The Rac pathway prevents cell fragmentation in a nonprotrusively migrating leader cell during C. elegans gonad organogenesis.

The C. elegans hermaphrodite distal tip cell (DTC) leads gonadogenesis. Loss-of-function mutations in a C. elegans ortholog of the Rac1 GTPase (ced-10) and its GEF complex (ced-5/DOCK180, ced-2/CrkII, ced-12/ELMO) cause gonad migration defects related to directional sensing; we discovered an additional defect class of gonad bifurcation in these mutants. Using genetic approaches, tissue-specific and whole-body RNAi, and in vivo imaging of endogenously tagged proteins and marked cells, we find that loss of Rac1 or its regulators causes the DTC to fragment as it migrates. Both products of fragmentation-the now-smaller DTC and the membranous patch of cellular material-localize important stem cell niche signaling (LAG-2 ligand) and migration (INA-1/integrin subunit alpha) factors to their membranes, but only one retains the DTC nucleus and therefore the ability to maintain gene expression over time. The enucleate patch can lead a bifurcating branch off the gonad arm that grows through germ cell proliferation. Germ cells in this branch differentiate as the patch loses LAG-2 expression. While the nucleus is surprisingly dispensable for aspects of leader cell function, it is required for stem cell niche activity long term. Prior work found that Rac1-/-;Rac2-/- mouse erythrocytes fragment; in this context, our new findings support the conclusion that maintaining a cohesive but deformable cell is a conserved function of this important cytoskeletal regulator.

Exploring the challenges of avoiding collisions with virtual pedestrians using a dual-task paradigm in individuals with chronic moderate to severe traumatic brain injury.

BACKGROUND: Individuals with a moderate-to-severe traumatic brain injury (m/sTBI), despite experiencing good locomotor recovery six months post-injury, face challenges in adapting their locomotion to the environment. They also present with altered cognitive functions, which may impact dual-task walking abilities. Whether they present collision avoidance strategies with moving pedestrians that are altered under dual-task conditions, however, remains unclear. This study aimed to compare between individuals with m/sTBI and age-matched control individuals: (1), the locomotor and cognitive costs associated with the concurrent performance of circumventing approaching virtual pedestrians (VRPs) while attending to an auditory-based cognitive task and; (2) gaze behaviour associated with the VRP circumvention task in single and dual-task conditions. METHODOLOGY: Twelve individuals with m/sTBI (age = 43.3 ± 9.5 yrs; >6 mo. post injury) and 12 healthy controls (CTLs) (age = 41.8 ± 8.3 yrs) were assessed while walking in a virtual subway station viewed in a head-mounted display. They performed a collision avoidance task with VRPs, as well as auditory-based cognitive tasks (pitch discrimination and auditory Stroop), both under single and dual-task conditions. Dual-task cost (DTC) for onset distance of trajectory deviation, minimum distance from the VRP, maximum lateral deviation, walking speed, gaze fixations and cognitive task accuracy were contrasted between groups using generalized estimating equations. RESULTS: In contrast to CTLs who showed locomotor DTCs only, individuals with m/sTBI displayed both locomotor and cognitive DTCs. While both groups walked slower under dual-task conditions, only individuals with m/sTBI failed to modify their onset distance of trajectory deviation and maintained smaller minimum distances and smaller maximum lateral deviation compared to single-task walking. Both groups showed shorter gaze fixations on the approaching VRP under dual-task conditions, but this reduction was less pronounced in the individuals with m/sTBI. A reduction in cognitive task accuracy under dual-task conditions was found in the m/sTBI group only. CONCLUSION: Individuals with m/sTBI present altered locomotor and gaze behaviours, as well as altered cognitive performances, when executing a collision avoidance task involving moving pedestrians in dual-task conditions. Potential mechanisms explaining those alterations are discussed. Present findings highlight the compromised complex walking abilities in individuals with m/sTBI who otherwise present a good locomotor recovery.

Designs of clinical swallowability assessments of solid oral dosage forms in regulatory submissions.

The swallowability of solid oral dosage forms (SODFs) is crucial for medication safety and adherence. Both regulatory agencies and sponsors are concerned with bringing swallowable SODFs to patients. However, no best practices are available for assessing swallowability. Therefore, we conducted a comparative analysis of clinical swallowability assessments (CSAs) for SODFs in regulatory submissions to identify current study design practices. CSAs were identified from a "swallowability" keyword search of a Food and Drug Administration database. Notable design trends among the 17 CSAs were not assessing swallowability as a primary endpoint (76 %); enrolling pediatric patients (76 %); administering assessments post-screening (76 %); and utilizing questionnaires (100 %). A design trend with near equal frequency(∼50 %) was single- or multiple-doses of product administration. Study subjects were the primary questionnaire respondents (82 %), usually using a Likert scale (92 %, 12/13). CSAs generally dichotomized the responses for analysis (65 %) without pre-specified threshold values (59 %). Overall, while study designs exhibited trends, methodology variations may impact swallowability measurements affecting the interpretation of results. Thus, developing robust and valid assessment tools for swallowability is imperative to produce clinically relevant data and inform regulatory decision-making. Collaboration between regulatory agencies and sponsors is warranted to create best practices and ensure high quality swallowability data.

Positive Bacterial Cultures on Spinal Wound Closure Do Not Predict Postoperative Outcomes.

BACKGROUND: Complex surgical back wounds represent significant morbidity in patients who have undergone spinal procedures requiring closure or revision by plastic surgeons. This study aimed to assess the utility of bacterial wound culture data for predicting surgical outcomes of wound management. METHODS: This study is a single-institution retrospective review of consecutive patients who required plastic surgery intervention for wound infection following spinal procedures between the years 2010 and 2021 (n = 70). Statistical analysis was performed for demographics, comorbidities, perioperative laboratory studies, and treatment methods. The primary outcomes of interest were rate of postoperative complications after soft tissue reconstruction and reconstructive failure. The secondary outcome of interest was time to healing in number of days. RESULTS: The overall complication rate after wound closure was 31.4%, with wound infection in 12.9%, seroma in 10%, dehiscence in 12.9%, and hematoma in 1.4%. Increasing number of debridements before wound closure increased the likelihood of a surgical complication of any kind (odds ratio [OR], 1.772; 95% confidence interval [CI], 1.045-3.002). Positive wound cultures before reconstruction were associated with development of seroma only (OR, 0.265; 95% CI, 0.078-0.893). Use of incisional vacuum-assisted closure devices significantly decreased the odds of postoperative wound dehiscence (OR, 0.179; 95% CI, 0.034-0.904) and increased odds of healing (hazard ratio, 3.638; 95% CI, 1.547-8.613). CONCLUSIONS: Positive wound cultures were not significantly associated with negative outcomes after complex closure or reconstruction of infected spinal surgical wounds. This finding emphasizes the importance of clinical judgment with a multidisciplinary approach to complex surgical back wounds over culture data for wound closure timing.

A Multidisciplinary Approach to End-Stage Limb Salvage in the Highly Comorbid Atraumatic Population: An Observational Study.

Background: The use of free tissue transfer (FTT) is efficacious for chronic, non-healing lower extremity (LE) wounds. The four pillars of managing patient comorbidities, infection control, blood flow status, and biomechanical function are critical in achieving successful limb salvage. The authors present their multidisciplinary institutional experience with a review of 300 FTTs performed for the complex LE limb salvage of chronic LE wounds. Methods: A single-institution, retrospective review of atraumatic LE FTTs performed by a single surgeon from July 2011 to January 2023 was reviewed. Data on patient demographics, comorbidities, preoperative management, intraoperative details, flap outcomes, postoperative complications, and long-term outcomes were collected. Results: A total of 300 patients who underwent LE FTT were included in our retrospective review. Patients were on average 55.9 ± 13.6 years old with a median Charlson Comorbidity Index of 4 (IQR: 3). The majority of patients were male (70.7%). The overall hospital length of stay (LOS) was 27 days (IQR: 16), with a postoperative LOS of 14 days (IQR: 9.5). The most prevalent comorbidities were diabetes (54.7%), followed by peripheral vascular disease (PVD: 35%) and chronic kidney disease (CKD: 15.7%). The average operative LE FTT time was 416 ± 115 min. The majority of flaps were anterolateral thigh (ALT) flaps (52.7%), followed by vastus lateralis (VL) flaps (25.3%). The immediate flap success rate was 96.3%. The postoperative ipsilateral amputation rate was 12.7%. Conclusions: Successful limb salvage is possible in a highly comorbid patient population with a high prevalence of diabetes mellitus, peripheral vascular disease, and end-stage renal disease. In order to optimize patients prior to their LE FTT, extensive laboratory, arterial, and venous preoperative testing and diabetes management are needed preoperatively. Postoperative monitoring and long-term follow-up with a multidisciplinary team are also crucial for long-term limb salvage success.

Surgical techniques and outcomes of thyroid chondroplasty in transfeminine individuals: A systematic review.

Thyroid chondroplasty (TC) in facial gender-affirming surgery (FGAS) is aimed at modifying the thyroid cartilage to achieve a more feminine laryngeal appearance. This study evaluated open versus endoscopic techniques to TC and associated outcomes and complications. A systematic review (SR) of articles pertaining to TC was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Twelve articles representing 368 patients were included for analysis. Nine articles described open approaches, and three articles described endoscopic techniques. The rate of total complications was 4.3% (n = 12) in the open approach compared to 15% (n = 13) in the endoscopic approach. Positive esthetic results were reported in 92% of cases performed with the open approach and 90% with the endoscopic approach. In the open approach, seven (2.5%) patients requested additional removal of cartilage, and three (1.1%) requested scar revision. In the endoscopic approach, three (3.7%) patients requested additional cartilage removal. In addition, data of individuals who underwent "cervical tracheoplasty" for gender dysphoria from the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) database was reviewed, and there was no incidence of wound or major complications among patients who underwent tracheoplasty alone. Although the advantage of the endoscopic approach is a scarless neck incision, the rate of complications is higher with the open approach. Endoscopic approaches are still not widely used, and continued investigations are warranted to improve familiarity with this approach and reduce postoperative complications.

Muscle versus Fascia Free Tissue Transfer for Treatment of Chronic Osteomyelitis in the Comorbid Population.

BACKGROUND: In patients with chronic lower extremity (LE) wounds, chronic osteomyelitis confers additional complexity to achieving adequate treatment. Previous reviews demonstrate increased rates of osteomyelitis recurrence in patients who receive muscle flaps compared with fasciocutaneous flaps for LE limb salvage; however, these studies were not limited to atraumatic populations who receive exclusively free flaps. Thus, this study compared rates of recurrence in chronic osteomyelitis patients undergoing LE reconstruction with fasciocutaneous versus muscle free flaps. METHODS: Patients undergoing free tissue transfer (FTT) between July 2011 and July 2021 were retrospectively reviewed. Patients were stratified into fasciocutaneous and muscle free flap groups. Primary outcomes included osteomyelitis recurrence, flap complications, limb salvage, and ambulatory status. RESULTS: Forty-eight patients with pathologic diagnosis of chronic osteomyelitis of the wound bed were identified, of which 58.3% received fasciocutaneous (n = 28) and 41.7% received muscle flaps (n = 20). The most common comorbidities included diabetes mellitus (n = 29, 60.4%), peripheral neuropathy (n = 27, 56.3%) and peripheral vascular disease (n = 24, 50.0%). Methicillin-resistant or methicillin -sensitive Staphylococcus aureus were the most common pathogen in 18.7% (n = 9) of procedures. The majority of patients underwent a median of three debridements followed by negative pressure wound therapy prior to receiving FTT. At a median follow-up of 16.6 months, the limb salvage and ambulatory rates were 79.2 (n = 38) and 83.3% (n = 40), respectively. The overall rate of microsurgical flap success was 93.8% (n = 45). Osteomyelitis recurred in 25% of patients (n = 12) at a median duration of 4.0 months. There were no significant differences in rates of osteomyelitis recurrence, flap complications, limb salvage, ambulation, and mortality. On multivariate analysis, flap composition remained a nonsignificant predictor of osteomyelitis recurrence (odds ratio: 0.975, p = 0.973). CONCLUSION: This study demonstrates that flap composition may not influence recurrence of osteomyelitis following free flap reconstruction of chronic LE wounds, suggesting that optimal flap selection should be based on wound characteristics and patient goals.

Getting there in one piece: The Rac pathway prevents cell fragmentation in a nonprotrusively migrating leader cell during organogenesis.

The C. elegans hermaphrodite distal tip cell (DTC) leads gonadogenesis. Loss-of-function mutations in a C. elegans ortholog of the Rac1 GTPase (ced-10) and its GEF complex (ced-5/DOCK180, ced-2/CrkII, ced-12/ELMO) cause gonad migration defects related to directional sensing; we discovered an additional defect class of gonad bifurcation in these mutants. Using genetic approaches, tissue-specific and whole-body RNAi, and in vivo imaging of endogenously tagged proteins and marked cells, we find that loss of Rac1 or its regulators causes the DTC to fragment as it migrates. Both products of fragmentation-the now-smaller DTC and the membranous patch of cellular material-localize important stem cell niche signaling (LAG-2/DSL ligand) and migration (INA-1/integrin subunit alpha) factors to their membranes, but only one retains the DTC nucleus and therefore the ability to maintain gene expression over time. The enucleate patch can lead a bifurcating branch off the gonad arm that grows through germ cell proliferation. Germ cells in this branch differentiate as the patch loses LAG-2 expression. While the nucleus is surprisingly dispensable for aspects of leader cell function, it is required for stem cell niche activity long-term. Prior work found that Rac1-/-;Rac2-/- mouse erythrocytes fragment; in this context, our new findings support the conclusion that maintaining a cohesive but deformable cell is a conserved function of this important cytoskeletal regulator.

At-home computerized executive-function training to improve cognition and mobility in normal-hearing adults and older hearing aid users: a multi-centre, single-blinded randomized controlled trial.

BACKGROUND: Hearing loss predicts cognitive decline and falls risk. It has been argued that degraded hearing makes listening effortful, causing competition for higher-level cognitive resources needed for secondary cognitive or motor tasks. Therefore, executive function training has the potential to improve cognitive performance, in turn improving mobility, especially when older adults with hearing loss are engaged in effortful listening. Moreover, research using mobile neuroimaging and ecologically valid measures of cognition and mobility in this population is limited. The objective of this research is to examine the effect of at-home cognitive training on dual-task performance using laboratory and simulated real-world conditions in normal-hearing adults and older hearing aid users. We hypothesize that executive function training will lead to greater improvements in cognitive-motor dual-task performance compared to a wait-list control group. We also hypothesize that executive function training will lead to the largest dual-task improvements in older hearing aid users, followed by normal-hearing older adults, and then middle-aged adults. METHODS: A multi-site (Concordia University and KITE-Toronto Rehabilitation Institute, University Health Network) single-blinded randomized controlled trial will be conducted whereby participants are randomized to either 12 weeks of at-home computerized executive function training or a wait-list control. Participants will consist of normal-hearing middle-aged adults (45-60 years old) and older adults (65-80 years old), as well as older hearing aid users (65-80 years old, ≥ 6 months hearing aid experience). Separate samples will undergo the same training protocol and the same pre- and post-evaluations of cognition, hearing, and mobility across sites. The primary dual-task outcome measures will involve either static balance (KITE site) or treadmill walking (Concordia site) with a secondary auditory-cognitive task. Dual-task performance will be assessed in an immersive virtual reality environment in KITE's StreetLab and brain activity will be measured using functional near infrared spectroscopy at Concordia's PERFORM Centre. DISCUSSION: This research will establish the efficacy of an at-home cognitive training program on complex auditory and motor functioning under laboratory and simulated real-world conditions. This will contribute to rehabilitation strategies in order to mitigate or prevent physical and cognitive decline in older adults with hearing loss. TRIAL REGISTRATION: Identifier: NCT05418998. https://clinicaltrials.gov/ct2/show/NCT05418998.

Implications of Single-Vessel Runoff on Long-Term Outcomes of Free Tissue Transfer for Lower Extremity Reconstruction.

BACKGROUND: Patients with complex lower extremity (LE) wounds and single-vessel LE runoff (1-VRO) are often considered for amputation. While more challenging, free tissue transfer (FTT) is a means for limb salvage. This study aims to demonstrate the feasibility of limb salvage with FTT in patients with 1-VRO. METHODS: Patients undergoing FTT by a single surgeon between 2011 and 2021 were retrospectively reviewed. Data collected included demographics, wound characteristics, vascular status, and operative details. Patients were divided into cohorts based on 1- versus 3-VRO of tibial vessel inflow. Outcomes of interest included postoperative complications such as flap necrosis, flap success, limb salvage, and ambulatory status. RESULTS: A total of 188 patients underwent FTT to LE, with 25 patients (13.3%) having 1-VRO. Patients with 1-VRO had a comparable prevalence of diabetes (56.0% vs. 50.0%, p = 0.569) and end-stage renal disease (8.0% vs. 3.7%, p = 0.319). Osteomyelitis was more common in the 1-VRO group (80.0% vs. 60.1%, p = 0.056). FTT donor sites and flap composition were similar between cohorts. At mean follow-up of 21.2 months (interquartile range 24.5:5.6, 30.1 months), limb salvage rates were similar between cohorts (84.0% vs. 91.4%, p = 0.241), with no significant differences in ambulatory status or mortality. Higher complication rates occurred in the 1-VRO cohort (48.0% vs. 21.5%, p = 0.004), of which partial flap necrosis was more prevalent in the 1-VRO group (8.0% vs. 1.2%, p = 0.029). There was no difference in flap success rates between groups (p = 0.805). More postflap angiograms were performed in the 1-VRO group (32.0% vs. 9.2%, p = 0.001), but there was no difference in need for repeat percutaneous endovascular intervention between groups. CONCLUSION: This study demonstrates that FTT reconstruction to the LE remains a reliable reconstruction option for limb salvage in patients with single-vessel supply to the LE. Reliance on advanced perioperative management and patient optimization is effective at reducing negative outcomes.

Longitudinal, prospective study of head impacts in male high school football players.

INTRODUCTION: Repetitive, subconcussive events may adversely affect the brain and cognition during sensitive periods of development. Prevention of neurocognitive consequences of concussion in high school football is therefore an important public health priority. We aimed to identify the player positions and demographic, behavioral, cognitive, and impact characteristics that predict the frequency and acceleration of head impacts in high school football players. METHODS: In this prospective study, three cohorts of adolescent male athletes (N = 53, 28.3% Hispanic) were recruited over three successive seasons in a high school American football program. Demographic and cognitive functioning were assessed at baseline prior to participating in football. Helmet sensors recorded impact frequency and acceleration. Each head impact was captured on film from five different angles. Research staff verified and characterized on-field impacts. Player-level Poisson regressions and year-level and impact-level linear mixed-effect models were used to determine demographic, behavioral, cognitive, and impact characteristics as predictors of impact frequency and acceleration. RESULTS: 4,678 valid impacts were recorded. Impact frequency positively associated with baseline symptoms of hyperactivity-impulsivity [ß(SE) = 1.05 impacts per year per unit of symptom severity (1.00), p = 0.01] and inattentiveness [ß(SE) = 1.003 impacts per year per T-score unit (1.001), p = 0.01]. Compared to quarterbacks, the highest acceleration impacts were sustained by kickers/punters [ß(SE) = 21.5 g's higher (7.1), p = 0.002], kick/punt returners [ß(SE) = 9.3 g's higher (4.4), p = 0.03], and defensive backs [ß(SE) = 4.9 g's higher (2.5), p = 0.05]. Impacts were more frequent in the second [ß(SE) = 33.4 impacts (14.2), p = 0.02)] and third [ß(SE) = 50.9 impacts (20.1), p = 0.01] year of play. Acceleration was highest in top-of-the-head impacts [ß(SE) = 4.4 g's higher (0.8), p<0.001]. CONCLUSION: Including screening questions for Attention-Deficit/Hyperactivity Disorder in pre-participation evaluations can help identify a subset of prospective football players who may be at risk for increased head impacts. Position-specific strategies to modify kickoffs and correct tackling and blocking may also reduce impact burden.

Multidisciplinary Approach to Sedation and Early Mobility of Intubated Critically Ill Neurologic Patients Improves Mobility at Discharge.

Background and Purpose: Over-sedation may confound neurologic assessment in critically ill neurologic patients and prolong duration of mechanical ventilation (MV). Decreased sedative use may facilitate early functional independence when combined with early mobility. The objective of this study was to evaluate the impact of a stepwise, multidisciplinary analgesia-first sedation pathway and early mobility protocol on medication use and mobility in the neuroscience intensive care unit (ICU). Methods: We performed a single-center prospective cohort study with adult patients admitted to a neuroscience ICU between March and June 2016-2018 who required MV for greater than 48 hours. Patients were included from three separate phases of the study: Phase I - historical controls (2016); Phase II - analgesia-first pathway (2017); Phase III - early mobility protocol (2018). Primary outcomes included propofol requirements during MV, total rehabilitation therapy provided, and functional mobility during ICU admission. Results: 156 patients were included in the analysis. Decreasing propofol exposure was observed during Phase I, II, and III (median 2243.7 mg/day vs 2065.6 mg/day vs 1360.8 mg/day, respectively; P = .04 between Phase I and III). Early mobility was provided in 59.7%, 40%, and 81.6% of patients while admitted to the ICU in Phase I, II, and III, respectively (P < .01). An increased proportion of patients in Phase III were walking or ambulating at ICU discharge (26.7%; 8/30) compared to Phase I (7.9%, 3/38, P = .05). Conclusions: An interdisciplinary approach with an analgesia-first sedation pathway with early mobility protocol was associated with less sedative use, increased rehabilitation therapy, and improved functional mobility status at ICU discharge.

Effects of Exercise Alone or Combined With Cognitive Training and Vitamin D Supplementation to Improve Cognition in Adults With Mild Cognitive Impairment: A Randomized Clinical Trial.

Importance: Exercise, cognitive training, and vitamin D may enhance cognition in older adults with mild cognitive impairment (MCI). Objective: To determine whether aerobic-resistance exercises would improve cognition relative to an active control and if a multidomain intervention including exercises, computerized cognitive training, and vitamin D supplementation would show greater improvements than exercise alone. Design, Setting, and Participants: This randomized clinical trial (the SYNERGIC Study) was a multisite, double-masked, fractional factorial trial that evaluated the effects of aerobic-resistance exercise, computerized cognitive training, and vitamin D on cognition. Eligible participants were between ages 65 and 84 years with MCI enrolled from September 19, 2016, to April 7, 2020. Data were analyzed from February 2021 to December 2022. Interventions: Participants were randomized to 5 study arms and treated for 20 weeks: arm 1 (multidomain intervention with exercise, cognitive training, and vitamin D), arm 2 (exercise, cognitive training, and placebo vitamin D), arm 3 (exercise, sham cognitive training, and vitamin D), arm 4 (exercise, sham cognitive training, and placebo vitamin D), and arm 5 (control group with balance-toning exercise, sham cognitive training, and placebo vitamin D). The vitamin D regimen was a 10 000 IU dose 3 times weekly. Main Outcomes and Measures: Primary outcomes were changes in ADAS-Cog-13 and Plus variant at 6 months. Results: Among 175 randomized participants (mean [SD] age, 73.1 [6.6] years; 86 [49.1%] women), 144 (82%) completed the intervention and 133 (76%) completed the follow-up (month 12). At 6 months, all active arms (ie, arms 1 through 4) with aerobic-resistance exercise regardless of the addition of cognitive training or vitamin D, improved ADAS-Cog-13 when compared with control (mean difference, -1.79 points; 95% CI, -3.27 to -0.31 points; P = .02; d = 0.64). Compared with exercise alone (arms 3 and 4), exercise and cognitive training (arms 1 and 2) improved the ADAS-Cog-13 (mean difference, -1.45 points; 95% CI, -2.70 to -0.21 points; P = .02; d = 0.39). No significant improvement was found with vitamin D. Finally, the multidomain intervention (arm 1) improved the ADAS-Cog-13 score significantly compared with control (mean difference, -2.64 points; 95% CI, -4.42 to -0.80 points; P = .005; d = 0.71). Changes in ADAS-Cog-Plus were not significant. Conclusions and Relevance: In this clinical trial, older adults with MCI receiving aerobic-resistance exercises with sequential computerized cognitive training significantly improved cognition, although some results were inconsistent. Vitamin D supplementation had no effect. Our findings suggest that this multidomain intervention may improve cognition and potentially delay dementia onset in MCI. Trial Registration: ClinicalTrials.gov Identifier: NCT02808676.

The association between information and communication technologies, loneliness and social connectedness: A scoping review.

Older adults are at a higher risk of loneliness, compared to other demographics. The use of Internet Communication and Technologies (ICTs) among older adults is steadily increasing and given ICTs provide a means of enhancing social connectedness suggests they may have positive effects on reducing loneliness. Therefore, the aim of this scoping review was to examine the research that explores how ICTs may be implicated in mitigating loneliness and increasing social connectedness among older adults. After the examination of 54 articles, we identified three major themes within the literature: (1) ICTs were associated with a reduction in loneliness and increase in wellbeing. (2) ICTs promoted social connectedness by facilitating conversations. (3) Factors such as training, self-efficacy, self-esteem, autonomy, and the design/features, or affordances, of ICTs contribute toward the associations between ICT use and wellbeing. The heterogeneity of methodologies, statistical reporting, the small sample sizes of interventional and observational studies, and the diversity of the experimental contexts underline the challenges of quantitative research in this field and highlights the necessity of tailoring ICT interventions to the needs and contexts of the older users.

Association of Soluble ST2 With Functional Outcome, Perihematomal Edema, and Immune Response After Intraparenchymal Hemorrhage.

BACKGROUND AND OBJECTIVES: Perihematomal edema (PHE) contributes to poor outcome after deep intraparenchymal hemorrhage (IPH), which is characterized by neuroinflammation and an influx of peripherally derived innate immune cells. We previously identified soluble ST2 (sST2) as a candidate for immune-mediated secondary brain injury. Leveraging prospectively collected cohorts from 2 centers, we sought to determine whether sST2 was associated with functional outcome, PHE, and the immune response following IPH. METHODS: Patients with deep IPH were enrolled within 36 hours of ictus, and blood was collected for sST2 and immune cell measurement. Hematoma volume and PHE were measured on serial CT scans. Good outcome was defined as a modified Rankin Scale score of 0-3 at 90 days. Linear mixed-effects models were used to analyze the relationship between sST2 and PHE over time. Flow cytometry was used to identify shifts in immune cell populations associated with sST2. Immunohistochemistry of human brain tissue was used to identify ST2-expressing cells in the perihematomal region. RESULTS: The 55 included patients had a median admission Glasgow Coma Scale score of 14 (interquartile range [IQR] 9-15), an intracerebral hemorrhage (ICH) score of 1 (IQR 1-2), and a hematoma volume of 8.6 mL (IQR 3.4-13.8 mL). Receiver operating curve analysis found the sST2 level to be predictive of poor outcome with an area under the curve of 0.763 (95% CI 0.632-0.894) and Youden optimum cut point of 61.8 ng/mL (p < 0.001). sST2 remained an independent predictor after adjustment for ICH score (adjusted odds ratio 2.53, 95% CI 1.03-6.19, p = 0.042). Measurement of PHE found those patients with high sST2 to have greater edema volume over time (ß = 1.07, 95% CI 0.51-1.63, p < 0.001). High sST2 was associated with a shift toward an innate peripheral immune response (monocytes and natural killer cells; 68.6% ± 5.1% vs 47.5% ± 4.0%; p = 0.003). DISCUSSION: Our findings demonstrate that elevated sST2 links the peripheral innate immune response to PHE volume and outcome after IPH. This knowledge is relevant to future studies that seek to identify patients with IPH at highest risk for immune-mediated injury or limit injury through targeted interventions.

Multiple routes to help you roam: A comparison of training interventions to improve cognitive-motor dual-tasking in healthy older adults.

Cognitive-motor dual-tasking is a complex activity that predicts falls risk and cognitive impairment in older adults. Cognitive and physical training can both lead to improvements in dual-tasking; however, less is known about what mechanisms underlie these changes. To investigate this, 33 healthy older adults were randomized to one of three training arms: Executive function (EF; n = 10), Aerobic Exercise (AE; n = 10), Gross Motor Abilities (GMA; n = 13) over 12 weeks (1 h, 3×/week). Single and dual-task performance (gait speed, m/s; cognitive accuracy, %) was evaluated before and after training, using the 2-back as concurrent cognitive load. Training arms were designed to improve cognitive and motor functioning, through different mechanisms (i.e., executive functioning - EF, cardiorespiratory fitness - CRF, and energy cost of walking - ECW). Compared to baseline, we observed few changes in dual-task gait speed following training (small effect). However, dual-task cognitive accuracy improved significantly, becoming facilitated by walking (large effect). There were no differences in the magnitude of improvements across training arms. We also found that older adults with lower cognitive ability (i.e., MoCA score < 26; n = 14) improved more on the dual-task cognitive accuracy following training, compared to older adults with higher cognitive ability (i.e., MoCA ≥26; n = 18). Taken together, the results suggest that regardless of the type of intervention, training appears to strengthen cognitive efficiency during dual-tasking, particularly for older adults with lower baseline cognitive status. These gains appear to occur via different mechanisms depending on the form of intervention. Implications of this research are paramount, as we demonstrate multiple routes for improving cognitive-motor dual-tasking in older adults, which may help reduce risk of cognitive impairment.

Expression of DEspR in acute intracerebral hemorrhage.

OBJECTIVES: Neuroinflammation and secondary injury play a central role in the pathophysiology of intracerebral hemorrhage. The dual endothelin-1/VEGFsignal-peptide receptor (DEspR) has been reported to mediate the inflammatory response after acute brain injury in a rodent model. We performed a pilot study to assess the expression of DEspR on circulating leukocytes in patients who presented with spontaneous intracerebral hemorrhage (ICH). MATERIALS AND METHODS: We performed a prospective observational study of patients presenting to two academic medical centers with ICH. Normal healthy volunteers (NHV) were also recruited for sample analysis. Whole blood was obtained, and flow cytometry was performed to examine DEspR expression on neutrophils, monocytes, and lymphocytes. RESULTS: A total of 19 patients were included in analysis. Median ICH volume was 39 cm3 [IQR 19 cm3, 73 cm3] and median ICH score was 2 [IQR 2, 3]. DEspR expression was more abundant on neutrophils (median 2.4% [IQR 0.5%, 5.8%], p = 0.0064) and monocytes (median 4.4% [IQR 1.7%, 15.8%], p = 0.003) relative to lymphocytes (median 0.9% [IQR 0.2%, 3.3%]). ICH patients had higher DEspR expression in all leukocytes relative to NHV (p < 0.05 for all). Among ICH patients, those with a medical history of hypertension showed higher DEspR expression on neutrophils and monocytes (p = 0.018) compared to those without hypertension. CONCLUSIONS: In this pilot study, DEspR is expressed on circulating neutrophils and monocytes in humans after ICH, with higher levels of expression in those with hypertension. Future work in larger cohorts should examine the relationship of DEspR expression with neuroinflammatory endpoints and long-term outcome.

Implementing Technology Literacy Programs in Retirement Homes and Residential Care Facilities: Conceptual Framework.

BACKGROUND: The COVID-19 pandemic caused widespread societal disruption, with governmental stay-at-home orders resulting in people connecting more via technology rather than in person. This shift had major impacts on older adult residents staying in retirement homes and residential care facilities, where they may lack the technology literacy needed to stay connected. The enTECH Computer Club from the University of Waterloo in Ontario, Canada created a knowledge translation toolkit to support organizations interested in starting technology literacy programs (TLPs) by providing guidance and practical tips. OBJECTIVE: This paper aimed to present a framework for implementing TLPs in retirement homes and residential care facilities through expanding on the knowledge translation toolkit and the framework for person-centered care. METHODS: Major concepts relating to the creation of a TLP in retirement homes and residential care facilities were extracted from the enTECH knowledge translation toolkit. The domains from the framework for person-centered care were modified to fit a TLP context. The concepts identified from the toolkit were sorted into the three framework categories: "structure," "process," and "outcome." Information from the knowledge translation toolkit were extracted into the three categories and synthesized to form foundational principles and potential actions. RESULTS: All 13 domains from the framework for person-centered care were redefined to shift the focus on TLP implementation, with 7 domains under "structure," 4 domains under "process," and 2 domains under "outcome." Domains in the "structure" category focus on developing an organizational infrastructure to deliver a successful TLP; 10 foundational principles and 25 potential actions were identified for this category. Domains in the "process" category focus on outlining procedures taken by stakeholders involved to ensure a smooth transition from conceptualization into action; 12 foundational principles and 9 potential actions were identified for this category. Domains in the "outcome" category focus on evaluating the TLP to consider making any improvements to better serve the needs of older adults and staff; 6 foundational principles and 6 potential actions were identified for this category. CONCLUSIONS: Several domains and their foundational principles and potential actions from the TLP framework were found to be consistent with existing literatures that encourage taking active steps to increase technology literacy in older adults. Although there may be some limitations to the components of the framework with the current state of the pandemic, starting TLPs in the community can yield positive outcomes that will be beneficial to both older adult participants and the organization in the long term.

Risk factors for neurological complications in left-sided infective endocarditis.

BACKGROUND AND PURPOSE: Neurological complications following infective endocarditis (IE) directly contribute to long-term morbidity. We examined the risk factors for different neurological complications of left-sided IE. METHODS: Using a database of consecutive adults admitted to a health system with left-sided IE from 2015 to 2019, the frequency of cerebral infarcts, intraparenchymal hemorrhage, cerebral microbleeds (CMB), mycotic aneurysm, and encephalopathy was determined. Variables with significant differences comparing each neurological complication (p < 0.1) were entered into regression models along with age to determine predictors. RESULTS: 211 patients with mean age 54 (±18) years, and 69 (33%) females were included. Infarcts were found in 118 (56%) patients, intraparenchymal hemorrhage was found in 17 (8%) patients, CMB were found in 58 (27%) patients, mycotic aneurysms were found in 22 (10%) patients, and encephalopathy occurred in 16 (8%) patients. In multivariable models, vegetation size ≥15 mm was associated with a higher risk of infarcts (aOR 2.26, 95% CI (1.12-4.57)), and the presence of a mycotic aneurysm was a risk factor for intraparenchymal hemorrhage (aOR 18.79, 95% CI (3.97-88.97)). Prosthetic valves (aOR 2.89, 95% CI (1.11-7.54)) and Staphylococcus aureus infection (aOR 3.50, 95% CI (1.08-11.36)) were associated with CMB. No risk factors emerged as predictors of encephalopathy. CONCLUSIONS: Large vegetation size is associated with stroke in patients with IE. Mycotic aneurysms are found at a higher frequency in young patients and are the primary cause of intraparenchymal hemorrhage. CMB may be related to prosthetic valves and Staphylococcus aureus infection.

Neurological Complications and Clinical Outcomes of Infective Endocarditis.

OBJECTIVES: The aim of this study is to explore the clinical features associated with neurological complications of infective endocarditis (IE) and to assess the impact of neurological complications on clinical outcomes. MATERIALS AND METHODS: The frequency of relevant clinical features was compared in a case series of IE patients with and without neurological complications admitted to a single health care system from 2015 to 2019. Variables with significant differences (p ≤ 0.05) in baseline characteristics in univariate logistic regression models were entered into multivariable models along with age to determine associations with neurological complications, unfavorable discharge outcomes (modified Rankin score ≥ 3), and in-hospital mortality. RESULTS: 260 patients with a mean age of 51 (±18) years and 103 (40%) females were included. Neurological complications occurred in 165 (63%) patients, with the most common being septic emboli (66 patients, 25%). In the regression analyses, antiplatelet usage (aOR 1.87, 95% CI [1.05-3.32]) and mitral valve vegetations (aOR 2.66, 95% CI [1.22-5.79]) were independently associated with neurological complications. Territorial infarction (aOR 4.13, 95% CI [1.89-9.06]) and encephalopathy (aOR 3.95, 95% CI [1.19-13.05]) were associated with an increased risk of unfavorable outcome, while cardiac surgery was associated with a lower risk of both unfavorable outcome (aOR 0.40, 95% CI [0.22-0.71]) and in-hospital mortality (aOR 0.18, 95% CI [0.09-0.35]). CONCLUSIONS: Neurological complications are common in IE patients and are associated with mitral valve endocarditis and antiplatelet usage. Of the neurological complications, territorial infarcts and encephalopathy are associated with unfavorable discharge outcomes.