Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 942
Filtrar
1.
J Steroid Biochem Mol Biol ; : 106597, 2024 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-39127416

RESUMO

This research aimed to develop novel selective secosteroids that are highly active against hormone-dependent breast cancer. A simple and convenient approach to N'-acylated 13,17-secoestra-1,3,5(10)-trien-17-oic acid hydrazides was disclosed and these novel types of secosteroids were screened for cytotoxicity against the hormone-dependent human breast cancer cell line MCF7. Most secosteroid N'-benzoyl hydrazides have demonstrated high cytotoxicity against MCF7 cells with IC50 values below 5µM, which are superior to that of the reference drug cisplatin. Hit compounds 2c, 2e and 2i were characterized by high cytotoxicity (IC50 = 1.6-1.9µM) and very good selectivity towards MCF7 breast cancer cells. The lead secosteroids 2c, 2e and 2i also exhibit antiestrogenic effects and alter the expression of cell cycle regulating proteins. The effect of selected compounds on PARP (poly(ADP-ribose) polymerase) and Bcl-2 (B-cell CLL/lymphoma 2) indicates their proapoptotic potential. The synthesized secosteroids may be considered as new promising anti-breast cancer agents targeting ERα and apoptosis pathways.

2.
ACS Nano ; 2024 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-39107108

RESUMO

Chiral molecules, a cornerstone of chemical sciences with applications ranging from pharmaceuticals to molecular electronics, come in mirror-image pairs called enantiomers. However, their synthesis often requires complex control of their molecular geometry. We propose a strategy called "electromagnetic enantiomers" for inducing chirality in molecules located within engineered nanocavities using light, eliminating the need for intricate molecular design. This approach works by exploiting the strong coupling between a nonchiral molecule and a chiral mode within a nanocavity. We provide evidence for this strong coupling through angular emission patterns verified by numerical simulations and with complementary evidence provided by luminescence lifetime measurements. In simpler terms, our hypothesis suggests that chiral properties can be conveyed on to a molecule with a suitable chromophore by placing it within a specially designed chiral nanocavity that is significantly larger (hundreds of nanometers) than the molecule itself. To demonstrate this concept, we showcase an application in display technology, achieving efficient emission of circularly polarized light from a nonchiral molecule. The electromagnetic enantiomer concept offers a simpler approach to chiral control, potentially opening doors for asymmetric synthesis.

3.
Neurosurg Rev ; 47(1): 332, 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-39009745

RESUMO

One of the most common complications of lumbar fusions is cage subsidence, which leads to collapse of disc height and reappearance of the presenting symptomology. However, definitions of cage subsidence are inconsistent, leading to a variety of subsidence calculation methodologies and thresholds. To review previously published literature on cage subsidence in order to present the most common methods for calculating and defining subsidence in the anterior lumbar interbody fusion (ALIF), oblique lateral interbody fusion (OLIF), and lateral lumbar interbody fusion (LLIF) approaches. A search was completed in PubMed and Embase with inclusion criteria focused on identifying any study that provided descriptions of the method, imaging modality, or subsidence threshold used to calculate the presence of cage subsidence. A total of 69 articles were included in the final analysis, of which 18 (26.1%) reported on the ALIF approach, 22 (31.9%) on the OLIF approach, and 31 (44.9%) on the LLIF approach, 2 of which reported on more than one approach. ALIF articles most commonly calculated the loss of disc height over time with a subsidence threshold of > 2 mm. Most OLIF articles calculated the total amount of cage migration into the vertebral bodies, with a threshold of > 2 mm. LLIF was the only approach in which most articles applied the same method for calculation, namely, a grading scale for classifying the loss of disc height over time. We recommend future articles adhere to the most common methodologies presented here to ensure accuracy and generalizability in reporting cage subsidence.


Assuntos
Vértebras Lombares , Fusão Vertebral , Humanos , Fusão Vertebral/métodos , Vértebras Lombares/cirurgia
4.
Curr Issues Mol Biol ; 46(7): 6580-6599, 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-39057034

RESUMO

Insulin is a promising neuroprotector. To better understand the mechanism of insulin action, it was important to show its ability to diminish autophagic neuronal death in animals with brain ischemic and reperfusion injury. In forebrain ischemia and reperfusion, the number of live neurons in the hippocampal CA1 region and frontal cortex of rats decreased to a large extent. Intracerebroventricular administration of the autophagy and apoptosis inhibitors to ischemic rats significantly increased the number of live neurons and showed that the main part of neurons died from autophagy and apoptosis. Intranasal administration of 0.5 IU of insulin per rat (before ischemia and daily during reperfusion) increased the number of live neurons in the hippocampal CA1 region and frontal brain cortex. In addition, insulin significantly diminished the level of autophagic marker LC3B-II in these forebrain regions, which markedly increased during ischemia and reperfusion. Our studies demonstrated for the first time the ability of insulin to decrease autophagic neuronal death, caused by brain ischemia and reperfusion. Insulin administered intranasally activated the Akt-kinase (activating the mTORC1 complex, which inhibits autophagy) and inhibited the AMP-activated protein kinase (which activates autophagy) in the hippocampus and frontal cortex of rats with brain ischemia and reperfusion.

5.
Langmuir ; 40(29): 15023-15030, 2024 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-39007426

RESUMO

Since delocalization of electronic states is a prerequisite for exerting unique electron transport properties, early actinides (An) with highly delocalized 5f/6d orbitals are natural candidates. However, given the experimental difficulties of such radioactive compounds and the complex relativistic effects in theoretical studies, understanding the electronic structure and bonding of actinides is underdeveloped on the periodic table. A further challenge is the very complicated electronic structures encountered in the confinement of actinides, as vividly illustrated by the weakly radioactive Th(Thorium)-encapsulated metal chalcogenide clusters, Th@Co6Te8L6 (L = PH3, PMe3, PEt3). Here we report the electronic structure and the electron transport properties of the Th@Co6Te8L6 clusters and compare them with those of the hollow Co6Te8L6 clusters using the nonequilibrium Green's function combined with relativistic density functional theory (NEGF-DFT). We found that the equilibrium conductance in Th@Co6Te8(PH3)6 (0.76 G0) has been greatly improved over that in Co6Te8(PH3)6 (0.03 G0), which has also been verified under an applied different bias voltage. The covalent bonding character between 6d (Th) and 3d (Co) atomic orbitals resulting from steric confinement is the source of the performance enhancement and a most important factor governing the accessibility of such 5f/6d orbitals. The results are of significance to the rapidly developing field of molecular nanoelectronics.

6.
Chem Commun (Camb) ; 60(62): 8099-8102, 2024 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-38993133

RESUMO

Electrochemical hydrocarboxylation of enol acetates with CO2 is developed. The disclosed process provides ß-acetoxycarboxylic acids in 25-66% yields, in contrast to the electrolysis of ketones, silyl enol ethers and vinyl tosylates with CO2, which leads mainly to alcohols.

7.
Nat Commun ; 15(1): 4846, 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38844481

RESUMO

The collective light-matter interaction of chiral supramolecular aggregates or molecular ensembles with confined light fields remains a mystery beyond the current theoretical description. Here, we programmably and accurately build models of chiral plasmonic complexes, aiming to uncover the entangled effects of excitonic correlations, intra- and intermolecular charge transfer, and localized surface plasmon resonances. The intricate interplay of multiple chirality origins has proven to be strongly dependent on the site-specificity of chiral molecules on plasmonic nanoparticle surfaces spanning the nanometer to sub-nanometer scale. This dependence is manifested as a distinct circular dichroism response that varies in spectral asymmetry/splitting, signal intensity, and internal ratio of intensity. The inhomogeneity of the surface-localized plasmonic field is revealed to affect excitonic and charge-transfer mixed intermolecular couplings, which are inherent to chirality generation and amplification. Our findings contribute to the development of hybrid classical-quantum theoretical frameworks and the harnessing of spin-charge transport for emergent applications.

8.
J Acoust Soc Am ; 155(6): 3702-3714, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38847593

RESUMO

This study presents the results of three-dimensional (3D) propagation modeling of noise from a transiting bulk carrier vessel. In the simulated scenario, the surface vessel is moving past a bottom-mounted hydrophone system. Sound levels are estimated in decidecade frequency bands as the vessel transits past the hydrophone, and the simulation results are compared against real measured data. The modelling is performed using the program AMPLE, which is based on the wide-angle mode parabolic equation theory for simulating 3D broadband acoustic fields in a shallow sea. The model is used to investigate the effect of 3D phenomena on the surface vessel sound propagation. It is shown that an inaccuracy of the noise simulation associated with the use of a two-dimensional model can be as high as 7-10 dB for certain distances and for frequency bands over which a major part of the source energy is distributed. An approach to the selection of data-adjusted media parameters based on the Bayesian optimization is suggested, and the influence of the various parameters on the sound levels is discussed.

9.
Clin Neurol Neurosurg ; 243: 108375, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38901378

RESUMO

OBJECTIVE: Rural location of a patient's primary residence has been associated with worse clinical and surgical outcomes due to limited resource availability in these parts of the US. However, there is a paucity of literature investigating the effect that a rural hospital location may have on these outcomes specific to lumbar spine fusions. METHODS: Using the National Inpatient Sample (NIS) database, we identified all patients who underwent primary lumbar spinal fusion in the years between 2009 and 2020. Patients were separated according to whether the operative hospital was considered rural or urban. Univariable and multivariable regression models were used for data analysis. RESULTS: Of 2,863,816 patients identified, 120,298 (4.2 %) had their operation at a rural hospital, with the remaining in an urban hospital. Patients in the urban cohort were younger (P < .001), more likely to have private insurance (39.81 % vs 31.95 %, P < .001), and fewer of them were in the first (22.52 % vs 43.00 %, P < .001) and second (25.96 % vs 38.90 %, P < .001) quartiles of median household income compared to the rural cohort. The urban cohort had significantly increased rates of respiratory (4.49 % vs 3.37 %), urinary (5.25 % vs 4.15 %), infectious (0.49 % vs 0.32 %), venous thrombotic (0.57 % vs 0.24 %, P < .001), and neurological (0.79 % vs 0.36 %) (all P < .001) perioperative complications. On multivariable analysis, the urban cohort had significantly increased odds of the same perioperative complications: respiratory (odds ratio[OR] = 1.48; 95 % confidence interval [CI], 1.26-1.74), urinary (OR = 1.34; 95 %CI, 1.20-1.50), infection (OR = 1.63; 95 %CI, 1.23-2.17), venous thrombotic (OR = 1.79; 95 %CI, 1.32-2.41), neurological injury (OR = 1.92; 95 %CI, 1.46-2.53), and localized infection (OR = 1.65; 95 %CI, 1.25-2.17) (all P < .001). CONCLUSIONS: Patients undergoing lumbar fusions experience significantly different outcomes based on the rural or urban location of the operative hospital.


Assuntos
Bases de Dados Factuais , Hospitais Rurais , Hospitais Urbanos , Vértebras Lombares , Complicações Pós-Operatórias , Fusão Vertebral , Humanos , Fusão Vertebral/efeitos adversos , Masculino , Hospitais Rurais/estatística & dados numéricos , Feminino , Pessoa de Meia-Idade , Idoso , Vértebras Lombares/cirurgia , Complicações Pós-Operatórias/epidemiologia , Estados Unidos/epidemiologia , Adulto , Resultado do Tratamento , Pacientes Internados , Demografia
10.
Neurosurgery ; 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38934614

RESUMO

BACKGROUND AND OBJECTIVES: In recent years, there has been an outpouring of scoring systems that were built to predict outcomes after various surgical procedures; however, research validating these studies in spinal surgery is quite limited. In this study, we evaluated the predictability of the American College of Surgeons National Surgical Quality Improvement Program Surgical Risk Calculator (ACS NSQIP SRC) for various postoperative outcomes after spinal deformity surgery. METHODS: A retrospective chart review was conducted to identify patients who underwent spinal deformity surgery at our hospital between January 1, 2014, and December 31, 2022. Demographic and clinical data necessary to use the ACS NSQIP SRC and postoperative outcomes were collected for these patients. Predictability was analyzed using the area under the curve (AUC) of receiver operating characteristic curves and Brier scores. RESULTS: Among the 159 study patients, the mean age was 64.5 ± 9.5 years, mean body mass index was 31.9 ± 6.6, and 95 (59.7%) patients were women. The outcome most accurately predicted by the ACS NSQIP SRC was postoperative pneumonia (observed = 5.0% vs predicted = 3.2%, AUC = 0.75, Brier score = 0.05), but its predictability still fell below the acceptable threshold. Other outcomes that were underpredicted by the ACS NSQIP SRC were readmission within 30 days (observed = 13.8% vs predicted = 9.0%, AUC = 0.63, Brier score = 0.12), rate of discharge to nursing home or rehabilitation facilities (observed = 56.0% vs predicted = 46.6%, AUC = 0.59, Brier = 0.26), reoperation (observed 11.9% vs predicted 5.4%, AUC = 0.60, Brier = 0.11), surgical site infection (observed 9.4% vs predicted 3.5%, AUC = 0.61, Brier = 0.05), and any complication (observed 33.3% vs 19%, AUC = 0.65, Brier = 0.23). Predicted and observed length of stay were not significantly associated (ß = 0.132, P = .47). CONCLUSION: The ACS NSQIP SRC is a poor predictor of outcomes after spinal deformity surgery.

11.
J Psychoactive Drugs ; : 1-11, 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38695483

RESUMO

Black, Indigenous, and People of Color (BIPOC), and other minoritized populations are insufficiently represented in research on therapeutic psychedelics. This research was a phenomenological qualitative exploration of a culturally diverse (Hispanic, African American, Asian, Native American, biracial, or LGBTQIA+) and low-income sample of 15 individuals receiving ketamine-assisted psychotherapy (KAP) at a sliding-scale fee community clinic. Participants were interviewed after a ketamine session, after a ketamine integration session, and one month later. The interviews inquired about mental and emotional state prior to treatment and the treatment context (traditionally called set and setting), preparation for treatment, experiences during the ketamine and integration sessions, barriers to treatment, perceived stigma if any, reflections on KAPs' impact, and relevance of culture to the treatment. The current analysis, which focuses on participant comments related to diversity, equity, and inclusion that are uniquely relevant to this sample and the research goals, yielded four major themes: Insufficient Financial Resources, Race, Ethnicity, and LGBTQIA+, Stigma, and Culture and Ritual. Themes and subthemes are presented accompanied by representative quotes. Results demonstrate the high salience of culture in the KAP experience and the need to incorporate issues of race, culture, stigma, ritual, and socioeconomic status into treatment planning and outcome research.

12.
World Neurosurg ; 187: 202-210.e4, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38750883

RESUMO

OBJECTIVE: Aneurysmal subarachnoid hemorrhage (aSAH) is associated with high mortality rates. There is a significant gap in the literature describing global disparities in demographics, management, and outcomes among patients with aSAH. We aimed to conduct a systematic review and meta-analysis to assess global disparities in aSAH presentation and management. METHODS: PubMed and Embase databases were queried from earliest records to November 2022 for aSAH literature. Presentation, demographics, comorbidities, treatment methods, and outcomes data were collected. Articles that did not report aSAH-specific patient management and outcomes were excluded. Pooled weighted prevalence rates were calculated. Random effects model rates were reported. RESULTS: After screening, 33 articles representing 10,553 patients were included. The prevalence of Fisher grade 3 or 4 aSAH in high- and lower-income countries (HIC and LIC), respectively, was 79.8% (P < 0.01) and 84.1 (P < 0.01). Prevalence of male aSAH patients in HIC and LIC, respectively, was 35.8% (P < 0.01) and 45.0% (P < 0.01). Prevalence of treatment in aSAH patients was 99.5% (P < 0.01) and 99.4% (P = 0.16) in HIC and LIC, respectively. In HIC, 35% (P < 0.01) of aneurysms in aSAH patients were treated with coiling. No LIC reported coiling for aSAH treatment; LIC only reported rates of surgical clipping, with a total prevalence of 92.4% (P < 0.01) versus 65.6% (P < 0.01) in HIC. CONCLUSION: In this analysis, we found similar rates of high-grade SAH hemorrhages in HIC and LIC but a lack of endovascular coil embolization treatments reported in LIC. Additional research and discussion are needed to identify reasons for treatment disparities and intervenable societal factors to improve aSAH outcomes worldwide.


Assuntos
Disparidades em Assistência à Saúde , Hemorragia Subaracnóidea , Humanos , Hemorragia Subaracnóidea/terapia , Hemorragia Subaracnóidea/epidemiologia , Procedimentos Endovasculares , Aneurisma Intracraniano/terapia , Aneurisma Intracraniano/epidemiologia , Saúde Global , Embolização Terapêutica , Procedimentos Neurocirúrgicos , Prevalência
13.
Proc Biol Sci ; 291(2023): 20240537, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38747705

RESUMO

The noasaurid ceratosaur Kiyacursor longipes gen. et sp. nov. is described based on a fragmentary skeleton including cervical vertebra, pectoral girdle, humerus and hind limbs from the Lower Cretaceous (Aptian) Ilek Formation at Shestakovo 1 locality in Western Siberia, Russia. This is the first ceratosaur from the Early Cretaceous of Asia, extending the stratigraphic range of Ceratosauria by 40 Myr on that continent. Kiyacursor shares unique hind limb proportions with Elaphrosaurus and Limusaurus, suggesting improved cursorial ability. These taxa show an ostrich-like specialization of the pes, with a large third metatarsal and greatly reduced second metatarsal. By contrast, all other fast running non-avian theropod dinosaurs have an arctometatarsalian pes, with the third metatarsal strongly reduced proximally. The new taxon lived in the Early Cretaceous ecosystem containing a number of other Jurassic relics, such as stem salamanders, protosuchian and shartegosuchid crocodyliforms, tritylodontid synapsids and docodontan mammaliaforms.


Assuntos
Dinossauros , Fósseis , Animais , Dinossauros/anatomia & histologia , Dinossauros/classificação , Fósseis/anatomia & histologia , Sibéria , Evolução Biológica
14.
Nano Lett ; 24(20): 6069-6077, 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38739779

RESUMO

Nanoparticles (NPs) can be conjugated with diverse biomolecules and employed in biosensing to detect target analytes in biological samples. This proven concept was primarily used during the COVID-19 pandemic with gold-NP-based lateral flow assays (LFAs). Considering the gold price and its worldwide depletion, here we show that novel plasmonic NPs based on inexpensive metals, titanium nitride (TiN) and copper covered with a gold shell (Cu@Au), perform comparable to or even better than gold nanoparticles. After conjugation, these novel nanoparticles provided high figures of merit for LFA testing, such as high signals and specificity and robust naked-eye signal recognition. Since the main cost of Au NPs in commercial testing kits is the colloidal synthesis, our development with the Cu@Au and the laser-ablation-fabricated TiN NPs is exciting, offering potentially inexpensive plasmonic nanomaterials for various bioapplications. Moreover, our machine learning study showed that biodetection with TiN is more accurate than that with Au.


Assuntos
Cobre , Ouro , Nanopartículas Metálicas , Titânio , Nanopartículas Metálicas/química , Titânio/química , Ouro/química , Cobre/química , Técnicas Biossensoriais/métodos , Técnicas Biossensoriais/economia , Humanos , COVID-19/virologia , COVID-19/diagnóstico , Coloide de Ouro/química , SARS-CoV-2/isolamento & purificação
15.
Int J Parasitol ; 54(8-9): 391-400, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38663543

RESUMO

Nearly all aerobic organisms are equipped with catalases, powerful enzymes scavenging hydrogen peroxide and facilitating defense against harmful reactive oxygen species. In trypanosomatids, this enzyme was not present in the common ancestor, yet it had been independently acquired by different lineages of monoxenous trypanosomatids from different bacteria at least three times. This observation posited an obvious question: why was catalase so "sought after" if many trypanosomatid groups do just fine without it? In this work, we analyzed subcellular localization and function of catalase in Leptomonas seymouri. We demonstrated that this enzyme is present in the cytoplasm and a subset of glycosomes, and that its cytoplasmic retention is H2O2-dependent. The ablation of catalase in this parasite is not detrimental in vivo, while its overexpression resulted in a substantially higher parasite load in the experimental infection of Dysdercus peruvianus. We propose that the capacity of studied flagellates to modulate the catalase activity in the midgut of its insect host facilitates their development and protects them from oxidative damage at elevated temperatures.


Assuntos
Catalase , Peróxido de Hidrogênio , Trypanosomatina , Catalase/metabolismo , Animais , Trypanosomatina/enzimologia , Trypanosomatina/genética , Peróxido de Hidrogênio/metabolismo , Citoplasma , Microcorpos/metabolismo
16.
J Org Chem ; 89(8): 5699-5714, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38564503

RESUMO

Four heteroatoms dance in the cascade of four pericyclic reactions initiated by ozonolysis of C═N bonds. Switching from imines to semicarbazones introduces the fifth heteroatom that slows this dance, delays reaching the thermodynamically favorable escape path, and allows efficient interception of carbonyl oxides (Criegee intermediates, CIs) by an external nucleophile. The new three-component reaction of alcohols, ozone, and oximes/semicarbazones greatly facilitates synthetic access to monoperoxyacetals (alkoxyhydroperoxides).

17.
Eur J Psychotraumatol ; 15(1): 2330305, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38590124

RESUMO

Military personnel and veterans are at heightened risk for exposure to traumatic events and posttraumatic stress disorder (PTSD), as well as intimate relationship problems associated with PTSD.The purpose of this study was to evaluate the relative efficacy of CBCT and PE in improving intimate relationship functioning in active duty military personnel or veterans and their intimate partners; both conditions were hypothesized to significantly improve PTSD. Method: In this study, 32 military service members or veterans with PTSD and their intimate partners were randomized to receive either Cognitive-Behavioral Conjoint Therapy for PTSD (n = 15; CBCT; [Monson, C. M., & Fredman, S. J. (2012). Cognitive-behavioral conjoint therapy for posttraumatic stress disorder: Harnessing the healing power of relationships. Guilford]), a trauma-focused couple therapy, or Prolonged Exposure (n = 17; PE; [Foa, E. B., Hembree, E. A., Dancu, C. V., Peterson, A. L., Cigrang, J. A., & Riggs, D. S. (2008). Prolonged exposure treatment for combat-related stress disorders - provider's treatment manual [unpublished]. Department of Psychiatry, University of Pennsylvania]), a front-line evidence-based individual treatment for PTSD.There were significant challenges with recruitment and a significant difference in dropout from treatment for the two therapies (65% for PE; 27% for CBCT). Treatment dropout was differentially related to pre-treatment relationship functioning; those with below average relationship functioning had higher dropout in PE compared with CBCT, whereas those with above average relationship functioning did not show differential dropout. In general, CBCT led to relational improvements, but this was not consistently found in PE. Clinician- and self-reported PTSD symptoms improved with both treatments.This study is the first to test a couple or family therapy against a well-established, front-line recommended treatment for PTSD, with expected superiority of CBCT over PE on relationship outcomes. Lessons learned in trial design, including considerations of equipoise, and the effects of differential dropout on trial analyses are discussed. This trial provides further support for the efficacy of CBCT in the treatment of PTSD and enhancement of intimate relationships.


Differential dropout from trial of couple versus individual therapy for PTSD.General pattern of improvements in relationship outcomes in couple therapy for PTSD.PTSD symptoms improved in the individual and couple therapy for PTSD.Lessons learned in trial design, including considerations of equipoise, and the effects of differential dropout by condition on trial analyses are discussed.


Assuntos
Militares , Transtornos de Estresse Pós-Traumáticos , Veteranos , Humanos , Transtornos de Estresse Pós-Traumáticos/terapia , Transtornos de Estresse Pós-Traumáticos/diagnóstico , Resultado do Tratamento , Cognição
18.
Int J Mol Sci ; 25(7)2024 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-38612902

RESUMO

Many tumors have well-defined vulnerabilities, thus potentially allowing highly specific and effective treatment. There is a spectrum of actionable genetic alterations which are shared across various tumor types and, therefore, can be targeted by a given drug irrespective of tumor histology. Several agnostic drug-target matches have already been approved for clinical use, e.g., immune therapy for tumors with microsatellite instability (MSI) and/or high tumor mutation burden (TMB), NTRK1-3 and RET inhibitors for cancers carrying rearrangements in these kinases, and dabrafenib plus trametinib for BRAF V600E mutated malignancies. Multiple lines of evidence suggest that this histology-independent approach is also reasonable for tumors carrying ALK and ROS1 translocations, biallelic BRCA1/2 inactivation and/or homologous recombination deficiency (HRD), strong HER2 amplification/overexpression coupled with the absence of other MAPK pathway-activating mutations, etc. On the other hand, some well-known targets are not agnostic: for example, PD-L1 expression is predictive for the efficacy of PD-L1/PD1 inhibitors only in some but not all cancer types. Unfortunately, the individual probability of finding a druggable target in a given tumor is relatively low, even with the use of comprehensive next-generation sequencing (NGS) assays. Nevertheless, the rapidly growing utilization of NGS will significantly increase the number of patients with highly unusual or exceptionally rare tumor-target combinations. Clinical trials may provide only a framework for treatment attitudes, while the decisions for individual patients usually require case-by-case consideration of the probability of deriving benefit from agnostic versus standard therapy, drug availability, associated costs, and other circumstances. The existing format of data dissemination may not be optimal for agnostic cancer medicine, as conventional scientific journals are understandably biased towards the publication of positive findings and usually discourage the submission of case reports. Despite all the limitations and concerns, histology-independent drug-target matching is certainly feasible and, therefore, will be increasingly utilized in the future.


Assuntos
Antineoplásicos , Neoplasias , Humanos , Antígeno B7-H1 , Proteína BRCA1 , Proteínas Tirosina Quinases , Proteína BRCA2 , Proteínas Proto-Oncogênicas , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Neoplasias/tratamento farmacológico , Neoplasias/genética
19.
World Neurosurg ; 187: e174-e180, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38636629

RESUMO

OBJECTIVE: Smoking tobacco cigarettes negatively impacts bone healing after spinal fusion. Smoking history is often assessed based on current smoker and nonsmoker status. However, in current research, smoking history has not been quantified in terms of pack years to estimate lifetime exposure and assess its effects. Our goal was to investigate the influence of smoking history, quantified in pack years, on bony fusion after anterior cervical discectomy and fusion (ACDF). METHODS: A retrospective chart review of consecutive patients who underwent ACDF for cervical disc degeneration between September 21, 2017 and October 17, 2018 was conducted. Patient demographics, procedural variables, and postoperative outcomes were analyzed. Multivariate logistic regression analysis was performed to identify predictive factors for bony fusion following ACDF. Receiver operating characteristic curve analysis was used to determine the optimal discrimination threshold for smoking history pack years in association with nonfusion. RESULTS: Among 97 patients identified, 90 (93%) demonstrated bony fusion on postoperative imaging. Mean number of smoking history pack years was 6.1 ± 13 for the fusion group and 16 ± 21 for the nonfusion group. Multivariate logistic regression analysis suggested that increased pack years of tobacco cigarette smoking was a significant predictor of nonfusion (95% confidence interval, [1.0,1.1], P = 0.045). The receiver operating characteristic curve analysis revealed that 6.1 pack years best stratified the risk for nonfusion (area under the curve, 0.8). CONCLUSIONS: Patients with a history of tobacco cigarette smoking ≥6.1 pack years may have an increased risk of nonfusion after ACDF.


Assuntos
Vértebras Cervicais , Fumar Cigarros , Discotomia , Degeneração do Disco Intervertebral , Fusão Vertebral , Humanos , Fusão Vertebral/efeitos adversos , Masculino , Feminino , Discotomia/efeitos adversos , Pessoa de Meia-Idade , Vértebras Cervicais/cirurgia , Estudos Retrospectivos , Fumar Cigarros/epidemiologia , Degeneração do Disco Intervertebral/cirurgia , Degeneração do Disco Intervertebral/epidemiologia , Degeneração do Disco Intervertebral/diagnóstico por imagem , Adulto , Idoso
20.
Arch Microbiol ; 206(4): 165, 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38485793

RESUMO

This article reports the results of quantitative intra- and intergeneric taxonomic relationships among Micrococcaceae strains and a novel endophytic bacterium (SG) isolated from a suspension culture of Arabidopsis thaliana (L.) Heynh in our laboratory. The known strain Rothia sp. ND6WE1A was used as a reference one for SG. Whole-genome sequencing and phylogenetic analysis were based on the 16S rRNA test. Quantitative analysis for the nucleotide identity (ANI) and calculation of evolutionary distances were based on the identified amino acids (AAI) test indicating the generic assignment of the reference strain within and between the identified monophyletic groups of Micrococcaceae. The amino acid data structure of Rothia sp. ND6WE1A was compared against the UniProt database (250 million records) of close lineage of Micrococcaceae, including other Rothia spp. These data presented unique and evolutionary amino acid alignments, eventually expected in the new SG isolate as well. The metagenomic entries of the respective genome and proteome, characterized at the genus and species levels, could be considered for evolutionary taxonomic reclassification of the isolated and the reference strain (SG + Rothia sp. ND6WE1A). Therefore, our results warrant further investigations on the isolated SG strain.


Assuntos
Micrococcaceae , Micrococcaceae/genética , Filogenia , Ácidos Graxos/análise , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , DNA Bacteriano/genética , Composição de Bases , Aminoácidos/metabolismo , Técnicas de Tipagem Bacteriana , Hibridização de Ácido Nucleico
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA