed-days per patient within 30 days following surgery decreased at an adjusted ratio of rate ratio (RRR) of 0.97 (95% CI 0.95 to 0.98; p<0.001), corresponding to a 3.3% reduction (95% CI 2.1% to 4.6%) for intervention hospitals versus control hospitals. Hospital costs reimbursed for this care per patient by the insurer significantly decreased at an adjusted ratio of cost ratio (RCR) of 0.99 (95% CI 0.98 to 1.00; p=0.01), corresponding to a 1.3% decrease (95% CI 0.0% to 2.6%). The consumption of a total of 8910 hospital bed-days (95% CI 5611 to 12 634 bed-days) and €2 615 524 (95% CI €32 366 to €5 405 528) was avoided in the intervention hospitals postintervention. CONCLUSIONS: Using control charts paired with indicator feedback to surgical teams was associated with significant reductions in hospital bed-days within 30 days following surgery, and hospital costs reimbursed for this care by the insurer. TRIAL REGISTRATION NUMBER: NCT02569450.

Metabolic Profile of Individuals with and without Type 2 Diabetes from Sub-Saharan Africa.

Epidemiological data predicts that sub-Saharan Africa will have the largest increase in type 2 diabetes (T2D) prevalence over the next two decades. Metabolomics studies have identified biomarkers that could improve T2D diagnosis and follow-up. However, no studies have characterized the metabolome of people from sub-Saharan Africa. Plasma samples from Senegalese individuals with T2D (n = 31) or without T2D (n = 34) were compared using measures of oxidative stress damage and plasma antioxidant enzyme activity and mass-spectrometry-based metabolomics analyses. Results showed that glucose, lactate, and tricarboxylic acid metabolites (fumarate, malate, and succinate) were increased in the T2D group, suggesting alterations in glycolysis and mitochondrial dysfunction. Several amino acids (leucine, isoleucine, valine, and tryptophan) and long-to-very-long-chain fatty acids were higher in the T2D group. Finally, elevated levels of ketone bodies and acylcarnitines were observed along with increased levels of oxidative stress damage and antioxidant activity. In conclusion, the T2D group exhibited modifications in metabolites previously shown to be associated with T2D risk in populations from other areas of the world. Future studies should seek to test whether these metabolites could be used as predictors for T2D-related complications in people from sub-Saharan Africa.

Continued Performance Improvement-What Practicing Surgeons Can Learn From Athletes.

This Viewpoint describes how surgeons can optimize performance with methods for continuous performance improvement used by athletes.

Diabetic lumbosacral plexopathy: an unpredictable clinical entity.

PURPOSE: Diabetic plexopathy is among the most unusual and disabling complication type 2 diabetic mellitus (T2DM) causing major suffering among affected individuals. The clinical presentation includes asymmetric muscle atrophy, weakness, and pain, typically associated with sudden weight loss. In part due to its rarity, this condition can be easily missed with serious consequences including potentially fatal complications. METHODS AND RESULTS: A single case report of a 59-year-old woman with T2DM complicated by a lumbosacral plexopathy that presented with unusual clinical signs, symptoms and metabolic changes including (i) a life-threatening cardiac arrest due to a massive saddle pulmonary embolism (PE) secondary to a lower limb deep venous thrombosis ipsilateral to the plexopathy and (ii) an unexpected partial spontaneous remission of T2DM. CONCLUSIONS: This case highlights the need for increased awareness and improved investigation and understanding of the pathogenesis and management of diabetic plexopathy, especially in rehabilitation settings for optimizing functional outcomes from rehabilitation input. Implications for rehabilitationDiabetic lumbosacral plexopathy (DLSP) is a distinct cause of neurological impairment requiring rehabilitation with a different natural history and prognosis. Its incidence almost three times higher than that of other common inflammatory neuropathies such as Guillain-Barré.Early recognition of DLSP in order to provide interventions, assessment, and therapeutic strategies in Rehabilitation.Diabetes plexopathy should remain an important consideration in the differential diagnoses when assessing any patient with diabetes presenting with acute pain and weakness in the extremities.

Coaching for Surgeons: A Scoping Review of the Quantitative Evidence.

To characterize quantitative studies on coaching interventions for professional surgeons to understand how surgical coaching is defined; examine how different coaching programs are designed, implemented, and evaluated; and identify any relevant research gaps. Background: Surgical coaching is gaining attention as an approach that could help surgeons optimize performance and improve overall wellbeing. However, surgical coaching programs and definitions of coaching vary widely between studies. Methods: A systematic literature search of PubMed, Scopus, Web of Science, CENTRAL, clinicaltrials.gov, and WHO ICTRP was conducted according to the PRISMA-ScR framework to identify studies and registered clinical trials written in English. Original quantitative studies on coaching interventions for professional surgeons were included. Characteristics of the coachees, coaching programs, study designs, outcomes, and findings were charted and analyzed. Results: From 2589 references, 8 studies (6 published; 2 registered trials) met inclusion criteria. Published studies targeted technical or nontechnical skills, included 2-26 surgeons as coachees, and used coaches who were surgeons. Two studies demonstrated that surgeons react positively to coaching. Studies showed inconsistent effects on technical/nontechnical skills. Only two studies measured patient adverse events and reported no significant positive impacts. The registered randomized trials targeted surgeons' physiological parameters or wellbeing and used professional coaches. These trials measure surgeon and patient outcomes. Conclusions: There is an emerging interest in coaching programs to improve surgeons' performance by targeting their professional skills and personal factors. However, more randomized trials are needed to evaluate the impact of coaching interventions on patient outcomes and surgeon wellness.

Plasma Levels of Acyl-Carnitines and Carboxylic Acids Correlate With Cardiovascular and Kidney Function in Subjects With Sickle Cell Trait.

Subjects with sickle cell trait (SCT) carry one copy of mutated ß-globin gene at position E6V at the origin of the production of sickle hemoglobin (HbS). Indeed, individuals with SCT have both normal hemoglobin and HbS, in contrast to patients with sickle cell disease who inherited of two copies of the mutated gene. Although SCT is generally benign/asymptomatic, carriers may develop certain adverse outcomes such as renal complications, venous thromboembolism, exercise-induced rhabdomyolysis … However, little is known about whether similar metabolic pathways are affected in individuals with SCT and whether these metabolic derangements, if present, correlate to clinically relevant parameters. In this study, we performed metabolomics analysis of plasma from individuals with sickle cell trait (n = 34) compared to healthy controls (n = 30). Results indicated a significant increase in basal circulating levels of hemolysis markers, mono- (pyruvate, lactate), di- and tri-carboxylates (including all Krebs cycle intermediates), suggestive of systems-wide mitochondrial dysfunction in individuals with SCT. Elevated levels of kynurenines and indoles were observed in SCT samples, along with increases in the levels of oxidative stress markers (advanced glycation and protein-oxidation end-products, malondialdehyde, oxylipins, eicosanoids). Increases in circulating levels of acyl-carnitines and fatty acids were observed, consistent with increased membrane lipid damage in individuals with sickle cell trait. Finally, correlation analyses to clinical co-variates showed that alterations in the aforementioned pathways strongly correlated with clinical measurements of blood viscosity, renal (glomerular filtration rate, microalbuminuria, uremia) and cardiovascular function (carotid-femoral pulse wave velocity, blood pressure).

Sex-related differences and effects of short and long trail running races on resting muscle-tendon mechanical properties.

The purpose of the study was to assess sex-related differences in resting mechanical properties and adaptations of skeletal muscles and tendons in response to trail running races of different distances using multi-site shear wave elastography assessments of the lower limb, force capacity and blood analyses. Sex differences in resting mechanical properties of knee extensor and plantar flexor muscles and tendons were characterized by shear wave velocity (SWV) measurements in healthy males (N = 42) and females (N = 25) trained in long-distance running. Effects of running distance on muscle and tendon properties were assessed in short (<60 km, N = 23) vs. long (>100 km, N = 26) distance races. Changes in isometric maximal voluntary contraction torque, serum C-reactive protein and creatine kinase activity were also quantified after running races. Higher SWV of relaxed triceps surae muscle was detected in females as compared to males before running races (+4.8%, p = 0.006), but the significant increases in triceps surae muscle group (+7.0%, p = 0.001) and patellar tendon SWV (+15.4%, p = 0.001) after short-distance races were independent of sex. A significant decrease in triceps surae muscle SWV was found after long-distance races in the whole experimental population (-3.1%, p = 0.049). Post-races increase in C-reactive protein and creatine kinase activity were significantly correlated to the relative decreases in triceps surae and quadriceps femoris skeletal muscle SWV (ρ = -0.56, p = 0.001 and ρ = -0.51, p = 0.001, respectively). Resting mechanical properties of muscles and tendons are affected by sex, and adaptations to trail races are related to running distance. Exercise-induced changes in resting skeletal muscle mechanical properties are associated with enhanced indirect markers of inflammation and muscle damage.

Association of Hospital Bed Turnover With Patient Outcomes in Digestive Surgery.

To determine the influence of hospital bed turnover rate (BTR) on the occurrence of complications following minor or major digestive surgery. Background: Performance improvement in surgery aims at increasing productivity while preventing complications. It is unknown whether this relationship can be influenced by the complexity of surgery. Methods: A nationwide retrospective cohort study was conducted, based on generalized estimating equation modeling to determine the effect of hospital BTR on surgical outcomes, adjusting for patient mix and clustering within 631 public and private French hospitals. All patients who underwent minor or major digestive surgery between January 1, 2013 and December 31, 2018 were included. Hospital BTR was defined as the annual number of stays per bed for digestive surgery and categorized into tertiles. The primary endpoint was a composite measurement of events occurring within 30 days after surgery: inpatient death, extended intensive care unit (ICU) admission, and reoperation. Results: Rate of adverse events was 2.51% in low BTR hospitals versus 2.25% in high BTR hospitals for minor surgery, and 16.79% versus 16.83% for major surgery. Patients who underwent minor surgery in high BTR hospitals experienced lower complications (odds ratio [OR], 0.89; 95% confidence interval [CI], 0.81-0.97; P = 0.009), mortality (OR, 0.87; 95% CI, 0.78-0.98, P = 0.02), ICU admission (OR, 0.83; 95% CI, 0.70-0.99; P = 0.03), and reoperation (OR, 0.91; 95% CI, 0.85-0.97; P = 0.002) compared to those in low BTR hospitals. Such differences were not consistently observed among patients admitted for major surgery. Conclusions: High turnover of patients in beds is beneficial for minor procedures, but questionable for major surgeries.

Mitochondrial Permeability Transition Causes Mitochondrial Reactive Oxygen Species- and Caspase 3-Dependent Atrophy of Single Adult Mouse Skeletal Muscle Fibers.

Elevated mitochondrial reactive oxygen species (mROS) and an increase in caspase-3 activity are established mechanisms that lead to skeletal muscle atrophy via the upregulation of protein degradation pathways. However, the mechanisms upstream of an increase in mROS and caspase-3 activity in conditions of muscle atrophy have not been identified. Based upon knowledge that an event known as mitochondrial permeability transition (MPT) causes an increase in mROS emission and the activation of caspase-3 via mitochondrial release of cytochrome c, as well as the circumstantial evidence for MPT in some muscle atrophy conditions, we tested MPT as a mechanism of atrophy. Briefly, treating cultured single mouse flexor digitorum brevis (FDB) fibers from adult mice with a chemical inducer of MPT (Bz423) for 24 h caused an increase in mROS and caspase-3 activity that was accompanied by a reduction in muscle fiber diameter that was able to be prevented by inhibitors of MPT, mROS, or caspase-3 (p < 0.05). Similarly, a four-day single fiber culture as a model of disuse caused atrophy that could be prevented by inhibitors of MPT, mROS, or activated caspase-3. As such, our results identify MPT as a novel mechanism of skeletal muscle atrophy that operates through mROS emission and caspase-3 activation.

Hemodialysis-Related Complement and Contact Pathway Activation and Cardiovascular Risk: A Narrative Review.

Individuals receiving long-term hemodialysis are at increased risk of developing cardiovascular disease (CVD). Traditional cardiovascular risk factors do not fully explain the high CVD risk in this population. During hemodialysis, blood interacts with the biomaterials of the hemodialysis circuit. This interaction can activate the complement system and the factor XII-driven contact system. FXII activation triggers both the intrinsic pathway of coagulation and the kallikrein-kinin pathway, resulting in thrombin and bradykinin production, respectively. The complement system plays a key role in the innate immune response, but also contributes to the pathogenesis of numerous disease states. Components of the complement pathway, including mannose binding lectin and C3, are associated with CVD risk in people with end-stage kidney disease (ESKD). Both the complement system and the factor XII-driven contact coagulation system mediate proinflammatory and procoagulant responses that could contribute to or accelerate CVD in hemodialysis recipents. This review summarizes what is already known about hemodialysis-mediated activation of the complement system and in particular the coagulation contact system, emphasizing the potential role these systems play in the identification of new biomarkers for CVD risk stratification and the development of potential therapeutic targets or innovative therapies that decrease CVD risk in ESKD patients.

Differential impacts of trail and ultra-trail running on cytokine profiles: An observational study.

BACKGROUND: Endurance running events are known to cause inflammation and result in increased cytokine production. However, the effects of ultramarathons on cytokine profiles are not well characterized. OBJECTIVE: The aim of this study was to describe and compare the effects of a trail (40 km) race and an ultra-trail (171 km) race on leukocyte concentrations and cytokine profiles. METHODS: The study was conducted during the Ultra-Trail du Mont Blanc® ultra-marathon running event, and included 11 runners who completed the 40 km trail run and 12 runners who completed the 171 km ultra-trail. Blood samples were taken before and after the races. RESULTS: Leukocyte concentrations significantly increased after both races. Circulating levels of IL-6, IL-1ß, MCP-1, and IFN-γ were significantly higher after the longer race compared to the shorter race. Furthermore, while both races resulted in significant increases in IL-6 and IL-8, only the longer race resulted in significant increases in MIP-1ß, IL-7, IL-17a, and IL-4. CONCLUSIONS: These results illustrate that a 171 km ultra-trail race results in greater modulations in cytokine profiles than a traditional trail race.

Oxidative stress, inflammation, blood rheology, and microcirculation in adults with sickle cell disease: Effects of hydroxyurea treatment and impact of sickle cell syndrome.

Inflammation and oxidative stress play a key role in the pathophysiology of sickle cell disease (SCD). However, the potential influence of different sickle genotypes, or hydroxyurea (HU) treatment, on these factors remains poorly documented. The present study compared several plasma markers of inflammation and oxidative stress, as well as microvascular function, between patients with sickle SC disease (HbSC, n = 19) and patients with sickle cell anemia (HbSS) under hydroxyurea (HU) treatment (n = 16), or not (n = 13). Hemorheological parameters and levels of inflammatory (IL-6, IL-8, IFN-γ, MCP-1, MIP-1ß, TNF-α) and oxidative stress (AOPP, MDA, MPO) markers were determined. Peripheral microcirculatory cutaneous blood flow and immediate microvascular response to local heat were evaluated using laser Doppler flowmetry. Oxidative stress and inflammation were lower in HbSC patients and HbSS patients under HU therapy compared to HbSS patients not treated with HU. Blood viscosity was higher in HbSC than in HbSS patients treated with or not with HU. Vasodilation response of the cutaneous microcirculation to heat stress was higher in HbSS patients receiving HU treatment. Our results clearly established that both sickle cell genotype and HU treatment modulate inflammation and oxidative stress.

Acute Cycling Exercise Induces Changes in Red Blood Cell Deformability and Membrane Lipid Remodeling.

Here we describe the effects of a controlled, 30 min, high-intensity cycling test on blood rheology and the metabolic profiles of red blood cells (RBCs) and plasma from well-trained males. RBCs demonstrated decreased deformability and trended toward increased generation of microparticles after the test. Meanwhile, metabolomics and lipidomics highlighted oxidative stress and activation of membrane lipid remodeling mechanisms in order to cope with altered properties of circulation resulting from physical exertion during the cycling test. Of note, intermediates from coenzyme A (CoA) synthesis for conjugation to fatty acyl chains, in parallel with reversible conversion of carnitine and acylcarnitines, emerged as metabolites that significantly correlate with RBC deformability and the generation of microparticles during exercise. Taken together, we propose that RBC membrane remodeling and repair plays an active role in the physiologic response to exercise by altering RBC properties.

Impact of Trail Running Races on Blood Viscosity and Its Determinants: Effects of Distance.

Blood rheology is a key determinant of tissue perfusion at rest and during exercise. The present study investigated the effects of race distance on hematological, blood rheological, and red blood cell (RBC) senescence parameters. Eleven runners participated in the Martigny-Combes à Chamonix 40 km race (MCC, elevation gain: 2300 m) and 12 others in the Ultra-Trail du Mont Blanc (UTMB, 171 km, elevation gain: 10,000 m). Blood samples were collected before and after the races. After the UTMB, the percentage of RBC phosphatidylserine (PS) exposure was not affected while RBC CD235a levels decreased and RBC-derived microparticles increased. In contrast, after the MCC, RBC PS exposure increased, while RBC CD235a and RBC-derived microparticles levels were not affected. The free hemoglobin and hemolysis rate did not change during the races. RBC aggregation and blood viscosity at moderate shear rates increased after the MCC. RBC deformability, blood viscosity at a high shear rate, and hematocrit decreased after the UTMB but not after the MCC. Our results indicate that blood rheology behavior is different between a 40 km and a 171 km mountain race. The low blood viscosity after the ultra-marathon might facilitate blood flow to the muscles and optimize aerobic performance.