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1.
Surg Obes Relat Dis ; 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38960826

ABSTRACT

BACKGROUND: An important quality benchmark after bariatric surgery is 30-day emergency department (ED) visits. OBJECTIVES: We aimed to identify risk factors for ED visits not requiring readmission and thus deemed preventable. SETTING: University Hospital. METHODS: Patients who underwent a minimally invasive sleeve gastrectomy between 2017 and 2022 at a single institution were identified. Among these patients, those who presented to the ED within 30 days after surgery were matched 3:1 to controls. Sociodemographic and clinical variables were collected from the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program database and the electronic medical record. Univariate conditional logistic regression analysis was performed to determine predictive factors of ED visits. RESULTS: Overall, 648 patients underwent sleeve gastrectomy, of which 53 (8.2%) presented to the ED within 30 days postoperatively without requiring readmission. Patients who presented to the ED were more likely to be unemployed (42% versus 24%, P = .04) and have government insurance (68% versus 41%, P = .001). Significant risk factors included lower versus upper socioeconomic bracket (odds ratio [OR] 3.6, P = .042), primary care physician (PCP) outside the health system versus within (OR 2.15, P = .032), greater number of PCP visits within the past year (OR 1.27, P < .001), and greater number of postoperative clinic phone calls (OR 2.04, P < .001). The number of ED visits within 1 year before surgery was a significant risk factor, with an OR of 1.44 for each visit (P < .001). CONCLUSIONS: Modifiable and unmodifiable risk factors contribute to ED visits after bariatric surgery. Identifying these risk factors can aid in the development of quality improvement initiatives.

2.
Surg Obes Relat Dis ; 2024 Jun 18.
Article in English | MEDLINE | ID: mdl-38987026

ABSTRACT

BACKGROUND: Undiagnosed obstructive sleep apnea (OSA) increases the risk of perioperative complications in bariatric patients. Validated screening methods exist, but are not specific to patients with severe obesity. OBJECTIVES: Determine the ideal OSA screening tool for bariatric surgery patients balancing accuracy and cost-effectiveness. SETTING: University Hospital. METHODS: Bariatric surgery patients from January 2018 to September 2023 were identified from the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP) database. For patients with a STOP-Bang score of ≥4 referred for polysomnogram additional variables were collected from the electronic medical record. The Berlin Score was retrospectively calculated. RESULTS: Out of 484 patients who underwent bariatric surgery, 167 (34.5%) had a STOP-Bang score ≥4. The receiver operating characteristic (ROC) curve for STOP-Bang scores ≥4 had an area under the curve (AUC) of 78.5% for predicting OSA and 83.7% for OSA requiring treatment (Apnea Hypopnea Index [AHI] ≥ 15), compared to Berlin Scores' AUC of 80.7% and 88.6%, respectively. A STOP-Bang score of 4 had a sensitivity of 55.6% and specificity of 36.8%, while a score of 5 had 29.3% and 66.2%, respectively. A Berlin Score of 3 had a sensitivity of 47.5% and specificity of 69.1%, with 30 patients (44.1%) starting OSA treatment. Thirty-five patients (21%) experienced a delay in insurance submission, averaging 41.5 days, related to OSA workup. CONCLUSION: The Berlin questionnaire outperforms STOP-Bang in predicting OSA requiring treatment. Raising the polysomnography referral score from STOP-Bang ≥4 to ≥5 or utilizing a Berlin Score of ≥3, may alleviate resource burden, reduce costs, and expedite medical optimization for bariatric surgery.

3.
Scand J Psychol ; 2024 Jun 14.
Article in English | MEDLINE | ID: mdl-38877602

ABSTRACT

The present study investigated the effects of expansive and contractive body displays on adaptive behavior and affective outcomes. Addressing limitations in past research, the effects were investigated in two different contexts (i.e., fear context and sadness context), compared with two types of control conditions and the moderating effects of motivational traits and symptoms of psychopathology were accounted for. A sample of 186 adults completed a fear experiment involving a mock job interview and a sadness experiment involving sad mood induction. For each experiment, participants were randomly assigned to one of four body manipulations: (1) expansive; (2) contractive; (3) active control (i.e., running in place); or 4) passive control (i.e., doing nothing). The primary outcome was adaptive behavior (i.e., appropriate job-interview behavior and positive recall bias). Secondary affective outcomes were emotions, action tendencies, and appraisals. Results revealed small, non-significant effects of body displays on primary outcomes (ds = 0.19-0.28). For secondary outcomes, significant effects were identified for positive emotions (ds = 0.33). Across secondary outcomes, pairwise comparisons revealed that expansive displays led to more favorable outcomes than contractive displays. For participants with the highest levels of depression, body display conditions led to less favorable affective outcomes than control conditions. The results suggest that body displays do not influence adaptive behavior within the investigated contexts. When compared to contractive displays, expansive displays were found to yield more favorable affective changes. Lastly, the findings indicate that further investigations into body manipulations in the context of psychopathology are warranted.

4.
Biomolecules ; 14(6)2024 Jun 09.
Article in English | MEDLINE | ID: mdl-38927078

ABSTRACT

Risk of cardiovascular disease mortality rises in women after menopause. While increased cardiovascular risk is largely attributed to postmenopausal declines in estrogens, the molecular changes in the heart that contribute to risk are poorly understood. Disruptions in intracellular calcium handling develop in ovariectomized mice and have been implicated in cardiac dysfunction. Using a mouse model of menopause in which ovarian failure occurs over 120 days, we sought to determine if perimenopause impacted calcium removal mechanisms in the heart and identify the molecular mechanisms. Mice were injected with 4-vinylcyclohexene diepoxide (VCD) to induce ovarian failure over 120 days, mimicking perimenopause. Hearts were removed at 60 and 120 days after VCD injections, representing the middle and end of perimenopause. SERCA2a function was significantly diminished at the end of perimenopause. Neither SERCA2a nor phospholamban expression changed at either time point, but phospholamban phosphorylation at S16 and T17 was dynamically altered. Intrinsic SERCA inhibitors sarcolipin and myoregulin increased >4-fold at day 60, as did the native activator DWORF. At the end of perimenopause, sarcolipin and myoregulin returned to baseline levels while DWORF was significantly reduced below controls. Sodium-calcium exchanger expression was significantly increased at the end of perimenopause. These results show that the foundation for increased cardiovascular disease mortality develops in the heart during perimenopause and that regulators of calcium handling exhibit significant fluctuations over time. Understanding the temporal development of cardiovascular risk associated with menopause and the underlying mechanisms is critical to developing interventions that mitigate the rise in cardiovascular mortality that arises after menopause.


Subject(s)
Disease Models, Animal , Perimenopause , Sarcoplasmic Reticulum Calcium-Transporting ATPases , Animals , Female , Sarcoplasmic Reticulum Calcium-Transporting ATPases/metabolism , Sarcoplasmic Reticulum Calcium-Transporting ATPases/genetics , Mice , Perimenopause/metabolism , Vinyl Compounds/pharmacology , Myocardium/metabolism , Calcium/metabolism , Calcium-Binding Proteins/metabolism , Primary Ovarian Insufficiency/metabolism , Cyclohexenes/pharmacology , Mice, Inbred C57BL , Phosphorylation
5.
Article in English | MEDLINE | ID: mdl-38722846

ABSTRACT

INTRODUCTION: Three-dimensional (3D) printed models may help patients understand complex anatomic pathologies such as femoroacetabular impingement syndrome (FAIS). We aimed to assess patient understanding and satisfaction when using 3D printed models compared with standard imaging modalities for discussion of FAIS diagnosis and surgical plan. METHODS: A consecutive series of 76 new patients with FAIS (37 patients in the 3D model cohort and 39 in the control cohort) from a single surgeon's clinic were educated using imaging and representative 3D printed models of FAI or imaging without models (control). Patients received a voluntary post-visit questionnaire that evaluated their understanding of the diagnosis, surgical plan, and visit satisfaction. RESULTS: Patients in the 3D model cohort reported a significantly higher mean understanding of FAIS (90.0 ± 11.5 versus 79.8 ± 14.9 out of 100; P = 0.001) and surgery (89.5 ± 11.6 versus 81.0 ± 14.5; P = 0.01) compared with the control cohort. Both groups reported high levels of satisfaction with the visit. CONCLUSION: In this study, the use of 3D printed models in clinic visits with patients with FAIS improved patients' perceived understanding of diagnosis and surgical treatment.


Subject(s)
Femoracetabular Impingement , Models, Anatomic , Patient Satisfaction , Printing, Three-Dimensional , Humans , Femoracetabular Impingement/surgery , Femoracetabular Impingement/diagnostic imaging , Female , Male , Adult , Middle Aged , Patient Education as Topic , Surveys and Questionnaires , Comprehension
6.
Orthop J Sports Med ; 12(5): 23259671241243345, 2024 May.
Article in English | MEDLINE | ID: mdl-38708007

ABSTRACT

Background: Hamstring strains are common among elite athletes, but their effect on return to the same level of play in American football has been incompletely characterized. Purpose: Data on National Collegiate Athletics Association Division I college football players with acute hamstring strains were gathered to identify the effects these injuries have on both return to play and athletic performance regarding velocity, workload, and acceleration. Study Design: Case Series; Level of evidence, 4. Methods: Injury data for a single Division I football team were prospectively recorded over a 4-year period. Players wore global navigation satellite system and local positioning system (GNSS/LPS) devices to record movement data in practices and games. The practice and game data were cross-referenced to evaluate players with isolated acute hamstring strains. Comparisons were made regarding players' pre- and postinjury ability to maintain high velocity (>12 mph [19.3 kph]), maximal velocity, triaxial acceleration, and inertial movement analysis (IMA). There were 58 hamstring injuries in 44 players, of which 25 injuries from 20 players had GNSS/LPS data. Results: Players were able to return to play from all 25 injury incidences at a mean of 9.2 days. At the final mean follow-up of 425 days, only 4 players had reached preinjury function in all measurements; 12 players were able to return in 2 of the 4 metrics; and only 8 players reached their preinjury ability to maintain high velocity. For those who did not achieve this metric, there was a significant difference between pre- and postinjury values (722 vs 442 m; P = .016). A total of 14 players were able to regain their IMA. Players who returned to prior velocity or acceleration metrics did so at a mean of 163 days across all metrics. Conclusion: While players may be able to return to play after hamstring strain, many players do not reach preinjury levels of acceleration or velocity, even after 13.5 months. Further studies are needed to confirm these findings, assess clinical relevance on imaging performance, and improve hamstring injury prevention and rehabilitation.

7.
Brief Bioinform ; 25(3)2024 Mar 27.
Article in English | MEDLINE | ID: mdl-38701421

ABSTRACT

Cancer is a complex cellular ecosystem where malignant cells coexist and interact with immune, stromal and other cells within the tumor microenvironment (TME). Recent technological advancements in spatially resolved multiplexed imaging at single-cell resolution have led to the generation of large-scale and high-dimensional datasets from biological specimens. This underscores the necessity for automated methodologies that can effectively characterize molecular, cellular and spatial properties of TMEs for various malignancies. This study introduces SpatialCells, an open-source software package designed for region-based exploratory analysis and comprehensive characterization of TMEs using multiplexed single-cell data. The source code and tutorials are available at https://semenovlab.github.io/SpatialCells. SpatialCells efficiently streamlines the automated extraction of features from multiplexed single-cell data and can process samples containing millions of cells. Thus, SpatialCells facilitates subsequent association analyses and machine learning predictions, making it an essential tool in advancing our understanding of tumor growth, invasion and metastasis.


Subject(s)
Single-Cell Analysis , Software , Tumor Microenvironment , Single-Cell Analysis/methods , Humans , Neoplasms/pathology , Machine Learning , Computational Biology/methods
8.
Mol Biol Cell ; 35(6): ar76, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38598303

ABSTRACT

Endosomal coats incorporate membrane-binding subunits such as sorting nexin (SNX) proteins. The Saccharomyces cerevisiae SNX-BAR paralogs Vin1 and Vps5 are respective subunits of the endosomal VINE and retromer complexes whose dimerizing BAR domains are required for complex assembly and membrane association. However, a degree of promiscuity is predicted for yeast BAR-BAR pairings, and recent work has implicated the unstructured N-terminal domains of Vin1 and Vps5 in coat formation. Here, we map N-terminal signals in both SNX-BAR paralogs that contribute to the assembly and function of two distinct endosomal coats in vivo. Whereas Vin1 leverages a polybasic region and adjacent hydrophobic motif to bind Vrl1 and form VINE, the N-terminus of Vps5 interacts with the retromer subunit Vps29 at two sites, including a conserved hydrophobic pocket in Vps29 that engages other accessory proteins in humans. We also examined the sole isoform of Vps5 from the milk yeast Kluyveromyces lactis and found that ancestral yeasts may have used a nested N-terminal signal to form both VINE and retromer. Our results suggest that the specific assembly of Vps5-family SNX-BAR coats depends on inputs from unique N-terminal sequence features in addition to BAR domain coupling, expanding our understanding of endosomal coat biology.


Subject(s)
Endosomes , Saccharomyces cerevisiae Proteins , Saccharomyces cerevisiae , Sorting Nexins , Vesicular Transport Proteins , Endosomes/metabolism , Saccharomyces cerevisiae Proteins/metabolism , Saccharomyces cerevisiae Proteins/genetics , Sorting Nexins/metabolism , Sorting Nexins/genetics , Saccharomyces cerevisiae/metabolism , Vesicular Transport Proteins/metabolism , Vesicular Transport Proteins/genetics , Protein Binding , Protein Domains , Humans , Amino Acid Sequence
9.
Front Microbiol ; 15: 1361270, 2024.
Article in English | MEDLINE | ID: mdl-38510998

ABSTRACT

Introduction: Bacteria inhabit the in- and outside of the human body, such as skin, gut or the oral cavity where they play an innoxious, beneficial or even pathogenic role. It is well known that bacteria can secrete membrane vesicles (MVs) like eukaryotic cells with extracellular vesicles (EVs). Several studies indicate that bacterial membrane vesicles (bMVs) play a crucial role in microbiome-host interactions. However, the composition of such bMVs and their functionality under different culture conditions are still largely unknown. Methods: To gain a better insight into bMVs, we investigated the composition and functionality of E. coli (DSM 105380) bMVs from the culture media Lysogeny broth (LB) and RPMI 1640 throughout the different phases of growth (lag-, log- and stationary-phase). bMVs from three time points (8 h, 54 h, and 168 h) and two media (LB and RPMI 1640) were isolated by ultracentrifugation and analyzed using nanoparticle tracking analysis (NTA), cryogenic electron microscopy (Cryo-EM), conventional transmission electron microscopy (TEM) and mass spectrometry-based proteomics (LC-MS/MS). Furthermore, we examined pro-inflammatory cytokines IL-1ß and IL-8 in the human monocyte cell line THP-1 upon bMV treatment. Results: Particle numbers increased with inoculation periods. The bMV morphologies in Cryo-EM/TEM were similar at each time point and condition. Using proteomics, we identified 140 proteins, such as the common bMV markers OmpA and GroEL, present in bMVs isolated from both media and at all time points. Additionally, we were able to detect growth-condition-specific proteins. Treatment of THP-1 cells with bMVs of all six groups lead to significantly high IL-1ß and IL-8 expressions. Conclusion: Our study showed that the choice of medium and the duration of culturing significantly influence both E. coli bMV numbers and protein composition. Our TEM/Cryo-EM results demonstrated the presence of intact E. coli bMVs. Common E. coli proteins, including OmpA, GroEL, and ribosome proteins, can consistently be identified across all six tested growth conditions. Furthermore, our functional assays imply that bMVs isolated from the six groups retain their function and result in comparable cytokine induction.

10.
JAMA Otolaryngol Head Neck Surg ; 150(5): 414-420, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38546619

ABSTRACT

Importance: In clinical trials, preoperative immune checkpoint inhibitors (ICIs) have shown clinical activity in advanced cutaneous squamous cell carcinoma (cSCC). However, these studies excluded patients with relevant comorbidities. Objective: To evaluate radiologic and pathologic response rates to neoadjuvant-intent programed cell death protein 1 (PD-1) ICIs in a clinical population. Design, Setting, and Participants: This cohort study of patients who were treated with neoadjuvant cemiplimab or pembrolizumab for advanced cSCC from January 2018 to January 2023 was conducted at 2 academic institutions in Boston, Massachusetts. Median follow-up was 9.5 months (range, 1.2-40.5). Exposures: Cemiplimab or pembrolizumab. Main Outcomes and Measures: Primary outcomes were radiologic and pathologic response rates. Secondary outcomes were 1-year recurrence-free survival, progression-free survival, disease-specific survival, and overall survival. Results: This cohort study included 27 patients (including 9 patients [33.3%] with a history of lymphoma). Most patients were male (18 of 27 [66.7%]), with a median age of 72 years (range, 53-87 years). Most primary tumors were located on the head/neck (21 of 27 [77.8%]). There were no unexpected delays in surgery. The median number of doses before surgery was 3.5 (range, 1.0-10.0). Five patients (18.5%) ultimately declined to undergo planned surgery due to clinical responses or stability, and 1 (3.7%) did not undergo surgery due to progressive disease. The overall pathologic response rate (pathological complete response [pCR] or major pathological response) was 47.4% (9 of 19), and the overall radiologic response rate (radiologic complete response or partial response) was 50.0% (8 of 16). The pCR rate (7 of 19 [36.8%]) was higher than the radiologic complete response rate (2 of 16 [12.5%]). The pCR rate among patients with cSCC and concomitant lymphoma was 25.0%. The 1-year recurrence-free survival rate was 90.9% (95% CI, 50.8%-98.7%), progression-free survival was 83.3% (95% CI, 27.3%-97.5%), disease-specific survival was 91.7% (95% CI, 53.9%-98.8%), and overall survival was 84.6% (95% CI, 51.2%-95.9%). Conclusions and Relevance: The results of this cohort study support the reproducibility of neoadjuvant-intent immunotherapy for cSCC in the clinical setting, including for patients with a history of lymphoma. Outside of clinical trials, it is not infrequent for patients to opt out of surgery for regressing tumors. The inclusion of higher-risk patients and preference for nonsurgical treatment are 2 factors that might explain the numerically lower pathologic response rate in this institutional experience.


Subject(s)
Antibodies, Monoclonal, Humanized , Carcinoma, Squamous Cell , Neoadjuvant Therapy , Skin Neoplasms , Humans , Male , Female , Aged , Skin Neoplasms/pathology , Skin Neoplasms/therapy , Skin Neoplasms/mortality , Middle Aged , Aged, 80 and over , Antibodies, Monoclonal, Humanized/therapeutic use , Carcinoma, Squamous Cell/therapy , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/mortality , Immune Checkpoint Inhibitors/therapeutic use , Cohort Studies , Retrospective Studies , Antineoplastic Agents, Immunological/therapeutic use , Immunotherapy/methods
11.
J Vasc Surg Cases Innov Tech ; 10(2): 101395, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38304294

ABSTRACT

Popliteal artery entrapment syndrome (PAES) is compression of the popliteal artery from embryologic myotendinous variation or calf muscle hypertrophy. PAES necessitates prompt diagnosis and complete release of the entrapped vasculature for symptom relief and to prevent chronic cumulative vascular damage. Our patient is a 27-year-old female referred for progressive bilateral claudication. Workup was consistent with bilateral PAES with preoperative imaging notable for an atypically proximal origin of the anterior tibial artery, which was also encased anterior to the popliteus muscle. Preoperative angiogram confirmed the diagnosis, and complete surgical release resolved symptoms by 4 months postoperatively.

12.
J Genet Couns ; 2024 Feb 09.
Article in English | MEDLINE | ID: mdl-38339832

ABSTRACT

Opportunities for genetic counselors to work in a variety of practice settings have greatly expanded, particularly in the laboratory. This study aimed to assess attitudes of genetic counselors working both within and outside of the laboratory setting regarding (1) the re-wording and/or expansion of key measures of genetic counselors' competency, including practice-based competencies (PBCs) and board examination, to include laboratory roles, (2) preparation and transferability of competencies developed in master's in genetic counseling (MGC) programs to different roles, (3) need of additional training for genetic counselors to practice in laboratory settings, and (4) preferred methods to obtain that training. An e-blast was sent to ABGC diplomats (N = 5458) with a link to a 29-item survey with 12 demographic questions to compare respondents to 2021 NSGC Professional Status Survey (PSS) respondents. Statistical comparisons were made between respondents working in the laboratory versus other settings. Among 399 responses received, there was an oversampling of respondents working in the laboratory (52% vs. 20% in PSS) and in non-direct patient care positions (47% vs. 25% in PSS). Most respondents agreed the PBCs were transferable to their work yet favored making the PBCs less direct patient care-focused, expanding PBCs to align with laboratory roles, adding laboratory-focused questions to the ABGC exam, and adding laboratory-focused training in MGC programs. Most agreed requiring post-MGC training would limit genetic counselors' ability to change jobs. Genetic counselors working in the laboratory reported being significantly less prepared by their MGC program for some roles (p < 0.001) or how the PBCs applied to non-direct patient care positions (p < 0.001). Only 53% of all respondents agreed that NSGC supports their professional needs and others in their practice area, and genetic counselors working in the laboratory were significantly less likely to agree (p = 0.002). These sentiments should be further explored.

13.
Am J Clin Pathol ; 161(5): 490-500, 2024 May 02.
Article in English | MEDLINE | ID: mdl-38206110

ABSTRACT

OBJECTIVES: Cowden syndrome (CS) is a multisystem disease with an elevated lifetime risk of internal malignancy. We aim to assess the role of PTEN immunostain as a screening test for CS in a variety of common CS-associated neoplasms, with a particular focus on cutaneous tumors. METHODS: We retrospectively searched for patients meeting criteria for CS and/or demonstrating germline PTEN mutation from 2008 to 2022. We then performed PTEN immunostains on tumors of these patients as well as control cases. RESULTS: Our study included 30 patients with CS who had a total of 25 CS-associated malignancies (13 thyroid, 8 breast, and 4 endometrial carcinomas). Specifically, there were 11 patients with biopsy-confirmed CS-associated cutaneous neoplasms, including 1 patient with multiple trichilemmomas and 3 with multiple sclerotic fibromas. In total, 45 CS-associated tumors (6 trichilemmomas, 7 sclerotic fibromas, 5 thyroid carcinomas, 18 adenomatous thyroid nodules, 6 breast carcinomas, and 3 endometrial carcinomas) and 31 non-CS cases (9 trichilemmomas, 5 sclerotic fibromas, 8 adenomatous thyroid nodules, and 3 thyroid, 3 breast, and 3 endometrial carcinomas) were available for PTEN immunohistochemical staining. PTEN expression was lost in 43 (96%) of 45 CS-associated lesions and retained in 30 (97%) of 31 sporadic tumors. The overall sensitivity and specificity of PTEN loss of expression as a screening test for CS were 96% and 97%, respectively. CONCLUSIONS: PTEN immunohistochemistry on CS-associated tumors, especially trichilemmomas, can serve as a readily accessible and cost-effective screening test for CS.


Subject(s)
Hamartoma Syndrome, Multiple , Immunohistochemistry , PTEN Phosphohydrolase , Humans , Hamartoma Syndrome, Multiple/diagnosis , Hamartoma Syndrome, Multiple/pathology , Hamartoma Syndrome, Multiple/genetics , PTEN Phosphohydrolase/metabolism , PTEN Phosphohydrolase/genetics , Female , Middle Aged , Adult , Retrospective Studies , Male , Aged , Biomarkers, Tumor/metabolism , Biomarkers, Tumor/analysis , Skin Neoplasms/diagnosis , Skin Neoplasms/pathology , Skin Neoplasms/metabolism , Thyroid Neoplasms/diagnosis , Thyroid Neoplasms/pathology , Thyroid Neoplasms/metabolism , Thyroid Neoplasms/genetics , Breast Neoplasms/diagnosis , Breast Neoplasms/pathology , Breast Neoplasms/metabolism , Breast Neoplasms/genetics
14.
Cell Metab ; 36(3): 526-540.e7, 2024 03 05.
Article in English | MEDLINE | ID: mdl-38272036

ABSTRACT

That uncoupling protein 1 (UCP1) is the sole mediator of adipocyte thermogenesis is a conventional viewpoint that has primarily been inferred from the attenuation of the thermogenic output of mice genetically lacking Ucp1 from birth (germline Ucp1-/-). However, germline Ucp1-/- mice harbor secondary changes within brown adipose tissue. To mitigate these potentially confounding ancillary changes, we constructed mice with inducible adipocyte-selective Ucp1 disruption. We find that, although germline Ucp1-/- mice succumb to cold-induced hypothermia with complete penetrance, most mice with the inducible deletion of Ucp1 maintain homeothermy in the cold. However, inducible adipocyte-selective co-deletion of Ucp1 and creatine kinase b (Ckb, an effector of UCP1-independent thermogenesis) exacerbates cold intolerance. Following UCP1 deletion or UCP1/CKB co-deletion from mature adipocytes, moderate cold exposure triggers the regeneration of mature brown adipocytes that coordinately restore UCP1 and CKB expression. Our findings suggest that thermogenic adipocytes utilize non-paralogous protein redundancy-through UCP1 and CKB-to promote cold-induced energy dissipation.


Subject(s)
Adipocytes, Brown , Adipose Tissue, Brown , Animals , Mice , Adipocytes, Brown/metabolism , Adipose Tissue, Brown/metabolism , Thermogenesis , Uncoupling Protein 1/genetics , Uncoupling Protein 1/metabolism , Creatine Kinase, BB Form/metabolism
15.
Curr Rev Musculoskelet Med ; 17(3): 59-67, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38182802

ABSTRACT

PURPOSE OF REVIEW: Arthroscopic treatment of femoroacetabular impingement syndrome (FAIS) continues to rise in incidence, and thus there is an increased focus on factors that predict patient outcomes. The factors that impact the outcomes of arthroscopic FAIS treatment are complex. The purpose of this review is to outline the current literature concerning predictors of patient outcomes for arthroscopic treatment of FAIS. RECENT FINDINGS: Multiple studies have shown that various patient demographics, joint parameters, and surgical techniques are all correlated with postoperative outcomes after arthroscopic FAIS surgery, as measured by both validated patient-reported outcome (PRO) scores and rates of revision surgery including hip arthroplasty. To accurately predict patient outcomes for arthroscopic FAIS surgery, consideration should be directed toward preoperative patient-specific factors and intraoperative technical factors. The future of accurately selecting patient predictors for outcomes will only improve with increased data, improved techniques, and technological advancement.

16.
J Am Acad Dermatol ; 90(2): 288-298, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37797836

ABSTRACT

BACKGROUND: The recent expansion of immunotherapy for stage IIB/IIC melanoma highlights a growing clinical need to identify patients at high risk of metastatic recurrence and, therefore, most likely to benefit from this therapeutic modality. OBJECTIVE: To develop time-to-event risk prediction models for melanoma metastatic recurrence. METHODS: Patients diagnosed with stage I/II primary cutaneous melanoma between 2000 and 2020 at Mass General Brigham and Dana-Farber Cancer Institute were included. Melanoma recurrence date and type were determined by chart review. Thirty clinicopathologic factors were extracted from electronic health records. Three types of time-to-event machine-learning models were evaluated internally and externally in the distant versus locoregional/nonrecurrence prediction. RESULTS: This study included 954 melanomas (155 distant, 163 locoregional, and 636 1:2 matched nonrecurrences). Distant recurrences were associated with worse survival compared to locoregional/nonrecurrences (HR: 6.21, P < .001) and to locoregional recurrences only (HR: 5.79, P < .001). The Gradient Boosting Survival model achieved the best performance (concordance index: 0.816; time-dependent AUC: 0.842; Brier score: 0.103) in the external validation. LIMITATIONS: Retrospective nature and cohort from one geography. CONCLUSIONS: These results suggest that time-to-event machine-learning models can reliably predict the metastatic recurrence from localized melanoma and help identify high-risk patients who are most likely to benefit from immunotherapy.


Subject(s)
Melanoma , Skin Neoplasms , Humans , Melanoma/pathology , Skin Neoplasms/pathology , Retrospective Studies , Neoplasm Recurrence, Local/epidemiology , Neoplasm Recurrence, Local/pathology
18.
bioRxiv ; 2023 Nov 14.
Article in English | MEDLINE | ID: mdl-38014067

ABSTRACT

Background: Cancer is a complex cellular ecosystem where malignant cells coexist and interact with immune, stromal, and other cells within the tumor microenvironment. Recent technological advancements in spatially resolved multiplexed imaging at single-cell resolution have led to the generation of large-scale and high-dimensional datasets from biological specimens. This underscores the necessity for automated methodologies that can effectively characterize the molecular, cellular, and spatial properties of tumor microenvironments for various malignancies. Results: This study introduces SpatialCells, an open-source software package designed for region-based exploratory analysis and comprehensive characterization of tumor microenvironments using multiplexed single-cell data. Conclusions: SpatialCells efficiently streamlines the automated extraction of features from multiplexed single-cell data and can process samples containing millions of cells. Thus, SpatialCells facilitates subsequent association analyses and machine learning predictions, making it an essential tool in advancing our understanding of tumor growth, invasion, and metastasis.

19.
J Genet Couns ; 2023 Oct 05.
Article in English | MEDLINE | ID: mdl-37795792

ABSTRACT

With genetic counselor licensure now available in 32 states, the number of laboratory genetic counselors (LGCs) who are required to be licensed in multiple states has risen substantially. Although previous studies have documented the complexity of the multistate licensing (MSL) process, there has been little research on the experiences of LGCs applying for and maintaining licensure. The purpose of this study was to identify perceived barriers, recommendations, and resources for LGCs pursuing MSL. A 15-item mixed-methods, anonymous questionnaire was used to survey genetic counselors currently or formerly employed by genetic testing laboratories. Responses were analyzed with a combination of descriptive statistics and inductive thematic analysis. Of the 150 eligible participants who completed the survey, the majority worked at a commercial, non-academic laboratory (84%, n = 126), had 1-4 years of laboratory genetic counseling experience (54%, n = 81), held non-patient-facing roles (65%, n = 97), and were required by their employer to hold licensure in at least one state (73%, n = 110). Most participants (86%, n = 129) felt there were barriers to MSL for LGCs, with three emergent themes: (1) resource burden, (2) complexity, and (3) legislative ambiguity. Participants described the current MSL process as tedious, cumbersome, confusing, overwhelming, and redundant. Several shared that the current licensing system undermines the intent to improve the status of the profession and actually negatively impacts patient care. Recommendations to improve MSL included overall process enhancements, like transitioning to online systems and a single central information repository for licensees, increased professional advocacy, and investing in collaborative pathways to licensure such as interstate compacts. Participants found national genetic counseling organizations, state-based genetic counseling organizations, and genetic counseling colleagues to be the most helpful resources for understanding licensure law and where to apply for licensure.

20.
Brain Behav ; 13(11): e3247, 2023 11.
Article in English | MEDLINE | ID: mdl-37679879

ABSTRACT

BACKGROUND: The incompatible response hypothesis suggests that emotions and other affective states can counteract each other when incompatible. With the present study, we focused on two negative emotions (anger and anxiety) associated with different action tendencies (approach vs. avoidance). Specifically, we wanted to investigate if an anxiety manipulation, subsequent to an anger manipulation, would show a counteracting effect of the approach action tendencies associated with the initial anger manipulation and vice versa for anxiety and avoidance tendencies. METHODS: We conducted a preregistered online experiment (N = 173). We evaluated changes from when the individual (1) was presented with a task in relation to a specific goal (e.g., anxiety induction: recordings of students' view on climate changes), (2) received a subsequent emotion induction framed within an unrelated task and goal (e.g., anger induction: student feedback on changes to the economic student compensation system), (3) after which they were asked to return to the initial task (e.g., from the anger induction back to the anxiety induction). Primary outcomes included visual and verbal measures of action tendencies, and secondary outcomes included appraisals and emotion experience. RESULTS: The results showed no evidence of a counteractive effect by inducing emotions unrelated to the initial task and with incompatible action tendencies. Rather, results pointed to spill-over effects, which should be seen in light of the anger conditions resulting not only in increase anger and irritability but also anxiety and nervousness. CONCLUSIONS: The lack of counteractive effects could be due to either the mixed emotions induced by the anger condition or the compatibility of motivational context (i.e., threat) of anxiety and anger. Future research needs to refine the incompatible response hypothesis, honing the ways in which incompatibility is needed for emotion alteration, for instance by investigating the role of the motivational context.


Subject(s)
Anger , Emotions , Humans , Emotions/physiology , Anger/physiology , Anxiety/psychology , Affect , Anxiety Disorders
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