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1.
Nature ; 594(7863): 369-373, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-34135523

RESUMEN

The central challenge in building a quantum computer is error correction. Unlike classical bits, which are susceptible to only one type of error, quantum bits (qubits) are susceptible to two types of error, corresponding to flips of the qubit state about the X and Z directions. Although the Heisenberg uncertainty principle precludes simultaneous monitoring of X- and Z-flips on a single qubit, it is possible to encode quantum information in large arrays of entangled qubits that enable accurate monitoring of all errors in the system, provided that the error rate is low1. Another crucial requirement is that errors cannot be correlated. Here we characterize a superconducting multiqubit circuit and find that charge noise in the chip is highly correlated on a length scale over 600 micrometres; moreover, discrete charge jumps are accompanied by a strong transient reduction of qubit energy relaxation time across the millimetre-scale chip. The resulting correlated errors are explained in terms of the charging event and phonon-mediated quasiparticle generation associated with absorption of γ-rays and cosmic-ray muons in the qubit substrate. Robust quantum error correction will require the development of mitigation strategies to protect multiqubit arrays from correlated errors due to particle impacts.

2.
Am J Hum Genet ; 109(8): 1421-1435, 2022 08 04.
Artículo en Inglés | MEDLINE | ID: mdl-35830857

RESUMEN

PPFIBP1 encodes for the liprin-ß1 protein, which has been shown to play a role in neuronal outgrowth and synapse formation in Drosophila melanogaster. By exome and genome sequencing, we detected nine ultra-rare homozygous loss-of-function variants in 16 individuals from 12 unrelated families. The individuals presented with moderate to profound developmental delay, often refractory early-onset epilepsy, and progressive microcephaly. Further common clinical findings included muscular hyper- and hypotonia, spasticity, failure to thrive and short stature, feeding difficulties, impaired vision, and congenital heart defects. Neuroimaging revealed abnormalities of brain morphology with leukoencephalopathy, ventriculomegaly, cortical abnormalities, and intracranial periventricular calcifications as major features. In a fetus with intracranial calcifications, we identified a rare homozygous missense variant that by structural analysis was predicted to disturb the topology of the SAM domain region that is essential for protein-protein interaction. For further insight into the effects of PPFIBP1 loss of function, we performed automated behavioral phenotyping of a Caenorhabditis elegans PPFIBP1/hlb-1 knockout model, which revealed defects in spontaneous and light-induced behavior and confirmed resistance to the acetylcholinesterase inhibitor aldicarb, suggesting a defect in the neuronal presynaptic zone. In conclusion, we establish bi-allelic loss-of-function variants in PPFIBP1 as a cause of an autosomal recessive severe neurodevelopmental disorder with early-onset epilepsy, microcephaly, and periventricular calcifications.


Asunto(s)
Epilepsia , Microcefalia , Malformaciones del Sistema Nervioso , Trastornos del Neurodesarrollo , Acetilcolinesterasa/genética , Animales , Drosophila melanogaster/genética , Epilepsia/genética , Pérdida de Heterocigocidad , Microcefalia/genética , Trastornos del Neurodesarrollo/genética , Linaje
3.
Semin Cancer Biol ; 89: 38-60, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36669712

RESUMEN

Cancer as a disease possess quite complicated pathophysiological implications and is among the prominent causes of morbidity and mortality on global scales. Anti-cancer chemotherapy, surgery, and radiation therapy are some of the present-day conventional treatment options. However, these therapeutic paradigms own several retreats, including lack of specificity, non-targeted toxicological implications, inefficient drug delivery to targeted cells, and emergence of cancer resistance, ultimately causing ineffective cancer management. Owing to the advanced and better biophysical characteristic features and potentiality for the tailoring and customizations and in several fashions, nanotechnology can entirely transubstantiate the cancer identification and its managements. Additionally, nanotechnology also renders several answers to present-day mainstream limitations springing-up in anti-cancer therapeutics. Nanocarriers, owing to their outstanding physicochemical features including but not limited to their particle size, surface morphological features viz. shape etc., have been employed in nanomedicinal platforms for targeting various transcription factors leading to worthy pharmacological outcomes. This transcription targeting activates the wide array of cellular and molecular events like antioxidant enzyme-induction, apoptotic cell death, cell-cycle arrest etc. These outcomes are obtained after the activation or inactivation of several transcription factors and cellular pathways. Further, nanoformulations have been precisely calibrated and functionalized with peculiar targeting groups for improving their efficiency to deliver the drug-payload to specified and targeted cancerous cells and tissues. This review undertakes an extensive, across-the-board and all-inclusive approach consisting of various studies encompassing different types of tailored and customized nanoformulations and nanomaterials designed for targeting the transcription factors implicated in the process of carcinogenesis, tumor-maturation, growth and metastasis. Various transcription factors viz. nuclear factor kappa (NF-κB), signal transducer and activators of transcription (STAT), Cmyc and Twist-related protein 1 (TWIST1) along with several types of nanoparticles targeting these transcription factors have been summarized here. A section has also been dedicated to the different types of nanoparticles targeting the hypoxia inducing factors. Efforts have been made to summarize several other transcription factors implicated in various stages of cancer development, growth, progression and invasion, and their targeting with different kinds of nanomedicinal agents.


Asunto(s)
Antineoplásicos , Neoplasias , Humanos , Nanomedicina , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Antineoplásicos/química , Factores de Transcripción , Sistemas de Liberación de Medicamentos , Neoplasias/tratamiento farmacológico , Neoplasias/genética
4.
Eur Respir J ; 63(2)2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38123239

RESUMEN

BACKGROUND: Short-term studies suggest that dietary nitrate (NO3 -) supplementation may improve the cardiovascular risk profile, lowering blood pressure (BP) and enhancing endothelial function. It is not clear if these beneficial effects are sustained and whether they apply in people with COPD, who have a worse cardiovascular profile than those without COPD. Nitrate-rich beetroot juice (NR-BRJ) is a convenient dietary source of nitrate. METHODS: The ON-BC trial was a randomised, double-blind, placebo-controlled parallel group study in stable COPD patients with home systolic BP (SBP) measurement ≥130 mmHg. Participants were randomly allocated (1:1) using computer-generated, block randomisation to either 70 mL NR-BRJ (400 mg NO3 -) (n=40) or an otherwise identical nitrate-depleted placebo juice (0 mg NO3 -) (n=41), once daily for 12 weeks. The primary end-point was between-group change in home SBP measurement. Secondary outcomes included change in 6-min walk distance (6MWD) and measures of endothelial function (reactive hyperaemia index (RHI) and augmentation index normalised to a heart rate of 75 beats·min-1 (AIx75)) using an EndoPAT device. Plasma nitrate and platelet function were also measured. RESULTS: Compared with placebo, active treatment lowered SBP (Hodges-Lehmann treatment effect -4.5 (95% CI -5.9- -3.0) mmHg), and improved 6MWD (30.0 (95% CI 15.7-44.2) m; p<0.001), RHI (0.34 (95% CI 0.03-0.63); p=0.03) and AIx75 (-7.61% (95% CI -14.3- -0.95%); p=0.026). CONCLUSIONS: In people with COPD, prolonged dietary nitrate supplementation in the form of beetroot juice produces a sustained reduction in BP, associated with an improvement in endothelial function and exercise capacity.


Asunto(s)
Enfermedades Cardiovasculares , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Nitratos/uso terapéutico , Enfermedades Cardiovasculares/prevención & control , Enfermedades Cardiovasculares/tratamiento farmacológico , Suplementos Dietéticos , Factores de Riesgo , Presión Sanguínea , Antioxidantes , Enfermedad Pulmonar Obstructiva Crónica/complicaciones , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Método Doble Ciego , Estudios Cruzados
5.
Magn Reson Med ; 92(4): 1363-1375, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-38860514

RESUMEN

PURPOSE: Hyperpolarized 129Xe MRI benefits from non-Cartesian acquisitions that sample k-space efficiently and rapidly. However, their reconstructions are complex and burdened by decay processes unique to hyperpolarized gas. Currently used gridded reconstructions are prone to artifacts caused by magnetization decay and are ill-suited for undersampling. We present a compressed sensing (CS) reconstruction approach that incorporates magnetization decay in the forward model, thereby producing images with increased sharpness and contrast, even in undersampled data. METHODS: Radio-frequency, T1, and T 2 * $$ {\mathrm{T}}_2^{\ast } $$ decay processes were incorporated into the forward model and solved using iterative methods including CS. The decay-modeled reconstruction was validated in simulations and then tested in 2D/3D-spiral ventilation and 3D-radial gas-exchange MRI. Quantitative metrics including apparent-SNR and sharpness were compared between gridded, CS, and twofold undersampled CS reconstructions. Observations were validated in gas-exchange data collected from 15 healthy and 25 post-hematopoietic-stem-cell-transplant participants. RESULTS: CS reconstructions in simulations yielded images with threefold increases in accuracy. CS increased sharpness and contrast for ventilation in vivo imaging and showed greater accuracy for undersampled acquisitions. CS improved gas-exchange imaging, particularly in the dissolved-phase where apparent-SNR improved, and structure was made discernable. Finally, CS showed repeatability in important global gas-exchange metrics including median dissolved-gas signal ratio and median angle between real/imaginary components. CONCLUSION: A non-Cartesian CS reconstruction approach that incorporates hyperpolarized 129Xe decay processes is presented. This approach enables improved image sharpness, contrast, and overall image quality in addition to up-to threefold undersampling. This contribution benefits all hyperpolarized gas MRI through improved accuracy and decreased scan durations.


Asunto(s)
Algoritmos , Simulación por Computador , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Isótopos de Xenón , Imagen por Resonancia Magnética/métodos , Humanos , Procesamiento de Imagen Asistido por Computador/métodos , Masculino , Relación Señal-Ruido , Femenino , Imagenología Tridimensional/métodos , Adulto , Fantasmas de Imagen , Artefactos , Compresión de Datos/métodos , Reproducibilidad de los Resultados , Pulmón/diagnóstico por imagen , Medios de Contraste/química
6.
J Surg Res ; 300: 389-401, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38851085

RESUMEN

INTRODUCTION: Vascularized composite allotransplantation (VCA) is the transplantation of multiple tissue types as a solution for devastating injuries. Despite the highly encouraging functional outcomes of VCA, the consequences of long-term immunosuppression remain the main obstacle in its application. In this review, we provide researchers and surgeons with a summary of the latest advances in the field of cell-based therapies for VCA tolerance. METHODS: Four electronic databases were searched: PubMed, Scopus, Cumulative Index to Nursing and Allied Health Literature , and Web of Science. We used the Preferred Reporting Items for Systematic Reviews and Meta-Analysis as the basis of our organization. RESULTS: Hematopoietic stem cells prolonged VCA survival. A combination of immature dendritic cells and tacrolimus was superior to tacrolimus alone. T cell Ig domain and mucin domain modified mature dendritic cells increased VCA tolerance. Bone marrow-derived mesenchymal stem cells prolonged survival of VCAs. A combination of adipose-derived mesenchymal stem cells, cytotoxic T-lymphocyte antigen 4 immunoglobulin, and antilymphocyte serum significantly improved VCA tolerance. Ex-vivo allotransplant perfusion with recipient's bone marrow-derived mesenchymal stem cells increased VCA survival. Recipient's adipose-derived mesenchymal stem cells and systemic immunosuppression prolonged VCA survival more than any of those agents alone. Additionally, a combination of peripheral blood mononuclear cells shortly incubated in mitomycin and cyclosporine significantly improved VCA survival. Finally, a combination of donor recipient chimeric cells, anti-αß-T cell receptor (TCR), and cyclosporine significantly prolonged VCA tolerance. CONCLUSIONS: Evidence from animal studies shows that cell-based therapies can prolong survival of VCAs. However, there remain many obstacles for these therapies, and they require rigorous clinical research given the rarity of the subjects and the complexity of the therapies. The major limitations of cell-based therapies include the need for conditioning with immunosuppressive drugs and radiation, causing significant toxicity. Safety concerns also persist as most research is on animal models. While completely replacing traditional immunosuppression with cell-based methods is unlikely soon, these therapies could reduce the need for high doses of immunosuppressants and improve VCA tolerance.


Asunto(s)
Alotrasplante Compuesto Vascularizado , Humanos , Alotrasplante Compuesto Vascularizado/métodos , Animales , Supervivencia de Injerto/inmunología , Supervivencia de Injerto/efectos de los fármacos , Tolerancia al Trasplante , Inmunosupresores/uso terapéutico , Tratamiento Basado en Trasplante de Células y Tejidos/métodos , Rechazo de Injerto/inmunología , Rechazo de Injerto/prevención & control , Trasplante de Células Madre Mesenquimatosas/métodos
7.
Nicotine Tob Res ; 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-39004425

RESUMEN

INTRODUCTION: The Illicit Tobacco Trade (ITT) subverts tobacco control efforts. Cigarette packs sold without legal health warnings undermine efforts to warn the public about the dangers of tobacco. Furthermore, cigarettes sold below minimum retail prices are indicative of tax evasion leading to revenue loss and budgetary deficits in high tobacco-burden economies. The extent of the ITT in rural areas of such countries might differ from urban. We estimated the extent of illicit cigarette sales in selected rural areas of Pakistan. AIMS AND METHODS: We analyzed cigarette packs collected from 85 villages in Pakistan as part of a cross-sectional consumer survey of 2550 rural households. We classified cigarette packs as noncompliant if these were missing: A text health warning, pictorial health warning (PHW), underage sale prohibition warning, retail price, or manufacturer details. To measure the extent of tax evasion, we estimated the proportion of packs purchased below the legal minimum retail price. RESULTS: Only 35% (429/1228) of rural smokers were able to show their cigarette packs. Out of these, 89% (382/429) of packs were noncompliant with the cigarette packaging and labeling laws. In rural areas, 83% (357/429) of packs did not have PHW and 33.8% (145/429) did not have printed retail prices. Among all packs, 41% (177/429) were purchased below the minimum retail price of 63 Pakistani Rupees and hence highly likely to have evaded taxes. CONCLUSIONS: We found a very high previously unreported proportion of noncompliant cigarette packs in selected rural areas of Pakistan indicating weaker implementation of tobacco control laws in rural areas. IMPLICATIONS: This paper presents previously unreported estimates of the share of illicit cigarette sales in rural areas of Pakistan. Most packs (89%) in our sample were noncompliant with the packaging and labeling regulations and a significant proportion (41%) were purchased below the minimum price. The extent of illicit tobacco was found to be far greater in rural than in urban areas of Pakistan. Taking advantage of poor law enforcement, the tobacco industry may be complicit in flooding the rural markets with illegal and cheap cigarettes. Given this disparity, law enforcement authorities must focus on rural areas.

8.
Biometals ; 37(4): 905-921, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38361146

RESUMEN

Palladium and platinum complexes, especially those that include cisplatin, can be useful chemotherapeutic drugs. Alternatives that have less adverse effects and require lower dosages of treatment could be provided by complexes containing pyridine bases. The complexes [Pd(SCN)2(4-Acpy)2] (1), [Pd(N3)2(4-Acpy)2] (2) [Pd(paOH)2].2Cl (3) and [Pt(SCN)2(paO)2] (4) were prepared by self-assembly method at ambient temperature; (4-Acpy = 4-acetylpyridine and paOH = pyridine-2-carbaldehyde-oxime). The structure of complexes 1-4 was confirmed using spectroscopic and X-ray crystallography methods. Complexes 1-4 have similar features in isomerism that include the trans coordination geometry of pyridine ligands with Pd or Pt ion. The 3D network structure of complexes 1-4 was constructed by an infinite number of discrete mononuclear molecules extending via H-bonds. The Pd and Pt complexes 1-4 with pyridine ligands were assessed on MCF-7, T47D breast cancer cells and HCT116 colon cancer cells. The study evaluated cell death through apoptosis and cell cycle phases in MCF-7 cells treated with palladium or platinum conjugated with pyridine base. Upon treatment of MCF-7 with these complexes, the expression of apoptotic signals (Bcl2, p53, Bax and c-Myc) and cell cycle signals (p16, CDK1A, CDK1B) were evaluated. Compared to other complexes and cisplatin, IC50 of complex 1 was lowest in MCF-7 cells and complex 2 in T47D cells. Complex 4 has the highest effectiveness on HCT116. The selective index (SI) of complexes 1-4 has a value of more than two for all cancer cell lines, indicating that the complexes were less toxic to normal cells when given the same dose. MCF-7 cells treated with complex 2 and platinum complex 4 exhibited the highest level of early apoptosis. p16 may be signal arrest cells in Sub G, which was observed in cells treated with palladium complexes that suppress excessive cell proliferation. High c-Myc expression of treated cells with four complexes 1-4 and cisplatin could induce p53. All complexes 1-4 elevated the expression of Bax and triggered by the tumor suppressor gene p53. p53 was downregulating the expression of Bcl2.


Asunto(s)
Antineoplásicos , Apoptosis , Complejos de Coordinación , Paladio , Piridinas , Humanos , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/síntesis química , Paladio/química , Paladio/farmacología , Piridinas/química , Piridinas/farmacología , Apoptosis/efectos de los fármacos , Complejos de Coordinación/farmacología , Complejos de Coordinación/química , Complejos de Coordinación/síntesis química , Transducción de Señal/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Platino (Metal)/química , Platino (Metal)/farmacología , Ensayos de Selección de Medicamentos Antitumorales , Línea Celular Tumoral , Compuestos Organoplatinos/farmacología , Compuestos Organoplatinos/química , Compuestos Organoplatinos/síntesis química , Cristalografía por Rayos X , Estructura Molecular , Relación Dosis-Respuesta a Droga
9.
BMC Vet Res ; 20(1): 26, 2024 Jan 18.
Artículo en Inglés | MEDLINE | ID: mdl-38233918

RESUMEN

BACKGROUND: Compared with corn, wheat contains higher crude protein, amino acids concentration. However, wheat contains a mass of anti-nutritional factors, resulting in increased of the digesta viscosity and impaired the intestinal function in ruminant. OBJECTIVE: This study aimed to investigate the effects of substitution of different amounts of wheat for corn on hepatic metabolism in the Tibetan lamb. METHODS: Ninety Tibetan lambs (Body weight = 12.37 ± 0.92 kg) were randomly assigned to three groups: 0% wheat diet (Control), 10% wheat diet (Low group), and 15% wheat diet (High group). The feeding trial lasted for 130 d, including a 10 d adaption period. Hepatic gene expression profiling was performed via RNA sequencing after the conclusion of the feeding trials. RESULTS: Results showed that greater level of glutathione peroxidase levels in L group compared with those of the C and H groups (P < 0.05). The immune indexes, including interleukin-1ß (IL-1ß), immunoglobulin A (IgA), and IgM were also elevated in L group compared with the other groups (P < 0.05). Compared with H group, the hepatocytes were arranged radially, and hepatic plates anastomosed with each other to form a labyrinth-like structure in L group. Transcriptomic analysis showed 872 differentially expressed genes (DEG) between H and L group, of which 755 were down-regulated and 117 were up-regulated. Through Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, 32 pathways were significantly enriched (Q-value < 0.05), such as the cAMP signaling pathway, Th1 and Th2 cell differentiation, leukocyte transendothelial migration, platelet activation and adipocytokine signaling pathway. Additionally, the expression of comment DEGs were verified via quantitative reverse-transcription polymerase chain reaction. CONCLUSION: In summary, our findings suggest that wheat can be supplemented up to 10% in Tibetan sheep, contributing to improve the hepatic oxidative stress, immune response and lipid metabolism through regulating the expression of related genes.


Asunto(s)
Oveja Doméstica , Triticum , Ovinos , Animales , Metabolismo de los Lípidos , Tibet , Estrés Oxidativo , Dieta/veterinaria , Inmunidad
10.
Metab Brain Dis ; 39(1): 77-88, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38129732

RESUMEN

Neuro-oncological and neurodegenerative disorders, represented paradigmatically by glioblastoma and Alzheimer's disease, respectively, persist as formidable challenges in the biomedical realm. The interconnected molecular underpinnings of these conditions necessitate rigorous and novel therapeutic examinations. This comprehensive research was anchored on the premise of unveiling the therapeutic potential and specificity of Lupenone, a potent phytoconstituent, in targeting the molecular pathways underpinning both glioblastoma and Alzheimer's amyloid beta pathology. This was gauged through its interactions with key protein structures, 5H08 and 2ZHV. An integrative approach was adopted, marrying advanced proteomics and modern computer-aided drug design techniques. Molecular docking of Lupenone with 5H08 and 2ZHV was meticulously executed, with subsequent molecular dynamics simulations providing insights into the stability, viability, and intricacies of these interactions. Lupenone demonstrated profound binding affinities, evidenced by robust docking scores of -9.54 kcal/mol for 5H08 and -10.59 kcal/mol for 2ZHV. These interactions underscored Lupenone's eminent therapeutic potential in mitigating glioblastoma and modulating the amyloid beta pathology inherent to Alzheimer's. The introduction of Proteolysis Targeting Chimeras (PROTACs) further magnified the therapeutic prospects, accentuating Lupenone's efficacy. The findings of this study not only underscore the therapeutic acumen of Lupenone in addressing the challenges posed by glioblastoma and Alzheimer's but also lay a strong foundation for its consideration as a leading candidate in future neuro-oncological and neurodegenerative research endeavors. Given the compelling in-silico data, a clarion call is made for its empirical validation in holistic in-vivo settings, potentially pioneering a new therapeutic epoch in both glioblastoma and Alzheimer's interventions.


Asunto(s)
Enfermedad de Alzheimer , Glioblastoma , Lupanos , Humanos , Péptidos beta-Amiloides/metabolismo , Simulación de Dinámica Molecular , Enfermedad de Alzheimer/metabolismo , Glioblastoma/tratamiento farmacológico , Simulación del Acoplamiento Molecular
11.
Mar Drugs ; 22(1)2024 Jan 03.
Artículo en Inglés | MEDLINE | ID: mdl-38248659

RESUMEN

The Marburg virus (MBV), a deadly pathogen, poses a serious threat to world health due to the lack of effective treatments, calling for an immediate search for targeted and efficient treatments. In this study, we focused on compounds originating from marine fungi in order to identify possible inhibitory compounds against the Marburg virus (MBV) VP35-RNA binding domain (VP35-RBD) using a computational approach. We started with a virtual screening procedure using the Lipinski filter as a guide. Based on their docking scores, 42 potential candidates were found. Four of these compounds-CMNPD17596, CMNPD22144, CMNPD25994, and CMNPD17598-as well as myricetin, the control compound, were chosen for re-docking analysis. Re-docking revealed that these particular compounds had a higher affinity for MBV VP35-RBD in comparison to the control. Analyzing the chemical interactions revealed unique binding properties for every compound, identified by a range of Pi-cation interactions and hydrogen bond types. We were able to learn more about the dynamic behaviors and stability of the protein-ligand complexes through a 200-nanosecond molecular dynamics simulation, as demonstrated by the compounds' consistent RMSD and RMSF values. The multidimensional nature of the data was clarified by the application of principal component analysis, which suggested stable conformations in the complexes with little modification. Further insight into the energy profiles and stability states of these complexes was also obtained by an examination of the free energy landscape. Our findings underscore the effectiveness of computational strategies in identifying and analyzing potential inhibitors for MBV VP35-RBD, offering promising paths for further experimental investigations and possible therapeutic development against the MBV.


Asunto(s)
Enfermedad del Virus de Marburg , Animales , Motivos de Unión al ARN , Hongos , Enlace de Hidrógeno , Simulación de Dinámica Molecular
12.
J Fish Dis ; 47(7): e13950, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38555528

RESUMEN

Disease interactions between farmed and wild populations have been poorly documented for most aquaculture species, in part due to the complexities to study this. Here, we tested 567 farmed Atlantic salmon escapees, captured in a Norwegian river during 2014-2018, for five viral infections that are prevalent in global salmonid aquaculture. Over 90% of the escapees were infected with one or more viruses. Overall prevalences were: 75.7% for piscine orthoreovirus (PRV-1), 43.6% for salmonid alphavirus (SAV), 31.2% for piscine myocarditis virus (PMCV), 1.2% for infectious pancreatic necrosis virus (IPNV) and 0.4% for salmon anaemia virus (ISAV). A significantly higher prevalence of PMCV infection was observed in immature compared to mature individuals. The prevalence of both SAV and PMCV infections was higher in fish determined by fatty acid profiling to be 'recent' as opposed to 'early' escapees that had been in the wild for a longer period of time. This is the first study to establish a time-series of viral infection status of escapees entering a river with a native salmon population. Our results demonstrate that farmed escapees represent a continuous source of infectious agents which could potentially be transmitted to wild fish populations.


Asunto(s)
Acuicultura , Enfermedades de los Peces , Ríos , Salmo salar , Animales , Enfermedades de los Peces/virología , Enfermedades de los Peces/epidemiología , Noruega/epidemiología , Prevalencia , Alphavirus/aislamiento & purificación , Alphavirus/fisiología , Infecciones por Alphavirus/veterinaria , Infecciones por Alphavirus/epidemiología , Infecciones por Alphavirus/virología
13.
Artículo en Inglés | MEDLINE | ID: mdl-38977475

RESUMEN

PURPOSE: This study aimed to assess the efficacy and safety of ballon dilation of the eustachian tube (BDET) in adult population suffering from Eustachian tube dysfunction (ETD). METHODS: Following PRISMA criteria, a systematic review was conducted by searching PubMed, Cochrane, and Embase databases from January 2015 to March 2024. The primary outcomes included Eustachian Tube Score (ETS), tympanometry, and Valsalva maneuver. The quality of studies was assessed using the Quality in Prognostic Studies (QUIPS) instrument. RESULTS: Overall, 11 studies were incorporated into the systematic review: two RCTs, three prospective investigations, and six retrospective studies. The balloon dilation in all investigations was performed using either Spiggle & Theis or Acclarent catheters for balloon dilation. There was heterogeneity across studies examining the effect of BDET on persistent ETD in terms of patient selection, period of follow-up, administration of conservative or surgical therapies, and use of assessment methods. Overall, the treatment yielded alleviation of symptoms, which either exhibited stability over time or demonstrated further improvement after an average duration of follow-up. Moreover, the incidence of complications was categorized as low and resolving spontaneously. The majority of the studies exhibited a high risk of bias related to confounding variables, and consequently, the overall risk of bias across most studies was considered high. CONCLUSION: The findings suggest BDET holds promise for ETD treatment, reducing symptom severity with minimal complications. Nonetheless, there is a need for improved studies that adhere to established indications, methodologies, and outcomes to establish a more robust body of evidence.

14.
Artículo en Inglés | MEDLINE | ID: mdl-39001919

RESUMEN

PURPOSE: Olfactory dysfunction is increasingly common among COVID-19 patients, impacting their well-being. Reports have demonstrated decreased levels of cyclic adenosine monophosphate and cyclic guanosine monophosphate among patients with chronic olfactory dysfunction. A prospective randomized clinical trial was developed to demonstrate the efficacy of an oral forskolin regimen treatment, an adenylyl cyclase activator that raises intracellular levels of cyclic adenosine monophosphate, for the treatment of olfactory dysfunction following COVID-19, compared to placebo regimen. METHODS: The study enrolled 285 participants with persistent olfactory dysfunction post COVID-19 infection, randomly assigning them to receive either placebo capsules (n = 120) or oral forskolin capsules (n = 165). Follow-up was conducted to track progress, with 18 participants from the placebo group and 12 from the forskolin group lost during this period. Olfactory function was assessed using the "Sniffin' Sticks" test, measuring threshold, discrimination and identification scores before and after treatment. RESULTS: Subjects administered forskolin capsules demonstrated a significant enhancement in their composite TDI (threshold, discrimination and identification) score, suggesting a notable amelioration in olfactory functionality. Moreover, the discrimination and identification scores notably improved within the forskolin group. Conversely, no significant alterations were observed in the threshold scores. CONCLUSION: This study suggests that forskolin can contribute potentially to improve chronic olfactory dysfunction post COVID-19. TRIAL REGISTRATION: DFM-IRB00012367-23-10-001.

15.
Chem Biodivers ; 21(2): e202301815, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38152840

RESUMEN

Pistacia chinensis subsp. integerrima (J.L. Stewart) Rech. f. is a plant known for its therapeutic applications in traditional medicine, which are related to its antimicrobial, anticancer, antioxidant, anti-inflammatory, analgesic, antidiarrheal, and muscle relaxant properties. The galls of P. chinensis are rich in triterpenes and flavonoids, and we here report the extraction of pistagremic acid (1), apigenin (2) and sakuranetin (3) from this source. The isolated compounds were tested against Aspergillus flavus, Candida albicans, Candida glabrata, Fusarium solani, Microsporum canis and Trichoderma longibrachiatum. The results highlighted the antimicrobial activity of flavonoids 2 and 3, suggesting that this class of molecules may be responsible for the effect related to the traditional use. On the other hand, when the compounds and the extract were tested for their antiproliferative activity on a panel of 4 human cancer cell lines, the triterpene pistagremic acid (1) showed a higher potential, thus demonstrating a different bioactivity profile. Structure-based docking and molecular dynamics simulations were used to help the interpretation of experimental results. Taken together, the here reported findings pave the way for the rationalization of the use of P. chinensis extracts, highlighting the contributions of the different components of galls to the observed bioactivity.


Asunto(s)
Pistacia , Triterpenos , Humanos , Antifúngicos/farmacología , Triterpenos/farmacología , Flavonoides/farmacología , Extractos Vegetales
16.
Bioprocess Biosyst Eng ; 47(8): 1197-1211, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38512495

RESUMEN

In the current study, the bottlebrush [Callistemon viminalis (Sol. ex Gaertn.) G. Don] plant was selected for the green synthesis of silver (Ag) and gold (Au) nanoparticles and to evaluate its antibacterial and antifungal activities. Phytochemical screening of C. viminalis confirmed the presence of alkaloids, anthraquinones, saponins, tannins, betacyanins, phlobatanins, coumarins, terpenoids, steroids, glycosides, and proteins. To characterize the synthesized Ag and Au NPs, UV-Visible spectroscopy, FTIR spectroscopy for functional group identification, field emission scanning electron microscopy (FE-SEM) for particle size, and elemental analysis were performed using EDX. The UV-Visible absorption spectra of the green-synthesized Ag and Au nanoparticles were found to have a maximum absorption band at 420 nm for Ag NPs and 525 nm for Au NPs. FE-SEM analysis of the synthesized NPs revealed a circular shape with a size of 100 nm. Elemental analysis was performed for the synthesis of Ag and Au NPs, which confirmed the purity of the nanoparticles. The greenly synthesized Ag and Au NPs were also evaluated for their anti-bacterial and anti-fungal activities, which exhibited prominent inhibition activities against Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, Pseudomonas aeruginosa, Candida albicans, C. krusei, Aspergillus sp., and Trichoderma species. The highest zone of inhibition 15.5 ± 0.75 and 15 ± 0.85 mm was observed for Ag NPs against E. coli and P. aeruginosa. Similarly, Trichoderma sp. and Aspergillus sp. were inhibited by Ag NPs up to 13.5 ± 0.95 and 13 ± 0.70 mm. This work will open doors for the development of new antimicrobial agents using green chemistry.


Asunto(s)
Antiinfecciosos , Oro , Tecnología Química Verde , Nanopartículas del Metal , Extractos Vegetales , Plata , Nanopartículas del Metal/química , Plata/química , Plata/farmacología , Oro/química , Extractos Vegetales/química , Extractos Vegetales/farmacología , Antiinfecciosos/farmacología , Antiinfecciosos/química , Pruebas de Sensibilidad Microbiana , Bacterias/efectos de los fármacos , Bacterias/crecimiento & desarrollo , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/síntesis química , Hongos/efectos de los fármacos , Antifúngicos/farmacología , Antifúngicos/química
17.
Artículo en Inglés | MEDLINE | ID: mdl-38330369

RESUMEN

OBJECTIVES: Prior research has found that to keep their family safe, some undocumented immigrants in the United States engage in "Know Your Rights" family communication-talking to family about their rights, should they be approached by the police or U.S. Immigration and Customs Enforcement (ICE). Although "Know Your Rights" family communication plays a functional role, this study used resilience theory to examine when such communication can be a promotive factor and a risk factor. METHOD: To test the hypotheses, we utilized three waves of survey data, with 1-month intervals, from 366 U.S. undocumented college students primarily from Latin America (76% cisgender women; Mage = 22 years, SD = 4.26). Path analysis was employed. RESULTS: We found that "Know Your Rights" family communication at Wave 1 was positively associated with: (a) greater knowledge of how to respond if approached by police or ICE and (b) greater knowledge of how to help their family if detained 1 month later (Wave 2). Through both types of knowledge taken together, "Know Your Rights" family communication was indirectly associated with higher levels of felt safety 2 months later (Wave 3). Nevertheless, through knowledge of how to help family, "Know Your Rights" family communication was also indirectly associated with higher levels of anxiety 2 months later (Wave 3). CONCLUSION: Given the distribution of "Know Your Rights" information on college campuses, our findings can provide evidence for the utility of such messages, while also potentially identifying when it is associated with higher levels of anxiety. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

18.
Aesthetic Plast Surg ; 2024 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-38992251

RESUMEN

BACKGROUND: Breast augmentation using silicone implants is common, with over 300,000 annual US surgeries. It was initially approved in 1962, there were safety concerns with the use of silicone implants, leading to a 1992-2006 FDA moratorium. Recently, Breast Implant Illness (BII) was described as a cluster of symptoms associated with silicone implants, with a lack of diagnostic criteria, which increased the likelihood of implant removal and a variety of treatment options. This comprehensive review aims to shed light on the extent, symptoms, management, and outcomes of BII. METHODS: Multiple electronic databases were systematically searched in May 2023 for studies on Breast Implant Illness utilizing terms related to BII and its symptoms, diagnosis, and treatment. Out of 1204 studies, 20 met the inclusion criteria and were included in the systematic review. The Newcastle-Ottawa Scale for the included cohort prospective and retrospective studies, and the tool for evaluating the methodological quality of case reports and case series were utilized during quality assessment. RESULTS: There were 20 papers on Breast Implant Illness published between 1995 and 2022, including a peak of papers published in 2020 and 2022. The majority of the studies came from the USA, with a variety of research methods, including case reports. Reports of arthralgia and fatigue were common findings. These symptoms were frequently alleviated by surgical procedures such as en bloc explantation and capsulectomy, highlighting the intricacy of the problem and the need for individualized treatment plans. CONCLUSION: The review underscores the critical need for further research into BII, advocating for a multidisciplinary strategy that prioritizes patient safety, informed decision-making, and comprehensive care. As the medical community progresses in understanding and managing BII, emphasizing evidence-based practices and patient-provider communication will be essential in addressing this complex condition effectively. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

19.
J Reconstr Microsurg ; 2024 Jul 22.
Artículo en Inglés | MEDLINE | ID: mdl-39038463

RESUMEN

BACKGROUND: Breast cancer is one of the most common types of cancer, with around 2.3 million cases diagnosed in 2020. One in five cancer patients develops chronic lymphedema caused by multifactorial triggers and treatment-related factors. This can lead to swelling, skin infections, and limb dysfunction, negatively affecting the patient's quality of life. This retrospective cohort study aimed to determine the associations between demographic and breast cancer characteristics and postoperative cellulitis in breast cancer survivors who underwent lymphovenous bypass surgery (LVB) at Mayo Clinic, Florida. METHODS: We performed a retrospective chart review. Data were collected retrospectively from 2016 to 2022. Sixty adult breast cancer survivors who underwent LVB were included in the final analysis based on specific inclusion and exclusion criteria. Patients were excluded if they did not meet the inclusion criteria or had incomplete follow-up data. Demographic and surgical data were extracted, including body mass index (BMI), type of anastomosis, number of anastomoses, and preoperative cellulitis status. Lymphedema measurements were performed using tape measurements. Fisher's exact test was used to determine statistically significant associations between variables and postoperative cellulitis. RESULTS: Postoperative cellulitis was more common in patients aged 60 to 69 years (43.2%), whites (75.0%), overweight or obese (90.9%), with one to four anastomoses (81.8%), and nonsmokers (79.5%). The mean International Society of Lymphology (ISL) criteria for both postoperative cellulitis and no postoperative cellulitis was 1.93. Statistically significant associations with postoperative cellulitis were found for the number of anastomoses (p = 0.021), smoking status (p = 0.049), preoperative cellulitis (p = 0.04), and the length of years with lymphedema diagnosis variable (p = 0.004). CONCLUSION: Our results suggest that a greater number of anastomoses, smoking, preoperative cellulitis, and years with lymphedema are significantly associated with an increased risk of postoperative cellulitis. Awareness of these risk factors is crucial for monitoring and early treatment of infections following surgery.

20.
J Sci Food Agric ; 2024 Jul 12.
Artículo en Inglés | MEDLINE | ID: mdl-38993070

RESUMEN

BACKGROUND: Mercuric chloride (HgCl2) is poisonous to humans and animals and typically damages the nervous system and other organs. Mercuric chloride exposition disclosed to initiation of oxidative stress pathway can result in a defect in male fertility and testis tissue. Synthesized selenium nanoparticles (SeNPs) were characterized with a diameter range minimal than 100 nm, having the effective sets of the biological matter. The present study aimed to evaluate the effect of biosynthesized SeNPs, prepared by leek extract on Wistar rats' testicles and brain. METHODS: Thirty-five Wistar male rats (120-150 g) were randomly split into five groups (n = 7), orally ingested with leek aqueous extract loaded on SeNPs, and then the animals were administered with mercury II chloride (HgCl2) to induce testis injury and damage the nervous system. RESULTS: The used dose of mercuric chloride led to oxidative stress damage in the testis of the rats which was evidenced by a decrease in testosterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH) and proliferating cell nuclear antigen (PCNA) levels, and an increase in nuclear factor-kappa B (NF-κB) and caspase-3. Also, HgCl2 decreased the levels of dopamine (DA), serotonin (5-HT), norepinephrine (NE) and brain-derived neurotrophic factor (BDNF) in the brains of rats. In addition, A decrease was observed in the levels of antioxidant markers, B-cell lymphoma-2 (Bcl-2), as well as an increase in malondialdehyde (MDA), nitric oxide (NO), NF-κB, tumor necrosis factor (TNF)-α, interleukin (IL)-1ß and Bax in both testes and brains. Pre-treatment with leek extract loaded on SeNPs significantly ameliorated testosterone, LH, FSH, PCNA and caspase-3 levels in the testis and DA, 5-HT, NE and BDNF in brains. Although the contents of MDA, NO, TNF-α, IL-1ß, NF-κB and Bax decreased significantly in both. glutathione, glutathione peroxidase, glutathione reductase, catalase, superoxide dismutase and Bcl-2 levels were significantly improved in both organs. CONCLUSION: Our findings suggest that treatment with aqueous leek extract loaded on SeNPs may offer promising prospects for the advancement of anti-inflammation activity against testis injury and also have a very key role in neurobehavioral alterations as a result of mercury toxicity. © 2024 Society of Chemical Industry.

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