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1.
Neuron ; 2024 Jul 11.
Article in English | MEDLINE | ID: mdl-39019041

ABSTRACT

Traumatic brain injury (TBI) heterogeneity remains a critical barrier to translating therapies. Identifying final common pathways/molecular signatures that integrate this heterogeneity informs biomarker and therapeutic-target development. We present the first large-scale murine single-cell atlas of the transcriptomic response to TBI (334,376 cells) across clinically relevant models, sex, brain region, and time as a foundational step in molecularly deconstructing TBI heterogeneity. Results were unique to cell populations, injury models, sex, brain regions, and time, highlighting the importance of cell-level resolution. We identify cell-specific targets and previously unrecognized roles for microglial and ependymal subtypes. Ependymal-4 was a hub of neuroinflammatory signaling. A distinct microglial lineage shared features with disease-associated microglia at 24 h, with persistent gene-expression changes in microglia-4 even 6 months after contusional TBI, contrasting all other cell types that mostly returned to naive levels. Regional and sexual dimorphism were noted. CEREBRI, our searchable atlas (https://shiny.crc.pitt.edu/cerebri/), identifies previously unrecognized cell subtypes/molecular targets and is a leverageable platform for future efforts in TBI and other diseases with overlapping pathophysiology.

2.
J Fish Biol ; 2024 Jul 11.
Article in English | MEDLINE | ID: mdl-38992895

ABSTRACT

Cisco (Coregonus artedi) are a widespread, cold-water zooplanktivore native to North America. Although Cisco are generally referred to as an "obligate zooplanktivore," there is some evidence that the species exhibits considerable variability in trophic niche. Here, we assessed how Cisco body size relates to trophic position, that is, trophic ontogeny. We analysed 13C and 15N isotopes from Cisco ranging from 127 to 271 mm in body length (n = 66) from Trout Lake, Vilas County, Wisconsin, USA. 15N isotopes showed smaller Cisco had a trophic position of ~3, which steadily increased to ~3.5 for larger Cisco. Further, 13C isotope signatures showed Cisco transitioned to be more pelagically reliant (lower 13C signatures). Using gillnet catch data, we found that larger Cisco were using deeper habitats than smaller Cisco. Our results support that Cisco have significant variability in trophic niche even though they are traditionally thought of as an obligate planktivore. Overall, we emphasize that researchers should be cautious when generalizing Cisco trophic function, particularly when considering the broader food web.

3.
Cancers (Basel) ; 16(13)2024 Jul 04.
Article in English | MEDLINE | ID: mdl-39001522

ABSTRACT

BACKGROUND: The current National Comprehensive Cancer Network advises neoadjuvant chemoradiotherapy followed by surgery for locally advanced cases of esophageal cancer. The role of immunotherapy in this context is under heavy investigation. METHODS: Patients with esophageal adenocarcinoma were identified in the National Cancer Database (NCDB) from 2004 to 2019. Three groups were generated as follows: (a) no immunotherapy, (b) neoadjuvant immunotherapy, and (c) adjuvant immunotherapy. Overall survival was evaluated using the Kaplan-Meier method and Cox proportional hazard analysis, adjusting for previously described risk factors for mortality. RESULTS: Of the total 14,244 patients diagnosed with esophageal adenocarcinoma who received neoadjuvant chemoradiation, 14,065 patients did not receive immunotherapy, 110 received neoadjuvant immunotherapy, and 69 received adjuvant immunotherapy. When adjusting for established risk factors, adjuvant immunotherapy was associated with significantly improved survival compared to no immunotherapy and neoadjuvant immunotherapy during a median follow-up period of 35.2 months. No difference was noted among patients who received no immunotherapy vs. neoadjuvant immunotherapy in the same model. CONCLUSIONS: In this retrospective analysis of the NCDB, receiving adjuvant immunotherapy offered a significant survival advantage compared to no immunotherapy and neoadjuvant immunotherapy in the treatment of esophageal adenocarcinoma. The addition of neoadjuvant immunotherapy to patients treated with neoadjuvant chemoradiation did not improve survival in this cohort. Further studies are warranted to investigate the long-term outcomes of immunotherapy in esophageal cancer.

4.
Article in English | MEDLINE | ID: mdl-39032079

ABSTRACT

PURPOSE: To histometrically compare the osseointegration and crestal bone healing of a novel tapered, self-cutting tissue-level test implant with a standard tissue-level control implant in a submerged healing regimen. MATERIALS AND METHODS: In a mandibular minipig model, implants were inserted and evaluated histometrically after a healing period of 3, 6, and 12 weeks. The primary outcome was the evaluation of bone-to-implant contact (BIC) and secondary outcomes were primary stability as per insertion torque and first BIC (fBIC). Outcomes for the test and control implants were compared using Wilcoxon signed-rank tests and mixed linear regression models. RESULTS: Insertion torque values were significantly higher for the test (50.0 ± 26.4 Ncm) compared to the control implants (35.2 ± 19.7 Ncm, p = .0071). BIC values of test implants were non-inferior to those of control implants over the investigated study period. After 12 weeks, the corresponding values measured were 81.62 ± 11.12% and 90.41 ± 4.81% (p = .1763) for test and control implants, respectively. Similarly, no statistical difference was found for fBIC values, except for the 12 weeks outcome that showed statistically lower values for the test (-675.58 ± 590.88 µm) compared to control implants (-182.75 ± 197.40 µm, p = .0068). CONCLUSIONS: Novel self-cutting tissue-level implants demonstrated noninferior osseointegration and crestal bone height maintenance to the tissue-level implants. Histometric outcomes between both implants demonstrated test implants were statistically noninferior to control implants, despite substantial differences in the bone engagement mechanism and resulting differences in insertion torque and qualitative bone healing patterns.

5.
Annu Rev Stat Appl ; 11: 255-277, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38962579

ABSTRACT

The landscape of survival analysis is constantly being revolutionized to answer biomedical challenges, most recently the statistical challenge of censored covariates rather than outcomes. There are many promising strategies to tackle censored covariates, including weighting, imputation, maximum likelihood, and Bayesian methods. Still, this is a relatively fresh area of research, different from the areas of censored outcomes (i.e., survival analysis) or missing covariates. In this review, we discuss the unique statistical challenges encountered when handling censored covariates and provide an in-depth review of existing methods designed to address those challenges. We emphasize each method's relative strengths and weaknesses, providing recommendations to help investigators pinpoint the best approach to handling censored covariates in their data.

6.
Behav Res Ther ; 181: 104605, 2024 Jul 14.
Article in English | MEDLINE | ID: mdl-39029333

ABSTRACT

OBJECTIVE: LGBTQ-affirmative cognitive-behavioral therapy (CBT) addresses minority stress to improve sexual minority individuals' mental and behavioral health. This treatment has never been tested in high-stigma contexts like China using online delivery. METHOD: Chinese young sexual minority men (n = 120; ages 16-30; HIV-negative; reporting depression and/or anxiety symptoms and past-90-day HIV-transmission-risk behavior), were randomized to receive 10 sessions of culturally adapted asynchronous LGBTQ-affirmative internet-based CBT (ICBT) or weekly assessments only. The primary outcome included HIV-transmission-risk behavior (i.e., past-30-day condomless anal sex). Secondary outcomes included HIV social-cognitive mechanisms (e.g., condom use self-efficacy), mental health (e.g., depression), and behavioral health (e.g., alcohol use), as well as minority stress (e.g., acceptance concerns), and universal (e.g., emotion regulation) mechanisms at baseline and 4- and 8-month follow-up. Moderation analyses examined treatment efficacy as a function of baseline stigma experiences and session completion. RESULTS: Compared to assessment only, LGBTQ-affirmative ICBT did not yield greater reductions in HIV-transmission-risk behavior or social-cognitive mechanisms. However, LGBTQ-affirmative ICBT yielded greater improvements in depression (d = -0.50, d = -0.63) and anxiety (d = -0.51, d = -0.49) at 4- and 8-month follow-up, respectively; alcohol use (d = -0.40) at 8-month follow-up; and certain minority stress (e.g., internalized stigma) and universal (i.e., emotion dysregulation) mechanisms compared to assessment only. LGBTQ-affirmative ICBT was more efficacious for reducing HIV-transmission-risk behavior for participants with lower internalized stigma (d = 0.42). Greater session completion predicted greater reductions in suicidality and rumination. CONCLUSIONS: LGBTQ-affirmative ICBT demonstrates preliminary efficacy for Chinese young sexual minority men. Findings can inform future interventions for young sexual minority men in contexts with limited affirmative supports.

7.
BMJ Open ; 14(7): e082387, 2024 Jul 18.
Article in English | MEDLINE | ID: mdl-39025812

ABSTRACT

OBJECTIVES: (1) To develop an intervention for to support patients diagnosed with an anterior cruciate ligament (ACL) rupture with decision-making regarding treatment. (2) To define evidence-based recommendations for the treatment of patients following an ACL rupture. DESIGN: Nominal group technique consensus study. SETTING: Online meetings with patients and key stakeholders working and receiving treatment in the National Health Service, UK. PARTICIPANTS: Consensus meetings composed of eight voting participants and five non-voting facilitators. Voting participants included five clinicians, one outpatient therapy manager and two patients with experience in an ACL rupture and reconstructive surgery. Non-voting facilitators supported group discussions and/or observed study procedures. This included a clinical academic expert, two methodology experts and two patient representatives. METHOD: Two online meetings were held. Pre-elicitation material was distributed ahead of the first meeting. Premeeting voting was conducted ahead of both meetings. A draft of the shared decision-making intervention and recommendations were shared ahead of the second meeting. Components were discussed and ranked for inclusion based on a 70% agreement threshold. RESULTS: The meetings led to the development of a shared decision-making intervention to support treatment decision-making following an ACL rupture. The intervention includes two components: (1) a patient information leaflet and key questions diagram and (2) option grid. The evidence-based recommendations encompass core components of treatment reaching the 70% threshold agreed by the group. The recommendations cover: (1) advice and education, (2) exercise guidance, (3) intervention delivery, (4) outcome measure use and (5) shared decision-making. CONCLUSION: This study has successfully developed a shared decision-making intervention to support ACL treatment decision-making, ready for testing in a future feasibility study. Evidence-based recommendations for the treatment of patients following ACL injury, ready for testing in a National Health Service (UK) setting, are also presented. TRIAL REGISTRATION NUMBER: NCT05529511.


Subject(s)
Anterior Cruciate Ligament Injuries , Consensus , Decision Making, Shared , Humans , Anterior Cruciate Ligament Injuries/therapy , Anterior Cruciate Ligament Injuries/surgery , Anterior Cruciate Ligament Reconstruction/methods , United Kingdom , Female , Male , Patient Participation
8.
RSC Med Chem ; 15(7): 2462-2473, 2024 Jul 17.
Article in English | MEDLINE | ID: mdl-39026632

ABSTRACT

The phosphoantigen (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMBPP) is an established activator of Vγ9/Vδ2 T cells and stimulates downstream effector functions including cytotoxicity and cytokine production. In order to improve its drug-like properties, we herein report the design, synthesis, serum stability, in vitro metabolism, and biological evaluation of a new class of symmetrical phosphonodiamidate prodrugs of methylene and difluoromethylene monophosphonate derivatives of HMBPP. These prodrugs, termed phosphonodiamidate ProPAgens, were synthesized in good yields, exhibited excellent serum stability (>7 h), and their in vitro metabolism was shown to be initiated by carboxypeptidase Y. These phosphonodiamidate ProPAgens triggered potent activation of Vγ9/Vδ2 T cells, which translated into efficient Vγ9/Vδ2 T cell-mediated eradication of bladder cancer cells in vitro. Together, these findings showcase the potential of these phosphonodiamidate ProPAgens as Vγ9/Vδ2 T cell modulators that could be further developed as novel cancer immunotherapeutic agents.

9.
J Emerg Nurs ; 2024 Jul 14.
Article in English | MEDLINE | ID: mdl-39001770
10.
ACS Macro Lett ; 13(7): 896-902, 2024 Jul 16.
Article in English | MEDLINE | ID: mdl-38959477

ABSTRACT

We investigate the universality of entanglement kinetics in polymer melts. We compare predictions of a recently developed constitutive equation for disentanglement to molecular dynamics simulations of both united-atom polyethylene and Kremer-Grest models for polymers in shear and extensional flow. We confirm that entanglements recover on the retraction time scale, rather than the reptation time scale. We find that the convective constraint release parameter ß is independent of molecular weight, but that it increases with the ratio of Kuhn length bK to packing length p as ß âˆ¼ (bK/p)α, with an exponent α = 1.9, which may suggest that disentanglement rate correlates with an increase in the tube diameter. These results may help shed light on which polymers are more likely to undergo shear banding.

11.
J Surg Res ; 301: 352-358, 2024 Jul 17.
Article in English | MEDLINE | ID: mdl-39024714

ABSTRACT

INTRODUCTION: Currently, there is no mandatory standard for reporting race and ethnicity in medical journals, presenting significant barriers to studying disparities in medical outcomes. We seek to investigate whether greater recent awareness of diversity and inclusion reflects in reporting of race and ethnicity by peer-reviewed cardiothoracic articles. METHODS: Pubmed was queried for clinical outcomes articles published from January 2017 to June 2023 in the Journal of Thoracic and Cardiovascular Surgery, Annals of Thoracic Surgery, Journal of Heart and Lung Transplantation, and CHEST Journal. Basic science, translational studies, and international studies were excluded. SAS Studio was used for statistical analysis. RESULTS: 817 papers were reviewed, 378 reported race/ethnicity with 354 (93%) reporting White, 267 (71%) reporting Black, 128 (34%) reporting Hispanic, and 119 (31%) reporting Asian. Over 8-y, there were no statistically significant changes in percent of articles that included White (odds ratio 0.808 95% confidence interval [0.624-1.047], P = 0.1068), Black (1.125 [0.984-1.288], P = 0.0857), or Asian (1.096 [0.960-1.250], P = 0.1751) groups. Hispanics were more likely to be reported in recent years (1.147 [1.006-1.307], P = 0.0397). Subset analysis was performed on cardiac (n = 157) and thoracic articles (n = 157) with no significant trends for race reporting in these subsets. CONCLUSIONS: Minorities remain underrepresented in reported patient populations in peer-reviewed cardiothoracic journals. Future efforts should prioritize accurately representing these populations in the literature. Inaccurate data and exclusion of minority populations can contribute to disparities observed in overall outcomes.

12.
J Pers Disord ; 38(3): 241-267, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38857161

ABSTRACT

Conceptual work integrating constructs from mainstream personality research (especially so-called "dark" traits) and clinical psychopathology research has been limited. Herein, we propose all socially and/or ethically aversive traits as "flavored" manifestations of the D factor of personality (D). We argue that the D framework provides the commonality of all aversive traits, including the aversive traits from the DSM-5 Alternative Model for Personality Disorders (AMPD), a more thorough theoretical foundation. Moreover, D covers aspects that are not captured by any of the aversive AMPD traits directly (e.g., greed), thus offering indications for possible expansions to the AMPD. We tested our predictions in two online studies (N = 1,781 and N = 2,006) using quota-representative samples of the German population regarding age and gender. Twelve aversive traits from mainstream personality research and eight aversive AMPD traits were assessed together with consequential behavior in an economic game. Analyses using structural equation modeling overall confirmed predictions.


Subject(s)
Personality Disorders , Personality , Humans , Female , Male , Adult , Middle Aged , Young Adult , Adolescent , Aged , Germany
13.
Abdom Radiol (NY) ; 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38831073

ABSTRACT

As the use of cross-sectional abdominal and pelvic imaging has increased exponentially in the past several decades, incidental musculoskeletal findings have become commonplace. These are often unrelated to the indication for the examination and are frequently referred to as the "radiologist's blind spot" on these studies. The differential diagnosis for abnormalities of the paraspinal and pelvic musculature is, in many cases, quite different from the anterior abdominal wall muscles. Furthermore, due to their relatively deep location, pathology involving the former muscle groups is more likely to be clinically occult, often presenting only incidentally when the patient undergoes cross-sectional imaging. Effective treatment of diseases of these muscles is dependent on adherence to a diverse set of diagnostic and treatment algorithms. The purpose of this review article is to familiarize the radiologist with the unique pathology of these often-overlooked muscles of the abdomen and pelvis.

14.
J Orthop Case Rep ; 14(6): 89-95, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38910980

ABSTRACT

Introduction: Osteochondromas are the most common benign tumors of the bone and can be sessile or pedunculated. Although osteochondromas are typically seen in the long bones, they are rarely seen in the small bones of the hand or foot. Verruca vulgaris, also known as the common wart, is one of the most common skin conditions presenting to physicians and must be distinguished either clinically or histologically from other hyperkeratotic conditions, including bone conditions such as bone tumors that can place pressure on the skin and cause callus formation that can mimic a wart or create skin deformity. A high index of suspicion for underlying bone mass or tumor should be entertained when evaluating patients for skin conditions, particularly of the hand or foot, with failure to improve with treatment. Case Report: This case report presents a 20-year-old male with a pedunculated osteochondroma of the left fourth distal phalanx with hyperkeratotic skin overlying the mass at the end of the toe. He was initially treated by a family doctor and podiatrist for verruca vulgaris for over 5 years with two treatments of liquid nitrogen cryotherapy and surgical excision of the mass when the treating podiatrist encountered bone and recommended radiographs. The family requested follow-up with our practice several days later after they were told the patient had a bone tumor. The patient requested surgical excision of the osteochondroma secondary to pain with activities and difficulties with his vocation as a pilot. Conclusion: All physicians must be mindful of an underlying bone tumor or mass in patients presenting with skin changes, particularly about the foot or hand. Knowledge that an underlying bone tumor can present as a verruca vulgaris may prevent a delay in diagnosis or unnecessary treatment when evaluating and treating a patient with a skin lesion. Fortunately, our case was a benign osteochondroma; a malignant tumor with a delay in diagnosis could lead to loss of limb or life.

15.
Urol Case Rep ; 55: 102762, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38911466

ABSTRACT

Penile strangulation secondary to utilization of a constrictive ring is a rare urologic emergency that requires urgent decompression to prevent prolonged vascular obstruction resulting in necrosis and gangrene. Current literature is mainly comprised of case presentations that focus on management in the acute setting via removal of the ring. Herein, we describe surgical management of a patient who presents in delayed fashion after self-removal of the constrictive ring. We discuss our penectomy-sparing technique of debridement and split thickness skin graft.

16.
J Pediatr Surg ; 2024 May 28.
Article in English | MEDLINE | ID: mdl-38914510

ABSTRACT

INTRODUCTION: Inguinal hernia repair (IHR) is a common pediatric operation performed via open or laparoscopic approaches. The objective of this survey study was to assess current approaches to IHR in a national sample of pediatric general surgeons. METHODS: A REDCap survey was distributed to all pediatric general surgeons at 21 US institutions in 2023. Descriptive statistics were used to analyze responses. RESULTS: The response rate was 70.0% (145/207) with median fellowship graduation year of 2011. Respondents reported they were primarily taught either an open (73.1%) or laparoscopic (6.9%) technique in fellowship, while 18.6% reported being taught both techniques equally. Overall, 60.7% of respondents reported currently performing both laparoscopic and open IHR, while 27.6% reported performing only open IHR and 11.7% reported performing only laparoscopic IHR. During unilateral open IHR, 75.8% of respondents check for and repair a contralateral inguinal hernia, most commonly by placing a laparoscope via the hernia sac (76.3%). Selective mesh use in adolescents was similar between laparoscopic and open repair approaches. For recurrent hernias, 37.2% of respondents indicated performing the approach that was not performed previously, while 38.6% and 22.8% indicated they routinely perform a laparoscopic or open approach, respectively, regardless of initial repair approach. CONCLUSION: Over two thirds of surgeons reported incorporating laparoscopic IHR into their practice despite nearly three-quarters of respondents indicating they were primarily taught an open approach in training. Training in laparoscopic IHR has been increasing over time, and respondents reported a wide variety of laparoscopic and open repair techniques. LEVEL OF EVIDENCE: IV.

17.
ACS Nano ; 18(25): 16151-16165, 2024 Jun 25.
Article in English | MEDLINE | ID: mdl-38861479

ABSTRACT

Immune modulation through the intracellular delivery of nucleoside-modified mRNA to immune cells is an attractive approach for in vivo immunoengineering, with applications in infectious disease, cancer immunotherapy, and beyond. Lipid nanoparticles (LNPs) have come to the fore as a promising nucleic acid delivery platform, but LNP design criteria remain poorly defined, making the rate-limiting step for LNP discovery the screening process. In this study, we employed high-throughput in vivo LNP screening based on molecular barcoding to investigate the influence of LNP composition on immune tropism with applications in vaccines and systemic immunotherapies. Screening a large LNP library under both intramuscular (i.m.) and intravenous (i.v.) injection, we observed differential influences on LNP uptake by immune populations across the two administration routes, gleaning insight into LNP design criteria for in vivo immunoengineering. In validation studies, the lead LNP formulation for i.m. administration demonstrated substantial mRNA translation in the spleen and draining lymph nodes with a more favorable biodistribution profile than LNPs formulated with the clinical standard ionizable lipid DLin-MC3-DMA (MC3). The lead LNP formulations for i.v. administration displayed potent immune transfection in the spleen and peripheral blood, with one lead LNP demonstrating substantial transfection of splenic dendritic cells and another inducing substantial transfection of circulating monocytes. Altogether, the immunotropic LNPs identified by high-throughput in vivo screening demonstrated significant promise for both locally- and systemically-delivered mRNA and confirmed the value of the LNP design criteria gleaned from our screening process, which could potentially inform future endeavors in mRNA vaccine and immunotherapy applications.


Subject(s)
Lipids , Mice, Inbred C57BL , Nanoparticles , RNA, Messenger , Animals , Nanoparticles/chemistry , RNA, Messenger/genetics , Mice , Lipids/chemistry , High-Throughput Screening Assays , Female , Injections, Intramuscular , Dendritic Cells/immunology , Dendritic Cells/metabolism , Injections, Intravenous , Immunotherapy , Liposomes
18.
Urol Clin North Am ; 51(3): 327-334, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38925735

ABSTRACT

Penile cancer is a rare cancer, where patients not only need to deal with the anxiety around a cancer diagnosis, but also manage the consequences of treatment on their self-esteem, body image, and intimate relationships. Many find it embarrassing and difficult to talk to family and friends. Due to this, changes in urination and other physical effects of treatment, many will withdraw from social activities too. Patients need psychosocial support and more needs to be done to address this unmet need. Holistic and multidisciplinary approaches in clinic, with access to counseling, may help patients adjust to their new situation.


Subject(s)
Penile Neoplasms , Psychosocial Support Systems , Humans , Male , Communication , Penile Neoplasms/complications , Penile Neoplasms/psychology , Penile Neoplasms/therapy , Social Interaction , Spouses/psychology , Suicide/psychology , Recurrence , Counseling
19.
Brain ; 2024 Jun 25.
Article in English | MEDLINE | ID: mdl-38916996

ABSTRACT

Lewy body dementia and Alzheimer's disease (AD) are leading causes of cognitive impairment, characterized by distinct but overlapping neuropathological hallmarks. Lewy body disease (LBD) is characterized by alpha-synuclein aggregates in the form of Lewy bodies as well as the deposition of extracellular amyloid plaques, with many cases also exhibiting neurofibrillary tangle (NFT) pathology. In contrast, Alzheimer's disease is characterized by amyloid plaques and neurofibrillary tangles. Both conditions often co-occur with additional neuropathological changes, such as vascular disease and TDP-43 pathology. To elucidate shared and distinct molecular signatures underlying these mixed neuropathologies, we extensively analyzed transcriptional changes in the anterior cingulate cortex, a brain region critically involved in cognitive processes. We performed bulk tissue RNAseq from the anterior cingulate cortex and determined differentially expressed genes (q-value < 0.05) in control (n = 81), Lewy body disease (n = 436), Alzheimer's disease (n = 53), and pathological amyloid cases consisting of amyloid pathology with minimal or no tau pathology (n = 39). We used gene set enrichment and weighted gene correlation network analysis (WGCNA) to understand the pathways associated with each neuropathologically defined group. Lewy body disease cases had strong up-regulation of inflammatory pathways and down-regulation of metabolic pathways. The Lewy body disease cases were further subdivided into either high Thal amyloid, Braak NFT, or low pathological burden cohorts. Compared to the control cases, the Lewy body disease cohorts consistently showed up-regulation for genes involved in protein folding and cytokine immune response, as well as down-regulation of fatty acid metabolism. Surprisingly, concomitant tau pathology within the Lewy body disease cases resulted in no additional changes. Some core inflammatory pathways were shared between Alzheimer's disease and Lewy body disease but with numerous disease-specific changes. Direct comparison of Lewy body disease cohorts versus Alzheimer's disease cases revealed strong enrichment of synaptic signaling, behavior, and neuronal system pathways. Females had a stronger response overall in both Lewy body and Alzheimer's disease, with several sex-specific changes. Overall, the results identify genes commonly and uniquely dysregulated in neuropathologically defined Lewy body disease and Alzheimer's disease cases, shedding light on shared and distinct molecular pathways. Additionally, the study underscores the importance of considering sex-specific changes in understanding the complex transcriptional landscape of these neurodegenerative diseases.

20.
Obes Surg ; 2024 Jun 25.
Article in English | MEDLINE | ID: mdl-38918268

ABSTRACT

PURPOSE: Metabolic and bariatric surgery (MBS) is presently the most evidence-based, effective treatment of obesity. Nevertheless, only half of the eligible individuals who are referred for this procedure complete it. This study aims to investigate the association between social support and MBS completion, considering race and ethnicity. METHODS: In this prospective cohort study, 413 participants were enrolled between 2019 and 2022. Using the 19-item Brief Family Relationship Scale, which comprises three subscales (eight-item Cohesion subscale, four-item Expressiveness subscale, and seven-item Conflict subscale), the quality of family relationship functioning was assessed. Multivariable logistic regression models were used to determine the association between MBS completion and social support status, adjusting for variables including race, ethnicity, age, gender, body mass index, and insurance. RESULTS: The mean age of the sample was 47.55 years (SD 11.57), with 87% of the participants being female and 39% non-Hispanic White. Nearly 35% of participants (n = 145) completed MBS. Multivariable logistic regression analysis showed overall cohesion (adjusted odds ratio [aOR], 1.52 [95% CI, 1.15-2.00]; p = .003) and overall expressiveness (aOR, 1.58 [95% CI, 1.22-2.05]; p < .001) were associated with higher odds of pursuing MBS. There was no significant interaction between overall cohesion, expressiveness, conflict, and race/ethnicity (p = .61, p = .63, p = .25, respectively). CONCLUSION: The findings indicated that there is a link between family-based social support and MBS completion, regardless of race and ethnicity. Future research should continue to explore the complex interplay between family dynamics and MBS outcomes, considering cultural variations to enhance the effectiveness of obesity interventions within diverse communities.

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