RESUMEN

BACKGROUND: X-linked acrogigantism (X-LAG; MIM: 300942) is a severe form of pituitary gigantism caused by chromosome Xq26.3 duplications involving GPR101. X-LAG-associated duplications disrupt the integrity of the topologically associating domain (TAD) containing GPR101 and lead to the formation of a neo-TAD that drives pituitary GPR101 misexpression and gigantism. As X-LAG is fully penetrant and heritable, duplications involving GPR101 identified on prenatal screening studies, like amniocentesis, can pose an interpretation challenge for medical geneticists and raise important concerns for patients and families. Therefore, providing robust information on the functional genomic impact of such duplications has important research and clinical value with respect to gene regulation and triplosensitivity traits. METHODS: We employed 4C/HiC-seq as a clinical tool to determine the functional impact of incidentally discovered GPR101 duplications on TAD integrity in three families. After defining duplications and breakpoints around GPR101 by clinical-grade and high-density aCGH, we constructed 4C/HiC chromatin contact maps for our study population and compared them with normal and active (X-LAG) controls. RESULTS: We showed that duplications involving GPR101 that preserved the centromeric invariant TAD boundary did not generate a pathogenic neo-TAD and that ectopic enhancers were not adopted. This allowed us to discount presumptive/suspected X-LAG diagnoses and GPR101 misexpression, obviating the need for intensive clinical follow-up. CONCLUSIONS: This study highlights the importance of TAD boundaries and chromatin interactions in determining the functional impact of copy number variants and provides proof-of-concept for using 4C/HiC-seq as a clinical tool to acquire crucial information for genetic counseling and to support clinical decision-making in cases of suspected TADopathies.

Asunto(s)

RESUMEN

BACKGROUND: Although guidelines recommend risk assessment for hospital-acquired venous thromboembolism (HA-VTE) to inform prophylaxis decisions, studies demonstrate inappropriate utilization of pharmacoprophylaxis in hospitalized medical patients. Predictors of pharmacoprophylaxis initiation in medical inpatients remain largely unknown. OBJECTIVE: To determine factors associated with HA-VTE pharmacoprophylaxis initiation in adults hospitalized on medical services. DESIGN: Cohort study using electronic health record data from adult patients hospitalized on medical services at four academic medical centers between 2016 and 2019. PARTICIPANTS: Among 111,550 admissions not on intermediate or full-dose anticoagulation, 48,520 (43.5%) received HA-VTE pharmacoprophylaxis on the day of or the day after admission. MAIN MEASURES: Candidate predictors of HA-VTE pharmacoprophylaxis initiation, including known HA-VTE risk factors, predicted HA-VTE risk, and bleeding diagnoses present on admission. KEY RESULTS: After adjustment for age, sex, race/ethnicity, and study site, the strongest clinical predictors of HA-VTE pharmacoprophylaxis initiation were malnutrition and chronic obstructive pulmonary disease. Thrombocytopenia and history of gastrointestinal bleeding were associated with decreased odds of HA-VTE pharmacoprophylaxis initiation. Patients in the highest two tertiles of predicted HA-VTE risk were less likely to receive HA-VTE pharmacoprophylaxis than patients in the lowest (1st) tertile (OR 0.84, 95% CI [0.81, 0.86] for 2nd tertile, OR 0.95, 95% CI [0.92, 0.98] for 3rd tertile). CONCLUSIONS: Among patients not already receiving anticoagulants, HA-VTE pharmacoprophylaxis initiation during the first two hospital days was lower in patients with higher predicted HA-VTE risk and those with risk factors for bleeding. Reasons for not initiating pharmacoprophylaxis in those with higher predicted risk could not be assessed.

RESUMEN

BACKGROUND AND OBJECTIVES: Studies have indicated that cadmium (Cd) exposure is associated with neurotoxicity. However, data linking Cd exposure to cognitive impairment are sparse. We aimed to investigate the association between urinary Cd concentration and cognitive impairment in US adults. METHODS: The REasons for Geographic and Racial Differences in Stroke (REGARDS) study is an ongoing population-based prospective cohort study that enrolled 30,239 Black and White US adults aged 45 years or older at baseline (2003-2007). In a randomly selected subcohort of REGARDS participants who were free of cognitive impairment or stroke at baseline, certain trace element concentrations, including urinary creatinine-corrected Cd, were measured using biospecimens collected and stored at baseline. During an average of 10 years of follow-up, global cognitive impairment was assessed annually using the Six-Item Screener, and domain-based cognitive impairment, including verbal learning, memory, and executive function, was evaluated every other year using the Enhanced Cognitive Battery. Multivariable-adjusted logistic regression models were used to examine the association between urinary Cd concentration and the odds of global or domain-based cognitive impairment. RESULTS: A total of 2,172 participants (mean age: 64.1 ± 9.0 years; female: 54.8%; Black participants: 38.7%) with available data on urinary Cd concentration, including 195 cases of global cognitive impairment and 53 cases of domain-based cognitive impairment, were included in the analyses. While there was no association between Cd and cognitive impairment in the full sample, there was a significant positive association of urinary Cd concentration with global cognitive impairment among White but not Black participants. The odds of cognitive impairment for White participants in the high urinary Cd concentration group (≥median) were doubled compared with those in the low urinary Cd group (odds ratio 2.07, 95% CI 1.18-3.64). Sex, age, region, smoking pack-years, alcohol consumption, and other related metals did not materially modify the associations of interest. DISCUSSION: Findings from this prospective cohort study suggest that urinary Cd concentrations are associated with global cognitive impairment among White but not Black individuals. Further studies with repeatedly measured Cd exposure, larger sample sizes, and longer duration are needed to confirm our findings and explore the potential explanations for the observed racial discrepancy, such as the impact of smoking.

Asunto(s)

RESUMEN

CONTEXT: In response to the COVID-19 pandemic, Congress passed the American Rescue Plan Act of 2021 (ARPA) that included a historic investment in the public health workforce. PROGRAM: Charged with implementing this investment, the U.S. Centers for Disease Control and Prevention (CDC) launched the Public Health Infrastructure Grant (PHIG). PHIG builds on CDC's experience working with state, local, and territorial public health departments and represents a new approach to strengthening the public health workforce. IMPLEMENTATION: Specifically, PHIG incorporates features that allow these public health departments to prioritize and tailor the funding to meet their communities' needs: 1) focus on workforce as core infrastructure, 2) streamlined programmatic and administrative requirements, 3) more equitable funding approach, and 4) enhanced support from national partners and CDC. DISCUSSION: The goal is to optimize the unprecedented opportunity afforded by ARPA and lead to a stronger public health workforce and infrastructure across the United States.

RESUMEN

BACKGROUND: Studies have identified individual blood biomarkers associated with chronic obstructive pulmonary disease (COPD) and related phenotypes. However, complex diseases such as COPD typically involve changes in multiple molecules with interconnections that may not be captured when considering single molecular features. METHODS: Leveraging proteomic data from 3,173 COPDGene Non-Hispanic White (NHW) and African American (AA) participants, we applied sparse multiple canonical correlation network analysis (SmCCNet) to 4,776 proteins assayed on the SomaScan v4.0 platform to derive sparse networks of proteins associated with current vs. former smoking status, airflow obstruction, and emphysema quantitated from high-resolution computed tomography scans. We then used NetSHy, a dimension reduction technique leveraging network topology, to produce summary scores of each proteomic network, referred to as NetSHy scores. We next performed a genome-wide association study (GWAS) to identify variants associated with the NetSHy scores, or network quantitative trait loci (nQTLs). Finally, we evaluated the replicability of the networks in an independent cohort, SPIROMICS. RESULTS: We identified networks of 13 to 104 proteins for each phenotype and exposure in NHW and AA, and the derived NetSHy scores significantly associated with the variable of interests. Networks included known (sRAGE, ALPP, MIP1) and novel molecules (CA10, CPB1, HIS3, PXDN) and interactions involved in COPD pathogenesis. We observed 7 nQTL loci associated with NetSHy scores, 4 of which remained after conditional analysis. Networks for smoking status and emphysema, but not airflow obstruction, demonstrated a high degree of replicability across race groups and cohorts. CONCLUSIONS: In this work, we apply state-of-the-art molecular network generation and summarization approaches to proteomic data from COPDGene participants to uncover protein networks associated with COPD phenotypes. We further identify genetic associations with networks. This work discovers protein networks containing known and novel proteins and protein interactions associated with clinically relevant COPD phenotypes across race groups and cohorts.

Asunto(s)

RESUMEN

Natural killer (NK) cells are innate lymphoid cells that protect a host from viral infections and malignancies. MicroRNA-146a (miR-146a) is an important regulator of immune function that is highly expressed in NK cells and is further upregulated during murine cytomegalovirus (MCMV) infection. Here we utilized mice with a global targeted deletion of miR-146a to understand its impact on the innate immune responses to MCMV infection. MiR-146a-/- mice were protected from lethal MCMV infection, which was intrinsic to the hematopoietic compartment based on bone marrow chimera experiments. NK cell depletion abrogated this protection, implicating NK cells as critical for the miR-146a-/- protection from MCMV. Surprisingly, NK cells from miR-146a-deficient mice were largely similar to control NK cells with respect to development, maturation, trafficking, and effector functions. However, miR-146a-/- mice had increased NK cell numbers and frequency of the most mature Stage IV (CD27-CD11b+) NK cells in the liver at baseline, enhanced STAT1 phosphorylation, and increased selective expansion of Ly49H+ NK cells and T cells during MCMV infection. This study demonstrates a critical role for miR-146a in the host response to MCMV, arising from mechanisms that include increased NK cell numbers and early T-cell expansion.

RESUMEN

Background: Radiotherapy (RT) is the primary treatment for diffuse midline glioma (DMG), a lethal pediatric malignancy defined by histone H3 lysine 27-to-methionine (H3K27M) mutation. Based on the loss of H3K27 trimethylation producing broad epigenomic alterations, we hypothesized that H3K27M causes a functional double-strand break (DSB) repair defect that could be leveraged therapeutically with PARP inhibitor and RT for selective radiosensitization and antitumor immune responses. Methods: H3K27M isogenic DMG cells and orthotopic brainstem DMG tumors in immune deficient and syngeneic, immune competent mice were used to evaluate the efficacy and mechanisms of PARP1/2 inhibition by olaparib or PARP1 inhibition by AZD9574 with concurrent RT. Results: H3K27M mutation caused an HRR defect characterized by impaired RT-induced K63-linked polyubiquitination of histone H1 and inhibition of HRR protein recruitment. H3K27M DMG cells were selectively radiosensitized by olaparib in comparison to isogenic controls, and this effect translated to efficacy in H3K27M orthotopic brainstem tumors. Olaparib and RT induced an innate immune response and induction of NK cell (NKG2D) activating ligands leading to increased NK cell-mediated lysis of DMG tumor cells. In immunocompetent syngeneic orthotopic DMG tumors, either olaparib or AZD9574 in combination with RT enhanced intratumoral NK cell infiltration and activity in association with NK cell-mediated therapeutic responses and favorable activity of AZD9574. Conclusions: The HRR deficiency in H3K27M DMG can be therapeutically leveraged with PARP inhibitors to radiosensitize and induce an NK cell-mediated antitumor immune response selectively in H3K27M DMG, supporting the clinical investigation of best-in-class PARP inhibitors with RT in DMG patients. Key points: H3K27M DMG are HRR defective and selectively radiosensitized by PARP inhibitor.PARP inhibitor with RT enhances NKG2D ligand expression and NK cell-mediated lysis.NK cells are required for the therapeutic efficacy of PARP inhibitor and RT. Importance of the Study: Radiotherapy is the cornerstone of H3K27M-mutant diffuse midline glioma treatment, but almost all patients succumb to tumor recurrence with poor overall survival, underscoring the need for RT-based precision combination therapy. Here, we reveal HRR deficiency as an H3K27M-mediated vulnerability and identify a novel mechanism linking impaired RT-induced histone H1 polyubiquitination and the subsequent RNF168/BRCA1/RAD51 recruitment in H3K27M DMG. This model is supported by selective radiosensitization of H3K27M DMG by PARP inhibitor. Notably, the combination treatment results in NKG2D ligand expression that confers susceptibility to NK cell killing in H3K27M DMG. We also show that the novel brain penetrant, PARP1-selective inhibitor AZD9574 compares favorably to olaparib when combined with RT, prolonging survival in a syngeneic orthotopic model of H3K27M DMG. This study highlights the ability of PARP1 inhibition to radiosensitize and induce an NK cell-mediated antitumor immunity in H3K27M DMG and supports future clinical investigation.

RESUMEN

Background: Warm autoimmune haemolytic anaemia (wAIHA) is an acquired haemolytic disorder most commonly treated with a combination of corticosteroids, rituximab and/or splenectomy. Third-line therapies for refractory cases include immunosuppressive agents. Mycophenolate mofetil is frequently used in these scenarios, although its use is supported by small studies and anecdotal evidence rather than large-scale data. Case description: We describe three cases of refractory warm autoimmune haemolytic anaemia successfully treated with mycophenolate mofetil. Case 1: A persistent case of autoimmune haemolytic anaemia in a 56-year-old was ultimately managed with mycophenolate mofetil, leading to successful steroid tapering and stable haemoglobin levels without relapse. Case 2: A woman with a complex oncological history, including lymphoma and breast cancer, achieved remission with mycophenolate therapy, maintaining stability post-steroid treatment. Case 3: Mycophenolate proved effective for a 63-year-old with cirrhosis after recurrent autoimmune anaemia and deep vein thrombosis, enabling cessation of steroids and maintaining remission. Conclusion: Management of this condition can be challenging and balancing the available treatments is crucial to reduce potential complications from long-term therapies that appear to be ineffective. Our case series demonstrates anecdotal experience on successful use of mycophenolate mofetil for complex refractory cases of wAIHA. LEARNING POINTS: Warm autoimmune haemolytic anaemia can be a challenging condition to manage. Refractory cases that are steroid-dependent can benefit from trialling steroid-sparing agents such as mycophenolate.Anti-CD20 agents such as rituximab can be very effective in refractory cases, however there is a small percentage of patients that might not be responsive to this monoclonal antibody.Autoimmune haemolytic anaemias can be frequently complicated by thrombotic events, and part of the backbone treatment is establishing good thromboprophylaxis.

RESUMEN

Purpose: The purpose of this study was to characterize nurses' attitudes toward music and implementation of music into patient care and to characterize barriers and facilitators toward the implementation of music into patient care. Design: A cross-sectional, quantitative, web-based questionnaire with minor qualitative elements. Methods: The questionnaire contained both open- and closed-ended questions. It was developed in Qualtrics and sent via email to nurses working on inpatient units at an academic medical center hospital in the southeastern United States. Findings: A total of 348 nurses responded to the questionnaire. Eighty-nine percent of nurses reported having used music in their care. The methods of implementation most employed by nurses were streaming (90%) or encouraging a patient to play music on the patient's personal device (76.8%). Eighty-eight percent of nurses reported that access to music streaming services (e.g., Spotify) would be very helpful or extremely helpful. In response to the open-ended questions, nurses indicated a lack of equipment as the primary barrier to implementing music in care. Conclusion: Nurses reported having a positive attitude toward the use of music, strongly endorsing its utility in patient care. Although most nurses reported implementing music, many nurses reported barriers and facilitators to the implementation of music in patient care.

RESUMEN

PURPOSE: In phase III CheckMate 238, adjuvant nivolumab significantly improved recurrence-free survival compared with ipilimumab in patients with resected stage IIIB-C/IV melanoma without a significant difference in overall survival (OS). Here, we investigate progression-free survival (PFS) and OS after postrecurrence systemic therapy. PATIENTS AND METHODS: Patients 15 years or older with resected stage IIIB-C/IV melanoma were stratified by stage and tumor PD-L1 status and randomly assigned to receive nivolumab 3 mg/kg every 2 weeks, or ipilimumab 10 mg/kg every 3 weeks for four doses and then every 12 weeks for 1 year or until disease recurrence, unacceptable toxicity, or withdrawal of consent. Patients with recurrence in each group were assessed for PFS and OS from subsequent systemic therapy (SST) initiation per recurrence timing (≤12 months [early] v >12 months [late] from initial therapy). RESULTS: Recurrences occurred in 198 (44%) of 453 nivolumab-treated patients (122 early, 76 late) and 232 (51%) of 453 ipilimumab-treated patients (160 early, 72 late). Median PFS on next-line systemic therapy for nivolumab-treated patients recurring early versus late was 4.7 versus 12.4 months (24-month rates, 16% v 31%); median OS was 19.8 versus 42.8 months (24-month rates: 37% v 73%). In response to subsequent therapy, patients on nivolumab with late versus early recurrence were more likely to benefit from anti-PD-1 monotherapy. Nivolumab-treated patients with either an early or late recurrence benefitted from an ipilimumab-based therapy or targeted therapy, each with similar OS. CONCLUSION: Postrecurrence survival was longer for patients who recurred >12 months. Patients on nivolumab who recurred early benefitted from SST but had better survival with ipilimumab-based regimens or targeted therapy compared with anti-PD-1 monotherapy.

RESUMEN

[This corrects the article DOI: 10.3389/fvets.2024.1327081.].

RESUMEN

Endogenous opioid neuropeptides serve as important chemical signaling molecules in both the central and peripheral nervous systems, but there are few analytical tools for directly monitoring these molecules in situ. The opioid peptides share the amino acid motif, Tyr-Gly-Gly-Phe-, at the N-terminus. Met-enkephalin is a small opioid peptide comprised of only five amino acids with methionine (Met) incorporated at the C-terminus. Tyrosine (Tyr) and Met are electroactive, and their distinct electrochemical signatures can be utilized for quantitative molecular monitoring. This work encompasses a thorough voltammetric characterization of Tyr and Met redox chemistry as individual amino acids and when incorporated into small peptide fragments containing the shared Tyr-Gly-Gly-Phe- motif. NMR spectroscopy was used to determine the structure and conformation at near-physiological conditions. Voltammetric data demonstrate how the peak oxidation potential and the rate of electron transfer are dependent on the local chemical environment. Both the proximity of the electroactive residue to the C- or N-terminus and the hydrophobicity of the additional nonelectroactive amino acids profoundly affect sensitivity. Finally, the work uses the electrochemical signal for individual amino acids in a "training set", with a combination of principal component analysis and least-squares regression to accurately predict the voltammetric signal for short peptides comprising different combinations of those amino acids. Overall, this study demonstrates how fast-scan cyclic voltammetry can be utilized to discriminate between peptides with small differences in the chemical structure, thus establishing a framework for reliable quantification of small peptides in a complex signal, broadly speaking.

RESUMEN

BACKGROUND: Disordered eating is a concern for patients seeking metabolic and bariatric surgery (MBS), but little is known about how these behaviors are reflected in typical dietary intake prior to surgery. OBJECTIVES: This study examined the relationships between disordered eating behavior and the content and context of typical dietary intake among patients seeking MBS using an innovative combination of rigorous self-report and interview assessments. SETTING: Participants were recruited from two academic medical centers in the United States. METHODS: Adults were enrolled prior to MBS. Participants completed the Eating Disorder Examination-Bariatric Surgery Version (EDE-BSV) and then reported details of their dietary intake for three consecutive days using a validated 24-hour dietary recall system. RESULTS: Among the sample (n = 140), objective overeating (OOE) was prevalent and related to greater daily energy and macronutrient intake. Individuals engaging in recurrent OOE were also more likely to consume meals past 8 pm Findings failed to identify significant associations between other disordered eating behaviors, such as objective binge eating (OBE), and contextual factors related to dietary intake. CONCLUSIONS: The timing of eating may play a greater role in recurrent overeating than social and physical aspects of the environment. Individuals reporting frequent OOE before MBS may benefit from targeted education and intervention aimed at reducing OOE and subsequently promoting better adherence to dietary recommendations.

RESUMEN

The ability to spatially map multiple layers of the omics information over different time points allows for exploring the mechanisms driving brain development, differentiation, arealization, and alterations in disease. Herein we developed and applied spatial tri-omic sequencing technologies, DBiT ARP-seq (spatial ATAC-RNA-Protein-seq) and DBiT CTRP-seq (spatial CUT&Tag-RNA-Protein-seq) together with multiplexed immunofluorescence imaging (CODEX) to map spatial dynamic remodeling in brain development and neuroinflammation. A spatiotemporal tri-omic atlas of the mouse brain was obtained at different stages from postnatal day P0 to P21, and compared to the regions of interest in the human developing brains. Specifically, in the cortical area, we discovered temporal persistence and spatial spreading of chromatin accessibility for the layer-defining transcription factors. In corpus callosum, we observed dynamic chromatin priming of myelin genes across the subregions. Together, it suggests a role for layer specific projection neurons to coordinate axonogenesis and myelination. We further mapped the brain of a lysolecithin (LPC) neuroinflammation mouse model and observed common molecular programs in development and neuroinflammation. Microglia, exhibiting both conserved and distinct programs for inflammation and resolution, are transiently activated not only at the core of the LPC lesion, but also at distal locations presumably through neuronal circuitry. Thus, this work unveiled common and differential mechanisms in brain development and neuroinflammation, resulting in a valuable data resource to investigate brain development, function and disease.

RESUMEN

OBJECTIVES: Child pedestrian injuries represent a significant public health challenge. Understanding the most complex cognitive skills required to cross streets helps us understand, improve, and protect children in traffic, as underdeveloped cognitive skill likely impacts children's pedestrian safety. One complex component of street-crossing is the cognitive-perceptual task of judging time-to-arrival of oncoming traffic. We examined capacity of 7- and 8-year-olds to judge time-to-arrival for vehicles approaching from varying distances and speeds, as well as improvement in those judgments following intensive street-crossing training in a virtual reality (VR) pedestrian simulator. METHODS: 500 seven- and eight-year-olds participated in a randomized trial evaluating use of a large kiosk VR versus smartphone-based VR headset to teach street-crossing skills. Prior to randomization into VR training condition and also prior to initiation of any training, children engaged in a video-based vehicle approach estimation task to assess ability to judge traffic time-to-arrival. They then engaged in multiple VR-based pedestrian safety training sessions in their randomly assigned condition until achieving adult functioning. Soon after training and again 6 months later, children repeated the vehicle estimation task. RESULTS: Prior to randomization or training, children were more accurate judging time to arrival for closer versus farther traffic, and rapidly-moving versus slower-moving traffic, but those results were subsumed by a speed x distance interaction. The interaction suggested distance cues were used more prominently than speed cues, and speed had varying effects at different distances. Training group had minimal effect on learning and all children became significantly better at judging vehicle arrival times following training. CONCLUSIONS: Children tend to underestimate vehicle arrival times. Distance cues are more impactful on time-to-arrival judgments than speed cues, but children's estimations based both on manipulations of vehicle speed and manipulations of vehicle distance improved post-training. Improvements were retained six months later. This finding is consistent with psychophysics research suggesting vehicle approach judgments rely on optical size and looming, which are impacted both by vehicle speeds and distances. Implementation of VR-based training for child pedestrian safety is recommended, as it may improve children's judgment of vehicle time-to-arrival, but it must be conducted cautiously to avoid iatrogenic effects.

RESUMEN

Archaea are widespread in the environment and play fundamental roles in diverse ecosystems; however, characterization of their unique biology requires advanced tools. This is particularly challenging when characterizing gene function. Here, we generate randomly barcoded transposon libraries in the model methanogenic archaeon Methanococcus maripaludis and use high-throughput growth methods to conduct fitness assays (RB-TnSeq) across over 100 unique growth conditions. Using our approach, we identified new genes involved in nutrient utilization and response to oxidative stress. We identified novel genes for the usage of diverse nitrogen sources in M. maripaludis including a putative regulator of alanine deamination and molybdate transporters important for nitrogen fixation. Furthermore, leveraging the fitness data, we inferred that M. maripaludis can utilize additional nitrogen sources including ʟ-glutamine, ᴅ-glucuronamide, and adenosine. Under autotrophic growth conditions, we identified a gene encoding a domain of unknown function (DUF166) that is important for fitness and hypothesize that it has an accessory role in carbon dioxide assimilation. Finally, comparing fitness costs of oxygen versus sulfite stress, we identified a previously uncharacterized class of dissimilatory sulfite reductase-like proteins (Dsr-LP; group IIId) that is important during growth in the presence of sulfite. When overexpressed, Dsr-LP conferred sulfite resistance and enabled use of sulfite as the sole sulfur source. The high-throughput approach employed here allowed for generation of a large-scale data set that can be used as a resource to further understand gene function and metabolism in the archaeal domain.IMPORTANCEArchaea are widespread in the environment, yet basic aspects of their biology remain underexplored. To address this, we apply randomly barcoded transposon libraries (RB-TnSeq) to the model archaeon Methanococcus maripaludis. RB-TnSeq coupled with high-throughput growth assays across over 100 unique conditions identified roles for previously uncharacterized genes, including several encoding proteins with domains of unknown function (DUFs). We also expand on our understanding of carbon and nitrogen metabolism and characterize a group IIId dissimilatory sulfite reductase-like protein as a functional sulfite reductase. This data set encompasses a wide range of additional conditions including stress, nitrogen fixation, amino acid supplementation, and autotrophy, thus providing an extensive data set for the archaeal community to mine for characterizing additional genes of unknown function.

Asunto(s)

RESUMEN

BACKGROUND: Cognitive impairment is common among adults with heart failure (HF) and associated with poor outcomes. However, less is known about the trajectory of cognitive decline after a first HF hospitalization. We examined the rate of cognitive decline among adults with incident HF hospitalization compared with those without HF hospitalization. METHODS AND RESULTS: The REGARDS (Reasons for Geographic and Racial Differences in Stroke) study is a prospective longitudinal study of 23 894 participants aged ≥45 years free of HF at baseline. HF hospitalization was expert adjudicated. Changes in global cognitive function (primary outcome) were assessed with the Six-Item Screener (range, 0-6). Secondary outcomes included change in Word List Learning (range, 0-30), Word List Delayed Recall (WLD; range, 0-10), and Animal Fluency Test (range, 0+). Segmented linear mixed-effects regression models were used. Over 5 years, mean scores across all 4 cognitive tests declined for all participants regardless of HF status. Those with incident HF hospitalization experienced faster declines in the Six-Item Screener versus those who were HF free (difference, -0.031 [95% CI, -0.047 to -0.016]; P<0.001), a finding that persisted in fully adjusted models. Those with incident HF hospitalization did not experience faster declines in Word List Learning, Word List Delayed Recall, or Animal Fluency Test scores compared with those without HF hospitalization. Participants with hospitalization for HF with preserved, compared with reduced, ejection fraction had faster decline in Animal Fluency Test. CONCLUSIONS: Global cognitive decline occurred faster among adults with incident HF hospitalization compared with those who remained free of HF hospitalization. This pattern was not seen for the other cognitive domains.

Asunto(s)

RESUMEN

PURPOSE: Obtain the perspectives of people with Parkinson's disease (PwPD) and their care partners (CPs) about their lived experiences with Parkinson's Disease (PD) to characterize a new model of care that meets their biopsychosocial and healthcare needs. METHODS: This phenomenological study included semi-structured focus groups exploring PD diagnosis/care experiences and conceptualizations of an ideal model of care among PwPD and CPs. Data were analyzed via thematic analysis. RESULTS: Twenty-five individuals (PwPD, n = 18; CPs, n = 7) participated across four focus groups. Researchers developed four themes to describe participants' lived experience with, barriers to, and needs for PD care. These themes characterize key hopes for care as: 1) person-centered, 2) coordinated, 3) provides access to education and information, and 4) builds on the benefits of community. CONCLUSIONS: Participants emphasized that, beyond clinical interactions and diagnosis-centered conversations, they wished for holistic healthcare that acknowledged the larger picture of their life with PD. An ideal model of care for PwPD should aim to be person centered, maximize collaboration and coordination across multiple disciplines, provide access to a wide range of information and resources, refer to community centers and support groups, and be designed with ease of navigation in mind.

Health professionals need to inquire about an individual's lived experience and employ strategies that center the person and personalizes their care while also integrating a coordinated interdisciplinary approach.An ideal model of care needs to integrate healthcare professionals as part of a larger care team that includes the person with Parkinson's disease, and facilitates communication and planning with those team membersAn ideal model of care needs to integrate the larger community and seek to refer and build relationships with health professionals, organizations, and non-medical providers that will facilitate holistic care and advocate for people with Parkinson's disease.