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1.
J Appl Lab Med ; 2024 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-39225064

RESUMEN

BACKGROUND: Cardiovascular disease, kidney health, and metabolic disease (CKM) syndrome is associated with significant morbidity and mortality, particularly from congestive heart failure (CHF). Guidelines recommend measurement of cardiac troponin (cTn) to identify subclinical heart failure (HF) in diabetics/CKM. However, appropriate thresholds and the impact from routine screening have not been elucidated. METHODS: cTnI was assessed using the Abbott high sensitivity (hs)-cTnI assay in outpatients with physician-ordered hemoglobin A1c (Hb A1c) and associated with cardiac comorbidities/diagnoses, demographics, and estimated glomerular filtration rate (eGFR). Risk thresholds used in CKM staging guidelines of >10 and >12 ng/L for females and males, respectively, were used. Multivariate logistic regression was applied. hs-cTnI was assessed in a high-fat-diet induced murine model of obesity and diabetes. RESULTS: Of 1304 patients, 8.0% females and 15.7% males had cTnI concentrations above the risk thresholds. Thirty-one (4.2%) females and 23 (4.1%) males had cTnI above the sex-specific 99% upper reference limit. A correlation between hs-cTnI and Hb A1c (R = 0.2) and eGFR (R = -0.5) was observed. hs-cTnI concentrations increased stepwise based on A1C of <5.7% (median = 1.5, IQR:1.3-1.8), 5.7%-6.4% (2.1, 2.0-2.4), 6.5%-8.0% (2.8, 2.5-3.2), and >8% (2.8, 2.2-4.3). Male sex (P < 0.001), eGFR (P < 0.001), and CHF (P = 0.004) predicted elevated hs-cTnI. Obese and diabetic mice had increased hs-cTnI (7.3 ng/L, 4.2-10.4) relative to chow-fed mice (2.6 ng/L, 1.3-3.8). CONCLUSION: A high proportion of outpatients with diabetes meet criteria for subclinical HF using hs-cTnI measurements. Glucose control is independently associated with elevated cTnI, a finding replicated in a murine model of metabolic syndrome.

2.
Radiology ; 312(3): e232748, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39225603

RESUMEN

Background MRI plays a crucial role in restaging locally advanced rectal cancer treated with total neoadjuvant therapy (TNT); however, prospective studies have not evaluated its ability to accurately select patients for nonoperative management. Purpose To evaluate the ability of restaging MRI to predict oncologic outcomes and identify imaging features associated with residual disease (RD) after TNT. Materials and Methods This was a secondary analysis of the Organ Preservation in Rectal Adenocarcinoma (OPRA) trial, which randomized participants from April 2014 to March 2020 with stages II or III rectal adenocarcinoma to undergo either induction or consolidation TNT. Participants enrolled in the OPRA trial who underwent restaging MRI were eligible for inclusion in the present study. Radiologists classified participants as having clinical complete response (cCR), near-complete clinical response (nCR), or incomplete clinical response (iCR) based on restaging MRI at a mean of 8 weeks ± 4 (SD) after treatment. Oncologic outcomes according to MRI response category were assessed using Kaplan-Meier curves. Logistic regression analysis was performed to identify imaging characteristics associated with RD. Results A total of 277 participants (median age, 58 years [IQR, 17 years]; 179 male) who were randomized in the OPRA trial had restaging MRI forms completed. The median follow-up duration was 4.1 years. Participants with cCR had higher rates of organ preservation compared with those with nCR (65.3% vs 41.6%, log-rank P < .001). Five-year disease-free survival for participants with cCR, nCR, and iCR was 81.8%, 67.6%, and 49.6%, respectively (log-rank P < .001). The MRI response category also predicted overall survival (log-rank P < .001), distant recurrence-free survival (log-rank P = .005), and local regrowth (log-rank P = .02). Among the 266 participants with at least 2 years of follow-up, 129 (48.5%) had RD. At multivariable analysis, the presence of restricted diffusion (odds ratio, 2.50; 95% CI: 1.22, 5.24) and abnormal nodal morphologic features (odds ratio, 5.04; 95% CI: 1.43, 23.9) remained independently associated with RD. Conclusion The MRI response category was predictive of organ preservation and survival. Restricted diffusion and abnormal nodal morphologic features on restaging MRI scans were associated with increased likelihood of residual tumor. ClinicalTrials.gov identifier: NCT02008656 © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Milot in this issue.


Asunto(s)
Imagen por Resonancia Magnética , Neoplasia Residual , Neoplasias del Recto , Humanos , Neoplasias del Recto/diagnóstico por imagen , Neoplasias del Recto/terapia , Neoplasias del Recto/patología , Femenino , Masculino , Persona de Mediana Edad , Imagen por Resonancia Magnética/métodos , Neoplasia Residual/diagnóstico por imagen , Espera Vigilante/métodos , Estudios Prospectivos , Adenocarcinoma/diagnóstico por imagen , Adenocarcinoma/patología , Adenocarcinoma/terapia , Anciano , Valor Predictivo de las Pruebas , Terapia Neoadyuvante/métodos , Resultado del Tratamiento , Estadificación de Neoplasias , Adulto
3.
Kidney Int ; 2024 Aug 29.
Artículo en Inglés | MEDLINE | ID: mdl-39216658

RESUMEN

Anti-neutrophil cytoplasmic autoantibody (ANCA) vasculitis has diverse patterns of injury including microscopic polyangiitis (MPA), granulomatosis with polyangiitis (GPA), and eosinophilic granulomatosis with polyangiitis (EGPA). Necrotizing and crescentic glomerulonephritis (NCGN) occurs in all syndromes and as renal limited vasculitis (RLV). Single dose intravenous ANCA IgG-specific for mouse myeloperoxidase (MPO) causes RLV in mice. Although multiple mouse models have elucidated ANCA-IgG induced necrotizing and crescentic glomerulonephritis (NCGN), pathogenesis of ANCA-induced granulomatosis and vasculitis outside the kidney has not been clarified. To investigate this, we used intravenous MPO-ANCA IgG in the same strain of mice to induce different patterns of lung disease mirroring patients with granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA). Repeated intravenous MPO-ANCA IgG induced GPA with NCGN, lung capillaritis, arteritis and granulomatosis. Lung leukocyte phenotypes were evaluated by immunohistochemical image analysis and by flow cytometry. ANCA lung capillaritis and microabscesses began within one day and evolved into granulomas in under seven days. Influenza plus single dose MPO-ANCA IgG induced MPA with NCGN, lung capillaritis and arteritis, but no granulomatosis. Allergic airway disease caused by house dust mites or ovalbumin plus single dose intravenous MPO-ANCA IgG induced EGPA with eosinophilic bronchiolitis, NCGN, capillaritis, arteritis, and granulomatosis. Thus, our study shows that the occurrence and pattern of lung lesions are determined by the same ANCA IgG accompanied by different synergistic immune factors.

4.
Artículo en Inglés | MEDLINE | ID: mdl-39200696

RESUMEN

The potential connection between exposure to glyphosate and glyphosate-based herbicides (GBHs) and breast cancer risk is a topic of research that is rapidly gaining the public's attention due to the conflicting reports surrounding glyphosate's potential carcinogenicity. In this review, we synthesize the current published biomedical literature works that have explored associations of glyphosate, its metabolite, aminomethylphosphonic acid (AMPA), and GBHs with breast cancer risk in humans and human cell-based models. Using PubMed as our search engine, we identified a total of 14 articles that were included in this review. In the four human studies, urinary glyphosate and/or AMPA were associated with breast cancer risk, endocrine disruption, oxidative stress biomarkers, and changes in DNA methylation patterns. Among most of the 10 human cell-based studies, glyphosate exhibited endocrine disruption, induced altered gene expression, increased DNA damage, and altered cell viability, while GBHs were more cytotoxic than glyphosate alone. In summary, numerous studies have shown glyphosate, AMPA, and GBHs to have potential carcinogenic, cytotoxic, or endocrine-disruptive properties. However, more human studies need to be conducted in order for more definitive and supported conclusions to be made on their potential effects on breast cancer risk.


Asunto(s)
Neoplasias de la Mama , Glicina , Glifosato , Herbicidas , Humanos , Glicina/análogos & derivados , Glicina/toxicidad , Herbicidas/toxicidad , Neoplasias de la Mama/inducido químicamente , Femenino , Organofosfonatos/toxicidad
5.
Nanoscale ; 2024 Aug 19.
Artículo en Inglés | MEDLINE | ID: mdl-39157856

RESUMEN

Single-walled carbon nanotubes (SWCNTs) possess outstanding photophysical properties which has garnered interest towards utilizing these materials for biosensing and imaging applications. The near-infrared (NIR) fluorescence within the tissue transparent region along with their photostability and sizes in the nanoscale make SWCNTs valued candidates for the development of optical sensors. In this review, we discuss recent advances in the development and the applications of SWCNT-based nano-biosensors. An overview of SWCNT's structural and photophysical properties, sensor development, and sensing mechanisms are described. Examples of SWCNT-based optical nanosensors for detection of disease biomarkers, pathogens (bacteria and viruses), plant stressors, and environmental contaminants including heavy metals and disinfectants are provided. Molecular detection in biofluids, in vitro, and in vivo (small animal models and plants) are highlighted, and sensor integration into portable substrates for implantable and wearable sensing devices has been discussed. Recent advancements, which include high throughput assays and the use of machine learning models to predict more sensitive and robust sensing outcomes are discussed. Current limitations and future perspectives on translation of SWCNT optical probes into clinical practices have been provided.

6.
Mil Med ; 189(Supplement_3): 190-195, 2024 Aug 19.
Artículo en Inglés | MEDLINE | ID: mdl-39160793

RESUMEN

INTRODUCTION: The association between hypothermia, coagulopathy, and acidosis in trauma is well described. Hypothermia mitigation starts in the prehospital setting; however, it is often a secondary focus after other life-saving interventions. The deployed environment further compounds the problem due to prolonged evacuation times in rotary wing aircraft, resource limitations, and competing priorities. This analysis evaluates hypothermia in combat casualties and the relationship to resuscitation strategy with blood products. METHODS: Using the data from the Department of Defense Joint Trauma Registry from 2003 to 2021, a retrospective analysis was conducted on adult trauma patients. Inclusion criteria was arrival at the first military treatment facility (MTF) hypothermic (<95ºF). Study variables included: mortality, year, demographics, battle vs non-battle injury, mechanism, theater of operation, vitals, and labs. Subgroup analysis was performed on severely injured (15 < ISS < 75) hypothermic trauma patients resuscitated with whole blood (WB) vs only component therapy. RESULTS: Of the 69,364 patients included, 908 (1.3%) arrived hypothermic; the vast majority of whom (N = 847, 93.3%) arrived mildly hypothermic (90-94.9°F). Overall mortality rate was 14.8%. Rates of hypothermia varied by year from 0.7% in 2003 to 3.9% in 2014 (P <0.005). On subgroup analysis, mortality rates were similar between patients resuscitated with WB vs only component therapy; though base deficit values were higher in the WB cohort (-10 vs -6, P < 0.001). CONCLUSION: Despite nearly 20 years of combat operations, hypothermia continues to be a challenge in military trauma and is associated with a high mortality rate. Mortality was similar between hypothermic trauma patients resuscitated with WB vs component therapy, despite greater physiologic derangements on arrival in patients who received WB. As the military has the potential to conduct missions in environments where the risk of hypothermia is high, further research into hypothermia mitigation techniques and resuscitation strategies in the deployed setting is warranted.


Asunto(s)
Hipotermia , Humanos , Hipotermia/complicaciones , Hipotermia/etiología , Estudios Retrospectivos , Masculino , Femenino , Adulto , Sistema de Registros/estadística & datos numéricos , Resucitación/métodos , Resucitación/estadística & datos numéricos , Resucitación/tendencias , Personal Militar/estadística & datos numéricos , Heridas y Lesiones/complicaciones , Heridas y Lesiones/terapia
7.
Sci Adv ; 10(33): eado4313, 2024 Aug 16.
Artículo en Inglés | MEDLINE | ID: mdl-39141734

RESUMEN

αß T cell receptors (TCRs) principally recognize aberrant peptides bound to major histocompatibility complex molecules (pMHCs) on unhealthy cells, amplifying specificity and sensitivity through physical load placed on the TCR-pMHC bond during immunosurveillance. To understand this mechanobiology, TCRs stimulated by abundantly and sparsely arrayed epitopes (NP366-374/Db and PA224-233/Db, respectively) following in vivo influenza A virus infection were studied with optical tweezers. While certain NP repertoire CD8 T lymphocytes require many ligands for activation, others are digital, needing just few. Conversely, all PA TCRs perform digitally, exhibiting pronounced bond lifetime increases through sustained, energizing volleys of structural transitioning. Optimal digital performance is superior in vivo, correlating with ERK phosphorylation, CD3 loss, and activation marker up-regulation in vitro. Given neoantigen array paucity, digital TCRs are likely critical for immunotherapies.


Asunto(s)
Linfocitos T CD8-positivos , Animales , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/metabolismo , Ratones , Receptores de Antígenos de Linfocitos T/metabolismo , Receptores de Antígenos de Linfocitos T/inmunología , Receptores de Antígenos de Linfocitos T alfa-beta/metabolismo , Receptores de Antígenos de Linfocitos T alfa-beta/química , Virus de la Influenza A/inmunología , Humanos , Activación de Linfocitos/inmunología , Infecciones por Orthomyxoviridae/inmunología , Infecciones por Orthomyxoviridae/virología , Pinzas Ópticas
8.
Chem Sci ; 2024 Aug 12.
Artículo en Inglés | MEDLINE | ID: mdl-39144453

RESUMEN

The abyssomicins are a structurally intriguing family of bioactive natural products that include compounds with potent antibacterial, antitumour and antiviral activities. The biosynthesis of the characteristic abyssomicin spirotetronate core occurs via an enzyme-catalysed intramolecular Diels-Alder reaction, which proceeds via one of two distinct stereochemical pathways to generate products differing in configuration at the C15 spirocentre. Using the purified spirotetronate cyclases AbyU (from abyssomicin C/atrop-abyssomicin C biosynthesis) and AbmU (from abyssomicin 2/neoabyssomicin biosynthesis), in combination with synthetic substrate analogues, here we show that stereoselectivity in the spirotetronate-forming [4 + 2]-cycloaddition is controlled by a combination of factors attributable to both the enzyme and substrate. Furthermore, an achiral substrate was enzymatically cyclised to a single enantiomer of a spirocyclic product. X-ray crystal structures, molecular dynamics simulations, and assessment of substrate binding affinity and reactivity in both AbyU and AbmU establish the molecular determinants of stereochemical control in this important class of biocatalysts.

9.
Artículo en Inglés | MEDLINE | ID: mdl-39214652

RESUMEN

Root anatomy plays a crucial role in regulating essential processes such as the absorption and movement of water and nutrients in plants. Root anatomy also impacts the energy costs of building and sustaining root tissues, tissue mechanics, and interactions with other organisms. Although several studies in maize have confirmed the functional utility of numerous root anatomical traits, such as that of cortical cell size and number for stress adaptation, there have been significant obstacles in measuring and analyzing root anatomical characteristics. This has resulted in gaps in our understanding of the genetic control and range of phenotypic variations among different cultivars, and how this diversity relates to overall fitness. Here, we review root anatomical phenotypes in maize and their function in stress adaptation, and briefly discuss phenotyping methods available for root anatomy. We further introduce a simple and accessible phenotyping approach that enables a comprehensive investigation of maize root anatomy. Detailed characterization of root traits and the implementation of robust methods for root anatomical phenotyping could have wide-ranging benefits across various areas of plant science, from fundamental research to enhancing crop breeding efforts.

10.
Artículo en Inglés | MEDLINE | ID: mdl-39214653

RESUMEN

Root anatomy plays a critical structural and functional role in the maize root system, and regulates edaphic stress tolerance. The function and genetic basis of several maize root anatomical traits for stress tolerance have been demonstrated. Leveraging root anatomical traits in maize thus holds great potential for developing cultivars with greater nutrient and water efficiency. Key for such approaches is the ability to characterize the root anatomy of plants of interest. Here, we outline a systematic method for preparing, imaging, and analyzing maize root cross-sections. The protocol describes root sectioning (by hand or using a vibratome), preparation of microscope slides and toluidine blue staining, imaging under a light microscope, and both manual and semiautomated methods for anatomical feature extraction from images. The protocol enables the visualization and quantification of various anatomical tissues and traits, and its simplicity, adaptability, and accessibility make it an ideal choice for both small- and large-scale phenotyping studies in maize and other plant species. This standardized protocol provides researchers with a comprehensive methodology to accurately dissect root structures, enabling in-depth analyses that are essential for understanding plant growth, development, and adaptive value for stress tolerance.

11.
Surg Endosc ; 2024 Aug 23.
Artículo en Inglés | MEDLINE | ID: mdl-39179689

RESUMEN

INTRODUCTION: Robotic-assisted metabolic and bariatric surgery (MBS) is gaining popularity. Revisional MBS is associated with higher perioperative morbidity compared to primary MBS. The optimal surgical approach to minimize complications in these complex cases is unclear. The goal of this study was to assess robot utilization in revisional MBS and compare laparoscopic and robotic revisional MBS outcomes in the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP) database. METHODS: A retrospective review of the MBSAQIP database was performed identifying revisional sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) cases from 2015 to 2022. Primary MBS, open/emergent cases, cases converted to another approach, and combined cases other than esophagogastroduodenoscopy were excluded. 30-Day outcomes for laparoscopic and robotic cases were compared using multivariate logistic regression adjusting for patient demographics, comorbidities, and operative variables. RESULTS: 41,404 Cases (14,474 SG; 26,930 RYGB) were identified. From 2015 to 2022, the percentage of revisional SG and RYGB cases performed robotically increased from 6.1% and 7.3% to 24.2% and 32.0% respectively. Laparoscopic SG had similar rates of overall morbidity, leak, bleeding, readmission, reoperation, and length of stay compared to robotic. Laparoscopic RYGB had significantly higher rates of overall morbidity (6.2% vs. 4.8%, p < 0.001, AOR 0.80 [0.70-0.93]), blood transfusion (1.5% vs. 1.0%, p < 0.05, AOR 0.74 [0.55-0.99]), superficial incisional SSI (1.2% vs. 0.4%, p < 0.001, AOR 0.30 [0.19-0.47]), and longer length of stay (1.87 vs. 1.76 days, p < 0.001) compared to robotic. Laparoscopic operative times were significantly shorter than robotic (SG: 86.4 ± 45.8 vs. 113.5 ± 51.7 min; RYGB: 130.7 ± 64.7 vs. 165.5 ± 66.8 min, p < 0.001). CONCLUSION: Robot utilization in revisional bariatric surgery is increasing. Robotic surgery has lower postoperative morbidity and shorter length of stay in revisional RYGB when compared to laparoscopic. Robotic platforms may have the capacity to improve the delivery of care for patients undergoing revisional bariatric surgery.

12.
bioRxiv ; 2024 Aug 06.
Artículo en Inglés | MEDLINE | ID: mdl-39149326

RESUMEN

Physiological variability in pancreatic cell type gene regulation and the impact on diabetes risk is poorly understood. In this study we mapped gene regulation in pancreatic cell types using single cell multiomic (joint RNA-seq and ATAC-seq) profiling in 28 non-diabetic donors in combination with single cell data from 35 non-diabetic donors in the Human Pancreas Analysis Program. We identified widespread associations with age, sex, BMI, and HbA1c, where gene regulatory responses were highly cell type- and phenotype-specific. In beta cells, donor age associated with hypoxia, apoptosis, unfolded protein response, and external signal-dependent transcriptional regulators, while HbA1c associated with inflammatory responses and gender with chromatin organization. We identified 10.8K loci where genetic variants were QTLs for cis regulatory element (cRE) accessibility, including 20% with lineage- or cell type-specific effects which disrupted distinct transcription factor motifs. Type 2 diabetes and glycemic trait associated variants were enriched in both phenotype- and QTL-associated beta cell cREs, whereas type 1 diabetes showed limited enrichment. Variants at 226 diabetes and glycemic trait loci were QTLs in beta and other cell types, including 40 that were statistically colocalized, and annotating target genes of colocalized QTLs revealed genes with putatively novel roles in disease. Our findings reveal diverse responses of pancreatic cell types to phenotype and genotype in physiology, and identify pathways, networks, and genes through which physiology impacts diabetes risk.

13.
Curr Opin Genet Dev ; 88: 102236, 2024 Aug 16.
Artículo en Inglés | MEDLINE | ID: mdl-39153332

RESUMEN

The human brain has evolved unique capabilities compared to other vertebrates. The mechanistic basis of these derived traits remains a fundamental question in biology due to its relevance to the origin of our cognitive abilities and behavioral repertoire, as well as to human-specific aspects of neuropsychiatric and neurodegenerative diseases. Comparisons of the human brain to those of nonhuman primates and other mammals have revealed that differences in the neuromodulatory systems, especially in the dopaminergic system, may govern some of these behavioral and cognitive alterations, including increased vulnerability to certain brain disorders. In this review, we highlight and discuss recent findings of human- and primate-specific alterations of the dopaminergic system, focusing on differences in anatomy, circuitry, and molecular properties.

14.
Blood ; 2024 Aug 23.
Artículo en Inglés | MEDLINE | ID: mdl-39178344

RESUMEN

Sickle cell disease (SCD) is canonically characterized by reduced red blood cell (RBC) deformability leading to microvascular obstruction and inflammation. While the biophysical properties of sickle RBCs are known to influence SCD vasculopathy, the contribution of poor RBC deformability to endothelial dysfunction has yet to be fully explored. Leveraging interrelated in vitro and in silico approaches, we introduce a new paradigm of SCD vasculopathy in which poorly deformable sickle RBCs directly cause endothelial dysfunction via mechanotransduction, where endothelial cells sense and pathophysiologically respond to aberrant physical forces independently of microvascular obstruction, adhesion, or hemolysis. We demonstrate that perfusion of sickle RBCs or pharmacologically-dehydrated healthy RBCs into small venule-sized "endothelialized" microfluidics leads to pathologic physical interactions with endothelial cells that directly induce inflammatory pathways. Using a combination of computational simulations and large venule-sized endothelialized microfluidics, we observed that perfusion of heterogeneous sickle RBC subpopulations of varying deformability, as well as suspensions of dehydrated normal RBCs admixed with normal RBCs leads to aberrant margination of the less-deformable RBC subpopulations towards the vessel walls, causing localized, increased shear stress. Increased wall stress is dependent on the degree of subpopulation heterogeneity and oxygen tension and leads to inflammatory endothelial gene expression via mechanotransductive pathways. Our multifaceted approach demonstrates that the presence of sickle RBCs with reduced deformability leads directly to pathological physical (i.e., direct collisions and/or compressive forces) and shear-mediated interactions with endothelial cells and induces an inflammatory response, thereby elucidating the ubiquity of vascular dysfunction in SCD.

15.
Access Microbiol ; 6(7)2024.
Artículo en Inglés | MEDLINE | ID: mdl-39130730

RESUMEN

This multi-arm, parallel group, single-blinded randomised controlled trial aimed to assess three commercially available mouthwashes effectiveness against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This manuscript has been written in accordance with the CONSORT statement. Methods. Eligible participants were SARS-CoV-2 positive with a positive test in the last 72 h. All participants had mild to moderate symptoms and could provide five saliva samples over a 60 min period. Participants delivered a baseline saliva sample and then used a mouthwash as per manufacturer's instructions. They provided further saliva samples at minute 1, 10, 30 and 60. Participants were randomised to one of four groups; OraWize+, Total Care Listerine, Cool Mint Listerine and water (control). The lab-based research team were blind to the intervention. The research question was: can SARS-CoV-2 be rendered inactive in saliva by using a mouthwash and how long does this effect last? The primary outcome was the amount of viable infectious SARS-CoV-2 virus in the sample, compared to the baseline sample. The secondary outcome measure was the amount of genetic material from the SARS-CoV-2 virus in the sample, measured via PCR testing. Results. In total 100 participants were recruited (25 per group). Eight participants did not receive the allocated intervention and did not have saliva samples collected. There were no adverse events. In total 42 of the 92 participants had viable virus which could be cultured at baseline. Statistical analysis of the primary outcome was not advised due to the reduced level of viable virus at baseline and the positive skewness present in the distribution of log10(titre) data. Observational data of the primary outcome measure is presented. Analysis of the secondary outcome PCR measure showed that there was strong evidence for a decrease in SARS-CoV-2 RNA levels compared to water for all mouthwashes after 1 min, OraWize+ -0.49 (-0.92, -0.05), p-value 0.029, Cool Mint Listerine -0.81 (-1.25, -0.38), p-value<0.001, Total Care Listerine -1.05 (-1.48, -0.62), p-value<0.001. For the remaining timepoints there was generally no evidence of virus level reduction compared to water although there is weak evidence for a decrease at ten minutes using Total Care Listerine -0.44 (-0.88, 0.01), p-value 0.053. Conclusion. The three mouthwashes included in this trial observationally demonstrated a reduction in virus titre level 1 min after use, with virus levels normalising up to 60 min compared to the control. Although an interesting observation, this result could not be statistically analysed. Using the secondary outcome PCR measure all three included mouthwashes reduced virus levels compared to water at 1 min and these results were statistically significant. Clinically this result does not support the use of the included mouthwashes to reduce SARS-CoV-2 levels in saliva.

16.
Environ Sci Technol ; 58(35): 15598-15606, 2024 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-39173619

RESUMEN

Coastal upwelling supplies nutrients supporting primary production while also adding the toxic trace metal mercury (Hg) to the mixed layer of the ocean. This could be a concern for human and environmental health if it results in the enhanced bioaccumulation of monomethylmercury (MMHg). Here, we explore how upwelling influences Hg cycling in the California Current System (CCS) biome through particle scavenging and sea-air exchange. We collected suspended and sinking particle samples from a coastal upwelled water parcel and an offshore non-upwelled water parcel and observed higher total particulate Hg and sinking flux in the upwelling region compared to open ocean. To further investigate the full dynamics of Hg cycling, we modeled Hg inventories and fluxes in the upper ocean under upwelling and non-upwelling scenarios. The model simulations confirmed and quantified that upwelling enhances sinking fluxes of Hg by 41% through elevated primary production. Such an enhanced sinking flux of Hg is biogeochemically important to understand in upwelling regions, as it increases the delivery of Hg to the deep ocean where net conversion to MMHg may take place.


Asunto(s)
Mercurio , California , Contaminantes Químicos del Agua , Agua de Mar/química , Monitoreo del Ambiente
17.
J Emerg Med ; 67(4): e379-e381, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39183117

RESUMEN

BACKGROUND: Hair thread tourniquet syndrome occurs when tissue is strangulated by a hair thread. It occurs most commonly in the digits of infants and young children, but can also occur in the genitalia. CASE REPORT: A 13-year-old postmenarchal girl with several days of severe vulvar pain and swelling presented to the emergency department. Diagnosis was unclear and she was referred to pediatric and adolescent gynecology. Pelvic examination under anesthesia revealed a hair thread tourniquet involving the bilateral labia minora. The hair tourniquet and portions of bilateral labia minora were excised. Why Should an Emergency Physician Be Aware of This? Genital hair thread tourniquet syndrome is uncommon but must be considered in patients with severe genital pain and swelling. Prompt diagnosis and treatment are important to prevent tissue necrosis and may be facilitated by means of a pelvic examination with sedation.


Asunto(s)
Diagnóstico Tardío , Cabello , Humanos , Femenino , Adolescente , Diagnóstico Tardío/efectos adversos , Vulva , Síndrome , Enfermedades de la Vulva/diagnóstico , Enfermedades de la Vulva/etiología
18.
Perspect Behav Sci ; 47(2): 365-392, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-39099743

RESUMEN

Delay discounting, the decrease in outcome value as a function of delay to receipt, is an extensive area of research. How delays are framed (i.e., temporal framing), as well as the sign and magnitude of an outcome, produce important effects on the degree to which outcomes are discounted. Here, we examined how recent experience (i.e., order of presentation) modifies these well-known findings. Experiment 1 examined the effects of temporal framing across gains and losses. Regardless of outcome sign, the order of task presentation affected the effect of temporal framing. In particular, when typical delay frames (e.g., 1 week) preceded delays framed as actual dates (e.g., February 15), discounting was less in the date-framed task. However, when dates were followed by the delay frame, there was no difference in the degree of discounting. The experience of date-framed delays persisted or carried over to the delay-framed task. Experiment 2 examined recent experience and the magnitude effect. In particular, $10 and $100 were discounted similarly between-subjects when it was the first task completed. However, once participants completed the second magnitude task, the magnitude effect was present both within-subjects and across subjects. Furthermore, $10 was discounted more steeply when it followed $100, and $100 was discounted less steeply when it followed $10. The impact of recent experience on delay discounting has important implications for understanding mechanisms that may contribute to delay discounting. Recent experience should be considered when designing delay discounting experiments as well as when implementing interventions to reduce steep delay discounting.

19.
Orthop J Sports Med ; 12(7): 23259671241257825, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39100214

RESUMEN

Background: The impact of early glenohumeral osteoarthritis (GHOA) on clinical outcomes after rotator cuff repair (RCR) remains unclear. The magnetic resonance imaging (MRI)-based Shoulder Osteoarthritis Severity (SOAS) score is a comprehensive approach to quantifying glenohumeral degeneration. Purpose: To investigate the association between SOAS scores and changes in American Shoulder and Elbow Surgeons (ASES) scores in patients who underwent RCR. Study Design: Cohort study; Level of evidence, 3. Methods: Two reviewers independently analyzed the preoperative MRI scans of 116 shoulders and assigned SOAS scores. Spearman correlation was used to calculate the association of mean SOAS scores with patient demographic characteristics and change in ASES scores over the 2-year follow-up period (ΔASES). Multivariate regression analysis was performed between the independent variables of patient age, sex, body mass index, and significant SOAS score components as determined by univariate analysis, with the dependent variable being ΔASES. Significance was defined as P < .05 for univariate analysis and P < .0125 after application of the Bonferroni correction for multivariate analysis. Results: The mean ASES scores were 55.8 ± 18.6 preoperatively and 92.1 ± 12.1 at 2 years postoperatively. The mean preoperative SOAS score was 15.2 ± 7.1. On univariate analysis, the total SOAS score was positively correlated with patient age (r S = 0.41; P < .001), whereas ΔASES was negatively correlated with patient age (r S = -0.27; P = .0032). Increasing SOAS subscores for supraspinatus/infraspinatus tear size (r S = -0.28; P = .024), tendon retraction (r S = -0.23; P = .015), muscle atrophy (r S = -0.20; P = .034), paralabral ganglia (r S = -0.23; P = .015), and cartilage degeneration (r S = -0.21; P = .024) were negatively correlated with ΔASES. A negative correlation was found between increasing total SOAS score and ΔASES (r S = -0.22; P = .016). On multivariate analysis, increasing supraspinatus/infraspinatus tear size was significantly and negatively correlated with ΔASES (ß = -3.3; P = .010). Conclusion: Increasing the total SOAS score was predictive of less improvement in ASES scores at 2 years postoperatively. On univariate analysis, SOAS subscores with the strongest negative correlations with ΔASES scores included tear size, muscle atrophy, tendon retraction, paralabral ganglia, and cartilage wear. On multivariate analysis, only tear size was significantly associated with a lower change in the ASES score.

20.
Alzheimers Dement (N Y) ; 10(3): e12492, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39104764

RESUMEN

Social connection is important for long-term care (LTC) residents' quality of life and care. However, there is a lack of consensus on how to measure it and this limits ability to find what improves and impairs social connection in LTC homes. We therefore aimed to systematically review and evaluate the measurement properties of existing measures of social connection for LTC residents, to identify which, if any, measures can be recommended. We searched eight electronic databases from inception to April 2022 for studies which reported on psychometric properties of a measure of any aspect(s) of social connection (including social networks, interaction, engagement, support, isolation, connectedness, and loneliness) for LTC residents. We used COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) guidelines to evaluate the measurement properties reported for each identified measure and make recommendations. We identified 62 studies reporting on 38 measures; 21 measured quality of life, well-being or life satisfaction and included a social connection subscale or standalone items and 17 measures specifically targeted social connection. We found there was little high-quality evidence on psychometric properties such as sufficient content validity (n = 0), structural validity (n = 3), internal consistency (n = 3), reliability (n = 1), measurement error (n = 0), construct validity (n = 4), criterion validity (n = 0) and responsiveness (n = 0). No measures demonstrated satisfactory psychometric properties on all these aspects, so none could be recommended for use. Thirty-four measures have the potential to be recommended but require further research to assess their quality and the remaining four are not recommended for use. Our review therefore found that no existing measures have sufficient evidence to be recommended for assessment of social connection in residents of LTC homes. Further validation and reliability studies of existing instruments or the development of new measures are needed to enable accurate measurement of social connection in LTC residents for future observational and interventional studies. Highlights: Social connection is fundamental to person-centered care in long-term care homes.There is insufficient evidence for the reliability and validity of existing measures.No current measures can be recommended for use based on existing evidence.A reliable and valid measure of social connection is needed for future research.

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