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1.
Obes Surg ; 2024 Jun 06.
Article in English | MEDLINE | ID: mdl-38839635

ABSTRACT

INTRODUCTION: Depressive and anxious symptoms and maladaptive eating behaviors fluctuate with stressful events for patients seeking bariatric surgery. These associations are less clear for patients postoperatively. Using the COVID-19 pandemic as a frame, we examined associations between changes in depressive and anxious symptoms and maladaptive eating behaviors between up to four years postoperatively. METHODS: Participants (N = 703) who underwent surgery between 2018 and 2021 completed web-based questionnaires between 2021 and 2022. Demographic and surgical data were obtained from electronic health records. Participants reported whether depressive and anxious symptoms increased or were stable/decreased during the COVID-19 pandemic, and completed eating behavior measures. RESULTS: Many participants reported increased depressive (27.5%) and anxious (33.7%) symptoms during the COVID-19 pandemic. Compared to those who reported stable or decreased symptoms, these participants were as follows: (1) more likely to endorse presence of binge, loss-of-control, graze, and night eating; (2) reported higher emotional eating in response to anger and frustration, depression, and anxiety; and (3) reported higher driven and compulsive eating behaviors. Frequency of binge, loss-of-control, graze, and night eating episodes did not differ between groups (e.g., increased vs. stable/decreased anxious symptoms) among participants who endorsed any episodes. CONCLUSION: A large portion of the sample reported increased depressive and anxious symptoms during the COVID-19 pandemic, and these increases were associated with maladaptive eating behaviors. Depressive and anxious symptoms and eating behaviors should be assessed postoperatively as significant stressors may be associated with increased distress and maladaptive eating behaviors that can affect postoperative outcomes. Postoperative interventions may be useful at simultaneously targeting these concerns.

2.
Int J Behav Med ; 2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38839712

ABSTRACT

BACKGROUND: Internalized weight bias (IWB) negatively impacts mental and physical health, and disproportionately affects women of higher weight. Although self-compassion training may be advantageous for reducing IWB and associated sequalae, further examination of its clinical significance and cultural acceptability is warranted. METHOD: A randomized pilot study was conducted to evaluate the feasibility, including cultural acceptability, and clinical significance of a 3-session self-compassion intervention (SCI) for women with IWB. Women with BMIs of > 25 and IWB (N = 34) were randomly assigned to the SCI or a waitlist control group. Participants completed pre, post, and 1-month follow-up surveys on IWB, self-compassion, body image, eating behaviors, physical activity, and affect. Analyses of covariance were employed and percentages of change were calculated to examine post-intervention between-group differences in outcomes. Cultural acceptability was evaluated through participants' ratings of the perceived inclusivity and relevancy of the SCI. RESULTS: There were 59% (n = 10) and 47% (n = 8) completion rates in the SCI and waitlist control groups, respectively. Compared to the waitlist control group, SCI participants reported greater pre-post improvements in self-compassion, IWB, body shame and surveillance, uncontrolled eating, and physical activity with medium to large effect sizes, and emotional eating with small effects. The SCI was perceived to be beneficial overall, and cultural acceptability ratings were mostly favorable despite individual differences. CONCLUSION: This brief SCI may be beneficial for women impacted by weight stigma and IWB. Attention to increased diversity and cultural acceptability is warranted in future trials.

3.
Appl Spectrosc ; : 37028241241557, 2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38840318

ABSTRACT

Spectral multivariate calibration aims to derive models characterizing mathematical relationships between sample analyte amounts and corresponding spectral responses. These models are effective at predicting target domain sample analyte amounts when target samples are within the analyte and spectral calibration source domain. Models fail when target samples shift (analyte amounts and/or spectra) from the original calibration domain model. A total recalibration solution requires acquisition of new sample reference values and spectra. However, obtaining enough reference values to distinguish the target domain may be challenging or expensive. A simpler approach adapts the original model to the target domain using target sample spectra without analyte reference values (unlabeled). Analytical chemists have developed several machine learning algorithms using unlabeled regression domain adaptation processes. Unfortunately, prediction accuracy declines for these methods depending on how much the target domain analyte distribution has shifted from the calibration distribution, and regression transfer learning methods are instead needed. Regression domain adaptation and transfer learning are often referred to as model updating in analytical chemistry, but regression domain adaptation only applies to spectral shifts. The regression transfer learning method presented in this paper named null augmentation regression constant analyte (NARCA) leverages unlabeled repeat spectra of a single target sample to update an original calibration model to the shifted target domain sample. With sample repeat spectra, the analyte amount can be assumed constant or nearly constant for NARCA and because models are formed for one sample, NARCA operates as a local modeling method. The performance of NARCA as a regression transfer learning method is evaluated using five near-infrared data sets.

4.
Drug Alcohol Depend ; 261: 111350, 2024 Jun 10.
Article in English | MEDLINE | ID: mdl-38875880

ABSTRACT

BACKGROUND: Patients with opioid use disorder (OUD) have increased emergency and hospital utilization. The PROUD trial showed that implementation of office-based addiction treatment (OBAT) increased OUD medication treatment compared to usual care, but did not decrease acute care utilization in patients with OUD documented pre-randomization (clinicaltrials.gov/study/NCT03407638). This paper reports secondary emergency and hospital utilization outcomes in patients with documented OUD in the PROUD trial. METHODS: This cluster-randomized implementation trial was conducted in 12 clinics from 6 diverse health systems (March 2015-February 2020). Patients who visited trial clinics and had an OUD diagnosis within 3 years pre-randomization were included in primary analyses; secondary analyses added patients with OUD who were new to the clinic or with newly-documented OUD post-randomization. Outcomes included days of emergency care and hospital utilization over 2 years post-randomization. Explanatory outcomes included measures of OUD treatment. Patient-level analyses used mixed-effect regression with clinic-specific random intercepts. RESULTS: Among 1988 patients with documented OUD seen pre-randomization (mean age 49, 53 % female), days of emergency care or hospitalization did not differ between intervention and usual care; OUD treatment also did not differ. In secondary analyses among 1347 patients with OUD post-randomization, there remained no difference in emergency or hospital utilization despite intervention patients receiving 32.2 (95 % CI 4.7, 59.7) more days of OUD treatment relative to usual care. CONCLUSIONS: Implementation of OBAT did not reduce emergency or hospital utilization among patients with OUD, even in the sample with OUD first documented post-randomization in whom the intervention increased treatment.

5.
J Public Health Manag Pract ; 30(4): 567-577, 2024.
Article in English | MEDLINE | ID: mdl-38870374

ABSTRACT

CONTEXT: Vision Zero (VZ) aims to reduce fatalities and serious injuries from road traffic crashes to zero through multidisciplinary coordination. While public health officials are often recognized as critical to VZ, their involvement in VZ across the United States has not been quantified. OBJECTIVE: To explore how United States public health officials were involved in VZ development and implementation. DESIGN: We used a mixed-method design including a quantitative assessment of VZ plans and in-depth interviewing with VZ coordinators. SETTING: United States. PARTICIPANTS: Twenty-two in-depth interviews with municipal (n = 12) and regional (n = 10) VZ coordinators and 43 VZ plans were reviewed. MAIN OUTCOME MEASURE: Public health involvement in VZ development and implementation. RESULTS: In the United States, 64 municipalities and 21 regional entities had first-time VZ plans published between 2014 and 2022. We abstracted a sample of municipal (n = 22) and all (n = 21) regional plans. Most plans described key groups involved in plan development (municipal 81.8%, regional 100%). About two-thirds (67.4%; 59.1% municipal, 76.2% regional) of the plans noted public health officials in the plan development. Most plans described the principles forming the foundation of their plan (83.7%), but few mentioned public health as part of the plan principles (22.7% municipal, 14.3% regional). Public health officials were involved in engaging the community (9.1% municipal, 33.3% regional) and providing data (22.7% municipal, 52.4% regional) for plan development, as documented in the plans. For proposed implementation, public health officials were identified as involved in: community engagement (31.8% municipal, 42.9% regional), sharing/analyzing data (40.9% municipal, 33.3% regional), and identifying/providing funding sources (13.6% municipal, 4.8% regional). The in-depth interviews provided further context and a more detailed understanding of public health involvement in VZ. CONCLUSIONS: Evidence from the VZ plans and interviews provided examples of how public health officials engaged in the development and implementation of VZ initiatives.


Subject(s)
Public Health , Humans , United States , Public Health/methods , Public Health/statistics & numerical data , Public Health/trends , Accidents, Traffic/statistics & numerical data , Accidents, Traffic/prevention & control , Accidents, Traffic/trends , Qualitative Research , Interviews as Topic/methods
6.
Pediatrics ; 2024 Jun 10.
Article in English | MEDLINE | ID: mdl-38853654

ABSTRACT

OBJECTIVE: To elicit expert consensus on quality indicators for the hospital-based care of opioid-exposed infants. METHODS: We used the ExpertLens online platform to conduct a 3-round modified Delphi panel. Expert panelists included health care providers, parents in recovery, quality experts, and public health experts. We identified 49 candidate quality indicators from a literature review and environmental scan. A total of 32 experts rated the importance and feasibility of the indicators using a 9-point Likert scale (Round 1), reviewed and discussed the initial ratings (round 2), and revised their original ratings (Round 3). Numeric scores corresponded with descriptive ratings of "low" (1-3), "uncertain" (4-6), or "high" (7-9). We measured consensus using the RAND/UCLA Appropriateness Method. RESULTS: Candidate quality indicators assessed structures, processes, and outcomes in multiple domains of clinical care. After the final round, 36 indicators were rated "high" on importance and feasibility. Experts had strong consensus on the importance of quality indicators to assess universal screening of pregnant people for substance use disorder, hospital staff training, standardized assessment for neonatal opioid withdrawal syndrome, nonpharmacologic interventions, and transitions of care. For indicators focused on processes and outcomes, experts saw feasibility as dependent on the information routinely documented in electronic medical records or billing records. To present a more complete picture of hospital quality, experts suggested development of composite measures that summarize quality across multiple indicators. CONCLUSIONS: A panel of experts reached consensus on a range of quality indicators for hospital-based care of opioid-exposed infants, with potential for use in national benchmarking, intervention studies, or hospital performance measurement.

7.
Cureus ; 16(5): e59811, 2024 May.
Article in English | MEDLINE | ID: mdl-38846216

ABSTRACT

BACKGROUND: Neurovascular compression syndromes (NVCS), encompassing conditions such as trigeminal neuralgia, hemifacial spasm, and glossopharyngeal neuralgia, significantly impair patient quality of life through abnormal vascular compression and micro-pulsation of vasculature on cranial nerves at the Obersteiner-Redlich zone. The modulation of pulsatile flow dynamics via endovascular stents presents a novel research frontier for alleviating these syndromes. AIM: The primary aim of this investigation was to delineate the impact of various endovascular stents on pulsatile flow within an in vitro model of a blood vessel, thereby elucidating their potential applicability in the therapeutic management of NVCS. MATERIALS AND METHODS: A simple in vitro analog of a posterior circulation artery was developed, employing an intravenous pump to replicate cardiac-induced blood flow. Within this model, alterations in pulsatile flow were quantitatively assessed following the introduction of three categorically distinct endovascular stents, varying in size. This assessment was facilitated through the employment of both micro-Doppler and Doppler ultrasound methodologies. RESULTS: The Pipeline 5x35 mm stent (Medtronic, Minneapolis, MN) demonstrated the most significant reductions in peak systolic velocity (Vmax) and pulsatility index (PI), PI especially over the stent, suggesting its potential for drastically altering blood flow dynamics. Similarly, Neuroform Atlas 4.5x30 mm and Neuroform Atlas 4x24 mm stents (Stryker, Kalamazoo, MI) also showed notable decreases in hemodynamic parameters, albeit to different extents. Statistical analysis confirmed that these changes were significantly different from the control (P < 0.0001 for PI and Vmax; P < 0.05 for inter-stent comparisons), except for proximal PI means, which did not significantly differ from the control (P = 0.2777). CONCLUSION: These findings affirm the potential of endovascular stents to substantially modulate arterial pulsatility. The observed decrease in pulsatile flow resultant from endovascular stent application has the potential to attenuate ectopic nerve excitation, a hallmark of NVCS. Consequently, this research highlights the prospective utility of endovascular stents in developing minimally invasive therapeutic approaches for NVCS.

11.
Laryngoscope ; 2024 Jun 19.
Article in English | MEDLINE | ID: mdl-38895915

ABSTRACT

OBJECTIVE: To examine the impact of increased body mass index (BMI) on (1) tracheotomy timing and (2) short-term surgical complications requiring a return to the operating room and 30-day mortality utilizing data from the Multi-Institutional Study on Tracheotomy (MIST). METHODS: A retrospective analysis of patients from the MIST database who underwent surgical or percutaneous tracheotomy between 2013 and 2016 at eight institutions was completed. Unadjusted and adjusted logistic regression analyses were used to assess the impact of obesity on tracheotomy timing and complications. RESULTS: Among the 3369 patients who underwent tracheotomy, 41.0% were obese and 21.6% were morbidly obese. BMI was associated with higher rates of prolonged intubation prior to tracheotomy accounting for comorbidities, indication for tracheotomy, institution, and type of tracheostomy (p = 0.001). Morbidly obese patients (BMI ≥35 kg/m2) experienced a longer duration of intubation compared with patients with a normal BMI (median days intubated [IQR 25%-75%]: 11.0 days [7-17 days] versus 9.0 days [5-14 days]; p < 0.001) but did not have statistically higher rates of return to the operating room within 30 days (p = 0.12) or mortality (p = 0.90) on multivariable analysis. This same finding of prolonged intubation was not seen in overweight, nonobese patients when compared with normal BMI patients (median days intubated [IQR 25%-75%]: 10.0 days [6-15 days] versus 10.0 days [6-15 days]; p = 0.36). CONCLUSION: BMI was associated with increased duration of intubation prior to tracheotomy. Although morbidly obese patients had a longer duration of intubation, there were no differences in return to the operating room or mortality within 30 days. LEVEL OF EVIDENCE: III Laryngoscope, 2024.

12.
J Am Coll Surg ; 2024 Jun 19.
Article in English | MEDLINE | ID: mdl-38895939

ABSTRACT

BACKGROUND: Previous research has highlighted concerns among trainees and attendings that general surgery training and fellowship are inadequately preparing trainees for practice. Providing trainees with supervision that matches their proficiency may help bridge this gap. We sought to benchmark operative performance and supervision levels among senior surgery residents (post-graduate year 4 or 5) and fellows performing general surgical oncology procedures. STUDY DESIGN: Observational data were obtained from the Society for Improving Medical Procedural Learning (SIMPL) OR application for core general surgical oncology procedures performed at 103 unique residency and fellowship programs. Procedures were divided into breast and soft tissue, endocrine, and hepatopancreatobiliary (HPB). Case evaluations completed by trainees and attendings were analyzed to benchmark trainee operative performance and level of supervision. RESULTS: There were 4,907 resident cases and 425 fellow cases. Practice-ready performance, as assessed by trainees and faculty, was achieved by relatively low proportions of residents and fellows for breast and soft tissue cases (residents: 38%, fellows: 48%), endocrine cases (residents: 22%, fellows: 41%), and HPB cases (residents: 10%, fellows: 40%). Among cases in which trainees did achieve practice-ready performance, supervision only was provided for low proportions of cases as rated by trainees (residents: 17%, fellows: 18%) and attendings (residents: 21%, fellows 25%). CONCLUSION: In a sample of 103 residency and fellowship programs, attending surgeons rarely provided senior residents and fellows with levels of supervision commensurate to performance for surgical oncology procedures, even for high performing trainees. These findings suggest a critical need for surgical training programs to prioritize providing greater levels of independence to trainees that have demonstrated excellent performance.

13.
Obes Rev ; : e13785, 2024 Jun 09.
Article in English | MEDLINE | ID: mdl-38853150

ABSTRACT

People with spinal cord injury (SCI) are at greater risk of developing obesity and related co-morbidities than those without SCI. The objectives of this systematic review were to examine the effectiveness of weight management interventions for people with SCI and to synthesize the experiences of people involved with SCI weight management (e.g., SCI healthcare professionals and caregivers). Five databases were searched (up to July 31, 2023) and 5,491 potentially eligible articles were identified. Following screening, 22 articles were included, comprising 562 adults. There was considerable heterogeneity in study design and weight loss interventions included behavioral nutritional and exercise education sessions, recalling food diaries, exercise interventions, and pharmaceuticals. The mean percentage change of the pooled body mass data equated to -4.0 ± 2.3%, with a range from -0.5 to -7.6%. In addition, 38% of the individuals with SCI who completed a weight loss intervention (N = 262) had a ≥5% reduction in body weight. Collectively, although on average the included interventions led to moderate weight loss, the finding that just over a third of individuals achieved clinically meaningful 5% weight loss suggests that available interventions for this population may need to be improved.

14.
Clin Oral Investig ; 28(7): 361, 2024 Jun 07.
Article in English | MEDLINE | ID: mdl-38847929

ABSTRACT

OBJECTIVES: To assess gingival crevicular fluid (GCF) levels of inflammatory and bone remodelling related biomarkers following transplantation of a tissue-engineered biocomplex into intrabony defects at several time-points over 12-months. MATERIALS AND METHODS: Group-A (n = 9) received the Minimal Access Flap (MAF) surgical technique combined with a biocomplex of autologous clinical-grade alveolar bone-marrow mesenchymal stem cells in collagen scaffolds enriched with an autologous fibrin/platelet lysate (aFPL). Group-B (n = 10) received the MAF surgery, with collagen scaffolds enriched with aFPL and Group-C (n = 8) received the MAF surgery alone. GCF was collected from the osseous defects of subjects via paper strips/30 sec at baseline, 6-weeks, 3-, 6-, 9-, 12-months post-surgery. Levels of inflammatory and bone remodelling-related biomarkers in GCF were determined by ELISA. RESULTS: Group-A demonstrated significantly higher GCF levels of BMP-7 at 6-9 months than baseline, with gradually decreasing levels of pro-inflammatory and pro-osteoclastogenic markers (TNF-α, RANKL) over the study-period; and an overall decrease in the RANKL/OPG ratio at 9-12 months than baseline (all p < 0.001). In comparison, only modest interim changes were observed in Groups-B and -C. CONCLUSIONS: At the protein level, the approach of MAF and biocomplex transplantation provided greater tissue regeneration potential as cell-based therapy appeared to modulate inflammation and bone remodelling in residual periodontal defects. CLINICAL RELEVANCE: Transplantation of a tissue engineered construct into periodontal intrabony defects demonstrated a biochemical pattern for inflammatory control and tissue regeneration over 12-months compared to the control treatments. Understanding the biological healing events of stem cell transplantation may facilitate the design of novel treatment strategies. CLINICAL DATABASE REGISTRATION: ClinicalTrials.gov ID: NCT02449005.


Subject(s)
Biomarkers , Bone Remodeling , Gingival Crevicular Fluid , Tissue Engineering , Tissue Scaffolds , Humans , Bone Remodeling/physiology , Collagen , Enzyme-Linked Immunosorbent Assay , Gingival Crevicular Fluid/chemistry , Surgical Flaps , Tissue Engineering/methods , Treatment Outcome
15.
JMIR Form Res ; 8: e56003, 2024 Jun 07.
Article in English | MEDLINE | ID: mdl-38848557

ABSTRACT

BACKGROUND: Efficacy of smartphone-based interventions depends on intervention content quality and level of exposure to that content. Smartphone-based survey completion rates tend to decline over time; however, few studies have identified variables that predict this decline over longer-term interventions (eg, 26 weeks). OBJECTIVE: This study aims to identify predictors of survey completion and message viewing over time within a 26-week smoking cessation trial. METHODS: This study examined data from a 3-group pilot randomized controlled trial of adults who smoke (N=152) and were not ready to quit smoking within the next 30 days. For 182 days, two intervention groups received smartphone-based morning and evening messages based on current readiness to quit smoking. The control group received 2 daily messages unrelated to smoking. All participants were prompted to complete 26 weekly smartphone-based surveys that assessed smoking behavior, quit attempts, and readiness to quit. Compliance was operationalized as percentages of weekly surveys completed and daily messages viewed. Linear regression and mixed-effects models were used to identify predictors (eg, intervention group, age, and sex) of weekly survey completion and daily message viewing and decline in compliance over time. RESULTS: The sample (mean age 50, SD 12.5, range 19-75 years; mean years of education 13.3, SD 1.6, range 10-20 years) was 67.8% (n=103) female, 74.3% (n=113) White, 77% (n=117) urban, and 52.6% (n=80) unemployed, and 61.2% (n=93) had mental health diagnoses. On average, participants completed 18.3 (71.8%) out of 25.5 prompted weekly surveys and viewed 207.3 (60.6%) out of 345.1 presented messages (31,503/52,460 total). Age was positively associated with overall weekly survey completion (P=.003) and daily message viewing (P=.02). Mixed-effects models indicated a decline in survey completion from 77% (114/148) in the first week of the intervention to 56% (84/150) in the last week of the intervention (P<.001), which was significantly moderated by age, sex, ethnicity, municipality (ie, rural/urban), and employment status. Similarly, message viewing declined from 72.3% (1533/2120) in the first week of the intervention to 44.6% (868/1946) in the last week of the intervention (P<.001). This decline in message viewing was significantly moderated by age, sex, municipality, employment status, and education. CONCLUSIONS: This study demonstrated the feasibility of a 26-week smartphone-based smoking cessation intervention. Study results identified subgroups that displayed accelerated rates in the decline of survey completion and message viewing. Future research should identify ways to maintain high levels of interaction with mobile health interventions that span long intervention periods, especially among subgroups that have demonstrated declining rates of intervention engagement over time. TRIAL REGISTRATION: ClinicalTrials.gov NCT03405129; https://clinicaltrials.gov/ct2/show/NCT03405129.

16.
Cancer Res ; 2024 Jun 06.
Article in English | MEDLINE | ID: mdl-38843355

ABSTRACT

Pancreatic ductal adenocarcinoma (PDAC) is associated with a five-year overall survival rate of just 13%, and development of chemotherapy resistance is nearly universal. PDAC cells overexpress wild-type IDH1 that can enable them to overcome metabolic stress, suggesting it could represent a therapeutic target in PDAC. Here, we found that anti-IDH1 therapy enhanced the efficacy of conventional chemotherapeutics. Chemotherapy treatment induced ROS and increased TCA cycle activity in PDAC cells, along with the induction of wild-type IDH1 expression as a key resistance factor. IDH1 facilitated PDAC survival following chemotherapy treatment by supporting mitochondrial function and antioxidant defense to neutralize reactive oxygen species through the generation of alpha-ketoglutarate and NADPH, respectively. Pharmacologic inhibition of wild-type IDH1 with ivosidenib synergized with conventional chemotherapeutics in vitro and potentiated the efficacy of sub-therapeutic doses of these drugs in vivo in murine PDAC models. This promising treatment approach is translatable through available and safe oral inhibitors and provides the basis of an open and accruing clinical trial testing this combination (NCT05209074).

17.
iScience ; 27(6): 110094, 2024 Jun 21.
Article in English | MEDLINE | ID: mdl-38883817

ABSTRACT

The selective vulnerability of dopaminergic neurons to trauma-induced neurodegeneration is conserved across species, from nematodes to humans. However, the molecular mechanisms underlying this hypersensitivity to blunt force trauma remain elusive. We find that extravesicular dopamine, a key driver of Parkinson's disease, extends its toxic role to the acute challenges associated with injury. Ectopic dopamine synthesis in serotonergic neurons sensitizes this resilient neuronal subtype to trauma-induced degeneration. While dopaminergic neurons normally maintain dopamine in a functional and benign state, trauma-induced subcellular redox imbalances elicit dopamine-dependent cytotoxicity. Cytosolic dopamine accumulation, through perturbations to its synthesis, metabolism, or packaging, is necessary and sufficient to drive neurodegeneration upon injury and during aging. Additionally, degeneration is further exacerbated by rapid upregulation of the rate-limiting enzyme in dopamine synthesis, cat-2, via the FOS-1 transcription factor. Fundamentally, our study in C. elegans unravels the molecular intricacies rendering dopaminergic neurons uniquely prone to physical perturbation across evolutionary lines.

18.
Heliyon ; 10(10): e31077, 2024 May 30.
Article in English | MEDLINE | ID: mdl-38799759

ABSTRACT

The overproduction of the toxic peptide amyloid-beta (Aß) generated from the cleavage of amyloid precursor protein (APP) is proposed to be a critical event in the development of Alzheimer's disease. Evidence suggests that the cleavage of APP occurs after its internalization from the cell surface. Previously, we identified a novel pathway for APP internalization, which trafficks cell surface APP directly to lysosomes by macropinocytosis, leading to its processing into Aß. We also demonstrated that ADP-ribosylation factor 6 (Arf6) is required for the macropinocytosis of APP. Here, we characterized the roles of Arf6's downstream effectors Rac1, Cdc42 and RhoA. Both pharmacological inhibition and siRNA knockdown of these proteins reduced the amount of APP colocalized with LAMP1-labeled lysosomes without affecting APP transport to early endosomes. Decreases in the production of both Aß40 and Aß42 were also observed by ELISA in response to inhibitor treatment. These findings together demonstrate that Rac1, Cdc42 and RhoA are components of the mechanism regulating the macropinocytosis of APP and targeting these components can reduce the production of Aß.

19.
Cureus ; 16(4): e58979, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38800330

ABSTRACT

Infective endocarditis (IE) remains a formidable challenge in clinical practice due to several causative agents, each presenting with unique diagnostic and therapeutic dilemmas. Kocuria kristinae, a coagulase-negative, catalase-positive Gram-positive coccus, has recently emerged as an uncommon but increasingly recognized pathogen in the cause of IE. This case report highlights the clinical characteristics, risk factors, and challenges associated with Kocuria kristinae-induced IE. We conducted a comprehensive literature review and identified several case reports on Kocuria kristinae as a causative agent. Due to its indolent nature and the subtle presentation of symptoms, along with its ability to form biofilms, delayed diagnosis of Kocuria is often seen, thereby emphasizing the need for heightened clinical suspicion. The predisposing factors for Kocuria kristinae infection include underlying cardiac abnormalities, prosthetic heart valves, and immunocompromised states. Additionally, antimicrobial susceptibility patterns and optimal treatment strategies remain unclear, warranting further investigation. This abstract presents the case of a 75-year-old male with IE secondary to Kocuria kristinae on a prosthetic mitral valve. We aim to highlight the need for increased awareness among clinicians to facilitate early recognition and prompt initiation of targeted therapeutic interventions. Unraveling the intricacies of Kocuria kristinae's pathogenicity is crucial for refining diagnostic approaches and optimizing patient outcomes.

20.
Mol Biol Cell ; 35(7): ar97, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38758654

ABSTRACT

Bacterial cell division is crucial for replication and requires careful coordination via proteins collectively called the divisome. The tubulin-like GTPase FtsZ is the master regulator of this process and serves to recruit downstream divisome proteins and regulate their activities. Upon assembling at mid-cell, FtsZ exhibits treadmilling motion driven by GTP binding and hydrolysis. Treadmilling is proposed to play roles in Z-ring condensation and in distribution and regulation of peptidoglycan (PG) cell wall enzymes. FtsZ polymer superstructure and dynamics are central to its function, yet their regulation is incompletely understood. We addressed these gaps in knowledge by evaluating the contribution of GTPase activity to FtsZ's function in vitro and in Caulobacter crescentus cells. We observed that a lethal mutation that abrogates FtsZ GTP hydrolysis impacts FtsZ dynamics and Z-ring positioning, but not constriction. Aberrant Z-ring positioning was due to insensitivity to the FtsZ regulator MipZ when GTPase activity is reduced. Z-ring mislocalization resulted in DNA damage, likely due to constriction over the nucleoid. Collectively, our results indicate that GTP hydrolysis serves primarily to position the Z-ring at mid-cell in Caulobacter. Proper Z-ring localization is required for effective coordination with chromosome segregation to prevent DNA damage and ensure successful cell division.


Subject(s)
Bacterial Proteins , Caulobacter crescentus , Cell Division , Cytoskeletal Proteins , GTP Phosphohydrolases , Guanosine Triphosphate , Caulobacter crescentus/metabolism , Caulobacter crescentus/genetics , Bacterial Proteins/metabolism , Cytoskeletal Proteins/metabolism , Guanosine Triphosphate/metabolism , GTP Phosphohydrolases/metabolism , Cell Division/physiology , Hydrolysis , Mutation
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