Genomic origin, fragmentomics, and transcriptional properties of long cell-free DNA molecules in human plasma.

Recent studies have revealed an unexplored population of long cell-free DNA (cfDNA) molecules in human plasma using long-read sequencing technologies. However, the biological properties of long cfDNA molecules (>500 bp) remain largely unknown. To this end, we have investigated the origins of long cfDNA molecules from different genomic elements. Analysis of plasma cfDNA using long-read sequencing reveals an uneven distribution of long molecules from across the genome. Long cfDNA molecules show overrepresentation in euchromatic regions of the genome, in sharp contrast to short DNA molecules. We observe a stronger relationship between the abundance of long molecules and mRNA gene expression levels, compared with short molecules (Pearson's r = 0.71 vs. -0.14). Moreover, long and short molecules show distinct fragmentation patterns surrounding CpG sites. Leveraging the cleavage preferences surrounding CpG sites, the combined cleavage ratios of long and short molecules can differentiate patients with hepatocellular carcinoma (HCC) from non-HCC subjects (AUC = 0.87). We also investigated knockout mice in which selected nuclease genes had been inactivated in comparison with wild-type mice. The proportion of long molecules originating from transcription start sites are lower in Dffb-deficient mice but higher in Dnase1l3-deficient mice compared with that of wild-type mice. This work thus provides new insights into the biological properties and potential clinical applications of long cfDNA molecules.

Accurate identification of structural variations from cancer samples.

Structural variations (SVs) are commonly found in cancer genomes. They can cause gene amplification, deletion and fusion, among other functional consequences. With an average read length of hundreds of kilobases, nano-channel-based optical DNA mapping is powerful in detecting large SVs. However, existing SV calling methods are not tailored for cancer samples, which have special properties such as mixed cell types and sub-clones. Here we propose the Cancer Optical Mapping for detecting Structural Variations (COMSV) method that is specifically designed for cancer samples. It shows high sensitivity and specificity in benchmark comparisons. Applying to cancer cell lines and patient samples, COMSV identifies hundreds of novel SVs per sample.

Evaluation of activities of daily living using an electronic version of the Longshi Scale in patients with stroke: reliability, consistency, and preference.

BACKGROUND: The Longshi Scale is a pictorial assessment tool for evaluating activities of daily living (ADL) in patients with stroke. The paper-based version presents challenges; thus, the WeChat version was created to enhance accessibility. Herein, we aimed to validate the inter-rater and test-retest reliabilities of the WeChat version of the Longshi Scale and explore its potential clinical applications. METHODS: We recruited 115 patients with stroke in the study. The ADL results of each patient were assessed using both the WeChat and paper-based version of the Longshi Scale; each evaluation was conducted by 28 health professionals and 115 caregivers separately. To explore the test-retest reliability of the WeChat version, 22 patients were randomly selected and re-evaluated by health professionals using the WeChat version. All evaluation criteria were recorded, and all evaluators were surveyed to indicate their preference between the two versions. RESULTS: Consistency between WeChat and the paper-based Longshi Scale was high for ADL scores by health professionals (ICC2,1 = 0.803-0.988) and caregivers (ICC2,1 = 0.845-0.983), as well as for degrees of disability (κw = 0.870 by professionals; κw = 0.800 by caregivers). Bland-Altman analysis showed no significant discrepancies. The WeChat version exhibited good test-retest reliability (κw = 0.880). The WeChat version showed similar inter-rater reliability in terms of the ADL score evaluated using the paper-based version (ICC2,1 = 0.781-0.941). The time to complete assessments did not differ significantly, although the WeChat version had a shorter information entry time (P < 0.001, 95% confidence interval: -43.463 to -15.488). Health professionals favored the WeChat version (53.6%), whereas caregivers had no significant preference. CONCLUSIONS: The WeChat version of the Longshi Scale is reliable and serves as a suitable alternative for health professionals and caregivers to assess ADL levels in patients with stroke. The WeChat version of the Longshi Scale is considered user-friendly by health professionals, although it is not preferred by caregivers. TRIAL REGISTRATION: This study was approved by the Ethics Committee of the Second People's Hospital of Shenzhen (approval number: 20210812003-FS01) and registered on the Clinical Trial Register Center website: clinicaltrials.gov on January 31, 2022 (registration no.: NCT05214638).

Effectiveness of educational interventions in reducing the stigma of healthcare professionals and healthcare students towards mental illness: A systematic review and meta-analysis.

AIM: To examine the effectiveness of educational interventions in reducing stigma among healthcare professionals and students towards people with mental illness. DESIGN: A systematic review and meta-analysis of randomized controlled trials (RCTs) and cluster RCTs. DATA SOURCES: Articles published from database inception to October 2023 were systematically searched from seven databases (CINAHL, Embase, ProQuest Dissertations and Theses Global, PsycINFO, PubMed, Scopus, Web of Science), following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. METHODS: Random-effect meta-analyses were conducted. Heterogeneity was evaluated using the I2 statistics and Cochran's Q chi-squared test. A quality appraisal conducted at the study level used the Cochrane risk of bias tool and an outcome-level quality assessment utilized the Grades of Recommendation, Assessment, Development and Evaluation Approach. Publication bias was assessed using the funnel plot. RESULTS: Twenty-five articles were included in this review. Meta-analysis reported statistically significant medium and small effect sizes for attitudes towards mental illness and attitudes towards people with mental illness respectively, showing the association between educational interventions and improved attitudes among healthcare professionals and students. However, a statistically non-significant effect was reported for knowledge of mental illness. Subgroup analyses indicated that face-to-face and contact-based interventions were particularly effective at reducing stigma. Notably, single-session interventions were just as effective as multiple sessions, suggesting a potential for resource-efficient approaches. CONCLUSION: Educational interventions demonstrate promise in fostering more positive attitudes towards mental health issues. Future research should aim to determine the long-term effects of these interventions and include patient feedback on the stigmatizing behaviours of healthcare professionals and students, to holistically evaluate the effect of interventions. NO PATIENT OR PUBLIC CONTRIBUTION: This study is a secondary review and does not require relevant contributions from patients or the public. WHAT DOES THIS PAPER CONTRIBUTE TO THE WIDER GLOBAL CLINICAL COMMUNITY?: Face-to-face contact-based educational sessions have proven to be the most effective. Reinforcing learning may be achieved through a series of repeated single-session interventions.

A qualitative systematic review of adolescent's perceptions of sleep: Awareness of, barriers to and strategies for promoting healthy sleep patterns.

AIMS: To consolidate adolescents' perspectives regarding various aspects of sleep and offer insights to promote healthier sleep habits during their critical developmental years. METHODS/DATA SOURCES: Six electronic databases (PubMed, CINAHL, Embase, Scopus, PsycINFO and Web of Science) were searched from their inception dates to June 2023. Data were extracted and meta-summarised using Sandelowski and Barroso's approach and synthesised using Thomas and Harden's thematic analysis framework. RESULTS: Meta-synthesis from 11 peer-reviewed published studies identified four main themes: (1) Awareness and understanding of sleep's significance, (2) The shadows and radiance of slumber, (3) Traversing the sleepscape: trouble bubbles and (4) Illuminating the path: Guiding lights to enhanced sleep. CONCLUSION/IMPLICATIONS: Our review findings suggest a lack of awareness and guidance regarding the significance of sleep and the cultivation of good sleep habits among adolescents. Identified barriers to adequate sleep encompass various factors, including overthinking, poor habits, family/environmental influences, extensive technology use, peer pressure, the fear of missing out, academic demands and involvement in extracurricular activities. Strategies to improve adolescents' sleep health involve multiple sleep strategies, including sleep education, workshops/seminars, parental involvement, incorporating digital well-being practices, the promotion of relaxation techniques and the provision of essential resources. Prioritising sleep health and implementing targeted interventions are key steps to empower adolescents, create supportive environments and shape a healthier future generation. Future research endeavours should focus on evaluating the effectiveness of interventions and exploring the influence of cultural factors. IMPACT: There exists a notable lack of awareness and guidance regarding the significance of sleep and the cultivation of good sleep habits among adolescents. Barriers to achieving adequate sleep among adolescents include overthinking, poor habits, family/environmental influences, extensive technology use, peer pressure, the fear of missing out, academic demands and involvement in extracurricular activities. The collaboration between healthcare institutions, professionals and educational institutions is crucial to facilitate (1) the implementation of sleep education workshops/seminars targeting adolescents, (2) increased parental involvement and role-modelling to instil good sleep practices among adolescents and (3) enhanced integration of digital well-being practices, the promotion of relaxation techniques and accessibility to essential sleep hygiene resources. REPORTING METHOD: Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution. TRIAL AND PROTOCOL REGISTRATION: This review was registered on the Prospective Register of Systematic Reviews (CRD42023403775).

Screening for Breast Cancer: US Preventive Services Task Force Recommendation Statement.

Importance: Among all US women, breast cancer is the second most common cancer and the second most common cause of cancer death. In 2023, an estimated 43 170 women died of breast cancer. Non-Hispanic White women have the highest incidence of breast cancer and non-Hispanic Black women have the highest mortality rate. Objective: The USPSTF commissioned a systematic review to evaluate the comparative effectiveness of different mammography-based breast cancer screening strategies by age to start and stop screening, screening interval, modality, use of supplemental imaging, or personalization of screening for breast cancer on the incidence of and progression to advanced breast cancer, breast cancer morbidity, and breast cancer-specific or all-cause mortality, and collaborative modeling studies to complement the evidence from the review. Population: Cisgender women and all other persons assigned female at birth aged 40 years or older at average risk of breast cancer. Evidence Assessment: The USPSTF concludes with moderate certainty that biennial screening mammography in women aged 40 to 74 years has a moderate net benefit. The USPSTF concludes that the evidence is insufficient to determine the balance of benefits and harms of screening mammography in women 75 years or older and the balance of benefits and harms of supplemental screening for breast cancer with breast ultrasound or magnetic resonance imaging (MRI), regardless of breast density. Recommendation: The USPSTF recommends biennial screening mammography for women aged 40 to 74 years. (B recommendation) The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening mammography in women 75 years or older. (I statement) The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of supplemental screening for breast cancer using breast ultrasonography or MRI in women identified to have dense breasts on an otherwise negative screening mammogram. (I statement).

Interventions for High Body Mass Index in Children and Adolescents: US Preventive Services Task Force Recommendation Statement.

Importance: Approximately 19.7% of children and adolescents aged 2 to 19 years in the US have a body mass index (BMI) at or above the 95th percentile for age and sex, based on Centers for Disease Control and Prevention growth charts from 2000. The prevalence of high BMI increases with age and is higher among Hispanic/Latino, Native American/Alaska Native, and non-Hispanic Black children and adolescents and children from lower-income families. Objective: The US Preventive Services Task Force (USPSTF) commissioned a systematic review to evaluate the evidence on interventions (behavioral counseling and pharmacotherapy) for weight loss or weight management in children and adolescents that can be provided in or referred from a primary care setting. Population: Children and adolescents 6 years or older. Evidence Assessment: The USPSTF concludes with moderate certainty that providing or referring children and adolescents 6 years or older with a high BMI to comprehensive, intensive behavioral interventions has a moderate net benefit. Recommendation: The USPSTF recommends that clinicians provide or refer children and adolescents 6 years or older with a high BMI (≥95th percentile for age and sex) to comprehensive, intensive behavioral interventions. (B recommendation).

Screening and Supplementation for Iron Deficiency and Iron Deficiency Anemia During Pregnancy: US Preventive Services Task Force Recommendation Statement.

Importance: Iron deficiency is the leading cause of anemia during pregnancy. According to survey data from 1999 to 2006, overall estimated prevalence of iron deficiency during pregnancy is near 18% and increases across the 3 trimesters of pregnancy (from 6.9% to 14.3% to 28.4%). An estimated 5% of pregnant persons have iron deficiency anemia. Objective: The US Preventive Services Task Force (USPSTF) commissioned a systematic review to evaluate the evidence on the benefits and harms of screening and supplementation for iron deficiency with and without anemia on maternal and infant health outcomes in asymptomatic pregnant persons. Population: Asymptomatic pregnant adolescents and adults. Evidence Assessment: The USPSTF concludes that the current evidence is insufficient, and the balance of benefits and harms of screening for iron deficiency and iron deficiency anemia in asymptomatic pregnant persons on maternal and infant health outcomes cannot be determined. The USPSTF also concludes that the current evidence is insufficient, and the balance of benefits and harms of iron supplementation in asymptomatic pregnant persons on maternal and infant health outcomes cannot be determined. Recommendation: The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for iron deficiency and iron deficiency anemia in pregnant persons to prevent adverse maternal and infant health outcomes. (I statement) The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of routine supplementation for iron deficiency and iron deficiency anemia in pregnant persons to prevent adverse maternal and infant health outcomes. (I statement).

Screening for Speech and Language Delay and Disorders in Children: US Preventive Services Task Force Recommendation Statement.

Importance: Speech and language delays and disorders can pose significant problems for children and their families. Evidence suggests that school-aged children with speech or language delays may be at increased risk of learning and literacy disabilities, including difficulties with reading and writing. Objective: The US Preventive Services Task Force (USPSTF) commissioned a systematic review to evaluate benefits and harms of screening for speech and language delay and disorders in children 5 years or younger. Population: Asymptomatic children 5 years or younger whose parents or clinicians do not have specific concerns about their speech, language, hearing, or development. Evidence Assessment: The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for speech and language delay and disorders in children who do not present with signs or symptoms or parent/caregiver concerns. Recommendation: The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for speech and language delay and disorders in children 5 years or younger without signs or symptoms. (I statement).

Interventions to Prevent Falls in Community-Dwelling Older Adults: US Preventive Services Task Force Recommendation Statement.

Importance: Falls are the leading cause of injury-related morbidity and mortality among older adults in the US. In 2018, 27.5% of community-dwelling adults 65 years or older reported at least 1 fall in the past year and 10.2% reported a fall-related injury. In 2021, an estimated 38 742 deaths resulted from fall-related injuries. Objective: The US Preventive Services Task Force (USPSTF) commissioned a systematic review to evaluate the effectiveness and harms of primary care-relevant interventions to prevent falls and fall-related morbidity and mortality in community-dwelling adults 65 years or older. Population: Community-dwelling adults 65 years or older at increased risk of falls. Evidence Assessment: The USPSTF concludes with moderate certainty that exercise interventions provide a moderate net benefit in preventing falls and fall-related morbidity in older adults at increased risk for falls. The USPSTF concludes with moderate certainty that multifactorial interventions provide a small net benefit in preventing falls and fall-related morbidity in older adults at increased risk for falls. Recommendation: The USPSTF recommends exercise interventions to prevent falls in community-dwelling adults 65 years or older who are at increased risk for falls. (B recommendation) The USPSTF recommends that clinicians individualize the decision to offer multifactorial interventions to prevent falls to community-dwelling adults 65 years or older who are at increased risk for falls. Existing evidence indicates that the overall net benefit of routinely offering multifactorial interventions to prevent falls is small. When determining whether this service is appropriate for an individual, patients and clinicians should consider the balance of benefits and harms based on the circumstances of prior falls, presence of comorbid medical conditions, and the patient's values and preferences. (C recommendation).

New USPSTF Breast Cancer Screening Recommendations: A Talk With Task Force Vice Chair Dr John Wong.

In this video article, Dr. John B. Wong, Vice Chair of the U.S. Preventive Services Task Force (USPSTF), discusses implications of the new USPSTF recommendation for biennial screening mammography for women 40­74 years old.

Suppression head impulse test in children-experiences in a tertiary paediatric vestibular centre.

The suppression head impulse paradigm (SHIMP) involves suppression of the vestibulo-ocular reflex (VOR) and anticompensatory saccades generated thereof. SHIMP is gaining importance to understand vestibular compensation with its different parameters (VOR gain/peak saccadic velocity PSV/latency of saccades). SHIMP studies are emerging in adults, but pediatric studies have hardly been performed. This study is a retrospective case note audit over a period of 2 months in a tertiary pediatric vestibular center in the United Kingdom to investigate whether SHIMP is safe/robust to be used in children conforming to existing standards/norms in normal children and whether it yields any meaningful inferences in pediatric vestibular hypofunction. This is the largest pediatric SHIMP study to date. A total of 44 referred children (6-18 years, female children>male children) with a range of complaints from dizziness, imbalance, motor incoordination, postural instability, and hearing loss were included, and their SHIMP parameters were measured. All children underwent comprehensive functional/objective audiovestibular assessments. Two groups were defined-Group A with normal vestibular function and Group B with abnormal vestibular function. The normal population showed an average SHIMP VOR gain of 0.98+/-0.08 and latency of overt saccades at 215.68+/-46.16 milliseconds agreeing with published evidence. The PSV of overt saccades was 315.39+/-56.30/s, and there was a gain asymmetry of 7.42+/-4.68 between the sides. Statistically significant differences with moderate/large effect sizes were observed between the groups in terms of VOR gain and PSV but not in saccade latencies. Covert saccades were rare in SHIMP, while overt saccades were observed in 100% of children. VOR gain difference between the head impulse paradigm (HIMP) and the SHIMP was significant as well. We observed statistically significant differences in side asymmetry of VOR gain between the groups. Furthermore, we identified a group of children with cerebellar lesions where overt saccades in SHIMP were rather low in number. Further research is recommended to investigate pediatric PSV, asymmetry, and inability to generate overt saccades that may suggest useful means to assess compensation and central function. We conclude that SHIMP yields valuable information and is a safe, easy to perform, and a reliable test that should be used in children to supplement HIMP.

AI-Led Mental Health Support (Wysa) for Health Care Workers During COVID-19: Service Evaluation.

BACKGROUND: The impact that the COVID-19 pandemic has had on health care workers' mental health, in particular, cannot be ignored. Not only did the pandemic exacerbate mental health challenges through elevated stress, anxiety, risk of infection, and social isolation, but regulations to minimize infection additionally hindered the conduct of traditional in-person mental health care. OBJECTIVE: This study explores the feasibility of using Wysa, an artificial intelligence-led mental health app, among health care workers. METHODS: A national tertiary health care cluster in Singapore piloted the use of Wysa among its own health care workers to support the management of their mental well-being during the pandemic (July 2020-June 2022). The adoption of this digital mental health intervention circumvented the limitations of in-person contact and enabled large-scale access to evidence-based care. Rates and patterns of user engagement were evaluated. RESULTS: Overall, the opportunity to use Wysa was well-received. Out of the 527 staff who were onboarded in the app, 80.1% (422/527) completed a minimum of 2 sessions. On average, users completed 10.9 sessions over 3.80 weeks. The interventions most used were for sleep and anxiety, with a strong repeat-use rate. In this sample, 46.2% (73/158) of health care workers reported symptoms of anxiety (Generalized Anxiety Disorder Assessment-7 [GAD-7]), and 15.2% (24/158) were likely to have symptoms of depression (Patient Health Questionnaire-2 [PHQ-2]). CONCLUSIONS: Based on the present findings, Wysa appears to strongly engage those with none to moderate symptoms of anxiety. This evaluation demonstrates the viability of implementing Wysa as a standard practice among this sample of health care workers, which may support the use of similar digital interventions across other communities.

Real-Time Gated Proton Therapy: Commissioning and Clinical Workflow for the Hitachi System.

Purpose: To describe the commissioning of real-time gated proton therapy (RGPT) and the establishment of an appropriate clinical workflow for the treatment of patients. Materials and Methods: Hitachi PROBEAT provides pencil beam scanning proton therapy with an advanced onboard imaging system including real-time fluoroscopy. RGPT utilizes a matching score to provide instantaneous system performance feedback and quality control for patient safety. The CIRS Dynamic System combined with a Thorax Phantom or plastic water was utilized to mimic target motion. The OCTAVIUS was utilized to measure end-to-end dosimetric accuracy for a moving target across a range of simulated situations. Using this dosimetric data, the gating threshold was carefully evaluated and selected based on the intended treatment sites and planning techniques. An image-guidance workflow was developed and applied to patient treatment. Results: Dosimetric data demonstrated that proton plan delivery uncertainty could be within 2 mm for a moving target. The dose delivery to a moving target could pass 3%/3 mm gamma analysis following the commissioning process and application of the clinical workflow detailed in this manuscript. A clinical workflow was established and successfully applied to patient treatment utilizing RGPT. Prostate cancer patients with implanted platinum fiducial markers were treated with RGPT. Their target motion and gating signal data were available for intrafraction motion analysis. Conclusion: Real-time gated proton therapy with the Hitachi System has been fully investigated and commissioned for clinical application. RGPT can provide advanced and reliable real-time image guidance to enhance patient safety and inform important treatment planning parameters, such as planning target volume margins and uncertainty parameters for robust plan optimization. RGPT improved the treatment of patients with prostate cancer in situations where intrafraction motion is more than defined tolerance.

Substandard housing and the risk of COVID-19 infection and disease severity: A retrospective cohort study.

In this study we examine associations between substandard housing and the risk of COVID-19 infection and severity during the first year of the pandemic by linking individual-level housing and clinical datasets. Residents of Chelsea, Massachusetts who were tested for COVID-19 at any Mass General Brigham testing site and who lived at a property that had received a city housing inspection were included (N = 2873). Chelsea is a densely populated city with a high prevalence of substandard housing. Inspected properties with housing code violations were considered substandard; inspected properties without violations were considered adequate. COVID-19 infection was defined as any positive PCR test, and severe disease defined as hospitalization with COVID-19. We used a propensity score design to match individuals on variables including age, race, sex, and income. In the severity model, we also matched on ten comorbidities. We estimated the risk of COVID-19 infection and severity associated with substandard housing using Cox Proportional Hazards models for lockdown, the first phase of reopening, and the full study period. In our sample, 32% (919/2873) of individuals tested positive for COVID-19 and 5.9% (135/2297) had severe disease. During lockdown, substandard housing was associated with a 48% increased risk of COVID-19 infection (95%CI 1.1-2.0, p = 0.006). Through Phase 1 reopening, substandard housing was associated with a 39% increased infection risk (95%CI 1.1-1.8, p = 0.020). The difference in risk attenuated over the full study period. There was no difference in severe disease risk between the two groups. The increased risk, observed only during lockdown and early reopening - when residents were most exposed to their housing - strengthens claims that substandard housing conveys higher infection risk. The results demonstrate the value of combining cross-sector datasets. Existing city housing data can be leveraged 1) to identify and prioritize high-risk areas for future pandemic response, and 2) for longer-term housing solutions.

Comparative Study of Eclipse and RayStation Multi-Criteria Optimization-Based Prostate Radiotherapy Treatment Planning Quality.

Multi-criteria optimization (MCO) function has been available on commercial radiotherapy (RT) treatment planning systems to improve plan quality; however, no study has compared Eclipse and RayStation MCO functions for prostate RT planning. The purpose of this study was to compare prostate RT MCO plan qualities in terms of discrepancies between Pareto optimal and final deliverable plans, and dosimetric impact of final deliverable plans. In total, 25 computed tomography datasets of prostate cancer patients were used for Eclipse (version 16.1) and RayStation (version 12A) MCO-based plannings with doses received by 98% of planning target volume having 76 Gy prescription (PTV76D98%) and 50% of rectum (rectum D50%) selected as trade-off criteria. Pareto optimal and final deliverable plan discrepancies were determined based on PTV76D98% and rectum D50% percentage differences. Their final deliverable plans were compared in terms of doses received by PTV76 and other structures including rectum, and PTV76 homogeneity index (HI) and conformity index (CI), using a t-test. Both systems showed discrepancies between Pareto optimal and final deliverable plans (Eclipse: -0.89% (PTV76D98%) and -2.49% (Rectum D50%); RayStation: 3.56% (PTV76D98%) and -1.96% (Rectum D50%)). Statistically significantly different average values of PTV76D98%,HI and CI, and mean dose received by rectum (Eclipse: 76.07 Gy, 0.06, 1.05 and 39.36 Gy; RayStation: 70.43 Gy, 0.11, 0.87 and 51.65 Gy) are noted, respectively (p < 0.001). Eclipse MCO-based prostate RT plan quality appears better than that of RayStation.

Bouveret's syndrome: An old diagnosis. A modern multimodality approach (endoscopic and robotic surgical) of gastric outlet obstruction: Report of two cases.

INTRODUCTION AND IMPORTANCE: Bouveret's syndrome is an uncommon condition characterized by the impaction of a gallstone in the pylorus or duodenum via a cholecysto-enteric fistula causing gastric outlet obstruction. We report two unusual cases of Bouveret's syndrome causing gastric outlet obstruction in two elderly patients. CASE PRESENTATION: Two elderly female patients presented to the surgical assessment unit with features of gastric outlet obstruction. In both cases, an urgent computed tomography (CT) of the abdomen showed pneumobilia, gastric distension, and gallstones impaction at the duodenal bulb. In Patient 1, endoscopic removal of the impacted gallstones was done successfully. She was discharged three days following an uneventful recovery. In Patient 2, an endoscopic removal of a single large gallstone was attempted, which was unsuccessful. She underwent robotic gastrotomy with extraction of the large gallstone with primary repair. She was discharged on 8th postoperative day. CLINICAL DISCUSSION: Treatment options for Bouveret's syndrome include endoscopic management and surgery. The selection of treatment options depends upon factors like the degree of obstruction, the impaction site, number, type or size of gallstones, patient co-morbidities and clinical parameters at presentation, as well as expertise available, both endoscopic and surgical. CONCLUSIONS: Bouveret's syndrome is one of the rare complications of gallstone. Endoscopic management can be effective at removing the impacted gallstones, which is particularly helpful for those elderly patients who have multiple medical co-morbidities, as in our first patient. Surgical management like minimal invasive surgery (robotic) can be beneficial in failed endoscopic attempt of removal of stone like in the second patient.

Addressing the functional needs of left ventricular assist device candidates: Development and feasibility of an occupational therapy pre-operative evaluation.

BACKGROUND: Everyday living with a left ventricular assist device (LVAD) is complex, particularly for people with physical or cognitive impairments or limited social supports. There is a need for standardized pre-operative functional evaluations. OBJECTIVES: Our objectives were to describe a pre-operative occupational therapy (OT) evaluation for LVAD candidates, assess its feasibility in routine care, and characterize functional needs. METHODS: We retrospectively reviewed electronic medical records of pre-operative OT consultations for LVAD candidates over four years (n = 209). Occupational profile, vision, and sensation were operationalized from documentation narratives. Daily functioning was measured with Activity Measure for Post-Acute Care, grip strength with dynamometer, cognition with Montreal Cognitive Assessment and Allen Cognitive Level Screen-5, and LVAD self-management with a performance-based ordinal scale. RESULTS: 89.5 % of consultations were completed, averaging 61.2 min (n = 187): 79.1 % (148/187) inpatient and 20.9 % (39/187) outpatient. Patients completed 87.7 % (164/187) to 100.0 % (187/187) of evaluation components. 21.9 % (41/187) of candidates lived alone. 6.4 % (12/187) and 7.0 % (13/185) had visual and sensory dysfunction. 57.4 % were independent with daily activities (104/181). 17.7 % (32/181) had impaired grip strength. 69.3 % (124/179) had impaired cognition, 29.7 % (51/172) with impaired functional cognition for everyday activities. 88.4 % (145/164) required physical or cueing assistance while practicing LVAD batteries management. OTs interpreted that 20.9 % (39/187) would likely require 24/7 post-operative support with LVAD self-care. CONCLUSION: Pre-operative OT evaluations were feasible and emphasized complex functional needs. Assessing LVAD self-care abilities may inform candidacy and facilitate early interventions to optimize functioning. OT should be consulted within interprofessional teams for all LVAD candidates.

Electroacupuncture Enhances the Functional Connectivity of Limbic System to Neocortex in the 5xFAD Mouse Model of Alzheimer's Disease.

Our previous study revealed that acupuncture may exhibit therapeutic effects on Alzheimer's disease (AD) through the activation of metabolism in memory-related brain regions. However, the underlying functional mechanism remains poorly understood and warrants further investigation. In this study, we used resting-state functional magnetic resonance imaging (rsfMRI) to explore the potential effect of electroacupuncture (EA) on the 5xFAD mouse model of AD. We found that the EA group exhibited significant improvements in the number of platforms crossed and the time spent in the target quadrant when compared with the Model group (p < 0.05). The functional connectivity (FC) of left hippocampus (Hip) was enhanced significantly among 12 regions of interest (ROIs) in the EA group (p < 0.05). Based on the left Hip as the seed point, the rsfMRI analysis of the entire brain revealed increased FC between the limbic system and the neocortex in the 5xFAD mice after EA treatment. Additionally, the expression of amyloid-ß(Aß) protein and deposition in the Hip showed a downward trend in the EA group compared to the Model group (p < 0.05). In conclusion, our findings indicate that EA treatment can improve the learning and memory abilities and inhibit the expression of Aß protein and deposition of 5xFAD mice. This improvement may be attributed to the enhancement of the resting-state functional activity and connectivity within the limbic-neocortical neural circuit, which are crucial for cognition, motor function, as well as spatial learning and memory abilities in AD mice.