Traumatic life events, everyday discrimination, and posttraumatic symptoms among sexual minority men.

OBJECTIVE: Experiences of everyday discrimination are linked with mental health issues for sexual minority individuals, including posttraumatic symptoms (PTS), yet it is unclear whether experiences of discrimination are linked with PTS after accounting for the influence of traumatic life events. This study sought to increase understanding of the link between everyday discrimination and PTS, among sexual minority men. METHOD: A sample of 290 gay men living in the United States completed an online survey including measures of traumatic life events, everyday discrimination, and PTS. RESULTS: Logistic regressions supported a link between everyday discrimination and meeting the cutoff for PTS, after accounting for traumatic life events. Furthermore, everyday discrimination was linked with higher scores on all symptom clusters of PTS. CONCLUSIONS: Study results provide support for a link between everyday discrimination and PTS at levels exceeding clinical cutoffs. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Proteomic Risk Score of Increased Respiratory Susceptibility: A Multi-Cohort Study.

RATIONALE: Accelerated decline in lung function is associated with incident COPD, hospitalizations and death. However, identifying this trajectory with longitudinal spirometry measurements is challenging in clinical practice. OBJECTIVE: To determine whether a proteomic risk score trained on accelerated decline in lung function can assess risk of future respiratory disease and mortality. METHODS: In CARDIA, a population-based cohort starting in young adulthood, longitudinal measurements of FEV1 percent predicted (up to six timepoints over 30 years) were used to identify accelerated and normal decline trajectories. Protein aptamers associated with an accelerated decline trajectory were identified with multivariable logistic regression followed by LASSO regression. The proteomic respiratory susceptibility score was derived based on these circulating proteins and applied to the UK Biobank and COPDGene studies to examine associations with future respiratory morbidity and mortality. MEASUREMENTS AND RESULTS: Higher susceptibility score was independently associated with all-cause mortality (UKBB: HR 1.56, 95%CI 1.50-1.61; COPDGene: HR 1.75, 95%CI 1.63-1.88), respiratory mortality (UKBB: HR 2.39, 95% CI 2.16-2.64; COPDGene: HR 1.83, 95%CI 1.33-2.51), incident COPD (UKBB: HR 1.84, 95%CI 1.71-1.98), incident respiratory exacerbation (COPDGene: OR 1.11, 95%CI 1.03-1.20), and incident exacerbation requiring hospitalization (COPDGene: OR 1.18, 95%CI 1.08-1.28). CONCLUSIONS: A proteomic signature of increased respiratory susceptibility identifies people at risk of respiratory death, incident COPD, and respiratory exacerbations. This susceptibility score is comprised of proteins with well-known and novel associations with lung health and holds promise for the early detection of lung disease without requiring years of spirometry measurements.

Ultrasound and x-ray imageable poloxamer-based hydrogel for loco-regional therapy delivery in the liver.

Intratumoral injections have the potential for enhanced cancer treatment efficacy while reducing costs and systemic exposure. However, intratumoral drug injections can result in substantial off-target leakage and are invisible under standard imaging modalities like ultrasound (US) and x-ray. A thermosensitive poloxamer-based gel for drug delivery was developed that is visible using x-ray imaging (computed tomography (CT), cone beam CT, fluoroscopy), as well as using US by means of integrating perfluorobutane-filled microbubbles (MBs). MBs content was optimized using tissue mimicking phantoms and ex vivo bovine livers. Gel formulations less than 1% MBs provided gel depositions that were clearly identifiable on US and distinguishable from tissue background and with minimal acoustic artifacts. The cross-sectional areas of gel depositions obtained with US and CT imaging were similar in studies using ex vivo bovine liver and postmortem in situ swine liver. The gel formulation enhanced multimodal image-guided navigation, enabling fusion of ultrasound and x-ray/CT imaging, which may enhance targeting, definition of spatial delivery, and overlap of tumor and gel. Although speculative, such a paradigm for intratumoral drug delivery might streamline clinical workflows, reduce radiation exposure by reliance on US, and boost the precision and accuracy of drug delivery targeting during procedures. Imageable gels may also provide enhanced temporal and spatial control of intratumoral conformal drug delivery.

Investigating the Association between Steatotic Liver Disease and CKD in a Nationally Representative Sample.

BACKGROUND: Steatotic liver disease (SLD) and chronic kidney disease (CKD) are common conditions that are strongly associated. Yet, there is a paucity of data regarding the prevalence of this overlap and the factors that may drive its occurrence. METHODS: Using the National Health and Nutrition Examination survey, we examined trends among adult participants from 2005 - 2020 that defined SLD with the Fatty Liver Index. We completed correlative analyses among adult participants from 2017 - 2020 that defined SLD based on FibroScan results. We utilized multivariable survey-weighted binomial generalized linear models to determine the factors that were associated with CKD, defined as eGFR <60 or urine albumin-creatinine-ratio >30. RESULTS: Among the 76,496 participants included in the trend analyses, the estimated prevalence of CKD was 15.7% (95%CI 15.2 - 16.2%) and SLD was 42.3% (95%CI 41.4 - 43.2%). As compared to those without SLD, those with SLD had a significantly higher estimated prevalence of CKD (SLD: 15.7%, 95%CI 14.9 - 16.5% v. No SLD 11.2%, 95%CI 10.7 - 11.7%). In multivariate analyses of 3,667 participants who underwent FibroScan and had SLD by Fatty Liver Index, adjusting for control and presence of DM, HTN, and HLD, compared to those with normal liver stiffness, those with moderate scarring (F2) had similar odds of CKD (1.53, 95CI 0.91-2.56), those with severe scarring (F3) had higher odds of CKD (2.28, 95CI 1.20-4.32), and those with cirrhosis had higher odds of CKD (2.21, 95CI 1.13-4.32). CONCLUSIONS: Our findings highlight that CKD is common among patients with SLD and that higher degrees of hepatic fibrosis are associated with CKD, independent of other co-morbidities of the metabolic syndrome.

A 65-Year-Old Female with Missed Open Clavicle Fracture and Subsequent Fracture-Related Infection, Treated with Distal Clavicle Resection.

Introduction: Open clavicle fractures are rare, and there are no current reported cases in the literature of a missed open clavicle with resultant fracture-related infection and osteomyelitis. Case Report: We present a 65-year-old female with no reported medical history, who presented to our institution with left clavicular pain and wound drainage 8 days after she was struck by a motor vehicle in her home country of Guyana. She was found to have a missed open clavicle fracture with an associated severe infection. She was subsequently treated with irrigation, debridement, and distal clavicle excision. Conclusion: We present this unique case with a potential procedure which could prove beneficial in cases of infection, trauma, or oncologic lesions in which the distal clavicle is deemed unsalvageable.

Differences in Somatosensory Function Related to Hand Dominance: Results of a Quantitative Sensory Testing Study in Healthy Volunteers.

Purpose: Quantitative sensory testing commonly utilizes the unaffected, contralateral side as a control to detect somatosensory dysfunction. There is scant evidence that somatosensory function for the volar dominant and non-dominant hands is equivalent, therefore intra-patient comparisons are unwarranted. This study aimed to identify dominance-related differences in palmar hand somatosensation, thereby determining if the unaffected contralateral hand is a valid comparator in clinical populations. Participants and Methods: With ethical approval (IREC_13_1_10) and informed consent, 110 healthy adult volunteers' participated in this clinical measurement study. Somatosensory function was assessed with the German Research Network on Neuropathic Pain (DFNS) quantitative sensory testing (QST) protocol. Half of the participants were tested on the dominant hand. Thirteen parameters of thermal and mechanical detection and pain threshold were evaluated at both the dorsal and volar hand (distal middle finger). Tests were performed in the same order and instructions were read from a standardized script. Results for dorsal hand tests were compared to DFNS normative data to confirm participants met study inclusion criteria. Between-group differences for age and sex were investigated with the independent samples t-test and Chi-square test of independence, respectively. Group differences for dominant and non-dominant hands for all 13 continuous QST parameters were investigated with the Mann-Whitney U-test. Results: Data for 106 participants were included in statistical analysis. Fifty percent of participants were tested on the dominant hand [n=53]; there were no differences for age or sex between groups (dominant or non-dominant hand test group). The dominant volar hand was significantly more sensitive to vibration detection threshold than the non-dominant hand (P=0.001). There were no significant differences related to dominance for other DFNS QST measures. Conclusion: For quantitative sensory testing with the DFNS protocol in healthy cohorts, the contralateral, unaffected hand is a valid control, with the exception of vibration detection threshold.

Standardized Data Elements for Patients With Acute Pulmonary Embolism: A Consensus Report from the Pulmonary Embolism Research Collaborative.

Recent advances in therapy and the promulgation of multidisciplinary pulmonary embolism teams show great promise to improve management and outcomes of acute pulmonary embolism (PE). However, the absence of randomized evidence and lack of consensus leads to tremendous variations in treatment and compromises the wide implementation of new innovations. Moreover, the changing landscape of health care, where quality, cost, and accountability are increasingly relevant, dictates that a broad spectrum of outcomes of care must be routinely monitored to fully capture the impact of modern PE treatment. We set out to standardize data collection in patients with PE undergoing evaluation and treatment, and thus establish the foundation for an expanding evidence base that will address gaps in evidence and inform future care for acute PE. To do so, >100 international PE thought leaders convened in Washington, DC, in April 2022 to form the Pulmonary Embolism Research Collaborative. Participants included physician experts, key members of the US Food and Drug Administration, patient representatives, and industry leaders. Recognizing the multidisciplinary nature of PE care, the Pulmonary Embolism Research Collaborative was created with representative experts from stakeholder medical subspecialties, including cardiology, pulmonology, vascular medicine, critical care, hematology, cardiac surgery, emergency medicine, hospital medicine, and pharmacology. A list of critical evidence gaps was composed with a matching comprehensive set of standardized data elements; these data points will provide a foundation for productive research, knowledge enhancement, and advancement of clinical care within the field of acute PE, and contribute to answering urgent unmet needs in PE management. Evidence produced through the Pulmonary Embolism Research Collaborative, as it is applied to data collection, promises to provide crucial knowledge that will ultimately produce a robust evidence base that will lead to standardization and harmonization of PE management and improved outcomes.

Microbubbles bound to drug-eluting beads enable ultrasound imaging and enhanced delivery of therapeutics.

Transarterial chemoembolization (TACE) is an image-guided minimally invasive treatment for liver cancer which involves delivery of chemotherapy and embolic material into tumor-supplying arteries to block blood flow to a liver tumor and to deliver chemotherapy directly to the tumor. However, the released drug diffuses only less than a millimeter away from the beads. To enhance the efficacy of TACE, the development of microbubbles electrostatically bound to the surface of drug-eluting beads loaded with different amounts of doxorubicin (0-37.5 mg of Dox/mL of beads) is reported. Up to 400 microbubbles were bound to Dox-loaded beads (70-150 microns). This facilitated ultrasound imaging of the beads and increased the release rate of Dox upon exposure to high intensity focused ultrasound (HIFU). Furthermore, ultrasound exposure (1 MPa peak negative pressure) increased the distance at which Dox could be detected from beads embedded in a tissue-mimicking phantom, compared with a no ultrasound control.

Challenges and Approaches to Establishing Multi-Pathogen Serosurveillance: Findings from the 2023 Serosurveillance Summit.

Multiplex-based serological surveillance is a valuable but underutilized tool to understand gaps in population-level exposure, susceptibility, and immunity to infectious diseases. Assays for which blood samples can be tested for antibodies against several pathogens simultaneously, such as multiplex bead immunoassays, can more efficiently integrate public health surveillance in low- and middle-income countries. On March 7-8, 2023 a group of experts representing research institutions, multilateral organizations, private industry, and country partners met to discuss experiences, identify challenges and solutions, and create a community of practice for integrated, multi-pathogen serosurveillance using multiplex bead assay technologies. Participants were divided into six working groups: 1) supply chain; 2) laboratory assays; 3) seroepidemiology; 4) data analytics; 5) sustainable implementation; and 6) use case scenarios. These working groups discussed experiences, challenges, solutions, and research needs to facilitate integrated, multi-pathogen serosurveillance for public health. Several solutions were proposed to address challenges that cut across working groups.

Entangling gates on degenerate spin qubits dressed by a global field.

Semiconductor spin qubits represent a promising platform for future large-scale quantum computers owing to their excellent qubit performance, as well as the ability to leverage the mature semiconductor manufacturing industry for scaling up. Individual qubit control, however, commonly relies on spectral selectivity, where individual microwave signals of distinct frequencies are used to address each qubit. As quantum processors scale up, this approach will suffer from frequency crowding, control signal interference and unfeasible bandwidth requirements. Here, we propose a strategy based on arrays of degenerate spins coherently dressed by a global control field and individually addressed by local electrodes. We demonstrate simultaneous on-resonance driving of two degenerate qubits using a global field while retaining addressability for qubits with equal Larmor frequencies. Furthermore, we implement SWAP oscillations during on-resonance driving, constituting the demonstration of driven two-qubit gates. Significantly, our findings highlight how dressing can overcome the fragility of entangling gates between superposition states and increase their noise robustness. These results constitute a paradigm shift in qubit control in order to overcome frequency crowding in large-scale quantum computing.

Appropriateness of the EQ-HWB for Use in Residential Aged Care: A Proxy Perspective.

BACKGROUND AND OBJECTIVE: The EQ Health and Wellbeing (EQ-HWB) is a new generic quality-of-life measure for use in evaluating interventions in health, public health and social care. This study aimed to explore proxies' views regarding the appropriateness of the EQ-HWB for measuring residents' quality of life living in residential aged care facilities. METHODS: Qualitative think-aloud and semi-structured interviews were conducted with family members and aged care staff across three facilities in Melbourne, Australia. Proxies completed the 25-item EQ-HWB proxy version 2 (i.e. proxy-person perspective) whilst talking through the reasons for choosing their response. All interviews were audio-recorded and transcribed verbatim. A thematic analysis was used for data analysis. RESULTS: The sample included 29 proxies; nine family members and 20 aged care staff. The first theme summarised proxies' ability to proxy report residents' health and well-being using the EQ-HWB, which highlighted challenges with adherence to the proxy perspective, proxies' limited knowledge about residents, disagreement with residents' self-evaluation and use of heuristics. The second theme reflected feedback on the suitability of the EQ-HWB for use in residential aged care. Although proxies perceived that the EQ-HWB covered important domains, there were concerns about ambiguity, inappropriate examples, double-barrelled items and perceived repetition. Suggestions were made to improve the response options, comprehensiveness, recall period, layout and instructions of the questionnaire. CONCLUSIONS: While the EQ-HWB captures domains relevant to residential aged care, modifications to item wording and examples are necessary to improve its appropriateness. Use of the proxy-person perspective revealed some challenges that require further consideration.

A Longitudinal Analysis of Memory Immune Responses in Convalescent Crimean-Congo Hemorrhagic Fever Survivors in Uganda.

Evaluating the adaptive immune responses to natural infection with Crimean-Congo hemorrhagic fever (CCHF) virus (CCHFV) in human survivors is critical to the development of medical countermeasures. However, the correlates of protection are unknown. As the most prevalent tick-borne human hemorrhagic fever virus with case fatality rates of 5%-30% and worldwide distribution, there is an urgent need to fill these knowledge gaps. Here, we describe adaptive immune responses in a cohort of Ugandan CCHF survivors via serial sampling over 6 years. We demonstrate persistent antibodies after infection and cross-neutralization against various clades of authentic CCHFV, as well as potent effector function. Moreover, we show for the first time persistent, polyfunctional antigen-specific memory T-cell responses to multiple CCHFV proteins up to 9 years after infection. Together, this data provides immunological benchmarks for evaluating CCHFV medical countermeasures and information that can be leveraged toward vaccine immunogen design and viral target identification for monoclonal antibody therapies.

Prophylactic Buried Dermal Flap: A Simple Method for Axillary Reconstruction after Lymph Node Dissection.

Breast cancer-related lymphedema is characterized by progressive limb enlargement and occurs in up to 30% of breast cancer patients following axillary lymph node dissection (ALND). Immediate lymphatic reconstruction (ILR) is a preventative technique used to reduce lymphedema rates by performing lymphovenous anastomoses of disrupted afferent lymphatics. This study presents a novel method of axillary reconstruction following ALND using a buried dermal flap that provides local tissue with intact subdermal lymphatics to the axillary dead space. A single-center retrospective review was performed to assess breast cancer patients who underwent modified radical mastectomy without reconstruction between 2018 and 2023. Groups were divided into those who had ILR alone (group 1) and those who had buried dermal flap with attempted ILR (group 2). There were 31 patients included in this study: 18 patients in group 1 and 13 patients in group 2. Patient demographics, comorbidities, and breast cancer history were similar between the groups. There was no significant difference in the mean number of lymphovenous anastomoses performed (1.6 versus 1.7, P = 0.84). Mean operative time of 224.4 ±â€…51.9 minutes in group 1 was similar to 223.4 ±â€…30.4 minutes in group 2 (P = 0.95). We introduce a novel method of axillary reconstruction following ALND using a buried dermal flap that is inset into the axillary dissection space and over the area of ILR. We propose that it is an efficient accessory procedure to augment ILR by providing supplementary intact lymphatic channels to the area of lymphatic injury, while obliterating the axillary dead space.

Physiological role and mechanisms of action for a long noncoding haplotype region.

Most common sequence variants associated with human traits are in noncoding regions of the genome, form haplotypes with other noncoding variants, and exhibit small effect sizes in the general population. Determining the physiological roles and mechanisms of action for these noncoding variants, particularly large haplotypes containing multiple variants, is both critical and challenging. To address this challenge, we developed an approach that integrates physiological studies in genetically engineered and phenotypically permissive animal models, precise editing of large haplotypes in human induced pluripotent stem cells (hiPSCs), and targeted chromatin conformation analysis. We applied this approach to examine the blood pressure associated rs1173771 locus, which includes a haplotype containing 11 single nucleotide polymorphisms (SNPs) spanning 17.4 kbp. Deleting the orthologous noncoding region in the genome of the Dahl salt-sensitive rat attenuated the salt-induced increase in systolic blood pressure by nearly 10 mmHg. This attenuation of hypertension appeared to be mediated by upregulation of the adjacent gene Npr3 (natriuretic peptide receptor 3) in arteries, enhancing vasodilation. The blood pressure-elevating and -lowering haplotypes were precisely reconstituted in hiPSCs using an efficient, two-step genome editing technique. The blood pressure-elevating haplotype decreased NPR3 expression in endothelial cells and vascular smooth muscle cells derived from the edited, isogenic hiPSCs. The influence of the haplotype was partially recapitulated by the sentinel SNP rs1173771. Additionally, the blood pressure-elevating haplotype showed significantly greater chromatin interactions with the NPR3 promoter region. This study illustrates the feasibility of ascertaining the physiological roles and mechanisms of action for large noncoding haplotypes. Our efficient, integrated, and targeted approach can be applied to investigate other noncoding variants.

An exploration of metacognitive practices in medical educators.

Metacognition is the ability to monitor and evaluate one's thoughts about learning and has been shown in some studies to improve the effectiveness of instructors. With dissection-based gross anatomy, instructors dynamically use their metacognition to monitor student learning and adapt their teaching at tableside. This study explored the metacognition of instructors as they taught in an anatomy course for allied health students. All instructors in a doctoral-level gross anatomy course at a single institution, including faculty, associate instructors (AIs), and teaching assistants (TAs), were invited to participate. At the start and end of the course, participating instructors completed pre- and post-questionnaires, which included the Teacher Metacognition Inventory (TMI), a 28-item survey that assesses metacognition as it relates to teaching. After labs, instructors completed reflective journals to provide deeper insight into their metacognition. Reflective journals were then thematically analyzed. Thirteen (52%) instructors participated in this study, including five faculty, three AI, and five TAs. Between the start and end of the course, total TMI score increased from 108.8 to 114.3 (p = 0.046). TAs exhibited the greatest change in total TMI score (Δmean = +11.4) followed by faculty (Δmean = +3.2) and AIs (Δmean = -0.7). Several themes were also identified. For example, TAs were more internally focused on content mastery, whereas faculty were externally focused on interpersonal factors (e.g., inclusive language). These insights into the metacognition of anatomy instructors, though limited in reliability and generalizability, may inform how to best support their professional development. Novices may benefit from content reviews, while experienced instructors may benefit from inclusivity or communications training.

Cryoablation Without Excision for Early-Stage Breast Cancer: ICE3 Trial 5-Year Follow-Up on Ipsilateral Breast Tumor Recurrence.

BACKGROUND: The ICE3 trial evaluated the safety and efficacy of cryoablation in women aged ≥60 years with low-risk, early-stage breast cancers, aiming to provide a non-operative treatment option and avoid potential surgical risks. This study presents 5-year follow-up trial results. METHODS: The ICE3 trial is an Institutional Review Board-approved, prospective, multicentered, non-randomized trial including women ≥ 60 years of age with unifocal, ultrasound visible, invasive ductal carcinoma ≤ 1.5 cm in size, histologic grade 1-2, hormone receptor (HR)-positive, and human epidermal growth factor receptor 2 (HER2)-negative. The primary study endpoint of 5-year ipsilateral breast tumor recurrence (IBTR) was evaluated based on Kaplan-Meier estimates. RESULTS: Overall, 194 patients meeting eligibility received successful cryoablation treatment per protocol and were included for analysis. The mean age was 74.9 years (55-94) with a mean tumor size of 7.4 mm transverse (2.8-14.0 mm) and 8.1 mm sagittal (2.5-14.9 mm). With a mean follow-up period of 54.16 months, the IBTR rate at 5 years was 4.3% and breast cancer survival was 96.7%. Of the 124 patients who received endocrine therapy only, the IBTR was 3.7%. No serious device-related adverse events were reported. Minor (88.2%) and moderate (9.6%) adverse events were mild in severity and resolved without residual effects. Quality-of-life score demonstrated statistically significant improvement (p < 0.001) in distress at 6 months as compared with baseline. CONCLUSIONS: Breast cryoablation presents a promising alternative to surgery in selected patients, offering the benefits of a minimally invasive procedure with minimal risks. Further studies are encouraged to confirm cryoablation as a viable alternative to surgical excision low-risk patients.

Epidemiological Principles in Claims of Causality: An Enquiry into Repetitive Head Impacts (RHI) and Chronic Traumatic Encephalopathy (CTE).

Determining whether repetitive head impacts (RHI) cause the development of chronic traumatic encephalopathy (CTE)-neuropathological change (NC) and whether pathological changes cause clinical syndromes are topics of considerable interest to the global sports medicine community. In 2022, an article was published that used the Bradford Hill criteria to evaluate the claim that RHI cause CTE. The publication garnered international media attention and has since been promoted as definitive proof that causality has been established. Our counterpoint presents an appraisal of the published article in terms of the claims made and the scientific literature used in developing those claims. We conclude that the evidence provided does not justify the causal claims. We discuss how causes are conceptualised in modern epidemiology and highlight shortcomings in the current definitions and measurement of exposures (RHI) and outcomes (CTE). We address the Bradford Hill arguments that are used as evidence in the original review and conclude that assertions of causality having been established are premature. Members of the scientific community must be cautious of making causal claims until the proposed exposures and outcomes are well defined and consistently measured, and findings from appropriately designed studies have been published. Evaluating and reflecting on the quality of research is a crucial step in providing accurate evidence-based information to the public.