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1.
Ann Med Surg (Lond) ; 86(10): 6105-6120, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39359774

RESUMO

Background: The intestinal microbiome has been recently linked to several metabolic and chronic disorders, one of which is coronary artery disease (CAD). Our study aimed to analyze the intestinal microbiome of CAD patients and assess the eligibility of dysbiosis as a diagnostic marker of CAD. Methods: PubMed, Scopus, Embase, and Web of Science were searched using terms, such as 'CAD' and 'microbiome'. Only observational controlled studies were included. R version 4.2.2 was used for the analysis. Results: A significant association was found between the CAD group and increased Simpson and Shannon Indices compared with the control group (MD=0.04, 95% CI=0.03-0.05, and MD=0.11, 95% CI=0.01-0.22, respectively). Our analysis yielded a statistically significant association between the CAD group and increased Prevotella genus (MD=13.27, 95% CI=4.12-22.42, P-value=0.004), Catenibacterium genus (MD=0.09, 95% CI=0.09-0.10), Pseudomonas genus (MD=0.54, 95% CI=0.29-0.78, P-value), and Subdoligranulum (MD=-0.06, 95% CI=-0.06 to -0.06) compared with the control group. Another significant association was detected between the CAD group and decreased Bacteroides vulgatus and Bacteroides dorei (MD=-10.31, 95% CI=-14.78 to -5.84, P-value <0.00001). Conclusion: Dysbiosis is an acceptable diagnostic marker of CAD. Decreased B. dorei and B. vulgatus among CAD patients suggests a protective role of these bacteria. Future clinical trials are necessary to investigate the potential benefit of supplementation of these bacteria in treating or preventing CAD.

2.
Cities ; 155: 105340, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39351125

RESUMO

Recent advances in data science and urban environmental health research utilise large-scale databases (100s-1000s of cities) to explore the complex interplay of urban characteristics such as city form and size, climate, mobility, exposure, and environmental health impacts. Cities are still hotspots of air pollution and noise, suffer urban heat island effects and lack of green space, which leads to disease and mortality burdens preventable with better knowledge. Better understanding through harmonising and analysing data in large numbers of cities is essential to identifying the most effective means of disease prevention and understanding context dependencies important for policy.

3.
World J Hepatol ; 16(9): 1211-1228, 2024 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-39351515

RESUMO

Extracellular vesicles (EVs) are small particles released by many cell types in different tissues, including the liver, and transfer specific cargo molecules from originating cells to receptor cells. This process generally culminates in activation of distant cells and inflammation and progression of certain diseases. The global chronic liver disease (CLD) epidemic is estimated at 1.5 billion patients worldwide. Cirrhosis and liver cancer are the most common risk factors for CLD. However, hepatitis C and B virus infection and obesity are also highly associated with CLD. Nonetheless, the etiology of many CLD pathophysiological, cellular, and molecular events are unclear. Changes in hepatic lipid metabolism can lead to lipotoxicity events that induce EV release. Here, we aimed to present an overview of EV features, from definition to types and biogenesis, with particular focus on the molecules related to steatosis-related liver disease, diagnosis, and therapy.

4.
J Clin Oncol ; : JCO2400635, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-39353166

RESUMO

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.In multiple myeloma (MM), measurable residual disease (MRD) is assessed in bone marrow (BM). However, less invasive evaluation of peripheral residual disease (PRD) in blood could be advantageous and less cumbersome. We investigated the prognostic value of PRD monitoring after 24 cycles of maintenance in 138 transplant-eligible patients with MM enrolled in the GEM2012MENOS65/GEM2014MAIN clinical trials. PRD was assessed using next-generation flow (NGF) and mass spectrometry (MS). Positive PRD by NGF in 16/138 (11.5%) patients was associated with a 13-fold increased risk of progression and/or death; median progression-free survival (PFS) and overall survival (OS) were 2.5 and 47 months, respectively. Considering patients' MRD status in BM as the reference, PRD detection using NGF showed positive and negative predictive values of 100% and 73%, respectively. Presence of PRD helped identifying patients at risk of imminent progression among those with positive MRD in BM. Patients with undetectable PRD according to both NGF and MS showed 2-year PFS and OS rates of 97% and 100%, respectively. In multivariate analyses including the Revised International Staging System and the complete remission status, only MRD in BM and PRD by NGF showed independent prognostic value for PFS. This study supports the use of less invasive PRD monitoring during maintenance or observation in transplant-eligible patients with MM.

5.
Pharmacoepidemiol Drug Saf ; 33(10): e70028, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39385712

RESUMO

PURPOSE: The US Food and Drug Administration's Sentinel Innovation Center aimed to establish a query-ready, quality-checked distributed data network containing electronic health records (EHRs) linked with insurance claims data for at least 10 million individuals to expand the utility of real-world data for regulatory decision-making. METHODS: In this report, we describe the resulting network, the Real-World Evidence Data Enterprise (RWE-DE), including data from two commercial EHR-claims linked assets collectively termed the Commercial Network covering 21 million lives, and four academic partner institutions collectively termed the Development Network covering 4.5 million lives. RESULTS: We discuss provenance and completeness of the data converted in the Sentinel Common Data Model (SCDM), describe patient populations, and report on EHR-claims linkage characterization for all contributing data sources. Further, we introduce a standardized process to store free-text notes in the Development Network for efficient retrieval as needed. CONCLUSIONS: Finally, we outline typical use cases for the RWE-DE where it can broaden the reach of the types of questions that can be addressed by the Sentinel system.


Assuntos
Registros Eletrônicos de Saúde , United States Food and Drug Administration , Estados Unidos , Humanos , Registros Eletrônicos de Saúde/estatística & dados numéricos , Revisão da Utilização de Seguros , Vigilância de Evento Sentinela
6.
J Am Coll Cardiol ; 84(15): 1391-1403, 2024 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-39357937

RESUMO

BACKGROUND: Atherosclerosis is a dynamic process. There is little evidence regarding whether quantification of atherosclerosis extent and progression, particularly in the carotid artery, in asymptomatic individuals predicts all-cause mortality. OBJECTIVES: This study sought to evaluate the independent predictive value (beyond cardiovascular risk factors) of subclinical atherosclerosis burden and progression and all-cause mortality. METHODS: A population of 5,716 asymptomatic U.S. adults (mean age 68.9 years, 56.7% female) enrolled between 2008 and 2009 in the BioImage (A Clinical Study of Burden of Atherosclerotic Disease in an At Risk Population) study underwent examination by vascular ultrasound to quantify carotid plaque burden (cPB) (the sum of right and left carotid plaque areas) and by computed tomography for coronary artery calcium (CAC). Follow-up carotid vascular ultrasound was performed on 732 participants a median of 8.9 years after the baseline exam. All participants were followed up for all-cause mortality, the primary outcome. Trend HRs are the per-tertile increase in each variable. RESULTS: Over a median 12.4 years' follow-up, 901 (16%) participants died. After adjustment for cardiovascular risk factors and background medication, baseline cPB and CAC score were both significantly associated with all-cause mortality (fully adjusted trend HR: 1.23; 95% CI: 1.16-1.32; and HR: 1.15; 95% CI: 1.08-1.23), respectively (both P < 0.001), thus providing additional prognostic value. cPB performed better than CAC score. In participants with a second vascular ultrasound evaluation, median cPB progressed from 29.2 to 91.3 mm3. cPB progression was significantly associated with all-cause mortality after adjusting for cardiovascular risk factors and baseline cPB (HR: 1.03; 95% CI: 1.01-1.04 per absolute 10-mm3 change; P = 0.01). CONCLUSIONS: Subclinical atherosclerosis burden (cPB and CAC) in asymptomatic individuals was independently associated with all-cause mortality. Moreover, atherosclerosis progression was independently associated with all-cause mortality.


Assuntos
Aterosclerose , Progressão da Doença , Humanos , Feminino , Masculino , Idoso , Pessoa de Meia-Idade , Aterosclerose/epidemiologia , Aterosclerose/mortalidade , Seguimentos , Doenças Assintomáticas , Doenças das Artérias Carótidas/mortalidade , Doenças das Artérias Carótidas/diagnóstico por imagem , Doenças das Artérias Carótidas/epidemiologia , Fatores de Risco , Placa Aterosclerótica/diagnóstico por imagem , Placa Aterosclerótica/mortalidade , Causas de Morte/tendências , Doença da Artéria Coronariana/mortalidade , Doença da Artéria Coronariana/diagnóstico por imagem , Estados Unidos/epidemiologia
7.
J Cell Physiol ; : e31450, 2024 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-39359018

RESUMO

Store-operated Ca2+ entry is a mechanism controlled by the filling state of the intracellular Ca2+ stores, predominantly the endoplasmic reticulum (ER), where ER-resident proteins STIM1 and STIM2 orchestrate the activation of Orai channels in the plasma membrane, and Orai1 playing a predominant role. Two forms of Orai1, Orai1α and Orai1ß, have been identified, which arises the question whether they are equally regulated by STIM proteins. We demonstrate that STIM1 preferentially activates Orai1α over STIM2, yet both STIM proteins similarly activate Orai1ß. Under resting conditions, there is a pronounced association between STIM2 and Orai1α. STIM1 and STIM2 are also shown to influence the protein levels of the Orai1 variants, independently of Ca2+ influx, via lysosomal degradation. Interestingly, Orai1α and Orai1ß appear to selectively regulate the protein level of STIM1, but not STIM2. These observations offer crucial insights into the regulatory dynamics between STIM proteins and Orai1 variants, enhancing our understanding of the intricate processes that fine-tune intracellular Ca2+ signaling.

8.
Clin Exp Optom ; : 1-11, 2024 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-39374946

RESUMO

Accumulating evidence has recognised central visual field defects (CVFDs) as a common feature of glaucoma. Current glaucoma screening guidelines include peripherally biased perimetry (24-2 protocols), but test grids exist to test the integrity of the central visual field (10-2 protocols). However, the added benefit of incorporating central visual field assessments alongside peripheral-biased testing grids remains unclear. This scoping review aimed to compare the diagnostic accuracy of central versus peripheral visual field tests. A systematic search of six databases yielded relevant studies among glaucoma subjects. These studies were synthesised narratively, focusing on diagnostic performance indicators such as the area under the curve, sensitivity, specificity, diagnostic agreement, and structure-function concordance. Of the 1875 studies screened, 16 were included in the review. The comparative analyses demonstrated a similar diagnostic performance when comparing the ability of the 24-2 and 10-2 test grids to detect glaucoma or CVFDs. When utilising the mean deviation, the 24-2 area under the curve ranged between 0.81-0.87 and 0.74-0.84 for the 10-2, whilst the area under the curve of the pattern standard deviation was 0.95 and 0.82, respectively. The pattern standard deviation showed sensitivities reaching 0.75 for the 24-2 and 0.60 for the 10-2, with specificities as high as 0.95 for both test grids. Across all disease stages, CVFDs detected on the 24-2 demonstrated up to 88% agreement with functional damage detected on the 10-2. The agreement between structure-function damage was greatest when combining test grids with optical coherence tomography (88.7%). This review indicates that the 24-2 and 10-2 testing protocols offer comparable diagnostic performance for glaucoma, including detecting CVFDs. While targeted macula screening could provide additional diagnostic value in certain contexts, the evidence remains inconclusive. Further longitudinal studies, incorporating optical coherence tomography, are necessary to confirm these findings and consider the routine inclusion of CVFD screening in clinical practice.

9.
Front Vet Sci ; 11: 1433628, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39376919

RESUMO

Regrouping practices are frequent in pig production, altering hierarchy and triggering aggressive behaviors. The present study aimed to investigate the physiological responses of piglets to an experimental model designed to induce stress through systematic social mixing in two trials. In Trial A, a total of 144 crossbred piglets (25 days postweaning) housed in one room within 36 pens (four piglets/pen) were used and randomly assigned to either a control group (piglets maintained in their pen, Ctrl-A) or a social challenge group (piglets mixed, SC-A). In Trial B, the same number of animals (33 days postweaning) and crossbreed line was used, and each piglet was assigned either to a control group (Ctrl-B) or a social challenge group (SC-B) in two independent rooms (rooms Ctrl and SC, 12 pens/ room, six piglets/pen). The social challenge consisted of daily moves of three out of four pen mates and five out of six pen mates, for Trials A and B, respectively. In the Ctrl groups, all piglets stayed in their original pen. Before the 1st mixing day and at the end of the 3rd mixing day, saliva (cortisol concentration) and blood (cortisol concentration changes, hemogram, and immunologic activation) samples were collected from two random piglets per pen. Skin lesion scores of all piglets were also recorded on the front, middle, and rear body regions. In Trial A, the total skin lesions score was higher in the SC-A group compared to the Ctrl-A group after the social challenge (0.53 vs. 0.17; p < 0.05), but an unexpected increase between sampling days in the Ctrl-A piglets (0.06 vs. 0.17; p < 0.05) was also recorded, suggesting that Ctrl-A pigs showed similar aggressivity levels to the SC-A group. Hematological parameters hemoglobin, red blood cell counts, and leukocyte counts present similar changes in both treatment groups after the social challenge. Contrarily, in Trial B, the lesion score only increased in the piglets in room SC (0.08 vs. 0.34; p < 0.05). Results suggest that stable groups may show aggressive behaviors if they are in the same room with socially challenged pigs. Thus, the physical separation of treatment groups in social stress studies is recommended.

10.
Chem Commun (Camb) ; 2024 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-39356152

RESUMO

Fluorination of two-dimensional (2D) antimonene hexagons synthesized through a colloidal bottom-up approach has been explored using microwave-induced plasma and reactive ion etching fluorination strategies through the generation of CF4. The stability of the fluorine bond has been corroborated through DFT calculations. This work paves the way for further halogen-derivative modifications of heavy 2D pnictogens.

11.
Braz J Cardiovasc Surg ; 39(5): e20230403, 2024 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-39241201

RESUMO

INTRODUCTION: With the introduction of minimally invasive cardiac surgery, more commonly cases of lung herniation are starting to appear. Acquired lung hernias are classified as postoperative, traumatic, pathologic, and spontaneous. Up to 83% of lung hernias are intercostal. Herein, we describe patients presenting with intercostal lung hernias following minimally invasive cardiac surgery at a single center in Medellín, Colombia. METHODS: We conducted a retrospective search of all patients presenting with intercostal lung hernias secondary to minimally invasive cardiac surgery at our clinic in Medellín since the beginning of our program, from 2010 to 2022. Mini-sternotomies were excluded from our study. We reviewed the incision type and other possible factors leading to intercostal lung hernia development. We also describe the approach taken for these patients. RESULTS: From 2010 up until 2022, 803 adult patients underwent minimally invasive cardiac surgeries through a mini-thoracotomy. At the time of data retrieval, nine patients presented with intercostal lung hernias at the previous incision site. Five hernias (55%) were from right 2nd intercostal parasternal mini-thoracotomies for aortic valve surgeries. Four hernias (45%) were from right 4th intercostal lateral mini-thoracotomies for mitral valve surgeries. Our preferred repair technique is a video-assisted thoracoscopic mesh approach. CONCLUSION: Minimally invasive cardiac surgical approaches are becoming more routine. Proper wound closure is critical in preventing lung hernias. Additionally, timely diagnosis and opportune hernia surgery using video-assisted thoracoscopic mesh repair can prevent further complications.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Pneumopatias , Procedimentos Cirúrgicos Minimamente Invasivos , Humanos , Estudos Retrospectivos , Masculino , Feminino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Procedimentos Cirúrgicos Cardíacos/métodos , Procedimentos Cirúrgicos Minimamente Invasivos/efeitos adversos , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Idoso , Pneumopatias/etiologia , Pneumopatias/cirurgia , Toracotomia/efeitos adversos , Toracotomia/métodos , Herniorrafia/efeitos adversos , Herniorrafia/métodos , Hérnia/etiologia , Adulto , Cirurgia Torácica Vídeoassistida/efeitos adversos , Cirurgia Torácica Vídeoassistida/métodos , Complicações Pós-Operatórias/etiologia
12.
Inorg Chem Front ; 11(18): 5913-5923, 2024 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-39263226

RESUMO

By reacting a 3,6-ditriazolyl-2,5-dihydroxybenzoquinone (H2trz2An) anilato linker with LnIII ions (LnIII = Dy, Tb, Ho), two different series of polymorphs, formulated as [Ln2(trz2An)3(H2O)4] n ·10H2O (DyIII, 1a; TbIII, 2a, HoIII, 3a) and [Ln2(trz2An)3(H2O)4] n ·7H2O (DyIII, 1b, TbIII, 2b, HoIII, 3b) have been obtained. In these series the two DyIII-coordination networks (1a and 1b) and the TbIII-coordination polymer (2b) show a Single Ion Magnet (SIM) behavior. 1-3a MOFs show reversible structural flexibility upon removal of a coordinated water molecule from a distorted hexagonal 2D framework to a distorted 3,6-brickwall rectangular 3D structure in [Ln2(trz2An)3(H2O)2] n ·2H2O (DyIII, 1a_des; TbIII, 2a_des, HoIII, 3a_des) involving shrinkage/expansion of the hexagonal-rectangular networks. Noteworthy, 2b represents the first example of a TbIII-anilate-based coordination polymer showing SIM behaviour to date and the best SIM properties within the polymorphs. Theoretical investigation via ab initio CASSCF calculations supports this behavior, since 2b shows less mixing between the m J states of the ground state among all the studied complexes.

14.
Angew Chem Int Ed Engl ; : e202412425, 2024 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-39292963

RESUMO

Ferromagnetic metal Fe3GeTe2 (FGT), whose structure exhibits weak van-der-Waals interactions between 5-atom thick layers, was subjected to liquid-phase exfoliation (LPE) in N-methyl pyrrolidone (NMP) to yield a suspension of nanosheets that were separated into several fractions by successive centrifugation at different speeds. Electron microscopy confirmed successful exfoliation of bulk FGT to nanosheets as thin as 6 nm. The ferromagnetic ordering temperature for the nanosheets gradually decreased with the increase in the centrifugation speed used to isolate the 2D material. These nanosheets were resuspended in NMP and treated with an organic acceptor, 7,7,8,8-tetracyano-quinodimethane (TCNQ), which led to precipitation of FGT-TCNQ composite. The formation of the composite material is accompanied by charge transfer from the FGT nanosheets to TCNQ molecules, generating TCNQ•- radical anions, as revealed by experimental vibrational spectra and supported by first principles calculations. Remarkably, a substantial increase in magnetic anisotropy was observed, as manifested by the increase in the coercive field from nearly zero in bulk FGT to 1.0 kOe in the exfoliated nanosheets and then to 5.4 kOe in the FGT-TCNQ composite. The dramatic increase in coercivity of the composite suggests that functionalization with redox-active molecules provides an appealing pathway to enhancing magnetic properties of 2D materials.

15.
bioRxiv ; 2024 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-39282416

RESUMO

BACKGROUND & AIMS: We aimed to investigate the relative efficacy of feeding different bile acids in preventing PNALD in neonatal pigs. METHODS: Newborn pigs given total parenteral nutrition (TPN) combined with minimal enteral feeding of chenodeoxycholic acid (CDCA), or increasing doses of obeticholic acid (OCA) for 19 days. RESULTS: Enteral OCA (5 and 15 mg/kg), but not CDCA (30 mg/kg) reduced blood cholestasis markers compared to TPN controls and increased bile acids in the gallbladder and intestine. Major bile acids in the liver and distal intestine were CDCA, HCA, HDCA and OCA, and their relative proportions were increased by the type of bile acid (CDCA or OCA) given enterally. High doses of OCA increased the total NR1H4-agonistic bile acid profile in the liver and intestine above 50% total bile acids. Both CDCA and OCA treatments suppressed hepatic cyp7a1 expression, but only OCA increased hepatobiliary transporters, ABCB11, ABCC$ and ABCB1. Plasma phytosterol levels were reduced and biliary levels were increased by CDCA and OCA and hepatic sterol transporters, abcg5/8, expression were increased by OCA. Both CDCA and OCA increased plasma FGF19 and OCA increased intestinal FGF19, FABP6, and SLC51A. Both CDCA and OCA increased intestinal mucosal growth, whereas CDCA increased the plasma GLP-2, GLP-1 and GIP. CONCLUSIONS: Enteral OCA prevented cholestasis and phytosterolemia by increased hepatic bile acid and sterol transport via induction of hepatobiliary transporter FXR target genes and not by suppression of bile acid synthesis genes. We also showed an intestinal trophic action of OCA that demonstrates a dual clinical benefit of FXR agonism in the prevention of PNALD in piglets.

17.
Perfusion ; : 2676591241283885, 2024 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-39250197

RESUMO

INTRODUCTION: An infrequent yet known complication of ECMO is abdominal compartment syndrome requiring emergency laparotomy. Also, the need for prolonged enteral nutrition while on ECMO may require endoscopic gastrostomy to maintain adequate nutritional status. Here we describe our experience with emergency laparotomy and endoscopic gastrostomy in patients on ECMO support. METHODS: We retrieved patient histories from our clinical archives and performed a retrospective description of all patients taken to an emergency laparotomy or endoscopic gastrostomy while on ECMO support at our cardiovascular referral center from July 2019 through June 2024. RESULTS: During the research period of 5 years a total of 401 patients were placed on ECMO support for either cardiogenic shock or respiratory failure. A total of 27 (7%) patients required an abdominal intervention while on ECMO. 14 (3.5%) patients required emergency laparotomy and 13 (3.2%) of patients required endoscopic gastrostomy tube placement. Overall 30-day mortality of all patients requiring a general surgery procedure while on ECMO support was 33%. CONCLUSION: ECMO support can result in many complications despite its many benefits. Patients who require emergency laparotomy while on ECMO have lower survival-to-discharge and higher mortality at 30 days. Endoscopic gastrostomy however, can be safely performed on ECMO with little to no bleeding complications despite anticoagulation.

18.
Gut ; 2024 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-39266051

RESUMO

BACKGROUND: Cholangiocarcinoma (CCA) is a very difficult-to-treat cancer. Chemotherapies are little effective and response to immune checkpoint inhibitors is limited. Therefore, new therapeutic strategies need to be identified. OBJECTIVE: We characterised the enzyme protein arginine-methyltransferase 5 (PRMT5) as a novel therapeutic target in CCA. DESIGN: We evaluated the expression of PRMT5, its functional partner MEP50 and methylthioadenosine phosphorylase (MTAP)-an enzyme that modulates the sensitivity of PRMT5 to pharmacological inhibitors-in human CCA tissues. PRMT5-targeting drugs, currently tested in clinical trials for other malignancies, were assessed in human CCA cell lines and organoids, as well as in two immunocompetent CCA mouse models. Transcriptomic, proteomic and functional analyses were performed to explore the underlying antitumoural mechanisms. RESULTS: PRMT5 and MEP50 proteins were correlatively overexpressed in most CCA tissues. MTAP was absent in 25% of intrahepatic CCA. PRMT5-targeting drugs markedly inhibited CCA cell proliferation, synergising with cisplatin and gemcitabine and hindered the growth of cholangiocarcinoma organoids. PRMT5 inhibition blunted the expression of oncogenic genes involved in chromatin remodelling and DNA repair, consistently inducing the formation of RNA loops and promoting DNA damage. Treatment with PRMT5-targeting drugs significantly restrained the growth of experimental CCA without adverse effects and concomitantly induced the recruitment of CD4 and CD8 T cells to shrinking tumourous lesions. CONCLUSION: PRMT5 and MEP50 are frequently upregulated in human CCA, and PRMT5-targeting drugs have significant antitumoural efficacy in clinically relevant CCA models. Our findings support the evaluation of PRMT5 inhibitors in clinical trials, including their combination with cytotoxic and immune therapies.

19.
Front Cell Infect Microbiol ; 14: 1420307, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39258253

RESUMO

Human Papillomavirus (HPV), a prevalent sexually transmitted infection, comprises high-risk (HR-HPV) and low-risk (LR-HPV) viruses, the former posing a high risk for developing malignancies whereas the latter mainly for benign warts. Despite increasing awareness of HPV's impact on men's health, the influence of HR-HPV and LR-HPV urogenital infections on male fertility potential remains uncertain. This study aimed to investigate whether male urogenital infection with HR- or LR-HPV associates with impaired sperm quality, oxidative stress, and inflammation. A total of 205 male patients attending an urology clinic were enrolled. Semen samples were analyzed for HPV using PCR and genotyped by RFLP. Semen quality was evaluated following WHO guidelines. Semen leukocytes, reactive oxygen species (ROS), and sperm viability were analyzed using flow cytometry. HPV was detected in 19% (39/205) of semen samples. HR-HPV infections were more prevalent, with HPV-16 being the most frequent genotype. Neither HR-HPV nor LR-HPV were associated with significant alterations in routine sperm quality parameters. However, HR-HPV+ individuals showed significantly higher levels of sperm necrosis and exhibited increased proportions of ROS+ spermatozoa compared to LR-HPV+ or control individuals. Furthermore, no significant semen inflammation was detected in patients infected with either HR-HPV or LR-HPV, and unexpectedly reduced semen leukocytes and inflammatory cytokines (IL-6 and IL-1ß) were observed in HR-HPV+ patients compared to controls. These observations underscore the importance of comprehensive HPV screening, including genotyping, in urology and fertility clinics to understand the progression of the infection, potential adverse effects on reproductive health, and the oncogenic risks involved.


Assuntos
Papillomaviridae , Infecções por Papillomavirus , Análise do Sêmen , Sêmen , Espermatozoides , Humanos , Masculino , Infecções por Papillomavirus/virologia , Adulto , Espermatozoides/virologia , Sêmen/virologia , Papillomaviridae/genética , Pessoa de Meia-Idade , Espécies Reativas de Oxigênio/metabolismo , Genótipo , Adulto Jovem , Inflamação , Estresse Oxidativo , Genitália Masculina/virologia , Adolescente , Citocinas/metabolismo
20.
Cureus ; 16(8): e68192, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39347297

RESUMO

Cardiac arrest is a common cause of death worldwide. Sodium bicarbonate (SB) has commonly been used during cardiopulmonary resuscitation (CPR) to correct metabolic acidosis (MA). However, the existence of evidence about its administration remains controversial. This systematic review aimed to summarize the effectiveness of SB in patients with in-hospital and out-of-hospital cardiac arrest. We searched Medline, Scopus, and the Cochrane Central Register of Controlled Trials (CENTRAL) for studies that used SB in cardiac arrest, from November 1962 until December 2023. A total of 372 records were identified and 12 studies were included. Despite few studies suggesting that SB may improve outcomes in prolonged CPR, the overall data revealed that SB was associated with lower rates of ROSC and outcomes. This review conceded that there is limited evidence to warrant the use of SB during CPR other than under specific conditions, which include hyperkalemic cardiac arrest, severe cardiotoxicity, or overdose due to tricyclic antidepressants. In conclusion, SB is not recommended for conventional use in patients with cardiac arrest. Further studies should be performed to determine whether it has any benefit in these scenarios.

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