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Background: Small extracellular vesicles (sEVs) mediate intercellular communication that contributes to hepatocellular carcinoma (HCC) progression via multifaceted pathways. The success of cell entry determines the effect of sEV on recipient cells. Here, we aimed to delineate the mechanisms underlying the uptake of sEV in HCC., Methods: Macropinocytosis was examined by the ability of cells to internalize dextran and sEV. Macropinocytosis was analyzed in Na(+)/H(+) exchanger 7 (NHE7)-knockdown and -overexpressing cells. The properties of cells were studied using functional assays. pH biosensor was used to evaluate the intracellular and endosomal pH. The expression of NHE7 in patients' liver tissues was examined by immunofluorescent staining. Inducible silencing of NHE7 in established tumors was performed to reveal the therapeutic potential of targeting NHE7., Results: The data revealed that macropinocytosis controlled the internalization of sEVs and their oncogenic effect on recipient cells. It was found that metastatic HCC cells exhibited the highest efficiency of sEV uptake relative to normal liver cells and non-metastatic HCC cells. Attenuation of macropinocytic activity by 5-(N-ethyl-N-isopropyl)-amiloride (EIPA) limited the entry of sEVs and compromised cell aggressiveness. Mechanistically, we delineated that high level of NHE7, a sodium-hydrogen exchanger, alkalized intracellular pH and acidized endosomal pH, leading to the maturation of macropinosomes. Inducible inhibition of NHE7 in established tumors developed in mice delayed tumor development and suppressed lung metastasis. Clinically, NHE7 expression was upregulated and linked to dismal prognosis of HCC., Conclusions: This study advances the understanding that NHE7 enhances sEV uptake by macropinocytosis to promote the malignant properties of HCC cells. Inhibition of sEV uptake via macropinocytosis can be exploited as a treatment alone or in combination with conventional therapeutic approaches for HCC., (© 2023 The Authors. Cancer Communications published by John Wiley & Sons Australia, Ltd on behalf of SUN YAT-SEN UNIVERSITY CANCER CENTER.)

Comorbidity network analysis (CNA) is a technique in which mathematical graphs encode correlations (edges) among diseases (nodes) inferred from the disease co-occurrence data of a patient group. The present study applied this network-based approach to identifying comorbidity patterns in older patients undergoing hip fracture surgery. This was a retrospective observational cohort study using electronic health records (EHR). EHR data were extracted from the one University Health System in the southeast United States. The cohort included patients aged 65 and above who had a first-time low-energy traumatic hip fracture treated surgically between October 1, 2015 and December 31, 2018 ( n  = 1,171). Comorbidity includes 17 diagnoses classified by the Charlson Comorbidity Index. The CNA investigated the comorbid associations among 17 diagnoses. The association strength was quantified using the observed-to-expected ratio (OER). Several network centrality measures were used to examine the importance of nodes, namely degree, strength, closeness, and betweenness centrality. A cluster detection algorithm was employed to determine specific clusters of comorbidities. Twelve diseases were significantly interconnected in the network (OER > 1, p -value < .05). The most robust associations were between metastatic carcinoma and mild liver disease, myocardial infarction and congestive heart failure, and hemi/paraplegia and cerebrovascular disease (OER > 2.5). Cerebrovascular disease, congestive heart failure, and myocardial infarction were identified as the central diseases that co-occurred with numerous other diseases. Two distinct clusters were noted, and the largest cluster comprised 10 diseases, primarily encompassing cardiometabolic and cognitive disorders. The results highlight specific patient comorbidities that could be used to guide clinical assessment, management, and targeted interventions that improve hip fracture outcomes in this patient group., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: We retrospectively analyzed the correlation between different endometrial preparation protocols and pregnancy outcomes in patients with polycystic ovary syndrome (PCOS) who underwent frozen embryo transfer (FET)., Methods: A total of 200 PCOS patients who underwent FET were divided into HRT group ( n  = 65), LE group ( n  = 65), GnRHa + HRT group ( n  = 70) according to different endometrial preparation protocols. The endometrial thickness on the day of endometrial transformation, the number of embryos transferred, and the number of high-quality embryos transferred were compared among the three groups. The pregnancy outcomes of FET in the three groups were compared and analyzed, and a further multivariate logistic regression model was used to analyze the factors influencing FET pregnancy outcomes in PCOS patients., Results: Endometrial thickness on the day of endometrial transformation, clinical pregnancy rate and live birth rate in GnRHa + HRT group were higher than those in the HRT group and LE group. The results of multivariate regression analysis showed that the pregnancy outcome of PCOS patients undergoing FET was significantly associated with the patient's age, endometrial preparation protocols, number of embryos transferred, endometrial thickness, and duration of infertility., Conclusion: Compared with HRT or LE alone, GnRHa + HRT protocol results in higher levels of endometrial thickness on the day of endometrial transformation, clinical pregnancy rate, and live birth rate. Female age, endometrial preparation protocols, number of embryos transferred, endometrial thickness, and duration of infertility are determined as factors influencing pregnancy outcomes in PCOS patients undergoing FET.

Postoperative pulmonary complications (PPCs) are the leading cause of death following hip fracture surgery. Dementia has been identified as a PPC risk factor that complicates the clinical course. By leveraging electronic health records, this retrospective observational study evaluated the impact of dementia on the incidence and severity of PPCs, hospital length of stay, and postoperative 30-day mortality among 875 older patients (≥65 years) who underwent hip fracture surgery between October 1, 2015 and December 31, 2018 at a health system in the southeastern United States. Inverse probability of treatment weighting using propensity scores was utilized to balance confounders between patients with and without dementia to isolate the impact of dementia on PPCs. Regression analyses revealed that dementia did not have a statistically significant impact on the incidence and severity of PPCs or postoperative 30-day mortality. However, dementia significantly extended the hospital length of stay by an average of 1.37 days.

Background: Medication optimization, including prescription of osteoporosis medications and deprescribing medications associated with falls, may reduce injurious falls. Our objective was to describe a remote, injury prevention service (NH PRIDE) designed to optimize medication use in nursing homes (NHs), and to describe its implementation outcomes in a pilot study., Methods: This was a non-randomized trial (pilot study) including NH staff and residents from five facilities. Long-stay residents at high-risk for injurious falls were identified using a validated risk calculator and staff referral. A remote team reviewed the electronic health record (EHR) and provided recommendations as Injury Prevention Plans (IPP). A research nurse served as a care coordinator focused on resident engagement and shared decision-making. Outcomes included implementation measures, as identified in the EHR, and surveys and interviews with staff., Results: Across five facilities, 274 residents were screened for eligibility, and 46 residents (16.8%) were enrolled. Most residents were female (73.9%) and had dementia (63.0%). An IPP was completed for 45 residents (97.8%). The nurse made a total of 93 deprescribing recommendations in 36 residents (80% of residents had one or more deprescribing recommendation; mean 2.2 recommendations/resident). Twenty of 45 residents (44.4%) had a recommendation for osteoporosis treatment. Among residents with recommendations, 21/36 (58.3%) had one or more deprescribing orders written and 6/20 (30.0%) had an osteoporosis medication prescribed. At 4 months, most medication changes persisted. Adverse side effects were rare. Staff members identified several areas for program refinement, including aligning recommendations with provider workflow and engaging consultant psychiatrists., Conclusions: A remote injury prevention service is safe and feasible to enhance deprescribing and osteoporosis treatment in long-stay NH residents at risk for injury. Additional investigation is needed to determine if this model could reduce injurious falls when deployed across NH chains., (© 2023 The American Geriatrics Society.)

Objective: Older adults with dementia are at higher risk for sustaining hip fracture and their long-term health outcomes after surgery are usually worse than those without dementia. Widespread adoption of electronic health records (EHRs) may allow hospitals to better monitor long-term health outcomes in patients with dementia after hospitalization. This study aimed to (1) estimate how dementia influences discharge location, mortality, and readmission 180 days and 1 year after hip fracture surgery in older adults, and (2) demonstrate the feasibility of using selection-bias reduced EHR data for research and long-term health outcomes monitoring., Design: Retrospective observational cohort study using EHRs., Setting and Participants: A cohort of 1171 patients over age 65 years who had an initial hip fracture surgery between October 2015 and December 2018 was extracted from EHRs of one health system; 376 of these patients had dementia., Methods: Logistic regression was applied to estimate influences of dementia on discharge disposition and Cox proportional hazards model for mortality. The Fine and Gray regression model was used to analyze readmission, accounting for the competing risk of death. To reduce selection bias in EHRs, inverse probability of treatment weighting using propensity scores was implemented before modeling., Results: Dementia had significant impacts on all outcomes: being discharged to facilities [odds ratio (OR) = 2.11, 95% confidence interval (CI) 1.19-3.74], 180-day mortality [hazard ratio (HR) = 1.69, 95% CI 1.20-2.38], 1-year mortality (HR = 1.78, 95% CI 1.33-2.38), 180-day readmission (HR = 1.62, 95% CI 1.39-1.89), and 1 year readmission (HR = 1.39, 95% CI 1.21-1.58)., Conclusions and Implications: Dementia was a significant risk factor for worse long-term outcomes. The inverse probability of treatment weighting approach can be used to reduce selection bias in EHR data for research and monitoring long-term health outcomes in the target population. Such monitoring could foster collaborations with post-acute and long-term health care services to improve recovery outcomes in patients with dementia after hip fracture surgery., (Copyright © 2022 AMDA – The Society for Post-Acute and Long-Term Care Medicine. All rights reserved.)

Background: Deprescribing initiatives in the long-term care (LTC) setting are often unsuccessful or not sustained. Prior research has considered how physicians and pharmacists feel about deprescribing, yet little is known about the perspectives of frontline nursing staff and residents. Our aim was to elicit perspectives from LTC nursing staff, patients, and proxies regarding their experiences and preferences for deprescribing in order to inform future deprescribing efforts in LTC., Methods: This study was a qualitative analysis of interviews with nurses, nurse aides, a nurse practitioner, residents, and proxies (family member and/or responsible party) from three LTC facilities. The research team used semi-structured interviews. Guides were designed to inform an injury prevention intervention. Interviews were recorded and transcribed. A qualitative framework analysis was used to summarize themes related to deprescribing. The full study team reviewed the summary to identify actionable, clinical implications., Results: Twenty-six interviews with 28 participants were completed, including 11 nurse aides, three residents, seven proxies, one nurse practitioner, and six nurses. Three themes emerged that were consistent across facilities: 1) build trust with team members, including residents and proxies; 2) identify motivating factors that lead to resident, proxy, nurse practitioner, and staff acceptance of deprescribing; 3) standardize supportive processes to encourage deprescribing. These themes suggest several actionable steps to improve deprescribing initiatives including: 1) tell stories about successful deprescribing, 2) provide deprescribing education to frontline staff, 3) align medication risk/benefit discussions with what matters most to the resident, 4) standardize deprescribing monitoring protocols, 5) standardize interprofessional team huddles and care plan meetings to include deprescribing conversations, and 6) strengthen non-pharmacologic treatment programs., Conclusions: By interviewing LTC stakeholders, we identified three important themes regarding successful deprescribing: Trust, Motivating Factors, and Supportive Processes. These themes may translate into actionable steps for clinicians and researchers to improve and sustain person-centered deprescribing initiatives., Trial Registration: NCT04242186., (© 2023. The Author(s).)

Background: Spermatozoa have the task of delivering an intact paternal genome to the oocyte and supporting successful embryo development. The detection of sperm DNA fragmentation (SDF) has been emerging as a complementary test to conventional semen analysis for male infertility evaluation, but the mechanism leading to SDF and its impact on assisted reproduction remain unclear. Therefore, the study identified and analyzed the differentially expressed proteins of sperm with high and low SDF., Methods: Semen samples from men attended the infertility clinic during June 2020 and August 2020 were analyzed, and sperm DNA fragmentation index (DFI) was detected by the sperm chromatin structure assay. Semen samples with low DFI (< 30%, control group) and high DFI (≥ 30%, experimental group) were optimized by density gradient centrifugation (DGC), and the differentially expressed proteins of obtained sperm were identified by the Sequential Window Acquisition of All Theoretical Mass Spectra Mass Spectrometry (SWATH-MS) and performed GO and KEGG analysis., Results: A total of 2186 proteins were identified and 1591 proteins were quantified, of which 252 proteins were identified as differentially expressed proteins, including 124 upregulated and 128 downregulated. These differentially expressed proteins were involved in metabolic pathways, replication/recombination/repair, acrosomal vesicles, kinase regulators, fertilization, tyrosine metabolism, etc. Western blotting results showed that the expression levels of RAD23B and DFFA proteins and the levels of posttranslational ubiquitination and acetylation modifications in the experimental group were significantly higher than those in the control group, which was consistent with the results of proteomics analysis., Conclusions: Proteomic markers of sperm with high DNA fragmentation can be identified by the SWATH-MS and bioinformatic analysis, and new protein markers and posttranslational modifications related to sperm DNA damage are expected to be intensively explored. Our findings may improve our understanding of the basic molecular mechanism of sperm DNA damage., (© 2023. The Author(s).)

Research Question: What are the molecular mechanisms leading to human sperm DNA damage?, Design: Semen samples were collected and the sperm DNA fragmentation index (DFI) was assessed. Differentially expressed RNA in spermatozoa with a high (DFI ≥30%, experimental group) or normal (DFI <30%, control group) DFI were identified by RNA-sequencing (RNA-seq) technology, and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis was performed. Three differentially expressed RNA related to sperm DNA damage and repair, namely PMS1, TP53BP1 and TLK2, were validated using real-time quantitative (RT-qPCR)., Results: A total of 19,970 expressed RNA were detected in the two groups. Compared with the control group, the expression levels of 189 RNA in the experimental group were significantly increased and those of 163 genes decreased. Gene Ontology enrichment analysis showed that these RNA were mainly concentrated in the ATPase-dependent transmembrane transport complex, extracellular exosome, somatic cell DNA recombination, protein binding, cytoplasm and regulation of localization. KEGG pathway analysis showed that these RNA were mainly related to the PI3K-Akt signalling pathway, endocytosis, p53 signalling pathway and cGMP-PKG signalling pathway. The RT-qPCR results showed that the expression levels of PMS1, TP53BP1 and TLK2 in the experimental group were significantly lower than in the control group (P = 0.01, 0.015 and 0.004, respectively), which was identical to the results of RNA sequencing., Conclusions: Differentially expressed RNA related to sperm DNA damage and repair may be identified by RNA-seq technology, which provides new insights into the understanding of sperm DNA damage and repair, and will help to discover new biomarkers related to sperm DNA damage., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

The complex care needs of older adults arising at the intersection of age-related illnesses, military service, and social barriers have presented challenges to the US Department of Veterans Affairs (VA) for decades. In response, the VA has invested in centers that integrate research, education, and clinical innovation, using approaches aligned with a learning health care system, to create, evaluate, and implement new care models. This article presents an integrative review of 6 community care models developed within the VA to manage multimorbidity, complex social needs, and avoid institutional care, examining how these models address complex care needs among older adults. The models reviewed include Home Based Primary Care, Medical Foster Home, the VA Caregiver Support Program, the Resources Enhancing Alzheimer's Caregiver Health (REACH)-VA program, the Caregivers of Older Adults Cared for at Home (COACH) program, and Veteran Directed Care. Core components and evaluation outcomes for each model are summarized, along with implications for more widespread implementation and research. Each model promotes coordinated care, integrates behavioral health, and leverages interprofessional expertise. All models are cost-neutral or incur only modest cost increases to improve outcomes. Broader implementation will require interprofessional workforce development, payment model realignment, and infrastructure to evaluate outcomes in new settings. The VA provides a blueprint for infrastructure that could be adapted to other domestic and international settings. Care models successfully implemented within the VA's single-payer system hold promise to address persistent dilemmas in long-term care, such as management of multimorbidity and social drivers of health, integration and support of family caregivers, and mental health integration. These models also demonstrate the value of incorporating care approaches that have been developed or tested outside the United States and argue for greater cross-fertilization of ideas from different health systems., (Published by Elsevier Inc.)

Background and Objectives: Engaging residents, their proxies, and skilled nursing facility (SNF) staff through effective communication has potential for improving fall-related injury prevention. The purpose of this study was to understand how multiple stakeholders develop and communicate fall-related injury prevention plans to enhance sustained implementation., Research Design and Methods: Descriptive qualitative study using framework analysis applied to open-ended semistructured interviews (n = 28) regarding experiences of communication regarding fall-related injury prevention, guided by the Patient and Family Engaged Care framework. Participants included residents at high risk of injury and their proxies, nursing assistants, nurses, and a nurse practitioner from 3 SNFs in the Eastern United States (Massachusetts and North Carolina)., Results: Interdisciplinary teams were viewed as essential for injury prevention. However, the roles of the interdisciplinary team members were sometimes unclear. Communication structures were often hierarchical, which reduced engagement of nursing assistants and frustrated proxies. Practices that enhanced engagement included knowing the residents, active listening skills, and use of strategies for respecting autonomy. Engagement was inhibited by time constraints, lack of proactive communication among staff, and by challenges eliciting the perspectives of residents with dementia. Resident barriers included desire for autonomy, strong preferences, and language differences., Discussion and Implications: Strengthening team meeting processes and cultivating open communication and collaboration could facilitate staff, resident, and proxy engagement in injury prevention planning and implementation. Skill building and targeting resources to improve communication can address barriers related to staff practices, resident characteristics, and time constraints., (© The Author(s) 2021. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background and Objectives: Social networks affect the health and well-being of older adults. Advancements in technology (e.g., digital devices and mHealth) enrich our ability to collect social networks and health data. The purpose of this scoping review was to identify and map the use of technology in measuring older adults' social networks for health and social care., Research Design and Methods: The Joanna Briggs Institute methodology was followed. PubMed (MEDLINE), Sociological Abstracts, SocINDEX, CINAHL, and Web of Science were searched for relevant articles. Conference abstracts and proceedings were searched via Conference Papers Index, the American Sociological Society, and The Gerontological Society of America. Studies published in English from January 2004 to March 2020 that aimed to improve health or social care for older adults and used technology to measure social networks were included. Data were extracted by 2 independent reviewers using an a priori extraction tool., Results: The majority of the 18 reviewed studies were pilot or simulation research conducted in Europe that focused on older adults living in the community. The various types of technologies used can be categorized as environment-based, person-based, and data-based., Discussion and Implications: Technology facilitates objective and longitudinal data collection on the social interactions and activities of older adults. The use of technology to measure older adults' social networks, however, is primarily in an exploratory phase. Multidisciplinary collaborations are needed to overcome operational, analytical, and implementation challenges. Future studies should leverage technologies for addressing social isolation and care for older adults, especially during the coronavirus disease 2019 pandemic., (© The Author(s) 2021. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

This retrospective cohort study used electronic health records to explore the effect of race/ethnicity, insurance status, and area deprivation on post-discharge outcomes in older patients undergoing hip fracture surgery between 2015 and 2018 ( N  = 1,150). Inverse probability of treatment weight-adjusted regression analysis was used to identify the effects of the predictors on outcomes. White patients had higher 90- and 365-day readmission risks than Black patients and higher all-period readmissions than the Other racial/ethnic (Hispanic, Asian, American Indian, and Multicultural) group ( p  < .000). Black patients had a higher risk of 30- and 90-day readmission than the Other racial/ethnic group ( p  < .000). Readmission risk across 1-year follow-up was generally higher among patients from less deprived areas than more deprived areas ( p  < .05). The 90- and 365-day mortality risk was lower for patients from less deprived areas (vs. more deprived areas) and patients with Medicare Advantage (vs. Medicare), respectively ( p  < .05). Our findings can guide efforts to identify patients for additional post-discharge support. Nevertheless, the findings regarding readmission risks contrast with previous knowledge and thus require more validation studies.

The aim of the current study was to investigate whether intestinal ischemic preconditioning (IP) reduces damage to the liver during hepatic ischemia reperfusion (IR). Sprague Dawley rats were used to model liver IR injury, and were divided into the sham operation group (SO), IR group and IP group. The results indicated that IR significantly increased Bax, caspase 3 and NF‑κBp65 expression levels, with reduced expression of Bcl‑2 compared with the IP group. Compared with the IR group, the levels of AST, ALT, MPO, MDA, TNF‑α and IL‑1 were significantly reduced in the IP group. Immunohistochemistry for Bcl‑2 and Bax indicated that Bcl‑2 expression in the IP group was significantly increased compared with the IR group. In addition, IP reduced Bax expression compared with the IR group. The average liver injury was worsened in the IR group and improved in the IP group, as indicated by the morphological evaluation of liver tissues. The present study suggested that IP may alleviates apoptosis, reduce the release of pro‑inflammatory cytokines, ameloriate reductions in liver function and reduce liver tissue injury. To conclude, IP provided protection against hepatic IR injury.

Transabdominal preperitoneal (TAPP) and total extraperitoneal (TEP) are the two types of laparoscopic repair of the inguinal hernia. The main advantages of laparoscopic repair, as compared to open repair, are a shorter hospital stay and a quicker recovery to normal activities. However, we cannot be overlooked or neglected the complication of laparoscopic inguinal hernia repair although it brings us lots of benefits. We report a case of small bowel obstruction caused by a displaced mesh used for the laparoscopic inguinal hernia repair and review of literature.

miRNA-20b has been shown to be aberrantly expressed in several tumor types. However, the clinical significance of miRNA-20b in the prognosis of patients with hepatocellular carcinoma (HCC) is poorly understood, and the exact role of miRNA-20b in HCC remains unclear. The aim of the present study was to investigate the association of the expression of miR-20b with clinicopathological characteristics and overall survival of HCC patients analyzed by Kaplan-Meier analysis and Cox proportional hazards regression models. Meanwhile, the HIF-1α and VEGF targets of miR-20b have been confirmed. We found not only miR-20b regulation of HIF-1α and VEGF in normal but also regulation of miR-20b in hypoxia. This mechanism would help the tumor cells adapt to the different environments thus promoting the tumor invasion and development. The whole study suggests that miR-20b, HIF-1α, and VEGF serve as a potential therapeutic agent for hepatocellular carcinoma.

The present study was conducted to investigate the effects of gossypol acetic acid (GAA) on the proliferation of human mucoepidermoid carcinoma cell line MEC-1 in vitro and its possible molecular mechanisms of DNA double-strand breaks (DSB). MTT assay was performed to test the inhibition of proliferation of MEC-1 cells by GAA. DSB and γH2AX foci formation induced by GAA were detected by neutral comet assay and immunostaining. GAA (5-40 μmol/L) inhibited the growth of MEC-1 cells in a dose- and time-dependent manner. One of the indexes of comet assay, percentage of head DNA was decreased, however other indexes, including tail length, percentage of tail DNA, tail moment (TM) and Olive tail moment (OTM) were increased when treated with 2.5- 40 μmol/L GAA for 24 h or 20 μmol/L GAA for 3-48 h, compared with those in control. The percentage of γH2AX-positive cells was also increased when MEC-1 was treated with 2.5-20 μmol/L GAA for 24 h or 20 μmol/L GAA for 3-48 h, compared with that in control. All these results show that GAA inhibits the proliferation of MEC-1, and DSB maybe one of the mechanisms of inhibitory effect of GAA on the growth of tumor cells.