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PLoS Biology Jun 2024Loss of synapses between spiral ganglion neurons and inner hair cells (IHC synaptopathy) leads to an auditory neuropathy called hidden hearing loss (HHL) characterized...
Loss of synapses between spiral ganglion neurons and inner hair cells (IHC synaptopathy) leads to an auditory neuropathy called hidden hearing loss (HHL) characterized by normal auditory thresholds but reduced amplitude of sound-evoked auditory potentials. It has been proposed that synaptopathy and HHL result in poor performance in challenging hearing tasks despite a normal audiogram. However, this has only been tested in animals after exposure to noise or ototoxic drugs, which can cause deficits beyond synaptopathy. Furthermore, the impact of supernumerary synapses on auditory processing has not been evaluated. Here, we studied mice in which IHC synapse counts were increased or decreased by altering neurotrophin 3 (Ntf3) expression in IHC supporting cells. As we previously showed, postnatal Ntf3 knockdown or overexpression reduces or increases, respectively, IHC synapse density and suprathreshold amplitude of sound-evoked auditory potentials without changing cochlear thresholds. We now show that IHC synapse density does not influence the magnitude of the acoustic startle reflex or its prepulse inhibition. In contrast, gap-prepulse inhibition, a behavioral test for auditory temporal processing, is reduced or enhanced according to Ntf3 expression levels. These results indicate that IHC synaptopathy causes temporal processing deficits predicted in HHL. Furthermore, the improvement in temporal acuity achieved by increasing Ntf3 expression and synapse density suggests a therapeutic strategy for improving hearing in noise for individuals with synaptopathy of various etiologies.
Topics: Animals; Hair Cells, Auditory, Inner; Synapses; Neurotrophin 3; Mice; Auditory Threshold; Evoked Potentials, Auditory; Reflex, Startle; Auditory Perception; Spiral Ganglion; Female; Male; Hearing Loss, Hidden
PubMed: 38935589
DOI: 10.1371/journal.pbio.3002665 -
STAR Protocols Jun 2024Here, we present a protocol to perform CRISPR-Cas9 genome editing in human resting primary natural killer (NK) and NK-92 cells. We describe steps for guide RNA...
Here, we present a protocol to perform CRISPR-Cas9 genome editing in human resting primary natural killer (NK) and NK-92 cells. We describe steps for guide RNA selection, ribonucleoprotein (RNP) complex formation, delivery via Nucleofection, and analysis of CRISPR edits to assess editing efficiencies. This protocol offers a tool for functional studies in NK cells, paving the way for potential applications in immunotherapy and beyond. We also discuss limitations such as off-target effects and cell-type-specific considerations.
PubMed: 38935511
DOI: 10.1016/j.xpro.2024.103123 -
JMIR Formative Research Jun 2024Serious illness conversations may help patients avoid unwanted treatments. We previously piloted the telehealth Serious Illness Care Program (SICP) for older adults with...
BACKGROUND
Serious illness conversations may help patients avoid unwanted treatments. We previously piloted the telehealth Serious Illness Care Program (SICP) for older adults with acute myeloid leukemia and myelodysplastic syndrome.
OBJECTIVE
In this study, we aimed to understand the experience of the telehealth SICP from the clinician's perspective.
METHODS
We studied 10 clinicians who delivered the telehealth SICP to 20 older adults with acute myeloid leukemia or myelodysplastic syndrome. Quantitative outcomes included confidence and acceptability. Confidence was measured using a 22-item survey (range 1-7; a higher score is better). Acceptability was measured using an 11-item survey (5-point Likert scale). Hypothesis testing was performed at α=.10 (2-tailed) due to the pilot nature and small sample size. Clinicians participated in audio-recorded qualitative interviews at the end of the study to discuss their experience.
RESULTS
A total of 8 clinicians completed the confidence measure and 7 clinicians completed the acceptability measure. We found a statistically significant increase in overall confidence (mean increase of 0.5, SD 0.6; P=.03). The largest increase in confidence was in helping families with reconciliation and goodbye (mean 1.4, SD 1.5; P=.04). The majority of clinicians agreed that the format was simple (6/7, 86%) and easy to use (6/7, 86%). Clinicians felt that the telehealth SICP was effective in understanding their patients' values about end-of-life care (7/7, 100%). A total of three qualitative themes emerged: (1) the telehealth SICP deepened relationships and renewed trust; (2) each telehealth SICP visit felt unique and personal in a positive way; and (3) uninterrupted, unrushed time optimized the visit experience.
CONCLUSIONS
The telehealth SICP increased confidence in having serious illness conversations while deepening patient-clinician relationships.
TRIAL REGISTRATION
ClinicalTrials.gov NCT04745676; https://www.clinicaltrials.gov/study/NCT04745676.
PubMed: 38935428
DOI: 10.2196/58503 -
BJS Open May 2024Posthepatectomy liver failure remains a potentially life-threatening complication after hepatectomy. Soluble suppression of tumourigenicity 2 is an injury-related...
BACKGROUND
Posthepatectomy liver failure remains a potentially life-threatening complication after hepatectomy. Soluble suppression of tumourigenicity 2 is an injury-related biomarker. The aim of the study was to assess soluble suppression of tumourigenicity 2 elevation after hepatectomy and whether it can predict posthepatectomy liver failure.
METHODS
This was a single-centre retrospective study including all patients who underwent a liver resection between 2015 and 2019. Plasma concentrations of soluble suppression of tumourigenicity 2 were measured before surgery and at postoperative days 1, 2, 5 and 7. Posthepatectomy liver failure was defined according to the International Study Group of Liver Surgery and the morbidity rate was graded according to the Clavien-Dindo classification.
RESULTS
A total of 173 patients were included (75 underwent major and 98 minor resection); plasma levels of soluble suppression of tumourigenicity 2 increased from 43.42 (range 18.69-119.96) pg/ml to 2622.23 (range 1354.18-4178.27) pg/ml on postoperative day 1 (P < 0.001). Postoperative day 1 soluble suppression of tumourigenicity 2 concentration accurately predicted posthepatectomy liver failure ≥ grade B (area under curve = 0.916, P < 0.001) and its outstanding performance was not affected by underlying disease, liver pathological status and extent of resection. The cut-off value, sensitivity, specificity, positive predictive value and negative predictive value of postoperative day 1 soluble suppression of tumourigenicity 2 in predicting posthepatectomy liver failure ≥ grade B were 3700, 92%, 85%, 64% and 97% respectively. Soluble suppression of tumourigenicity 2high patients more frequently experienced posthepatectomy liver failure ≥ grade B (64.3% (n = 36) versus 2.6% (n = 3)) and Clavien-Dindo IIIa higher morbidity rate (23.2% (n = 13) versus 5.1% (n = 6)) compared with soluble suppression of tumourigenicity 2low patients.
CONCLUSIONS
Soluble suppression of tumourigenicity 2 may be a reliable predictor of posthepatectomy liver failure ≥ grade B as early as postoperative day 1 for patients undergoing liver resection. Its role in controlling hepatic injury/regeneration needs further investigation. Registration number: ChiCTR-OOC-15007210 (www.chictr.org.cn/).
Topics: Humans; Male; Female; Hepatectomy; Retrospective Studies; Middle Aged; Liver Failure; Postoperative Complications; Aged; Biomarkers; Adult; Liver Neoplasms; Predictive Value of Tests
PubMed: 38935425
DOI: 10.1093/bjsopen/zrae043 -
JMIR Research Protocols Jun 2024Individuals at high risk for type 2 diabetes are also at an increased risk for developing cardiovascular disease (CVD). Although there are separate trials examining the...
Effects of Lifestyle Interventions on Cardiovascular Disease Risk and Risk Factors Among Individuals at High Risk for Type 2 Diabetes: Protocol for a Systematic Review and Meta-Analysis of Randomized Controlled Trials.
BACKGROUND
Individuals at high risk for type 2 diabetes are also at an increased risk for developing cardiovascular disease (CVD). Although there are separate trials examining the effects of lifestyle interventions on absolute CVD risk among people at high risk for type 2 diabetes, a comprehensive evidence synthesis of these trials is lacking.
OBJECTIVE
We will systematically synthesize the evidence on the effects of lifestyle interventions in reducing absolute CVD risk and CVD risk factors among people at high risk for type 2 diabetes.
METHODS
We adhered to the PRISMA-P (Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols) statement in reporting the details of this protocol. Randomized controlled trials of diabetes prevention that examined the effects of lifestyle interventions for at least 6 months on absolute CVD risk and CVD risk factors among individuals at high risk for type 2 diabetes will be eligible. We will systematically search the MEDLINE, Embase, PsycINFO, CENTRAL, and Scopus databases and ClinicalTrials.gov using a mix of Medical Subject Headings and text words. Two authors will independently screen the abstract and title of the articles retrieved from the search, followed by full-text reviews using the inclusion and exclusion criteria and data extraction from the eligible studies. Article screening and data extraction will be performed in the Covidence software. The primary outcome will be the changes in absolute 10-year CVD risk, as estimated by risk prediction models. The secondary outcomes are the changes in CVD risk factors, including behavioral, clinical, biochemical, and psychosocial risk factors, and incidence of type 2 diabetes.
RESULTS
An initial database search was conducted in July 2023. After screening 1935 articles identified through the database search, 42 articles were considered eligible for inclusion. It is anticipated that the study findings will be submitted for publication in a peer-reviewed journal by the end of 2024.
CONCLUSIONS
This study will provide up-to-date, systematically synthesized evidence on the effects of lifestyle interventions on absolute CVD risk and CVD risk factors among individuals at high risk for type 2 diabetes.
TRIAL REGISTRATION
PROSPERO CRD42023429869; https://tinyurl.com/59ajy7rw.
INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID)
DERR1-10.2196/53517.
Topics: Humans; Diabetes Mellitus, Type 2; Cardiovascular Diseases; Systematic Reviews as Topic; Randomized Controlled Trials as Topic; Meta-Analysis as Topic; Risk Factors; Life Style; Risk Reduction Behavior; Female; Male; Heart Disease Risk Factors
PubMed: 38935416
DOI: 10.2196/53517 -
JAMA Network Open Jun 2024Varenicline is the most effective sole pharmacotherapy for smoking cessation. If used in combination with nicotine replacement therapy (NRT), cessation rates may be... (Randomized Controlled Trial)
Randomized Controlled Trial
IMPORTANCE
Varenicline is the most effective sole pharmacotherapy for smoking cessation. If used in combination with nicotine replacement therapy (NRT), cessation rates may be further improved, but the efficacy and safety of the combination need to be evaluated.
OBJECTIVE
To examine whether hospitalized smokers treated with varenicline and NRT lozenges achieve higher prolonged smoking abstinence rates compared with those treated with varenicline alone.
DESIGN, SETTING, AND PARTICIPANTS
A double-blind, placebo-controlled randomized clinical trial was conducted in adult medical or surgical inpatients of 5 Australian public hospitals with a history of smoking 10 cigarettes or more per day, interested in quitting, and available for 12-month follow-up between May 1, 2019, and May 1, 2021 (final 12-month data collection in May 2022). Data analysis was performed from June 1 to August 30, 2023.
INTERVENTIONS
A 12-week varenicline regimen was initiated during hospitalization at standard doses in all participants. Participants were randomized to additionally use NRT (2 mg) or placebo lozenges if there was an urge to smoke. Behavioral support (Quitline) was offered to all participants.
MAIN OUTCOMES AND MEASURES
The primary outcome was biochemically verified sustained abstinence at 6 months. Secondary outcomes included self-reported prolonged abstinence, 7-day point prevalence abstinence (3, 6, and 12 months), and medicine-related adverse events.
RESULTS
A total of 320 participants (mean [SD] age, 52.5 [12.1] years; 183 [57.2%] male) were randomized. The conduct of biochemical verification was affected by COVID-19 restrictions; consequently, the biochemically verified abstinence in the intervention vs control arms (18 [11.4%] vs 16 [10.1%]; odds ratio [OR], 1.14; 95% CI, 0.56-2.33) did not support the combination therapy. The secondary outcomes in the intervention vs control arms of 7-day point prevalence abstinence at 6 months (54 [34.2%] vs 37 [23.4%]; OR, 1.71; 95% CI, 1.04-2.80), prolonged abstinence at 12 months (47 [29.9%] vs 30 [19.1%]; OR, 1.77; 95% CI, 1.05-3.00), and 7-day point prevalence abstinence at 12-months (48 [30.6%] vs 31 [19.7%]; OR, 1.79; 95% CI, 1.07-2.99) significantly improved with the combination therapy. The self-reported 6-month prolonged abstinence (61 [38.6%] vs 47 [29.7%]; OR, 1.49; 95% CI, 0.93-2.39) favored the combination therapy but was not statistically significant. Medicine-related adverse events were similar in the 2 groups (102 [74.5%] in the intervention group vs 86 [68.3%] in the control group).
CONCLUSIONS AND RELEVANCE
In this randomized clinical trial of the combination of varenicline and NRT lozenges in hospitalized adult daily smokers, the combination treatment improved self-reported abstinence compared with varenicline alone, without compromising safety, but it did not improve biochemically validated abstinence.
TRIAL REGISTRATION
anzctr.org.au Identifier: ACTRN12618001792213.
Topics: Humans; Varenicline; Male; Female; Smoking Cessation; Tobacco Use Cessation Devices; Middle Aged; Double-Blind Method; Adult; Smoking Cessation Agents; Australia; Hospitalization; Smokers; Aged; Treatment Outcome; Nicotine Replacement Therapy
PubMed: 38935378
DOI: 10.1001/jamanetworkopen.2024.18120 -
JAMA Network Open Jun 2024The US has the highest maternal mortality rate among developed countries. The Centers for Disease Control and Prevention deems nearly all of these deaths preventable,... (Observational Study)
Observational Study
IMPORTANCE
The US has the highest maternal mortality rate among developed countries. The Centers for Disease Control and Prevention deems nearly all of these deaths preventable, especially those attributable to mental health conditions. Coordination between US health care and social service systems could help further characterize circumstances and risks associated with perinatal suicide mortality.
OBJECTIVE
To examine contextual and individual precipitating circumstances and risks associated with perinatal suicide.
DESIGN, SETTING, AND PARTICIPANTS
This cross-sectional observational study used a convergent mixed methods design to explore factors contributing to maternal suicides and deaths of undetermined intent (hereinafter, undetermined deaths) identified in National Violent Death Reporting System (NVDRS) data for January 1, 2003, to December 31, 2021. Analyses included decedents who were aged 10 to 50 years and pregnant or post partum at death (collectively, the perinatal group) and demographically matched female decedents who were not pregnant or recently pregnant (nonperinatal group) at death. Analyses were performed between December 2022 and December 2023.
EXPOSURES
Pregnancy status at death (perinatal or nonperinatal).
MAIN OUTCOMES AND MEASURES
The main outcomes included contributing circumstances associated with suicides and undetermined deaths cited in coroner, medical examiner, or law enforcement case narratives. The study examined quantitative differences between groups using a matched analysis and characterized key themes of salient suicide circumstances using qualitative content analysis.
RESULTS
This study included 1150 perinatal decedents identified in the NVDRS: 456 (39.6%) were pregnant at death, 203 (17.7%) were pregnant within 42 days of death, and 491 (42.7%) were pregnant within 43 to 365 days before death, yielding 694 postpartum decedents. The nonperinatal comparison group included 17 655 female decedents aged 10 to 50 years. The mean (SD) age was 29.1 (7.4) years for perinatal decedents and 35.8 (10.8) years for nonperinatal decedents. Compared with matched nonperinatal decedents, perinatal decedents had higher odds of the following identified contributing circumstances: intimate partner problems (IPPs) (odds ratio [OR], 1.45 [95% CI, 1.23-1.72]), recent argument (OR, 1.33 [95% CI, 1.09-1.61]), depressed mood (OR, 1.39 [95% CI, 1.19-1.63]), substance abuse or other abuse (OR, 1.21 [95% CI, 1.03-1.42]), physical health problems (OR, 1.37 [95% CI, 1.09-1.72]), and death of a family member or friend (OR, 1.47 [95% CI, 1.06-2.02]). The findings of the qualitative analysis emphasized the importance of mental health and identified 128 decedents (12.4%) with postpartum depression.
CONCLUSIONS AND RELEVANCE
This study provides insights into complex factors surrounding maternal suicide, and it highlights opportunities for further research to understand long-term consequences of perinatal mental health. These findings also underscore the need for targeted evidence-based interventions and effective policies targeting mental health, substance use, and IPPs to prevent maternal suicide and enhance maternal health outcomes.
Topics: Humans; Female; Pregnancy; Cross-Sectional Studies; Adult; Suicide; United States; Adolescent; Middle Aged; Young Adult; Child; Risk Factors; Maternal Mortality; Perinatal Mortality
PubMed: 38935375
DOI: 10.1001/jamanetworkopen.2024.18887 -
International Journal of Implant... Jun 2024This propensity score matching, multicenter, cross-sectional study was performed to examine the effects of various prosthetic methods for dental clinic outpatients with...
Effects of various prosthetic methods for patients with Kennedy Class I partial edentulism on oral hypofunction, subjective symptoms, and oral health-related quality of life.
PURPOSE
This propensity score matching, multicenter, cross-sectional study was performed to examine the effects of various prosthetic methods for dental clinic outpatients with Kennedy Class I partial edentulism (KCIPE) on oral hypofunction, subjective frailty symptoms, and oral health-related quality of life (QOL).
METHODS
Patients (n = 348) were classified into the following three groups for analysis: NT, patients with natural dentition providing intermaxillary contact in four occlusal supporting zones; RPD, patients with KCIPE who received removable partial dentures; and ISFP, patients with KCIPE who received implant-supported fixed prostheses. Participants' basic characteristics were recorded, and oral function tests were conducted. Subjective symptoms of physical and oral frailty were investigated via questionnaire. Oral health-related QOL was assessed using the Japanese short version of the Oral Health Impact Profile (OHIP-JP16). Propensity score matching was performed to adjust for patient background factors that could influence oral hypofunction in each group.
RESULTS
Compared with the ISFP group, the RPD group had significantly higher rates of poor oral hygiene, reduced occlusal force, decreased masticatory function, and declines in swallowing function and oral hypofunction; the odds ratio for oral hypofunction was 4.67. Compared with the ISFP group, the RPD group had significantly greater subjective symptoms of physical frailty and oral frailty, as well as higher OHIP scores.
CONCLUSIONS
Prosthetic treatment of KCIPE affected oral hypofunction, subjective frailty symptoms, and oral health-related QOL in dental clinic outpatients.
Topics: Humans; Quality of Life; Cross-Sectional Studies; Male; Female; Middle Aged; Oral Health; Jaw, Edentulous, Partially; Denture, Partial, Removable; Aged; Surveys and Questionnaires; Propensity Score; Dental Prosthesis, Implant-Supported; Denture, Partial, Fixed; Adult
PubMed: 38935335
DOI: 10.1186/s40729-024-00555-w -
European Journal of Sport Science Jun 2024This review and meta-analysis aimed to describe the current rugby-7s injury epidemiological literature by examining injury data from both sexes, all levels of play, and... (Review)
Review
This review and meta-analysis aimed to describe the current rugby-7s injury epidemiological literature by examining injury data from both sexes, all levels of play, and their associated risk factors. Studies published up until March 2024 were included. These studies were retrieved from six databases using search terms related to rugby-7s or sevens, tackle, collision, collision sport, injury, athlete, incidence rate, mechanism, and risk factor. Only peer-reviewed original studies using prospective or retrospective cohort designs with a clearly defined rugby-7s sample were considered. Included studies needed to report one injury outcome variable. Non-English and qualitative studies; reviews, conference papers, and abstracts were excluded. Twenty studies were included. The meta-analysis used the DerSimonian-Laird continuous random-effects method to calculate the pooled estimated means and 95% confidence interval. The estimated mean injury incidence rate for men was 108.5/1000 player-hours (95% CI: 85.9-131.0) and 76.1/1000 player-hours (95% CI: 48.7-103.5) for women. The estimated mean severity for men was 33.9 days (95% CI: 20.7-47.0) and 44.2 days (95% CI: 32.1-56.3) for women. Significantly more match injuries occurred in the second half of matches, were acute, located at the lower limb, diagnosed as joint/ligament, and resulted from being tackled. Fatigue, player fitness, and previous injuries were associated with an increased risk of injury. There were no statistically significant differences between women's and men's injury profiles. However, the inherent cultural and gendered factors which divide the two sports should not be ignored. The findings from this review will help pave the way forward beyond the foundational stages of injury prevention research in rugby-7s.
PubMed: 38935238
DOI: 10.1002/ejsc.12156 -
Journal of the American Heart... Jun 2024Women are known to be disadvantaged compared with men in the early links of the Chain of Survival, receiving fewer bystander interventions. We aimed to describe...
BACKGROUND
Women are known to be disadvantaged compared with men in the early links of the Chain of Survival, receiving fewer bystander interventions. We aimed to describe sex-based disparities in emergency medical service resuscitation quality and processes of care for out-of-hospital cardiac arrest.
METHODS AND RESULTS
We conducted a retrospective analysis of patients who were nontraumatic with out-of-hospital cardiac arrest aged ≥16 years where resuscitation was attempted between March 2019 and June 2023. We investigated 18 routinely captured performance metrics and performed adjusted logistic and quantile regression analyses to assess sex-based differences in these metrics. During the study period, 10 161 patients with out-of-hospital cardiac arrest met the eligibility criteria, of whom 3216 (32%) were women. There were no clinically relevant sex-based differences observed in regard to external cardiac compressions; however, women were 34% less likely to achieve a systolic blood pressure >100 mm Hg on arrival at the hospital (adjusted odds ratio [AOR], 0.66 [95% CI, 0.47-0.92]). Furthermore, women had a longer time to 12-lead ECG acquisition after return of spontaneous circulation (median adjusted difference, 1.00 minute [95% CI, 0.38-1.62]) and 33% reduced odds of being transported to a 24-hour percutaneous coronary intervention-capable facility (AOR, 0.67 [95% CI, 0.49-0.91]). Resuscitation was also terminated sooner for women compared with men (median adjusted difference, -4.82 minutes [95% CI, -6.77 to -2.87]).
CONCLUSIONS
Although external cardiac compression quality did not vary by sex, significant sex-based disparities were seen in emergency medical services processes of care following out-of-hospital cardiac arrest. Further investigation is required to elucidate the underlying causes of these differences and examine their influence on patient outcomes.
PubMed: 38934889
DOI: 10.1161/JAHA.123.033974