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1.
Cell ; 183(1): 94-109.e23, 2020 10 01.
Article in English | MEDLINE | ID: mdl-32937105

ABSTRACT

Cardiomyocytes are subjected to the intense mechanical stress and metabolic demands of the beating heart. It is unclear whether these cells, which are long-lived and rarely renew, manage to preserve homeostasis on their own. While analyzing macrophages lodged within the healthy myocardium, we discovered that they actively took up material, including mitochondria, derived from cardiomyocytes. Cardiomyocytes ejected dysfunctional mitochondria and other cargo in dedicated membranous particles reminiscent of neural exophers, through a process driven by the cardiomyocyte's autophagy machinery that was enhanced during cardiac stress. Depletion of cardiac macrophages or deficiency in the phagocytic receptor Mertk resulted in defective elimination of mitochondria from the myocardial tissue, activation of the inflammasome, impaired autophagy, accumulation of anomalous mitochondria in cardiomyocytes, metabolic alterations, and ventricular dysfunction. Thus, we identify an immune-parenchymal pair in the murine heart that enables transfer of unfit material to preserve metabolic stability and organ function. VIDEO ABSTRACT.


Subject(s)
Macrophages/metabolism , Mitochondria/metabolism , Myocytes, Cardiac/metabolism , Aged , Animals , Apoptosis , Autophagy , Female , Heart/physiology , Homeostasis , Humans , Macrophages/physiology , Male , Mice , Mice, Inbred C57BL , Middle Aged , Mitochondria/physiology , Myocardial Infarction/metabolism , Myocardium/metabolism , Myocytes, Cardiac/physiology , Phagocytosis/physiology , Reactive Oxygen Species/metabolism , Receptor Protein-Tyrosine Kinases/metabolism , c-Mer Tyrosine Kinase/metabolism
2.
Development ; 151(4)2024 Feb 15.
Article in English | MEDLINE | ID: mdl-38240380

ABSTRACT

Skeletal muscle stem cells (MuSCs) are recognised as functionally heterogeneous. Cranial MuSCs are reported to have greater proliferative and regenerative capacity when compared with those in the limb. A comprehensive understanding of the mechanisms underlying this functional heterogeneity is lacking. Here, we have used clonal analysis, live imaging and single cell transcriptomic analysis to identify crucial features that distinguish extraocular muscle (EOM) from limb muscle stem cell populations. A MyogeninntdTom reporter showed that the increased proliferation capacity of EOM MuSCs correlates with deferred differentiation and lower expression of the myogenic commitment gene Myod. Unexpectedly, EOM MuSCs activated in vitro expressed a large array of extracellular matrix components typical of mesenchymal non-muscle cells. Computational analysis underscored a distinct co-regulatory module, which is absent in limb MuSCs, as driver of these features. The EOM transcription factor network, with Foxc1 as key player, appears to be hardwired to EOM identity as it persists during growth, disease and in vitro after several passages. Our findings shed light on how high-performing MuSCs regulate myogenic commitment by remodelling their local environment and adopting properties not generally associated with myogenic cells.


Subject(s)
Muscle, Skeletal , Oculomotor Muscles , Mice , Animals , Muscle, Skeletal/metabolism , Oculomotor Muscles/metabolism , Mice, Inbred C57BL , Cell Proliferation , Stem Cells
3.
Am J Hum Genet ; 109(12): 2196-2209, 2022 12 01.
Article in English | MEDLINE | ID: mdl-36459980

ABSTRACT

The TERT/CLPTM1L risk locus on chromosome 5p15.33 is a pleiotropic cancer risk locus in which multiple independent risk alleles have been identified, across well over ten cancer types. We previously conducted a genome-wide association study in uveal melanoma (UM), which uncovered a role for the TERT/CLPTM1L risk locus in this intraocular tumor and identified multiple highly correlated risk alleles. Aiming to unravel the biological mechanisms in UM of this locus, which contains a domain enriched in active chromatin marks and enhancer elements, we demonstrated the allele-specific enhancer activity of this risk region using reporter assays. In UM, we identified the functional variant rs452384, of which the C risk allele is associated with higher gene expression, increased CLPTM1L expression in UM tumors, and a longer telomere length in peripheral blood mononuclear cells. Electrophoretic mobility shift assays and quantitative mass spectrometry identified NKX2.4 as an rs452384-T-specific binding protein, whereas GATA4 preferentially interacted with rs452384-C. Knockdown of NKX2.4 but not GATA4 resulted in increased TERT and CLPTM1L expression. In summary, the UM risk conferred by the 5p locus is at least partly due to rs452384, for which NKX2.4 presents strong differential binding activity and regulates CLPTM1L and TERT expression. Altogether, our work unraveled some of the complex regulatory mechanisms at the 5p15.33 susceptibility region in UM, and this might also shed light on shared mechanisms with other tumor types affected by this susceptibility region.


Subject(s)
Genome-Wide Association Study , Uveal Neoplasms , Humans , Alleles , Leukocytes, Mononuclear , Uveal Neoplasms/genetics
4.
Proc Natl Acad Sci U S A ; 119(40): e2208717119, 2022 Oct 04.
Article in English | MEDLINE | ID: mdl-36161890

ABSTRACT

Ice polymorphs show extraordinary structural diversity depending on pressure and temperature. The behavior of hydrogen-bond disorder not only is a key ingredient for their structural diversity but also controls their physical properties. However, it has been a challenge to determine the details of the disordered structure in ice polymorphs under pressure, because of the limited observable reciprocal space and inaccuracies related to high-pressure techniques. Here, we present an elucidation of the disordered structure of ice VII, the dominant high-pressure form of water, at 2.2 GPa and 298 K, from both single-crystal and powder neutron-diffraction techniques. We reveal the three-dimensional atomic distributions from the maximum entropy method and unexpectedly find a ring-like distribution of hydrogen in contrast to the commonly accepted discrete sites. In addition, total scattering analysis at 274 K clarified the difference in the intermolecular structure from ice VIII, the ordered counterpart of ice VII, despite an identical molecular geometry. Our complementary structure analyses robustly demonstrate the unique disordered structure of ice VII. Furthermore, these findings are related to proton dynamics, which drastically vary with pressure, and will contribute to an understanding of the structural origin of anomalous physical properties of ice VII under pressures.

5.
Clin Infect Dis ; 78(2): 476-483, 2024 02 17.
Article in English | MEDLINE | ID: mdl-37864849

ABSTRACT

BACKGROUND: With more than 7500 cases reported since April 2022, Spain has experienced the highest incidence of mpox in Europe. From 12 July onward, the modified vaccinia Ankara-Bavaria Nordic (MVA-BN) smallpox vaccine was offered as pre-exposure prophylaxis for those receiving pre-exposure prophylaxis for human immunodeficiency virus (HIV-PrEP). Our aim was to assess the effectiveness of 1 dose of MVA-BN vaccine as pre-exposure prophylaxis against mpox virus (MPXV) infection in persons on HIV-PrEP. METHODS: National retrospective cohort study between 12 July and 12 December 2022. Individuals aged ≥18 years receiving HIV-PrEP as of 12 July with no previous MPXV infection or vaccination were eligible. Each day, we matched individuals receiving a first dose of vaccine and unvaccinated controls of the same age and region. We used a Kaplan-Meier estimator, calculated risk ratios (RR) and vaccine effectiveness (VE = [1 - RR]x100). RESULTS: We included 5660 matched pairs, with a median follow-up of 62 days (interquartile range, 24-97). Mpox cumulative incidence was 5.6 per 1000 (25 cases) in unvaccinated and 3.5 per 1000 (18 cases) in vaccinated. No effect was found during days 0-6 post-vaccination (VE, -38.3; 95% confidence interval [CI], -332.7 to 46.4), but VE was 65% at ≥7 days (95% CI, 22.9 to 88.0) and 79% at ≥14 days (95% CI, 33.3 to 100.0) post-vaccination. CONCLUSIONS: One dose of MVA-BN vaccine offered protection against mpox in most-at-risk population shortly after the vaccination. Further studies need to assess the VE of a second dose and the duration of protection over time.


Subject(s)
HIV Infections , Mpox (monkeypox) , Vaccines , Vaccinia , Humans , Adolescent , Adult , Vaccinia/prevention & control , Cohort Studies , Retrospective Studies , Vaccinia virus , Vaccination , Monkeypox virus , HIV Infections/epidemiology , HIV Infections/prevention & control
6.
Breast Cancer Res ; 26(1): 34, 2024 02 26.
Article in English | MEDLINE | ID: mdl-38409028

ABSTRACT

The role of parathyroid hormone (PTH)-related protein (PTHrP) in breast cancer remains controversial, with reports of PTHrP inhibiting or promoting primary tumor growth in preclinical studies. Here, we provide insight into these conflicting findings by assessing the role of specific biological domains of PTHrP in tumor progression through stable expression of PTHrP (-36-139aa) or truncated forms with deletion of the nuclear localization sequence (NLS) alone or in combination with the C-terminus. Although the full-length PTHrP molecule (-36-139aa) did not alter tumorigenesis, PTHrP lacking the NLS alone accelerated primary tumor growth by downregulating p27, while PTHrP lacking the NLS and C-terminus repressed tumor growth through p27 induction driven by the tumor suppressor leukemia inhibitory factor receptor (LIFR). Induction of p27 by PTHrP lacking the NLS and C-terminus persisted in bone disseminated cells, but did not prevent metastatic outgrowth, in contrast to the primary tumor site. These data suggest that the PTHrP NLS functions as a tumor suppressor, while the PTHrP C-terminus may act as an oncogenic switch to promote tumor progression through differential regulation of p27 signaling.


Subject(s)
Breast Neoplasms , Parathyroid Hormone-Related Protein , Humans , Female , Parathyroid Hormone-Related Protein/genetics , Parathyroid Hormone-Related Protein/metabolism , Breast Neoplasms/pathology , Receptors, OSM-LIF , Nuclear Localization Signals , Cell Proliferation/genetics , Leukemia Inhibitory Factor Receptor alpha Subunit
7.
BMC Microbiol ; 24(1): 163, 2024 May 14.
Article in English | MEDLINE | ID: mdl-38745280

ABSTRACT

Spontaneous fermentation of cereals like millet involves a diverse population of microbes from various sources, including raw materials, processing equipment, fermenting receptacles, and the environment. Here, we present data on the predominant microbial species and their succession at each stage of the Hausa koko production process from five regions of Ghana. The isolates were enumerated using selective media, purified, and phenotypically characterised. The LAB isolates were further characterised by 16S rRNA Sanger sequencing, typed using (GTG)5 repetitive-PCR, and whole genome sequencing, while 28S rRNA Sanger sequencing was performed for yeast identification. The pH of the millet grains ranged from mean values of 6.02-6.53 to 3.51-3.99 in the final product, depending on the processors. The mean LAB and yeast counts increased during fermentation then fell to final counts of log 2.77-3.95 CFU/g for LAB and log 2.10-2.98 CFU/g for yeast in Hausa koko samples. At the various processing stages, the counts of LAB and yeast revealed significant variations (p < 0.0001). The species of LAB identified in this study were Limosilactobacillus pontis, Pediococcus acidilactici, Limosilactobacillus fermentum, Limosilactobacillus reuteri, Pediococcus pentosaceus, Lacticaseibacillus paracasei, Lactiplantibacillus plantarum, Schleiferilactobacillus harbinensis, and Weissella confusa. The yeasts were Saccharomyces cf. cerevisiae/paradoxus, Saccharomyces cerevisiae, Pichia kudriavzevii, Clavispora lusitaniae and Candida tropicalis. The identification and sequencing of these novel isolates and how they change during the fermentation process will pave the way for future controlled fermentation, safer starter cultures, and identifying optimal stages for starter culture addition or nutritional interventions. These LAB and yeast species are linked to many indigenous African fermented foods, potentially acting as probiotics in some cases. This result serves as the basis for further studies into the technological and probiotic potential of these Hausa koko microorganisms.


Subject(s)
Fermentation , Fermented Foods , Food Microbiology , Millets , Yeasts , Ghana , Yeasts/classification , Yeasts/isolation & purification , Yeasts/genetics , Yeasts/metabolism , Fermented Foods/microbiology , Millets/microbiology , Lactobacillales/classification , Lactobacillales/isolation & purification , Lactobacillales/genetics , Lactobacillales/metabolism , RNA, Ribosomal, 16S/genetics , Phylogeny , Hydrogen-Ion Concentration , Edible Grain/microbiology
8.
Sex Transm Infect ; 100(4): 231-235, 2024 May 31.
Article in English | MEDLINE | ID: mdl-38744451

ABSTRACT

INTRODUCTION/OBJECTIVES: The use of non-occupational post-exposure prophylaxis (nPEP) emerges as a strategic intervention to reduce HIV infection risk following sexual encounters in our setting. Notwithstanding, there is a scarcity of contemporary data regarding adherence to this treatment, its effectiveness and tolerance. Our study aims to delve into these factors among individuals who have resorted to nPEP after high-risk sexual encounters. METHODS: We conducted a retrospective observational study of cases administered nPEP for HIV from 1 January 2018 to 31 December 2021 at a tertiary hospital in Madrid. The study included all adults over 18 years who sought care at the emergency department of the Fundación Jiménez Díaz Hospital following a risky sexual encounter and were subsequently recommended HIV nPEP treatment. RESULTS: 878 individuals received nPEP for HIV and underwent initial serological tests. Of these, 621 had comprehensive follow-ups. The prescribed regimen for all was raltegravir (RAL) 1200 mg combined with tenofovir/emtricitabine (TDF/FTC) 245/200 mg daily for 28 days. The study revealed a 1.1% rate (n=10) of previously undetected infection and a 0.16% (n=1) failure rate of nPEP. Regarding regimen tolerability, 5.6% (n=35) experienced symptoms linked to the treatment, yet none necessitated discontinuation of the regimen. On the contrary, six per cent (n=53) reported symptoms consistent with an STI during one of the medical visits; specifically, 4.4% had urethritis, and 1.6% had proctitis. CONCLUSION: nPEP with RAL/TDF/FTC demonstrates high efficacy and safety, contingent on proper adherence. There is an observed increase in STI prevalence in this cohort, with nearly half of the participants not engaging in appropriate follow-up after initiating nPEP.


Subject(s)
Anti-HIV Agents , HIV Infections , Post-Exposure Prophylaxis , Humans , HIV Infections/prevention & control , HIV Infections/epidemiology , Male , Retrospective Studies , Adult , Female , Anti-HIV Agents/therapeutic use , Anti-HIV Agents/administration & dosage , Middle Aged , Spain/epidemiology , Medication Adherence/statistics & numerical data , Young Adult
9.
Inorg Chem ; 63(27): 12641-12650, 2024 Jul 08.
Article in English | MEDLINE | ID: mdl-38920333

ABSTRACT

Metal halide perovskites with a two-dimensional structure are utilized in photovoltaics and optoelectronics. High-crystallinity CsSn2Br5 specimens have been synthesized via ball milling. Differential scanning calorimetry curves show melting at 553 K (endothermic) and recrystallization at 516 K (exothermic). Structural analysis using synchrotron X-ray diffraction data, collected from 100 to 373 K, allows for the determination of Debye model parameters. This analysis provides insights into the relative Cs-Br and Sn-Br chemical bonds within the tetragonal structure (space group: I4/mcm), which remains stable throughout the temperature range studied. Combined with neutron data, X-N techniques permit the identification of the Sn2+ lone electron pair (5s2) in the two-dimensional framework, occupying empty space opposite to the four Sn-Br bonds of the pyramidal [SnBr4] coordination polyhedra. Additionally, diffuse reflectance UV-vis spectroscopy unveils an indirect optical gap of approximately ∼3.3 eV, aligning with the calculated value from the B3LYP-DFT method (∼3.2 eV). The material exhibits a positive Seebeck coefficient as high as 6.5 × 104 µV K-1 at 350 K, which evolves down to negative values of -3.0 × 103 µV K-1 at 550 K, surpassing values reported for other halide perovskites. Notably, the thermal conductivity remains exceptionally low, between 0.32 and 0.25 W m-1 K-1.

10.
Am J Respir Crit Care Med ; 207(6): 757-767, 2023 03 15.
Article in English | MEDLINE | ID: mdl-36342964

ABSTRACT

Rationale: Obstructive sleep apnea (OSA) is associated with impaired glycemic control and a higher risk of vascular complications, such as diabetic kidney disease (DKD). However, the effect of apnea-hypopnea suppression on DKD progression is unclear. Objectives: To assess the effect of continuous positive airway pressure (CPAP) on the urinary albumin-to-creatinine ratio (UACR) in patients with DKD and OSA. Methods: In a 52-week, multicentric, open-label, parallel, and randomized clinical trial, 185 patients with OSA and DKD were randomized to CPAP and usual care (n = 93) or usual care alone (n = 92). Measurements and Main Results: UACR, estimated glomerular filtration rate, serum concentrations of creatinine and glycated hemoglobin, insulin resistance, lipid concentrations, sleepiness, and quality of life. A 52-week change in UACR from baseline did not differ significantly between the CPAP group and the usual-care group. However, in per-protocol analyses that included 125 participants who met prespecified criteria for adherence, CPAP treatment was associated with a great reduction in UACR (mean difference, -10.56% [95% confidence interval, -19.06 to -2.06]; P = 0.015). CPAP effect on UACR was higher in nonsleepy patients with more severe OSA, worse renal function, and a more recent diagnosis of DKD. CPAP treatment also improved glycemic control and insulin resistance, as well as sleepiness and health-related quality of life. Conclusions: In patients with OSA and DKD, the prescription of CPAP did not result in a statistically significant reduction in albuminuria. However, good adherence to CPAP treatment in addition to usual care may result in long-term albuminuria reduction compared with usual care alone. Clinical trial registered with www.clinicaltrials.gov (NCT02816762).


Subject(s)
Albuminuria , Diabetic Nephropathies , Insulin Resistance , Sleep Apnea, Obstructive , Humans , Albuminuria/etiology , Continuous Positive Airway Pressure/methods , Creatinine , Diabetes Mellitus , Diabetic Nephropathies/complications , Diabetic Nephropathies/therapy , Quality of Life , Sleep Apnea, Obstructive/complications , Sleep Apnea, Obstructive/therapy , Sleepiness
11.
Pediatr Dermatol ; 41(3): 428-432, 2024.
Article in English | MEDLINE | ID: mdl-38128581

ABSTRACT

BACKGROUND: Retronychia is characterized by proximal ingrowing of the nail plate into the proximal nail fold. It is always associated with the presence of two or more overlapping nail plates under the proximal nail fold, clinical signs of chronic proximal paronychia refractory to antimicrobial treatment, and a yellowish nail that does not grow. It mainly affects young female adults, with less than 30 pediatric cases described in the literature so far. METHODS: Retrospective and observational study of patients between 0 and 18 years with a clinical and/or ultrasound diagnosis of retronychia attending a pediatric dermatology service between December 2020 and January 2022. RESULTS: We identified 9 patients with retronychia, 7 girls and 2 boys. In all cases, the hallux nails were affected with 5 unilateral and 4 bilateral cases. On physical examination we observed the following signs: thickened and opaque nail plate (one patient), yellowish nail plate (7 patients), double nail plate (6 patients), and erythema with edema, pain, and suppuration of the proximal nail fold (7 patients). Ultrasound was performed in 7 patients and specific findings of retronychia were found in 5 of them. All patients received topical treatment and were referred for the appropriate surgical treatment. To date, only one patient underwent nail avulsion, which was followed by complete recovery. CONCLUSIONS: Retronychia is underdiagnosed, particularly in the pediatric population. We present a series of 9 cases of retronychia in children, with clinical and ultrasonographic findings consistent with those of adults. We emphasize the importance of recognizing this entity, which will allow early and adequate treatment.


Subject(s)
Nails, Ingrown , Humans , Male , Female , Child , Retrospective Studies , Nails, Ingrown/therapy , Adolescent , Child, Preschool , Infant , Paronychia/therapy , Paronychia/diagnosis , Ultrasonography , Nails/pathology
12.
Mycorrhiza ; 34(1-2): 107-117, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38151658

ABSTRACT

The Andean paramo, hereafter "paramo", is a Neotropical high-mountain region between the treeline and permanent snowline (3500-4800 m) and is considered the world's coolest biodiversity hotspot. Because of paramo's high humidity, solar radiation and temperature variation, mycorrhizal symbiosis is expected to be essential for plants. Existing theory suggests that replacement of arbuscular mycorrhizal (AM) by ectomycorrhizal (ECM) and then ericoid mycorrhizal plants (ERM) can be expected with increasing elevation. Previous findings also suggest that non-(NM) and facultatively mycorrhizal (FM) species predominate over obligatory mycorrhizal (OM) species at high elevations. However, these expectations have never been tested outside of the northern temperate zone. We addressed the distribution and environmental drivers of plant mycorrhizal types (AM, ECM and ERM) and statuses (NM, FM and OM) along the paramo's elevational gradient. We used vegetation plots from the VegParamo database, climatic and edaphic data from online repositories, and up-to-date observation information about plant mycorrhizal traits at species and genus level, the latter being proposed as hypotheses. AM plants were dominant along the entire gradient, and ERM plants were most abundant at the lowest elevations (2500-3000 m). The share of FM plants increased and that of OM plants decreased with elevation, while NM plants increased above 4000 m. Temperature and soil pH were positively related to the abundance of AM plants and negatively to ERM plants. Our results reveal patterns that contrast with those observed in temperate northern-hemisphere ecosystems.


Subject(s)
Mycorrhizae , Symbiosis , Ecosystem , Plants , Biodiversity , Soil , Soil Microbiology
13.
Genomics ; 115(1): 110528, 2023 01.
Article in English | MEDLINE | ID: mdl-36462728

ABSTRACT

Functional enrichment analysis is a cornerstone in bioinformatics as it makes possible to identify functional information by using a gene list as source. Different tools are available to compare gene ontology (GO) terms, based on a directed acyclic graph structure or content-based algorithms which are time-consuming and require a priori information of GO terms. Nevertheless, quantitative procedures to compare GO terms among gene lists and species are not available. Here we present a computational procedure, implemented in R, to infer functional information derived from comparative strategies. GOCompare provides a framework for functional comparative genomics starting from comparable lists from GO terms. The program uses functional enrichment analysis (FEA) results and implement graph theory to identify statistically relevant GO terms for both, GO categories and analyzed species. Thus, GOCompare allows finding new functional information complementing current FEA approaches and extending their use to a comparative perspective. To test our approach GO terms were obtained for a list of aluminum tolerance-associated genes in Oryza sativa subsp. japonica and their orthologues in Arabidopsis thaliana. GOCompare was able to detect functional similarities for reactive oxygen species and ion binding capabilities which are common in plants as molecular mechanisms to tolerate aluminum toxicity. Consequently, the R package exhibited a good performance when implemented in complex datasets, allowing to establish hypothesis that might explain a biological process from a functional perspective, and narrowing down the possible landscapes to design wet lab experiments.


Subject(s)
Aluminum , Arabidopsis , Genomics/methods , Computational Biology/methods , Algorithms , Gene Ontology , Arabidopsis/genetics
14.
Pediatr Emerg Care ; 2024 May 30.
Article in English | MEDLINE | ID: mdl-38809592

ABSTRACT

OBJECTIVES: The majority of pediatric patients in the United States (US) are evaluated and treated at general emergency departments. It is possible that discrepancies in length of emergency medicine (EM) residency training may allow for variable exposure to pediatric patients, critical resuscitations, and didactic events. The goal of this pilot study was to compare leadership skills of graduating EM residents from 3- to 4-year programs during simulated pediatric resuscitations using a previously validated leadership assessment tool, the Concise Assessment of Leader Management (CALM). METHODS: This was a prospective, multicenter, simulation-based cohort pilot study that included graduating 3rd- and 4th-year EM resident physicians from 6 EM residency programs. We measured leadership performance across 3 simulated pediatric resuscitations (sepsis, seizure, cardiac arrest) using the CALM tool and compared leadership scores between the 3rd- and 4th-year resident cohorts. We also correlated leadership to self-efficacy scores. RESULTS: Data was analyzed for 47 participating residents (24 3rd-year residents and 23 4th-year residents). Out of a total possible CALM score of 66, residents from 3-year programs scored 45.2 [SD ± 5.2], 46.8 [SD ± 5.0], and 46.6 [SD ± 4.7], whereas residents from 4-year programs scored 45.5 [SD ± 5.2], 46.4 [SD ± 5.0], and 48.2 [SD ± 4.3] during the sepsis, seizure, and cardiac arrest cases, respectively. The mean leadership score across all 3 cases for the 3-year cohort was 46.2 [SD ± 4.8] versus 46.7 [SD ± 4.5] (P = 0.715) for the 4-year cohort. CONCLUSIONS: These data show feasibility for a larger cohort project and, while not statistically significant, suggest no difference in leadership skills between 3rd- and 4th-year EM residents in our study cohort. This pilot study provides the basis of future work that will assess a larger multicenter cohort with the hope to obtain a more generalizable dataset.

15.
J Aging Phys Act ; : 1-15, 2024 May 31.
Article in English | MEDLINE | ID: mdl-38823794

ABSTRACT

Older adults are the least physically active group with specific barriers to regular exercise, and online exercise programs could overcome some of those barriers. This scoping review aimed to describe the characteristics of supervised group-based synchronous online exercise programs for older adults living in the community, their feasibility, acceptability, and potential benefits. MEDLINE (Ovid), Embase, SPORTDiscus, and the Cumulative Index to Nursing and Allied Health Literature were searched until November 2022. The included studies met the following criteria: participants aged 50 years and above, a minimum of a 6-week group-based supervised and synchronous intervention, and original articles available in English. Eighteen articles were included, with 1,178 participants (67% female, average age of 71 [57-93] years), most (83%) published in the past 3 years. From the limited reported studies, delivering supervised, synchronous online exercise programs (one to three times/week, between 8 and 32 weeks) for older adults living in the community seems feasible, accepted, and can improve physical function.

16.
Int J Mol Sci ; 25(8)2024 Apr 10.
Article in English | MEDLINE | ID: mdl-38673757

ABSTRACT

Chimeric antigen receptor T cell (CAR T cell) therapy has emerged as a prominent adoptive cell therapy and a therapeutic approach of great interest in the fight against cancer. This approach has shown notorious efficacy in refractory hematological neoplasm, which has bolstered its exploration in the field of solid cancers. However, successfully managing solid tumors presents considerable intrinsic challenges, which include the necessity of guiding the modified cells toward the tumoral region, assuring their penetration and survival in adverse microenvironments, and addressing the complexity of identifying the specific antigens for each type of cancer. This review focuses on outlining the challenges faced by CAR T cell therapy when used in the treatment of solid tumors, as well as presenting optimizations and emergent approaches directed at improving its efficacy in this particular context. From precise localization to the modulation of the tumoral microenvironment and the adaptation of antigen recognition strategies, diverse pathways will be examined to overcome the current limitations and buttress the therapeutic potential of CAR T cells in the fight against solid tumors.


Subject(s)
Immunotherapy, Adoptive , Neoplasms , Receptors, Chimeric Antigen , T-Lymphocytes , Tumor Microenvironment , Humans , Neoplasms/therapy , Neoplasms/immunology , Immunotherapy, Adoptive/methods , Tumor Microenvironment/immunology , Receptors, Chimeric Antigen/immunology , Receptors, Chimeric Antigen/metabolism , T-Lymphocytes/immunology , Animals , Antigens, Neoplasm/immunology , Receptors, Antigen, T-Cell/immunology , Receptors, Antigen, T-Cell/metabolism
17.
J Sci Food Agric ; 104(6): 3487-3497, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38133882

ABSTRACT

BACKGROUND: Some environmental enrichment methods, such as occupational enrichment (OE), can improve fish growth, but little is known about its effects on fillet quality. In this study, we evaluated the effects of OE using underwater currents on different aspects of fillet quality and muscle metabolism in rainbow trout (Oncorhynchus mykiss), before and after a handling procedure (fasting). The trout were placed in groups of 30 in separate tanks in three treatments for 30 days: no artificial currents (CON), randomly fired underwater currents (RFC), and continuous underwater currents (CUC). Additionally, half of the individuals in each treatment were fasted (5 days, 45.2 °C days). RESULTS: Slaughter weight, condition factor, and relative growth were lower in CON fish, indicating a positive effect of OE on growth. Rigor mortis, muscle pH, and muscle glycogen levels were similar among treatments, indicating no effect of OE on classical measures of fillet quality. However, significant differences were found regarding fillet colour and muscle enzymes. The fillets of RFC fish were more salmon-pink in colour, which is favoured by consumers. Also, activity levels of pyruvate kinase and glycogen phosphorylase in muscle were significantly higher in CUC fish, probably due to increased energy demands, as pumps were on continually in that treatment. CONCLUSION: Overall, RFC fish seemed to have received enough stimulation to improve growth while not being excessive in terms of exhausting the animals (avoiding negative effects on muscle metabolism), whereas OE may have provided a hormetic effect, allowing fish to better adjust to fasting. © 2023 Society of Chemical Industry.


Subject(s)
Oncorhynchus mykiss , Animals , Oncorhynchus mykiss/metabolism , Seafood/analysis , Rigor Mortis
18.
J Sci Food Agric ; 104(6): 3705-3718, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38160248

ABSTRACT

BACKGROUND: Rosaceae fruits have been used in traditional medicine for the prevention and treatment of diseases. However, these fruits have not extensively been studied regarding their phenolic composition. Thus, this research focuses on the determination of phenolic compounds by high-performance liquid chromatography electrospray ionization time-of-flight mass spectrometry, flavan-3-ols by high-performance liquid chromatography with fluorescence detection, and the antioxidant activity by 2,2-diphenyl-1-picrylhydrazyl, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid), and ferric reducing antioxidant power of the fruits of five species of genera Crataegus and Sorbus (Rosaceae). RESULTS: We found a total of 71 phenolic compounds from which 30 were identified in these berries for the first time. Crataegus monogyna and Crataegus laciniata revealed higher total phenolic and flavan-3-ol contents than the other species and the highest antioxidant activities. CONCLUSIONS: Therefore, the fruits evaluated have demonstrated to be important sources of bioactive compounds with huge potential for being used in nutraceutical or food scopes. Additional studies could be needed to evaluate the influence of the different production areas on the phenolic content. © 2023 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.


Subject(s)
Antioxidants , Rosaceae , Antioxidants/chemistry , Rosaceae/chemistry , Fruit/chemistry , Phenols/chemistry , Chromatography, High Pressure Liquid/methods
19.
BMC Nurs ; 23(1): 101, 2024 Feb 06.
Article in English | MEDLINE | ID: mdl-38321514

ABSTRACT

BACKGROUND: Delirium is one of the most common adverse events in older people during hospitalization, especially in the emergency department. Reliable, easy-to-use instruments are necessary to properly manage delirium in this setting. This study aims to evaluate the diagnostic validity of the Spanish version of the 4 'A's Test (4AT) in the ED. METHODS: A diagnostic accuracy study was conducted in patients over 65 years old admitted to the Emergency Department who did not have a formal diagnosis of dementia or a severe mental health disorder. Face and content validity were evaluated by an expert panel. Emergency nurses performed the evaluation with 4AT, whilst blinded and trained researchers assessed patients with the Revised Delirium Rating Scale as the gold standard. The content validity index, sensitivity, specificity, positive and negative predictive values, likelihood ratios, Youden's Index and ROC curves were calculated to evaluate the diagnostic accuracy of the instrument. RESULTS: Of 393 eligible patients, 380 were finally analyzed. Content validity yielded a median content validity index of 4 (interquartile range: 0). The Spanish 4AT sensitivity (95.83%; 95% ECI: 78.9-99.9%), specificity (92.98%; 95% CI: 89.8-95.4%), positive predictive value (47.92%) and negative predictive value (99.7%) were satisfactory. Youden's index was 0.89. Positive likelihood ratio was 13.65, and negative likelihood ratio 0.045. The area under the curve was 0.97. CONCLUSIONS: The Spanish version of the 4AT for use in the Emergency Departments is easy-to-use and applicable. The validation results indicate that it is a valid instrument with sufficient predictive validity to identify patients at risk of delirium in the Emergency Departments. Moreover, it is a tool that facilitates the management of an adverse event that is associated with increased mortality and morbidity.

20.
Fish Physiol Biochem ; 50(2): 463-475, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38060080

ABSTRACT

This study investigated the effects of occupational enrichment, specifically underwater currents, on the stress status of rainbow trout (Oncorhynchus mykiss). A total of 540 fish were divided into three groups: control tanks without artificial currents (CO), tanks with randomly fired underwater currents (RFC), and tanks with continuous current throughout the day (CT). After 30 days, half of the fish in each group underwent a 5-day pre-slaughter fasting (5D), while the others were fed until the day before slaughter (0D). Fish in the RFC group exhibited lower levels of plasma cortisol and acetylcholinesterase enzyme activity in hypothalamus and optic tract than other groups, suggesting an improved stress status. RFC group also showed higher levels of non-esterified fatty acids (NEFA) in 5D fish and higher liver glycogen stores, suggesting improved energy reserves. In comparison, the CT group had higher LDH levels, possibly due to their increased swimming activity. The CO group had significantly lower NEFA levels at 5D compared to the RFC group, suggesting lower energy reserves. The RFC fish had darker and yellow-reddish skin and liver color, suggesting an improved stress status and lower lipid reserves, respectively. Overall, although a significant stress response was not observed in fasted individuals, possibly due to the relatively short fasting period, the study suggests that providing occupational enrichment using randomly fired underwater currents for 1 month helped to improve stress status in rainbow trout, indicating that occupational enrichment during the grow-out phase can positively impact the welfare of rainbow trout during routine handling procedures.


Subject(s)
Oncorhynchus mykiss , Animals , Oncorhynchus mykiss/physiology , Fatty Acids, Nonesterified/pharmacology , Acetylcholinesterase , Liver , Fasting/physiology
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