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1.
J Adv Nurs ; 2024 Oct 01.
Article in English | MEDLINE | ID: mdl-39352080

ABSTRACT

AIM: To identify whether the introduction of low-low hospital beds resulted in changes in the incidence, associated patient harms and event characteristics of bed-related falls where implemented. DESIGN: This retrospective quality improvement study covered 36 months: 18 months pre-intervention and 18 months post-intervention. METHODS: Our analysis incorporated patient fall data from a hospital in upstate New York. Pre-/post-intervention data covered 18 months on either side of introduction at the units of implementation. Data were sourced from contemporaneously recorded incident reports and the organisation's business intelligence records. Analysis addressed the incidence rate, frequency, patient harm classification and recurrence of bed-related falls, as well as Morse Fall Scale risk classification, patient age, gender and other individualised risk factors. Lastly, we reviewed the presence of individualised interventions, staff assistance during the event, patient census and staffing ratios. Chi-square goodness of fit tests were employed to compare the distribution, and Brunner-Munzel tests the stochastic equality, of the pre- and post-implementation categorical and continuous data. RESULTS: There were no significant differences in the incidence rate of bed-related falls, patient harms or in the need for medical intervention following implementation of the low-low hospital beds. Neither were there any significant differences in the proportion of events resulting in detectable harm or the need for medical intervention post-implementation. The total number of bed-involved falls substantively increased following implementation of the low-low beds, as did the number of events resulting in detectable harms and medical intervention. Among these, substantive increases were noted among events resulting in minor temporary harm and patients referred for diagnostic imaging. The number of events involved patients experiencing recurrent falls of any kind increased significantly post-implementation. CONCLUSION: We found that the introduction of low-low hospital beds preceded no change in the incidence of bed-related falls, associated patient harms or the need for post-event medical intervention where implemented. While data limitations precluded definitive determination with respect to certain event characteristics, several post-implementation changes, including substantive increases in the number of falls occurring during ingress and egress, may suggest a potential for relationship worthy of future study. IMPLICATIONS AND IMPACT: Low-low hospital beds are purported to help reduce the occurrence and severity of bed-related falls, both serious problems in inpatient settings. This study describes null outcomes following an implementation of such beds, with implications for adoption in similar settings. REPORTING METHOD: We adhered to the relevant Enhancing the Quality and Transparency of Health Research guidelines, specifically following the Standards for Quality Improvement Reporting Excellence standards. PATIENT OR PUBLIC CONTRIBUTION: No patient or public involvement in the design or conduct of the study. Nurses and medical staff were involved in intervention implementation, data collection and the conception, design and conduct of the study.

2.
Proc Natl Acad Sci U S A ; 121(41): e2407046121, 2024 Oct 08.
Article in English | MEDLINE | ID: mdl-39348540

ABSTRACT

Methamphetamine use and HIV disproportionately affect sexual and gender minority (SGM) people assigned male at birth. Identifying risk factors for methamphetamine use is crucial to inform preventive interventions. In this cohort study with 1,296 SGM people assigned male at birth, ages 16 to 29, and who resided in Chicago, Poisson regression analyses indicated the prevalence of methamphetamine use increased from 2015 to 2023 [Incidence Rate Ratio (IRR) = 1.07; 95% CI = 1.01 to 1.13; P = 0.02]. This increase was most pronounced among those ages 25 or older at baseline (IRR = 2.20; 95% CI = 1.33 to 3.63; P = 0.002), and 23.9 [Interquartile Range (IQR) = 22.1 to 26.9] was the median age of first-time methamphetamine use. In 826 participants with a prior HIV diagnosis or previous inflammatory measurements, Cox proportional-hazards models examined risk factors for incident, first-time methamphetamine use. Adjusting for other substance use, the rate of incident, first-time methamphetamine use was two-fold greater after HIV diagnosis [adjusted hazard ratio (aHR) = 2.02; 95% CI = 1.27 to 3.23; P = 0.003]. For each SD higher C-reactive protein, the rate of incident, first-time methamphetamine use was 18% greater (aHR = 1.18; 95% CI, 1.05 to 1.34; P = 0.008). HIV seroconversion and inflammation could increase the risk of initiating methamphetamine use in SGM people assigned male at birth.


Subject(s)
HIV Infections , Inflammation , Methamphetamine , Sexual and Gender Minorities , Humans , Male , Methamphetamine/adverse effects , Adult , HIV Infections/epidemiology , Sexual and Gender Minorities/statistics & numerical data , Adolescent , Young Adult , Inflammation/epidemiology , Risk Factors , Amphetamine-Related Disorders/epidemiology , Female , Chicago/epidemiology , Cohort Studies , Prevalence
3.
Nucleic Acids Res ; 2024 Aug 16.
Article in English | MEDLINE | ID: mdl-39149883

ABSTRACT

Acinetobacter baumannii is an opportunistic Gram-negative pathogen that infects critically ill patients. The emergence of antimicrobial resistant A. baumannii has exacerbated the need to characterize environmental adaptation, antibiotic resistance and pathogenicity and their genetic regulators to inform intervention strategies. Critical to adaptation to changing environments in bacteria are small regulatory RNAs (sRNAs), however, the role that sRNAs play in the biology of A. baumannii is poorly understood. To assess the regulatory function of sRNAs and to uncover their RNA interaction partners, we employed an RNA proximity ligation and sequencing method (Hi-GRIL-seq) in three different environmental conditions. Forty sRNAs were ligated to sRNA-RNA chimeric sequencing reads, suggesting that sRNA-mediated gene regulation is pervasive in A. baumannii. In-depth characterization uncovered the sRNA Aar to be a post-transcriptional regulator of four mRNA targets including the transcript encoding outer membrane protein CarO. Aar initiates base-pairing with these mRNAs using a conserved seed region of nine nucleotides, sequestering the ribosome binding sites and inhibiting translation. Aar is differentially expressed in multiple stress conditions suggesting a role in fine-tuning translation of the Aar-target molecules. Our study provides mechanistic insights into sRNA-mediated gene regulation in A. baumannii and represents a valuable resource for future RNA-centric research endeavours.

4.
Sol Phys ; 299(8): 114, 2024.
Article in English | MEDLINE | ID: mdl-39185303

ABSTRACT

HXI on ASO-S and STIX onboard Solar Orbiter are the first simultaneously operating solar hard X-ray imaging spectrometers. ASO-S's low Earth orbit and Solar Orbiter's periodic displacement from the Sun-Earth line enables multi-viewpoint solar hard X-ray spectroscopic imaging analysis for the first time. Here, we demonstrate the potential of this new capability by reporting the first results of 3D triangulation of hard X-ray sources in the SOL2023-12-31T21:55 X5 flare. HXI and STIX observed the flare near the east limb with an observer separation angle of 18°. We triangulated the brightest regions within each source, which enabled us to characterise the large-scale hard X-ray geometry of the flare. The footpoints were found to be in the chromosphere within uncertainty, as expected, while the thermal looptop source was centred at an altitude of 15.1 ± 1 Mm. Given the footpoint separation, this implies a more elongated magnetic-loop structure than predicted by a semi-circular model. These results show the strong diagnostic power of joint HXI and STIX observations for understanding the 3D geometry of solar flares. We conclude by discussing the next steps required to fully exploit their potential.

5.
Open Forum Infect Dis ; 11(8): ofae444, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39183815

ABSTRACT

Background: We estimated the predictive value of rectal (bacterial sexually transmitted infection [bSTI]) pathogen detection for future HIV seroconversion among young adult sexual and gender minorities (YSGMs) assigned male at birth (AMAB). Methods: Data were collected between March 2018 and August 2022 from RADAR, a longitudinal cohort study of YSGMs AMAB living in the Chicago metropolitan area (n = 1022). Rates of rectal bSTIs and the proportion of self-reported rectal bSTI symptoms are reported. We examined whether the presence of rectal bSTIs predicted HIV seroconversion using generalized estimating equations (GEEs). Results: Participants tested reactive for rectal Mycoplasma genitalium (MGen), Neisseria gonorrhoeae (NG), and Chlamydia trachomatis (CT) at a rate of 20.8 (95% CI, 18.4-23.5), 6.5 (95% CI, 5.0-8.2), and 8.4 (95% CI, 6.8-10.3) cases per 100 persons, respectively. There were no statistically significant pairwise differences in self-reported rectal bSTI symptoms between participants with self-collected swabs testing nonreactive vs reactive for rectal MGen (χ2 = 0.04; P = .84), NG (χ2 = 0.45; P = .37), or CT (χ2 = 0.39; P = .46). In multivariate GEE analysis, rectal NG (adjusted odds ratio, 5.11; 95% CI, 1.20-21.77) was a statistically significant predictor of HIV seroconversion after controlling for other bSTIs, demographics, and sexual risk behavior. Conclusions: Our findings provide a robust longitudinal estimation of the relationship between primarily asymptomatic rectal NG nucleic acid detection and HIV infection. These findings highlight the importance of asymptomatic screening for bSTIs and targeting biobehavioral intervention to prevent HIV infection among YSGMs with rectal bSTI agents detected.

6.
PLoS One ; 19(3): e0295558, 2024.
Article in English | MEDLINE | ID: mdl-38466700

ABSTRACT

BACKGROUND: Reversible cerebral vasoconstriction syndrome (RCVS) is a syndrome of recurrent thunderclap headaches and reversible vasoconstriction of the cerebral arteries on neuroimaging within 3 months of onset. Initial non-contrast computed tomography (CT) can reveal abnormalities such as ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage (SAH) can be present in patients with RCVS and may delay diagnosis. AIMS: We conducted a systematic review and meta-analysis in accordance with the PRISMA guidelines. We aimed to estimate the prevalence of imaging abnormalities on initial non-contrast CT head in adult patients with RCVS. DATA SOURCES & ELIGIBILITY CRITERIA: We searched electronic databases including MEDLINE, EMBASE, and the Cochrane Register of Clinical Trials from inception to August 2, 2022. Eligible studies included articles reporting the prevalence of non-contrast CT abnormalities on initial neuroimaging in patients with RCVS, aged 18 and older. Case series, observational studies and clinical trials were included. Data was extracted directly from included papers using a standardized data charting form. RESULTS: The search yielded 722 titles with duplicates removed. Twenty studies that included 379 patients with RCVS met inclusion criteria. We classified non-contrast CT abnormalities as either ischemic stroke, ICH, or SAH. We pooled prevalence data using a random effects model with the inverse-variance weighted method. The most common imaging finding was SAH with a pooled prevalence of 24% (95% CI:17%-33%), followed by ICH at 14% (95% CI:8%-22%), and ischemic stroke at 10% (95% CI:7%-14%). The pooled prevalence of any of these imaging abnormalities on initial non-contrast CT was 31% (95% CI:23%-40%). Risk of bias was moderate to very-high-risk for case-series and low-risk for observational studies. CONCLUSION: Our review demonstrates that one-third of patients with RCVS will have an abnormality on initial non-contrast CT head, including either an ischemic stroke, ICH, or SAH. These findings highlight the diagnostic challenges of RCVS imaging and contribute to our understanding of this disease.


Subject(s)
Tomography, X-Ray Computed , Humans , Tomography, X-Ray Computed/methods , Prevalence , Headache Disorders, Primary/diagnostic imaging , Headache Disorders, Primary/epidemiology , Vasoconstriction , Neuroimaging/methods , Syndrome , Subarachnoid Hemorrhage/diagnostic imaging , Subarachnoid Hemorrhage/epidemiology
7.
Nat Microbiol ; 9(4): 1130-1144, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38528147

ABSTRACT

Plasticity in gene expression allows bacteria to adapt to diverse environments. This is particularly relevant in the dynamic niche of the human intestinal tract; however, transcriptional networks remain largely unknown for gut-resident bacteria. Here we apply differential RNA sequencing (RNA-seq) and conventional RNA-seq to the model gut bacterium Bacteroides thetaiotaomicron to map transcriptional units and profile their expression levels across 15 in vivo-relevant growth conditions. We infer stress- and carbon source-specific transcriptional regulons and expand the annotation of small RNAs (sRNAs). Integrating this expression atlas with published transposon mutant fitness data, we predict conditionally important sRNAs. These include MasB, which downregulates tetracycline tolerance. Using MS2 affinity purification and RNA-seq, we identify a putative MasB target and assess its role in the context of the MasB-associated phenotype. These data-publicly available through the Theta-Base web browser ( http://micromix.helmholtz-hiri.de/bacteroides/ )-constitute a valuable resource for the microbiome community.


Subject(s)
Bacteroides thetaiotaomicron , Humans , Bacteroides thetaiotaomicron/genetics , Transcriptome , RNA , Protein Synthesis Inhibitors , Tetracyclines
8.
Cell Chem Biol ; 31(4): 729-742.e13, 2024 Apr 18.
Article in English | MEDLINE | ID: mdl-38492573

ABSTRACT

The molecular chaperone heat shock protein 90 (Hsp90) has an essential but largely undefined role in maintaining proteostasis in Plasmodium falciparum, the most lethal malaria parasite. Herein, we identify BX-2819 and XL888 as potent P. falciparum (Pf)Hsp90 inhibitors. Derivatization of XL888's scaffold led to the development of Tropane 1, as a PfHsp90-selective binder with nanomolar affinity. Hsp90 inhibitors exhibit anti-Plasmodium activity against the liver, asexual blood, and early gametocyte life stages. Thermal proteome profiling was implemented to assess PfHsp90-dependent proteome stability, and the proteasome-the main site of cellular protein recycling-was enriched among proteins with perturbed stability upon PfHsp90 inhibition. Subsequent biochemical and cellular studies suggest that PfHsp90 directly promotes proteasome hydrolysis by chaperoning the active 26S complex. These findings expand our knowledge of the PfHsp90-dependent proteome and protein quality control mechanisms in these pathogenic parasites, as well as further characterize this chaperone as a potential antimalarial drug target.


Subject(s)
Antimalarials , Plasmodium falciparum , Plasmodium falciparum/metabolism , Proteasome Endopeptidase Complex/metabolism , Proteome/metabolism , Antimalarials/chemistry , HSP90 Heat-Shock Proteins , Molecular Chaperones/metabolism
9.
J Infect Dis ; 229(1): 232-236, 2024 Jan 12.
Article in English | MEDLINE | ID: mdl-37816091

ABSTRACT

BACKGROUND: Syphilis rates in the United States have increased. Few studies have examined syphilis incidence and prevalence prospectively among young sexual and gender minorities (YSGM). METHODS: This study of YSGM assigned male at birth comes from a Chicago-based prospective cohort at 2 visits 6 months apart (N = 882). Syphilis cases were identified through serologic test results and self-reported history. RESULTS: In this sample, 25.1% had a lifetime prevalence, and 3.3% were incident cases with a crude incidence rate of 6.76 per 100 person-years. CONCLUSIONS: Lifetime syphilis and incidence are high in this sample of YSGM relative to general population samples.


Subject(s)
HIV Infections , Sexual and Gender Minorities , Syphilis , Adult , Infant, Newborn , Humans , Male , United States/epidemiology , Syphilis/epidemiology , Incidence , Longitudinal Studies , Prospective Studies , Prevalence , Sexual Behavior , Homosexuality, Male , HIV Infections/epidemiology
12.
J Pers Med ; 13(10)2023 Oct 21.
Article in English | MEDLINE | ID: mdl-37888124

ABSTRACT

Autism spectrum disorder (ASD), characterized by social, communication, and behavioral abnormalities, affects 1 in 36 children according to the CDC. Several co-occurring conditions are often associated with ASD, including sleep and immune disorders and gastrointestinal (GI) problems. ASD is also associated with sensory sensitivities. Some individuals with ASD exhibit episodes of challenging behaviors that can endanger themselves or others, including aggression and self-injurious behavior (SIB). In this work, we explored the use of artificial intelligence models to predict behavior episodes based on past data of co-occurring conditions and environmental factors for 80 individuals in a residential setting. We found that our models predict occurrences of behavior and non-behavior with accuracies as high as 90% for some individuals, and that environmental, as well as gastrointestinal, factors are notable predictors across the population examined. While more work is needed to examine the underlying connections between the factors and the behaviors, having reasonably accurate predictions for behaviors has the potential to improve the quality of life of some individuals with ASD.

13.
AIDS ; 37(15): 2381-2387, 2023 Dec 01.
Article in English | MEDLINE | ID: mdl-37696260

ABSTRACT

BACKGROUND: Preexposure prophylaxis (PrEP) significantly reduces HIV infection risk but is dependent on adherence. Available approaches to measuring adherence have limitations related to accuracy, cost, practicality, and timeliness. This study compared the performance of two methods implementable in clinics and research studies [interview and urine point of care (POC) assay] to the gold-standard for measuring recent and longer term adherence in dried blood spots (DBS). METHODS: Participants were recruited from RADAR, a cohort study of young MSM, or via online advertisements. At 3 monthly visits, an interviewer administered 7-day timeline follow-back (TLFB) questionnaire, DBS samples were tested for tenofovir-diphosphate (TFV-DP) to estimate average dosing over the prior month and emtricitabine-triphosphate (FTC-TP) to assess recent dosing (past 2-3 days), and a urine POC TFV test to qualitatively assess recent adherence (past 4 days). RESULTS: Eighty-three PrEP users contributed 163 observations. At visit 1, self-reported adherence was 86% (4+ doses in last 7 days), versus urine TFV (74%), DBS FTC-TP (76%), and DBS TFV-DP (69%). The objective measures of short-term adherence performed similarly well in predicting longer term adherence. In multivariable logistic regression analyses, the urine assay was a significant predictor of DBS TFV-DP (adjusted OR = 19.4, P  < 0.0001); self-report did not add significantly. CONCLUSION: The urine POC TFV assay had excellent predictive values for adherence and self-report did not add significantly to prediction. The POC assay provides results in several minutes to enable same-visit counseling, requires no specialized training, and is projected to be low-cost.


Subject(s)
Adenine/analogs & derivatives , Anti-HIV Agents , HIV Infections , Organophosphates , Pre-Exposure Prophylaxis , Sexual and Gender Minorities , Male , Humans , Tenofovir/therapeutic use , Tenofovir/urine , HIV Infections/drug therapy , HIV Infections/prevention & control , Anti-HIV Agents/therapeutic use , Homosexuality, Male , Point-of-Care Systems , Cohort Studies , Medication Adherence , Emtricitabine/therapeutic use
14.
Nat Commun ; 14(1): 5585, 2023 09 11.
Article in English | MEDLINE | ID: mdl-37696797

ABSTRACT

The success of the CD8 T cell-mediated immune response against infections and tumors depends on the formation of a long-lived memory pool, and the protection of effector cells from exhaustion. The advent of checkpoint blockade therapy has significantly improved anti-tumor therapeutic outcomes by reversing CD8 T cell exhaustion, but fails to generate effector cells with memory potential. Here, using in vivo mouse models, we show that let-7 miRNAs determine CD8 T cell fate, where maintenance of let-7 expression during early cell activation results in memory CD8 T cell formation and tumor clearance. Conversely, let-7-deficiency promotes the generation of a terminal effector population that becomes vulnerable to exhaustion and cell death in immunosuppressive environments and fails to reject tumors. Mechanistically, let-7 restrains metabolic changes that occur during T cell activation through the inhibition of the PI3K/AKT/mTOR signaling pathway and production of reactive oxygen species, potent drivers of terminal differentiation and exhaustion. Thus, our results reveal a role for let-7 in the time-sensitive support of memory formation and the protection of effector cells from exhaustion. Overall, our data suggest a strategy in developing next-generation immunotherapies by preserving the multipotency of effector cells rather than enhancing the efficacy of differentiation.


Subject(s)
CD8-Positive T-Lymphocytes , MicroRNAs , Phosphatidylinositol 3-Kinases , Animals , Mice , Antibodies , CD8-Positive T-Lymphocytes/metabolism , Cell Differentiation , Neoplasms , Phosphatidylinositol 3-Kinases/genetics , MicroRNAs/genetics , MicroRNAs/metabolism
15.
Sex Res Social Policy ; 20(2): 589-598, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37637938

ABSTRACT

Introduction: The Sexual Orientation Microaggression Inventory (SOMI) has been used to measure sexual orientation-based microaggression experiences. However, at 19 items, the SOMI may be difficult to fit into survey batteries where microaggressions are not the primary predictor or the time researchers have with each participant is very limited. Methods: We sought to identify an eight-item short form of the SOMI (SOMI-SF) in a sample of sexual minority (SM) youth (N = 879) and confirm the validity and reliability of the SOMI-SF by administering both versions to separate cohorts of male-assigned (N = 533) and female-assigned (N = 430) at birth SM youth. Data was collected from April 2018 to May 2020. Results: We found high reliability (α > 0.80) and validity (significant association with SM victimization, depression symptoms, anxiety symptoms, and internalized stigma) in all three samples for the SOMI-SF. Conclusions: For researchers looking to conserve time and limit burden, the SOMI-SF is a high quality option for measuring sexual orientation microaggressions. Policy Implications: The greater ease of administering the SOMI-SF means that sexual orientation microaggressions can be measured in a greater number of contexts. With a growing literature linking these experiences to poorer health outcomes for SM populations, measuring these experiences quickly and accurately can improve our understanding of the mechanisms creating those links and impact policy necessary to alleviate them.

16.
Int J Mol Sci ; 24(13)2023 Jun 23.
Article in English | MEDLINE | ID: mdl-37445722

ABSTRACT

PTPN11 encodes the SHP2 protein tyrosine phosphatase that activates the mitogen-activated protein kinase (MAPK) pathway upstream of KRAS and MEK. PTPN11/Shp2 somatic mutations occur frequently in Juvenile myelomonocytic leukaemia (JMML); however, the role of mutated PTPN11 in lung cancer tumourigenesis and its utility as a therapeutic target has not been fully addressed. We applied mass-spectrometry-based genotyping to DNA extracted from the tumour and matched the normal tissue of 356 NSCLC patients (98 adenocarcinomas (LUAD) and 258 squamous cell carcinomas (LUSC)). Further, PTPN11 mutation cases were identified in additional cohorts, including TCGA, Broad, and MD Anderson datasets and the COSMIC database. PTPN11 constructs harbouring PTPN11 E76A, A72D and C459S mutations were stably expressed in IL-3 dependent BaF3 cells and NSCLC cell lines (NCI-H1703, NCI-H157, NCI-H1299). The MAPK and PI3K pathway activation was evaluated using Western blotting. PTPN11/Shp2 phosphatase activity was measured in whole-cell protein lysates using an Shp2 assay kit. The Shp2 inhibitor (SHPi) was assessed both in vitro and in vivo in a PTPN11-mutated cell line for improved responses to MAPK and PI3K targeting therapies. Somatic PTPN11 hotspot mutations occurred in 4/98 (4.1%) adenocarcinomas and 7/258 (2.7%) squamous cells of 356 NSCLC patients. Additional 26 PTPN11 hotspot mutations occurred in 23 and 3 adenocarcinomas and squamous cell carcinoma, respectively, across the additional cohorts. Mutant PTPN11 significantly increased the IL-3 independent survival of Ba/F3 cells compared to wildtype PTPN11 (p < 0.0001). Ba/F3, NCI-H1703, and NCI-H157 cells expressing mutant PTPN11 exhibited increased PTPN11/Shp2 phosphatase activity and phospho-ERK1/2 levels compared to cells expressing wildtype PTPN11. The transduction of the PTPN11 inactivating mutation C459S into NSCLC cell lines led to decreased phospho-ERK, as well as decreased phospho-AKT in the PTPN11-mutated NCI-H661 cell line. NCI-H661 cells (PTPN11-mutated, KRAS-wild type) were significantly more sensitive to growth inhibition by the PI3K inhibitor copanlisib (IC50: 13.9 ± 4.7 nM) compared to NCI-H1703 (PTPN11/KRAS-wild type) cells (IC50: >10,000 nM). The SHP2 inhibitor, in combination with the PI3K targeting therapy copanlisib, showed no significant difference in tumour development in vivo; however, this significantly prevented MAPK pathway induction in vitro (p < 0.0001). PTPN11/Shp2 demonstrated the in vitro features of a driver oncogene and could potentially sensitize NSCLC cells to PI3K inhibition and inhibit MAPK pathway activation following PI3K pathway targeting.


Subject(s)
Adenocarcinoma , Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Humans , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/pathology , Protein Tyrosine Phosphatase, Non-Receptor Type 11/metabolism , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Phosphatidylinositol 3-Kinases/metabolism , MAP Kinase Signaling System/genetics , Interleukin-3/genetics , Proto-Oncogene Proteins p21(ras)/genetics , Cell Line, Tumor , Oncogenes , Mitogen-Activated Protein Kinases/metabolism , Mutation , Adenocarcinoma/genetics
17.
Arch Sex Behav ; 52(5): 2083-2096, 2023 07.
Article in English | MEDLINE | ID: mdl-37253920

ABSTRACT

Prior research suggests that better mental health and higher relationship quality are associated with better sexual function and satisfaction. Such insights can inform intervention development for mental, relationship, and sexual health concerns. This study examined the interactions among these variables in a racially and ethnically diverse group of young men who have sex with men (YMSM) in serious relationships (N = 348). Data were drawn from wave 5 of a longitudinal cohort study. We examined cross-sectional associations between depression and stress (predictors) and sexual function, sexual satisfaction, and anal discomfort (outcomes) and to what extent these associations were moderated by relationship quality. Higher endorsement of depression and stress was associated with worse sexual functioning, lower sexual satisfaction, and more anal discomfort. We also found that fewer negative interactions, stronger commitment, and higher relationship satisfaction were associated with better sexual functioning and higher sexual satisfaction. Higher relationship satisfaction and commitment were found to attenuate the association between stress and sexual satisfaction. Contrary to expectations, higher relationship satisfaction also showed a trend toward exacerbating the association between depression and sexual functioning. These results suggest that, for YMSM, high relationship satisfaction and commitment may protect sexual satisfaction from being negatively impacted by high stress. However, YMSM in highly satisfying relationships may experience poor sexual functioning associated with depression as particularly distressing. This study addressed a major gap in the literature by focusing on mental, relationship, and sexual health in a diverse sample. Future research should examine a wider range of sexual functioning outcomes and include minority stress in study design.


Subject(s)
Homosexuality, Male , Sexual and Gender Minorities , Male , Humans , Homosexuality, Male/psychology , Longitudinal Studies , Depression , Cross-Sectional Studies , Personal Satisfaction , Sexual Behavior/psychology
18.
Ir J Med Sci ; 192(6): 3051-3062, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37081289

ABSTRACT

BACKGROUND/AIMS: Data are limited on the frequency of 'consensus decisions' between sub-specialists attending a neurovascular multidisciplinary meeting (MDM) regarding management of patients with extracranial carotid/vertebral stenoses and post-MDM 'adherence' to such advice. METHODS: This prospective audit/quality improvement project collated prospectively-recorded data from a weekly Neurovascular/Stroke Centre MDM documenting the proportion of extracranial carotid/vertebral stenosis patients in whom 'consensus management decisions' were reached by neurologists, vascular surgeons, stroke physicians-geriatricians and neuroradiologists. Adherence to MDM advice was analysed in asymptomatic carotid stenosis (ACS), symptomatic carotid stenosis (SCS), 'indeterminate symptomatic status stenosis' (ISS) and vertebral artery stenosis (VAS) patients, including intervals between index event to MDM + / - intervention. RESULTS: One hundred fifteen patients were discussed: 108 with carotid stenosis and 7 with VAS. Consensus regarding management was noted in 96.5% (111/115): 100% with ACS and VAS, 96.2% with SCS and 92.9% with ISS. Adherence to MDM management advice was 96.4% (107/111): 100% in ACS, ISS and VAS patients; 92% (46/50) in SCS patients. The median interval from index symptoms to revascularisation in 50-99% SCS patients was 12.5 days (IQR: 9-18.3 days; N = 26), with a median interval from MDM to revascularisation of 5.5 days (IQR: 1-7 days). Thirty patients underwent revascularisation. Two out of twenty-nine patients (6.9%) with either SCS or ISS had a peri-procedural ipsilateral ischaemic stroke, with no further strokes/deaths during 3-months follow-up. CONCLUSIONS: The high frequency of inter-specialty consensus regarding management and adherence to proposed treatment supports a collaborative/multidisciplinary model of care in patients with extracranial arterial stenoses. Service development should aim to shorten times between MDM discussion-intervention and optimise prevention of stroke/death.


Subject(s)
Brain Ischemia , Carotid Stenosis , Endarterectomy, Carotid , Stroke , Humans , Carotid Stenosis/surgery , Stroke/prevention & control , Constriction, Pathologic/etiology , Consensus , Treatment Outcome , Risk Factors
19.
J Foot Ankle Surg ; 62(4): 737-741, 2023.
Article in English | MEDLINE | ID: mdl-36966965

ABSTRACT

There is growing literature supporting the use of intramedullary fixation for fracture care because of its smaller incisions, improved biomechanical outcomes, and faster time to weightbearing than traditional internal fixation methods. The aim of this study is to investigate the postoperative outcomes in ankle fractures treated with intramedullary nail fixation in the largest patient cohort to date. From 2015 to 2021, 151 patients were evaluated following surgical treatment of fibular fractures with intramedullary nail fixation. Patients were identified through a medical record database search for appropriate ankle fracture procedure codes. Patient information was reviewed for fracture type, adjunct procedures, time to weightbearing and postoperative complications. Radiographs were assessed for quality and time to radiographic union. The mean time to weightbearing was 4.8 weeks. Minor wound dehiscence was identified in 2 patients (1.3%). Superficial infection was present in 4 patients (2.6%) and a deep infection developed in 2 patients (1.3%). Two patients developed a nonunion (1.5%). There were no DVTs reported, although 1 patient developed a PE postoperatively. Radiographic quality of reduction and time to union is comparable to literature reported plate and screw construct outcomes. Reduction was classified as good in 86.1% of patients and radiographic union was appreciated in 98.5% of patients. This is the largest cohort study evaluating the outcomes of intramedullary nail fixation for ORIF of ankle fractures. These data reinforce that intramedullary nailing provides a minimally invasive approach with accurate anatomic reduction, excellent fracture union rates, low complication rates, and an early return to weightbearing.


Subject(s)
Ankle Fractures , Fibula Fractures , Fracture Fixation, Intramedullary , Humans , Ankle Fractures/diagnostic imaging , Ankle Fractures/surgery , Ankle Fractures/etiology , Cohort Studies , Retrospective Studies , Treatment Outcome , Bone Nails , Fracture Fixation, Internal/methods , Fracture Fixation, Intramedullary/methods , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Bone Plates , Fibula/surgery
20.
Neuroimaging Clin N Am ; 33(2): 299-313, 2023 May.
Article in English | MEDLINE | ID: mdl-36965947

ABSTRACT

In this review, we discuss the basics of functional MRI (fMRI) techniques including task-based and resting state fMRI, and overview the major findings in patients with traumatic brain injury. We summarize the studies that have longitudinally evaluated the changes in brain connectivity and task-related activation in trauma patients during different phases of trauma. We discuss how these data may potentially be used for prognostication, treatment planning, or monitoring and management of trauma patients.


Subject(s)
Brain Injuries , Magnetic Resonance Imaging , Humans , Magnetic Resonance Imaging/methods , Brain/diagnostic imaging , Head
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