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1.
Front Endocrinol (Lausanne) ; 15: 1398375, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39377072

RESUMO

Background: Vibration platforms have demonstrated systemic effects generated by the use of mechanical vibrations, which are similar to those of any physical activity. The effect that whole body vibration (WBV) generates on the organism could be recommended in Diabetes Mellitus 2 (DM 2) patients. Objective: To systematically review and meta-analyze the available evidence on the effects of WBV on glycemic control in patients with DM 2. Material and methods: Exhaustive bibliographic searches were carried out until October 2023 in different biomedical portals and databases: Public Medline (PubMed), Scientific Electronic Library Online (SciELO), VHL Regional Portal, Cochrane Central and Latin American and Caribbean Literature in Health Sciences (LILACS). Randomized clinical trials based on the effects of Whole Body Vibration on glycosylated hemoglobin levels, with control group and participants were non-insulin dependent were the inclusion criteria. Two reviewers extracted data independently. A third reviewer was available for discrepancies. Results: Six articles with 223 participants met the criteria and were included in the systematic review; only four of them met the criteria to be part of the meta-analysis. This meta-analysis reveals a positive and significant effect size (µ ê=0.5731), indicating a substantial difference between the groups studied. Although there is some variability between studies (heterogeneity of 30.05%), the overall direction of the effects is consistent. These findings conclusively suggest the presence of a significant influence of the variable evaluated, underscoring the robustness and consistency of the relationship observed in the literature reviewed. Conclusion: There are no conclusive results due to the lack of data for some variables, which prevents comparison; but WBV may be an effective therapy to improve glycemic control in DM 2 patients. More studies with more patients and longer follow-up are needed.


Assuntos
Diabetes Mellitus Tipo 2 , Vibração , Vibração/uso terapêutico , Humanos , Diabetes Mellitus Tipo 2/terapia , Ensaios Clínicos Controlados Aleatórios como Assunto , Glicemia/análise , Glicemia/metabolismo
3.
Am J Hematol ; 2024 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-39394928

RESUMO

Avatrombopag is the newest thrombopoietin receptor agonist (TPO-RA) approved to treat immune thrombocytopenia (ITP). Real-world evidence regarding effectiveness/safety is limited. The Spanish ITP Group (GEPTI) performed a retrospective study with patients starting avatrombopag for the first time. A total of 268 ITP patients were recruited. The median (interquartile range [IQR]) follow-up time was 47.5 (30.4-58.9) weeks. Among the 193 patients with baseline platelet counts <50 × 109/L, 174 (90.1%) of them achieved response (PC ≥50 × 109/L), and 113 (87.6%) of the 129 who persisted on avatrombopag at last visit had platelet levels above such threshold. Results were similar when only those patients switching to avatrombopag due to previous treatment failure were considered (n = 104). Patients reached response in 13 (7-21) days. Among patients with baseline levels ≥50 × 109/L, 73/75 (97.3%) reported response, which was maintained by 53 (94.6%) of the 56 who continued on avatrombopag at the end of the study. Loss-of-response was always <10%. ITP duration did not influence response. Approximately 79% (34/43) of heavily pretreated (≥4 lines) patients with baseline platelet counts <50 × 109/L switching after previous failure achieved PC ≥50 × 109/L. Previous use of eltrombopag and/or romiplostim did not influence response, regardless of whether previous TPO-RA(s) succeeded or failed. Avatrombopag allowed dose-reduction/suspension of corticosteroids in 40/50 (80.0%) patients with baseline platelet counts <50 × 109/L. Overall, 40/268 (14.9%) thrombocytosis and 12/268 (4.5%) thromboembolic events were reported. Our real-world cohort supports the use of avatrombopag to manage ITP, regardless of disease severity and treatment history.

4.
Biochem Biophys Res Commun ; 734: 150610, 2024 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-39217810

RESUMO

Hyperglycemia, the hallmark of diabetes mellitus (DM), is the main cause of DM-related systemic complications, including reproductive issues. Furthermore, the incidence of DM in males of reproductive ages is becoming an increasing concern, as the complexity of sperm capacitation (an essential process for fertilizing the egg) extends beyond conventional sperm parameters such as count, viability, and motility. Capacitation defects cause male infertility, and DM-related hyperglycemia may affect this process. We explore the effects of uncontrolled hyperglycemia on sperm using alloxan-induced hyperglycemic Wistar rats. In addition to assessing conventional sperm parameters, we also evaluated functional indicators, including hyperactivation (HA) with a pharmacological approach and assessed its effects with a computer-assisted sperm analysis (CASA); fluorescence indicators to monitor membrane potential (EmR, DiSC3(5)) and mitochondrial membrane potential (Ψ, JC-1); CatSper activity, using its ability to permeate Na+ ions, and ATP levels with the luciferin-luciferase reaction. We confirmed previous findings with our hyperglycemic model, which replicated the typical reduction on conventional sperm parameters. In sperm from hyperglycemic rats, we observed increased motility and HA levels after pharmacological treatment. Additionally, CatSper activity was unaffected by hyperglycemia, while EmR was hyperpolarized under non-capacitating condition. Finally, we noted a low percentage of hyperpolarized Ψ and reduced ATP content. This study highlights the significance of impact of hyperglycemia on sperm physiology and capacitation. We proposed that low ATP levels perturb energy state, signaling pathways, ion channels activity, motility, and HA. Our findings offer insight into DM-associated infertility and potential treatment strategies.

5.
Front Plant Sci ; 15: 1441884, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39319005

RESUMO

Cascade cropping systems (CCS) utilize leachate from a primary crop to grow secondary crops and enhance the efficient use of water and fertilizers in areas with scarce water resources. A preliminary study investigated the effect of melatonin in a cascade cropping system to potentially improve plant tolerance to abiotic stresses. This study aimed to cultivate Salicornia fruticosa in this cropping system to reduce nutrient discharge and assess the impact of exogenous melatonin on Salicornia growth and quality. The CCS included a primary crop of Salicornia grown in an agro-industrial compost or peat. Leachates from these media were used to cultivate the same plant once again in a floating system under four treatments: compost leachate (T1), peat leachate (T2), 100% nutrient solution (NS) (T3), 50% NS (T4) strength. Four concentrations of exogenous melatonin were applied in foliar spray: 0, 100, 200, and 400 µM. Melatonin application increased yield, with the highest values observed when plants were grown in T1. Water use efficiency was also maximized in T1 and with both 200 and 400 µM melatonin applications. The highest nitrogen use efficiency was achieved in plants grown in peat leachate. The lipid membrane damage was assessed revealing that plants grown in compost leachate exhibited the lowest MDA values regardless of melatonin concentrations. The accumulation of some antinutritional compounds (nitrate, oxalate, and sodium) were the highest in those plants grown in compost leachate. Overall, shoots grown in peat leachate exhibited the best phytochemical profile (total phenol content, total flavonoids, and antioxidant capacity), with peak values in plants treated with 200 µM melatonin. These findings suggest that S. fruticosa can be effectively cultivated using leachate from a previous crop in a floating system and that exogenous melatonin application enhances the yield and nutritional quality of Salicornia shoots.

6.
Biomedicines ; 12(9)2024 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-39335498

RESUMO

Glaucoma is the second leading cause of blindness worldwide and is, in most cases, a consequence of elevated intraocular pressure (IOP), ultimately resulting in the death of retinal ganglion cells (RGCs). Current treatments are mostly focused on normalizing IOP, but we propose the additional use of neuroprotective agents, including methylene blue (MB), to block the loss of RGCs. Wistar rats were subjected to episcleral vein cauterization (EVC) in the left eye while the right eye was sham-operated. One week later, they were divided into two groups, which were injected with either 2.0 mg/kg MB or phosphate-buffered saline (PBS), twice a day, for 7 days. Fifteen days after surgery, rats were tested with scotopic electroretinography (ERG) or pattern electroretinography (PERG). After sacrifice, the number of RGCs and the thickness of the inner retina (IR) were evaluated both in the peripheral and central areas of the retina. Scotopic ERG showed a marked reduction (p < 0.0001) on the a- and b-wave amplitude and oscillatory potential (OP) complexity of the eyes subjected to EVC. These parameters were significantly (p < 0.01) restored by the application of MB. PERG indicated that EVC was responsible for a very significant decrease in N2 amplitude (p < 0.0001) and prolongation of N2 implicit time (p < 0.0001). Treatment with MB significantly restored N2 amplitude (p < 0.0001). In parallel with the ERG results, morphological analysis showed a significant loss of RGCs (p < 0.0001) and IR thickness (p < 0.0001) in both the peripheral and central retinas subjected to EVC, which was significantly prevented (p < 0.0001) by MB treatment. We have shown that MB treatment can be effective in preventing physiological and morphological hallmarks of optic neuropathy in a model of ocular hypertension, which faithfully recapitulates human open-angle glaucoma. Due to its high safety profile, this drug could therefore represent a new pharmacologic strategy to prevent vision loss in glaucoma patients.

7.
Pathogens ; 13(9)2024 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-39338973

RESUMO

Historical seroprevalence data for Anisakis in Spain vary greatly depending on the sampling region owing to different fish consumption habits. As a result of European Regulation (EC) No. 853/2004, the Royal Decree 1420/2006 on the prevention of parasitosis by Anisakis in fishery products supplied by establishments that serve food to final consumers or to communities came into force in Spain. In this study, a prevalence study of Anisakis in Madrid has been conducted to verify the prophylactic effects of the application of the law. Sera from 500 blood donors from the Fundación Jiménez Díaz University Hospital (Madrid/2021-2023) were collected, and the levels of anti-Anisakis IgG, IgA, and IgE were analyzed by ELISA, comparing them with those obtained with 110 donors from the Red Cross and the "Gómez Ulla" Central Defense Hospital (Madrid/2001-2002). The percentages of positivity in the 2021-2023 donor group were IgG (13.6%), IgA (13.6%), and IgE (2.2%), while in the 2001-2002 donors they were positive for IgG (15.45%), IgA (14.54%), and IgE (11.65%). A reduction of more than 80% was observed in the prevalence of anti-Anisakis IgE in the healthy population of Madrid, which confirmed the positive effect of RD1420/2006, which was later incorporated into RD1021/2022.

8.
Sci Rep ; 14(1): 20104, 2024 08 29.
Artigo em Inglês | MEDLINE | ID: mdl-39209855

RESUMO

Furthering our knowledge of the skin microbiome is essential to understand health and disease in canines. To date, studies into the canine skin microbiome have focused on 16S rRNA high throughput sequencing however, these lack the granularity of species and strain level taxonomic characterisation and their associated functions. The aim of this study was to provide a comprehensive assessment of the skin microbiome by analysing the skin microbiome of 72 healthy adult colony dogs, across four distinct skin sites and four breeds, using metagenomic sequencing. Our analysis revealed that breed and skin site are drivers of variation, and a core group of taxa and genes are present within the skin microbiome of healthy dogs, comprising 230 taxa and 1219 gene families. We identified 15 species within the core microbiome that are represented by more than one strain. The biosynthesis of secondary metabolites pathway was enriched in the core microbiome suggesting the skin microbiome may play a role in colonisation resistance and protection from invading pathogens. Additionally, we uncovered the novelty of the canine skin microbiome and show that further investigation is required to increase the suitability of current databases for metagenomic sequencing of canine skin samples.


Assuntos
Metagenômica , Microbiota , Pele , Cães , Animais , Pele/microbiologia , Metagenômica/métodos , Metagenoma , RNA Ribossômico 16S/genética , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Sequenciamento de Nucleotídeos em Larga Escala
9.
World J Surg Oncol ; 22(1): 226, 2024 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-39192281

RESUMO

BACKGROUND: Surgeries for sarcomas in the abdominal wall require wide resections, often radical en bloc resections, which generate major defects involving a very complex repair. The combined use of porcine dermal xenografts, together with composite meshes, may assist in the repair of these defects with minimal complications. METHOD: We present a series of 19 patients (10 males and 9 females), with a mean age of 53.2 years (range: 11-86 years) treated in the Sarcoma Unit of the Virgen de la Arrixaca University Hospital from January 2015 to December 2021. Histopathologically, there were four chondrosarcomas (21%), three Ewing sarcomas (15.7%), two desmoid tumours (10.5%), two undifferentiated pleomorphic sarcomas (10.5%), two well-differentiated liposarcomas (10.5%), two leiomyosarcomas (10.5%), one synovial sarcoma, one dermatofibrosarcoma protuberans, one fibromyxoid sarcoma (or Evans tumour), and one metastasis from an adenocarcinoma of unknown origin. All the patients were resected following surgical oncology principles and reconstructed by means of the combined use of a composite mesh acting as a neoperitoneum and a porcine dermal xenograft acting as an abdominal neofascia. RESULTS: The mean size of the defects generated after surgery for tumour excision was 262.8 cm2 (range: 150-600 cm2). After a mean follow-up of 38 months, six patients (31.5%) developed complications-two cases of wound dehiscence, one case of surgical wound infection, one case of graft partial necrosis, one case of anastomotic leak and one death due to multiorgan failure secondary to massive bronchoaspiration. CONCLUSION: Surgeries for sarcomas of the abdominal wall require wide oncological resections, which generate major abdominal wall defects. The repair of these defects by means of the combined use of synthetic and biological meshes is a technique associated with minimal complications and excellent medium-term results.


Assuntos
Parede Abdominal , Derme Acelular , Procedimentos de Cirurgia Plástica , Sarcoma , Telas Cirúrgicas , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Adulto , Adolescente , Parede Abdominal/cirurgia , Parede Abdominal/patologia , Idoso de 80 Anos ou mais , Criança , Adulto Jovem , Sarcoma/cirurgia , Sarcoma/patologia , Procedimentos de Cirurgia Plástica/métodos , Seguimentos , Prognóstico , Animais
10.
Pharmaceuticals (Basel) ; 17(8)2024 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-39204142

RESUMO

Background:Bougainvillea x buttiana is an ornamental plant with antioxidant, anti-inflammatory, and cytotoxic activities, which has been traditionally used to treat respiratory diseases. This study aimed to investigate whether the acetonic extract of Bougainvillea x buttiana var. Rose (BxbRAE-100%) has analgesic and anti-inflammatory properties and its potential action mechanisms. Methods: Analgesic and anti-inflammatory activities were evaluated using three murine pain models and two acute inflammation models. In vitro, the ability of the extract to inhibit proteolytic activity and the activities of the enzymes phospholipase A2 (PLA2) and cyclooxygenase (COX) were evaluated. In silico analysis was performed to predict the physicochemical and Absorption, distribution, metabolism, and excretion (ADME) profiles of the compounds previously identified in BxbRAE-100%. Results: In vivo BxbRAE-100% decreased the nociceptive behaviors in the writhing model, the tail immersion, and the formalin test, suggesting that the extract has the potential to relieve pain at peripheral and central levels. Additionally, topical or oral BxbRAE-100% treatment reduced dose-dependent 12-O-Tetradecanoylphorbol-13-acetate (TPA)-induced ear inflammation and carrageenan-induced paw edema, respectively. In vitro, BxbRAE-100% significantly inhibited proteolytic activity and PLA2, COX-1 and COX-2 activities. In silico, the compounds previously identified in BxbRAE-100% met Lipinski's rule of five and showed adequate ADME properties. Conclusions: These results support the use of B. x buttiana in Traditional Mexican Medicine and highlight its potential for the development of new treatments for pain and inflammation.

11.
Med Clin (Barc) ; 2024 Aug 01.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-39095264

RESUMO

INTRODUCTION AND OBJECTIVE: Clinical manifestations secondary to amyloid deposition in connective tissue may allow early detection of amyloidosis. We sought to identify the prevalence of connective tissue amyloidosis in patients undergoing orthopedic surgery and evaluate for cardiac involvement. MATERIAL AND METHODS: Descriptive cross-sectional study that included patients >50 years referred for orthopedic surgery at our center. A sample of the affected connective tissue was taken during the intervention to evaluate the presence of amyloid material. Those with confirmed amyloidosis were further evaluated with complementary tests for cardiac involvement. RESULTS: Forty-eight patients were included. Mean age was 65.4 years and 41.7% were women. The most frequent surgery was supraspinatus tendon rupture (50%). Transthyretin amyloid deposits were detected in 2 patients (4.2%). The absence of variants in the protein gene established the diagnosis of ATTRwt in both cases. None of them presented cardiac involvement. CONCLUSIONS: In this study, 4.2% of patients referred for orthopedic surgery presented transthyretin amyloidosis in the affected connective tissue.

12.
Sci Rep ; 14(1): 18897, 2024 08 14.
Artigo em Inglês | MEDLINE | ID: mdl-39143116

RESUMO

There is growing evidence that a relationship exists between mental and emotional wellbeing and the gut microbiota. Little is known regarding how the microbiota reacts to repeated acute stress events in dogs, and whether it is a predictor of stress response. In this study, we explored the impact on the gut microbiota and digestive health with two common events many pet dogs find stressful. Twenty healthy adult dogs, living within a colony, were exposed to either car travel or separation three times across eight-week intervals. Faecal samples were collected 24 h before, within 24 h, and 24-48 h after. Faecal quality and pH, and microbiota diversity and composition were analysed in context with wider published work on physiological stress measures. No significant changes were observed in faecal quality or pH with either stress event at any timepoint, indicating all pets remained in good digestive health. Microbiota analysis demonstrated no significant impact on alpha or beta diversity with either stressor. Microbial signatures previously linked to stress were not identified in these dogs and no changes were observed in the functional gut composition. Irrespective of whether the pet was considered "stressed" (i.e., exhibited an increase in serum cortisol), there was no effect on the microbiota and no taxa were predictive of stress response. Collectively, this work demonstrates, for this population, certain acute stress events have no meaningful impact on the canine gut microbiota, and it has no impact on the associated stress response.


Assuntos
Fezes , Microbioma Gastrointestinal , Estresse Psicológico , Animais , Cães , Fezes/microbiologia , Estresse Psicológico/microbiologia , Masculino , Feminino , Estresse Fisiológico
13.
Commun Biol ; 7(1): 993, 2024 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-39143195

RESUMO

The pupillary light reflex (PLR) adapts the amount of light reaching the retina, protecting it and improving image formation. Two PLR mechanisms have been described in vertebrates. First, the pretectum receives retinal inputs and projects to the Edinger-Westphal nucleus (EWN), which targets the ciliary ganglion through the oculomotor nerve (nIII). Postganglionic fibers enter the eye-globe, traveling to the iris sphincter muscle. Additionally, some vertebrates exhibit an iris-intrinsic PLR mechanism mediated by sphincter muscle cells that express melanopsin inducing muscle contraction. Given the high degree of conservation of the lamprey visual system, we investigated the mechanisms underlying the PLR to shed light onto their evolutionary origins. Recently, a PLR mediated by melanopsin was demonstrated in lampreys, suggested to be brain mediated. Remarkably, we found that PLR is instead mediated by direct retino-iridal cholinergic projections. This retina-mediated PLR acts synergistically with an iris-intrinsic mechanism that, as in other vertebrates, is mediated by melanopsin and has contribution of gap junctions between muscle fibers. In contrast, we show that lampreys lack the brain-mediated PLR. Our results suggest that two eye-intrinsic PLR mechanisms were present in early vertebrate evolution, whereas the brain-mediated PLR has a more recent origin.


Assuntos
Iris , Reflexo Pupilar , Retina , Animais , Reflexo Pupilar/fisiologia , Iris/fisiologia , Iris/metabolismo , Retina/fisiologia , Retina/metabolismo , Lampreias/fisiologia , Contração Muscular/fisiologia , Opsinas de Bastonetes/metabolismo , Opsinas de Bastonetes/genética , Luz , Vertebrados/fisiologia
14.
Nat Commun ; 15(1): 6698, 2024 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-39107305

RESUMO

The common bean (Phaseolus vulgaris L.) is a crucial legume crop and an ideal evolutionary model to study adaptive diversity in wild and domesticated populations. Here, we present a common bean pan-genome based on five high-quality genomes and whole-genome reads representing 339 genotypes. It reveals ~234 Mb of additional sequences containing 6,905 protein-coding genes missing from the reference, constituting 49% of all presence/absence variants (PAVs). More non-synonymous mutations are found in PAVs than core genes, probably reflecting the lower effective population size of PAVs and fitness advantages due to the purging effect of gene loss. Our results suggest pan-genome shrinkage occurred during wild range expansion. Selection signatures provide evidence that partial or complete gene loss was a key adaptive genetic change in common bean populations with major implications for plant adaptation. The pan-genome is a valuable resource for food legume research and breeding for climate change mitigation and sustainable agriculture.


Assuntos
Domesticação , Genoma de Planta , Phaseolus , Phaseolus/genética , Adaptação Fisiológica/genética , Genótipo , Variação Genética , Produtos Agrícolas/genética , Seleção Genética , Evolução Molecular , Mutação , Melhoramento Vegetal/métodos
16.
Artigo em Inglês | MEDLINE | ID: mdl-39054217

RESUMO

OBJECTIVE: To identify published research on the Shock Index (SI) in patients with septic shock or severe sepsis and to describe its main findings and conclusions. DESIGN: Systematic review of the literature following the recommendations of the PRISMA protocol (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). SETTINGS: The following databases were consulted: Pubmed, Embase, Library Cochrane and Lilacs. PATIENTS: Patients older than 14 years with septic shock. Pregnant women and population with COVID-19 were excluded. INTERVENTIONS: Studies reporting measurement of the shock index or its modified variants. MAIN VARIABLES OF INTEREST: Absolute frequencies and relative frequencies were assessed with measures of central tendency and dispersion. Effect estimators (OR, RR and HR) were extracted according to the context of each study. RESULTS: Seventeen articles were included, of which 11 investigated the SI as a predictor of mortality. Seven of them found significant differences in the SI when comparing survivors to non-survivors and observed a relationship between the SI evolution and clinical outcomes. Additional research evidenced a relation between the Modified Shock Index and myocardial depression, as well as mortality. Furthermore, they identified a relationship between the Diastolic Shock Index, the dose of administered dobutamine, and mortality. CONCLUSIONS: The results suggest that both the SI and its modified versions, particularly in serial assessments, can be considered for evaluating patient prognosis. The SI can also aid in determining fluid management for patients.

17.
Pharmaceuticals (Basel) ; 17(7)2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-39065741

RESUMO

Panama boasts an expansive mangrove area and stands as one of the most biodiverse countries in America. While mangrove plants have long been utilized in traditional medicine, there are still unstudied species whose potential medicinal applications remain unknown. This study aimed to extract bioactive compounds from Mora oleifera (Triana ex Hemsl.) Ducke, an understudied mangrove species. Through bioassay-guided fractionation of the crude extract, we isolated seven active compounds identified as lupenone (1), lupeol (2), α-amyrin (3), ß-amyrin (4), palmitic acid (5), sitosterol (6), and stigmasterol (7). Compound structures were determined using spectroscopic analyses, including APCI-HR-MS and NMR. Compounds 1-7 displayed concentration-dependent inhibition of the alpha-glucosidase enzyme, with IC50 values of 0.72, 1.05, 2.13, 1.22, 240.20, 18.70, and 163.10 µM, respectively. Their inhibitory activity surpassed acarbose, the positive control (IC50 241.6 µM). Kinetic analysis revealed that all compounds acted as competitive inhibitors. Docking analysis predicted that all triterpenes bonded to the same site as acarbose in human intestinal alpha-glucosidase (PDB: 3TOP). A complementary metabolomic analysis of M. oleifera active fractions revealed the presence of 64 compounds, shedding new light on the plant's chemical composition. These findings suggest that M. oleifera holds promise as a valuable botanical source for developing compounds for managing blood sugar levels in individuals with diabetes.

18.
Ageing Res Rev ; 99: 102408, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38969142

RESUMO

Alzheimer's disease (AD) and osteoporosis are two diseases that mainly affect elderly people, with increases in the occurrence of cases due to a longer life expectancy. Several epidemiological studies have shown a reciprocal association between both diseases, finding an increase in incidence of osteoporosis in patients with AD, and a higher burden of AD in osteoporotic patients. This epidemiological relationship has motivated the search for molecules, genes, signaling pathways and mechanisms that are related to both pathologies. The mechanisms found in these studies can serve to improve treatments and establish better patient care protocols.


Assuntos
Doença de Alzheimer , Osteoporose , Humanos , Doença de Alzheimer/epidemiologia , Osteoporose/epidemiologia , Incidência
19.
Artigo em Inglês | MEDLINE | ID: mdl-38990702

RESUMO

Lymphangioleiomyomatosis (LAM) is a devastating disease primarily found in women of reproductive age that leads to cystic destruction of the lungs. Recent work has shown that LAM causes immunosuppression and that checkpoint inhibitors can be used as LAM treatment. Toll-like receptor (TLR) agonists can also re-activate immunity and the TLR9 agonist, CpG-ODN, has been effective in treating lung cancer in animal models. Here we investigate the use of TLR9 agonist CpG-ODN as LAM immunotherapy in combination with checkpoint inhibitor, anti-PD1, standard of care rapamycin and determine the immune mechanisms underlying therapeutic efficacy. We used survival studies, flow cytometry, ELISA, and histology to assess immune response and survival after intranasal treatment with CpG-ODN in combination with rapamycin or anti-PD1 therapy in a mouse model of metastatic LAM. We found that local administration of CpG-ODN enhances survival in a mouse model of LAM. We found that a lower dose led to longer survival likely due to fewer local side effects but increased LAM nodule count and size compared to the higher dose. CpG-ODN treatment also reduced regulatory T cells and increased the number of Th17 helper T cells as well as cytotoxic T cells. These effects appear to be mediated in part by plasmacytoid dendritic cells (pDCs), as depletion of pDCs reduces survival and abrogates Th17 T cell response. Finally, we found that CpG-ODN treatment is effective in early stage and progressive disease and is additive with anti-PD1 therapy and rapamycin. In summary, we have found that TLR9 agonist CpG-ODN can be used as LAM immunotherapy and effectively synergizes with rapamycin and anti-PD1 therapy in LAM.

20.
Ann Intensive Care ; 14(1): 108, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38980442

RESUMO

BACKGROUND: Dynamic arterial elastance (Eadyn) has been investigated for its ability to predict hypotension during the weaning of vasopressors. Our study focused on assessing Eadyn's performance in the context of critically ill adult patients admitted to the intensive care unit, regardless of diagnosis. MAIN BODY: Our study was conducted in accordance with the Preferred Reported Items for Systematic Reviews and Meta-Analysis checklist. The protocol was registered in PROSPERO (CRD42023421462) on May 26, 2023. We included prospective observational studies from the MEDLINE and Embase databases through May 2023. Five studies involving 183 patients were included in the quantitative analysis. We extracted data related to patient clinical characteristics, and information about Eadyn measurement methods, results, and norepinephrine dose. Most patients (76%) were diagnosed with septic shock, while the remaining patients required norepinephrine for other reasons. The average pressure responsiveness rate was 36.20%. The synthesized results yielded an area under the curve of 0.85, with a sensitivity of 0.87 (95% CI 0.74-0.93), specificity of 0.76 (95% CI 0.68-0.83), and diagnostic odds ratio of 19.07 (95% CI 8.47-42.92). Subgroup analyses indicated no variations in the Eadyn based on norepinephrine dosage, the Eadyn measurement device, or the Eadyn diagnostic cutoff to predict cessation of vasopressor support. CONCLUSIONS: Eadyn, evaluated through subgroup analyses, demonstrated good predictive ability for the discontinuation of vasopressor support in critically ill patients.

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