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1.
J Intensive Care Med ; : 8850666241246748, 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38602149

RESUMO

Malnutrition in adult intensive care unit patients is associated with poor clinical outcomes. Providing adequate nutritional support to the critically ill adult should be an important goal for the intensivist. This narrative review aims to delineate the role of parenteral nutrition (PN) in meeting nutritional goals. We examined the data regarding the safety and efficacy of PN compared to enteral nutrition. In addition, we describe practical considerations for the use of PN in the ICU including patient nutritional risk stratification, nutrient composition selection for PN, route of PN administration, and biochemical monitoring.

2.
Cureus ; 16(2): e54721, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38524046

RESUMO

Background A death certificate is an important document that serves as a tool for gathering epidemiological data and as an essential legal document. Although it is a mandatory document to be given for all deaths, the quality of its filling is often an ignored aspect and errors are frequently encountered. This documentation process can be mastered with minimal educational efforts. This study aimed to determine the utility of an educational measure in improving the accuracy of death certificate documentation. Methods and materials This pre- and post-interventional study was conducted at Maharaja Agrasen Medical College, Agroha, a tertiary care teaching hospital in Hisar, Haryana, India, wherein an audit of death certificates was done before and after an educational intervention on doctors responsible for filling death certificates. Errors in the death certificates were classified into major and minor errors and compared in the pre- and post-intervention groups. Results A total of 184 pre-intervention and 136 post-intervention death certificates were audited. In the pre-intervention certificates, at least one major and one minor error were present in 88% and 92.93% of the certificates, respectively, which was reduced to 33% (p < 0.01; relative risk (RR) = 3.62; 95% confidence interval (CI) = 2.69-4.91) and 38% (p < 0.01; RR = 3.33; 95% CI = 2.53-4.37), respectively, post-intervention. Reduction in all types of major and minor errors was statistically significant (p < 0.05). Conclusions Errors in death certification are a common but frequently ignored problem that can have a negative impact on epidemiological data and can be drastically reduced with simple educational measures, which need to be carried out regularly.

3.
J Clin Aesthet Dermatol ; 17(3 Suppl 2): S3-S8, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38495846

RESUMO

Early identification and intervention in patients with cutaneous squamous cell carcinoma (cSCC) who are at high risk for metastasis is important for optimal outcomes. Prognostic tools (e.g., American Joint Committee on Cancer, 8th edition [AJCC-8]) and management guidelines (National Comprehensive Cancer Network® [NCCN]) are useful in helping to identify high-risk patients with cSCC who might benefit from adjuvant therapies, such as radiation and/or immunotherapies; however, traditional staging and management guidelines rely on clinicopathologic risk factors to predict risk, which limits their prognostic accuracy. Gene expression profiling (GEP) is a clinically available, objective metric that can be used in conjunction with traditional clinicopathological staging to help clinicians stratify risk in patients with cSCC. The validated 40-GEP test can accurately classify patients with at least one high-risk feature as being at low (Class 1), higher (Class 2A), or highest (Class 2B) biological risk of nodal or distant metastasis within three years of diagnosis. A multidisciplinary panel comprising radiation oncologists and dermatologists/Mohs micrographic surgeons with expertise in cSCC management convened in June 2023 to discuss the utility of 40-GEP testing in cSCC clinical decision-making in regard to adjuvant radiation therapy (ART). The panel identified gaps in clinical practice in which 40-GEP testing has particular utility: in escalation of care for lower-stage patients with high-risk tumors; in de-escalation of care for patients for whom the risks of ART may outweigh the benefits; and in decision-making regarding elective radiation to the nodal basin. The expert panel developed a risk-based clinical workflow for ART in patients with cSCC, utilizing 40-GEP testing within NCCN management guidelines and AJCC-8 staging.

4.
bioRxiv ; 2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38496484

RESUMO

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), continues to be a major public health problem worldwide. The human immunodeficiency virus (HIV) is another equally important life-threatening pathogen. Further, co-infections with HIV and Mtb have severe effects in the host, with people infected with HIV being fifteen to twenty-one times more likely to develop active TB. The use of an appropriate animal model for HIV/Mtb co-infection that can recapitulate the diversity of the immune response in humans would be a useful tool for conducting basic and translational research in HIV/Mtb infections. The present study was focused on developing a humanized mouse model for investigations on HIV-Mtb co-infection. Using NSG-SGM3 mice that can engraft human stem cells, our studies showed that they were able to engraft human CD34+ stem cells which then differentiate into a full-lineage of human immune cell subsets. After co-infection with HIV and Mtb, these mice showed decrease in CD4+ T cell counts overtime and elevated HIV load in the sera, similar to the infection pattern of humans. Additionally, Mtb caused infections in both lungs and spleen, and induced the development of granulomatous lesions in the lungs, detected by CT scan and histopathology. Distinct metabolomic profiles were also observed in the tissues from different mouse groups after co-infections. Our results suggest that the humanized NSG-SGM3 mice are able to recapitulate the effects of HIV and Mtb infections and co-infection in the human host at pathological, immunological and metabolism levels, providing a dependable small animal model for studying HIV/Mtb co-infection.

6.
Environ Sci Pollut Res Int ; 31(12): 18672-18682, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38349494

RESUMO

Decoupling cooling and ventilation tasks with an existing air conditioning methodology are a promising performance-enhancement technology. In this direction, different configurations of a desiccant-integrated independent ventilation element attached to a conventional cooling system are proposed in this study. This work establishes a quantitative comparative performance analysis among the different process air cooling (obtained through desiccant dehumidification) techniques for three different climates, namely, hot-dry, tropical, and Mediterranean. EnergyPlus simulations have been executed on a small-scale office building of 400-m2 area. The building constructional details and other required simulation input parameters follow benchmark standards. As the chemical dehumidification increases, the process air, i.e., supply air temperature that cannot be sent directly to the room, needs to be cooled. Three approaches for process air cooling have been considered: direct expansion (DX) cooling coil, indirect evaporative cooling (IEC), and sensible heat recovery wheel (SHRW). A solar collector assembly with a supporting heating arrangement is coupled with desiccant unit for regeneration. Outdoor air is used for regeneration in the case of the DX cooling coil and IEC, whereas return air is used in the heat recovery wheel case. Annual simulation results reveal that the SHRW-aided case performs superior than DX coil case for the pertinent climatic conditions, with 9.6 to 45.01% of annual energy savings. For the IEC, energy consumption was 1.8 to 18.38% less than that of DX coil. Also, using return air in this best-suited case reduces the net thermal energy requirement for regeneration by 14.63 to 71.65% with respect to DX coil.


Assuntos
Ar Condicionado , Energia Solar , Higroscópicos , Temperatura , Temperatura Alta
7.
J Am Acad Dermatol ; 2023 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-38081390

RESUMO

BACKGROUND: Amid a movement toward value-based healthcare, increasing emphasis has been placed on outcomes and cost of medical services. To define and demonstrate the quality of services provided by Mohs surgeons, it is important to identify and understand the key aspects of Mohs micrographic surgery (MMS) that contribute to excellence in patient care. OBJECTIVE: The purpose of this study is to develop and identify a comprehensive list of metrics in an initial effort to define excellence in MMS. METHODS: Mohs surgeons participated in a modified Delphi process to reach a consensus on a list of metrics. Patients were administered surveys to gather patient perspectives. RESULTS: Twenty-four of the original 66 metrics met final inclusion criteria. Broad support for the initiative was obtained through physician feedback. LIMITATIONS: Limitations of this study include attrition bias across survey rounds and participation at the consensus meeting. Furthermore, the list of metrics is based on expert consensus instead of quality evidence-based outcomes. CONCLUSION: With the goal of identifying metrics that demonstrate excellence in performance of MMS, this initial effort has shown that Mohs surgeons and patients have unique perspectives and can be engaged in a data-driven approach to help define excellence in the field of MMS.

8.
ACS Omega ; 8(50): 47573-47584, 2023 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-38144049

RESUMO

Amaranthus (family Amaranthaceae) is a potentially nutritious pseudocereal also known as a functional food owing to its high nutritional quality grains especially rich in essential amino acids. Emerging study, however, unambiguously indicates that apart from essential nutrients like protein, other phytochemicals present in amaranth seeds provide excellent health benefits. Squalene is one such phytonutrient found in Amaranthus seeds, which is also its largest vegetal source. In this research work, GC-MS and NMR spectroscopy-based metabolomics have been utilized for the compositional analysis of Amaranthus seeds coupled with a multivariate data set. Investigation of nonpolar and polar seed extracts of six different cultivars of amaranth identified 47 primary and secondary metabolites. One-way ANOVA showed significant quantitative metabolic variations in different cultivars of amaranth. Multivariate principal component analysis of both the GC-MS and NMR analyzed data broadly classified in two groups showed significant variations in the polar (lysine, arginine, GABA, and myoinositol) and nonpolar (squalene, tryptophan, and alkylated phenols, which are potential nutraceutical agents) metabolites. The squalene content estimated using HPLC varied significantly (1.61 to 4.72 mg g-1 seed dry weight) among six different cultivars. Positive correlations were found among the cellular antioxidant activity and squalene content. Cultivar AM-3 having the maximum squalene content showed the highest antioxidant activity evaluated on the cellular level over human embryonic kidney cells, clearly revealing potent intercellular reactive oxygen species scavenging capacity and strong membrane lipid peroxidation inhibition potential. Oxidative stress markers such as MDA, SOD, GSH, and CAT levels in cells further corroborated the research work. The study also indicated high concentrations of lysine (80.49 mg g-1 dry seeds) in AM-2, squalene (0.47% by weight) in AM-3, and 2,4-di-tert-butyl phenol (18.64% peak area) and myoinositol (79.07 mg g-1 dry seeds) in AM-5. This novel comparative metabolomic study successfully profiles the nutrient composition of amaranth cultivars and provides the opportunity for the development of nutraceuticals and natural antioxidants from this functional food.

9.
World J Virol ; 12(4): 233-241, 2023 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-37970568

RESUMO

BACKGROUND: Hepatitis B virus (HBV) and hepatitis C virus (HCV) viral load (VL) estimation is essential for the management of both HBV and HCV infections. Due to a longer turnaround time for VL estimation, many patients drop out from the cascade of care. To achieve the global goals of reducing morbidity and mortality due to HBV/HCV and moving towards their elimination by 2030, molecular diagnostic platforms with faster and random (i.e. single sample) access are needed. AIM: To evaluate the performance of the recently launched NeuMoDx 96 random access system with the conventional COBAS®AmpliPrep/COBAS TaqMan system for HBV and HCV VL estimation. METHODS: Archived once-thawed plasma samples were retrieved and tested on both platforms. Correlation between the assays was determined by linear regression and Bland-Altman analysis. The study included samples from 186 patients, 99 for HBV of which 49 were true infected HBV cases (hepatitis B surface antigen, anti-hepatitis B core antibody, and HBV DNA-positive) and 87 for HCV assay in which 39 were true positives for HCV infection (anti-HCV and HCV RNA-positive). RESULTS: The median VL detected by NeuMoDx for HBV was 2.9 (interquartile range [IQR]: 2.0-4.3) log10 IU/mL and by COBAS it was 3.70 (IQR: 2.28-4.56) log10 IU/mL, with excellent correlation (R2 = 0.98). In HCV, the median VL detected by NeuMoDx was 4.9 (IQR: 4.2-5.4) log10 IU/mL and by COBAS it was 5.10 (IQR: 4.07-5.80) log10 IU/mL with good correlation (R2 = 0.96). CONCLUSION: The overall concordance between both the systems was 100% for both HBV and HCV VL estimation. Moreover, no genotype-specific bias for HBV/HCV VL quantification was seen in both the systems. Our findings reveal that NeuMoDx HBV and HCV quantitative assays have shown overall good clinical performance and provide faster results with 100% sensitivity and specificity compared to the COBAS AmpliPrep/COBAS TaqMan system.

10.
Ageing Res Rev ; 92: 102086, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37821047

RESUMO

The Kisspeptin1 (KISS1)/neurokinin B (NKB)/Dynorphin (Dyn) [KNDy] neurons in the hypothalamus regulate the reproduction stage in human beings and rodents. KNDy neurons co-expressed all KISS1, NKB, and Dyn peptides, and hence commonly regarded as KISS1 neurons. KNDy neurons contribute to the "GnRH pulse generator" and are implicated in the regulation of pulsatile GnRH release. The estradiol (E2)-estrogen receptor (ER) interactions over GnRH neurons in the hypothalamus cause nitric oxide (NO) discharge, in addition to presynaptic GABA and glutamate discharge from respective neurons. The released GABA and glutamate facilitate the activity of GnRH neurons via GABAA-R and AMPA/kainate-R. The KISS1 stimulates MAPK/ERK1/2 signaling and cause the release of Ca2+ from intracellular store, which contribute to neuroendocrine function, increase apoptosis and decrease cell proliferation and metastasis. The ageing in women deteriorates KISS1/KISS1R interaction in the hypothalamus which causes lower levels of GnRH. Because examining the human brain is so challenging, decades of clinical research have failed to find the causes of KNDy/GnRH dysfunction. The KISS1/KISS1R interactions in the brain have a neuroprotective effect against Alzheimer's disease (AD). These findings modulate the pathophysiological role of the KNDy/GnRH neural network in polycystic ovarian syndrome (PCOS) associated with ageing and, its protective role in cancer and AD. This review concludes with protecting effect of the steroid-derived acute regulatory enzyme (StAR) against neurotoxicity in the hippocampus, and hypothalamus, and these measures are fundamental for delaying ageing with PCOS. StAR could serve as novel diagnostic marker and therapeutic target for the most prevalent hormone-sensitive breast cancers (BCs).


Assuntos
Doença de Alzheimer , Síndrome do Ovário Policístico , Animais , Feminino , Humanos , Núcleo Arqueado do Hipotálamo/metabolismo , Dinorfinas/metabolismo , Ácido gama-Aminobutírico , Glutamatos , Hormônio Liberador de Gonadotropina/metabolismo , Kisspeptinas/metabolismo , Neurocinina B/metabolismo , Receptores de Kisspeptina-1 , Roedores
11.
Natl J Maxillofac Surg ; 14(2): 233-241, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37661970

RESUMO

Background: Anterior segmental Bi-jaw orthognathic surgery is indicated primarily for the correction of dentoalveolar protrusion. They are also indicated for correcting apertognathia, closing interproximal spaces between segments and can be incorporated with other osteotomies to obtain better results. Aim: The aim of this study was to analyze and compare the soft- and hard-tissue changes in patients who underwent combined anterior segmental bi-jaw orthognathic surgery. Settings and Design: To compare and evaluate soft- and hard-tissue changes before and after combined anterior segmental bi-jaw orthognathic surgery by assessing (a) parameters in vertical dimension and (b) parameters in horizontal dimension and patient satisfaction was also assessed following surgery at 6 months' time interval. Materials and Methods: It is a prospective, single center and analytical study with sample size of 20 patients. It required routine setup for orthognathic surgery and manual tracing of lateral cephalograms. The surgical outcomes were assessed by hard tissue (Sella Nasion Point A (SNA) angle, Sella Nasion Point B (SNB) angle, Point A Nasion Point B (ANB) angle, NAPg, U1-NF, L1-MP angles; NA, NB, B-Pg, Nasion-Anterior nasal spine (N-ANS) distance, Anterior nasal spine-Gnathion (ANS-Gn) distance, and overjet and overbite) and soft tissue (facial convexity, NL, LM angles; LM fold, UL and LL protrusions, Upper lip length (ULL), Lower lip length (LLL), Sn-A, Si-B, Pg-Pg*, Ls-U1, Li-L1 distances, interlabial gap, and U1 exposure) variables pre and postsurgery. Statistical Analysis: Descriptive statistics involved the mean and standard deviation, and recorded data were subjected to the statistical analysis using IBM SPSS 20 statistical package. The paired t-test, Pearson correlation coefficient were used. The level of significance P < 0.05 was taken as statistically significant and P < 0.01 as very significant. Results: Overall improvement after surgery in both hard- and soft-tissue parameters was observed and significant changes were seen in every variable, except Si-B (P > 0.05). Correlations between soft- and hard-tissue changes were significant in both sagittal and vertical planes. Patients' satisfaction score showed that all patients had the high overall rate of satisfaction. Conclusions: Our study concludes that combined anterior segmental bimaxillary orthognathic surgery is a simple technique with minimal postoperative complications and limited relapse. The changes in facial esthetics and occlusion following orthognathic surgery depend highly on the stability achieved during the postoperative period.

12.
Trop Anim Health Prod ; 55(5): 298, 2023 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-37723324

RESUMO

Dairy sector has recently focused a lot of attention on the addition of agricultural by-products as functional feed additives as an environmentally friendly and sustainable technology. Depotash vinasse (DPV) serves as a cheap source of nutrients and a binder for animal feed in dairy sector. However, there is little information available on the usage of depotash vinasse on animals. Therefore, the aim of the present study was to assess the role of depotash vinasse as pellet binder on nutrient digestibility, blood parameters and milk production in early lactating Murrah buffaloes. Fifteen Murrah buffaloes (daily milk yield 8.5 to 9.0 kg/day) were randomly assigned to three groups, viz., control, group 1 (G1) and group 2 (G2) on the basis of milk yield and days in milk. The control group animals received a basal diet of concentrate mix, oat greens and wheat straw, G1 animals received molasses as a binder (8%), while G2 received DPV as binder (8%). Results revealed that there was no significant effect on nutrient digestibility. Blood parameters and hepatic enzymes were statistically similar (P > 0.05). Supplementation of depotash vinasse as binder had no effect on plasma minerals and was comparable to control group. There were no changes in milk production and 6% fat-corrected milk yield in treated groups as compared to control. It was concluded that depotash vinasse (8%) may be used for pellet production with no negative impact on milk yield and composition, nutrient digestibility and blood biochemical parameters in early lactating buffaloes.


Assuntos
Bison , Búfalos , Animais , Feminino , Melaço , Lactação , Agricultura
13.
Front Immunol ; 14: 1169152, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37691928

RESUMO

Multicellular organisms are constantly subjected to pathogens that might be harmful. Although insects lack an adaptive immune system, they possess highly effective anti-infective mechanisms. Bacterial phagocytosis and parasite encapsulation are some forms of cellular responses. Insects often defend themselves against infections through a humoral response. This phenomenon includes the secretion of antimicrobial peptides into the hemolymph. Specific receptors for detecting infection are required for the recognition of foreign pathogens such as the proteins that recognize glucans and peptidoglycans, together referred to as PGRPs and ßGRPs. Activation of these receptors leads to the stimulation of signaling pathways which further activates the genes encoding for antimicrobial peptides. Some instances of such pathways are the JAK-STAT, Imd, and Toll. The host immune response that frequently accompanies infections has, however, been circumvented by diseases, which may have assisted insects evolve their own complicated immune systems. The role of ncRNAs in insect immunology has been discussed in several notable studies and reviews. This paper examines the most recent research on the immune regulatory function of ncRNAs during insect-pathogen crosstalk, including insect- and pathogen-encoded miRNAs and lncRNAs, and provides an overview of the important insect signaling pathways and effector mechanisms activated by diverse pathogen invaders.


Assuntos
Fagocitose , RNA não Traduzido , Animais , RNA não Traduzido/genética , Peptídeos Antimicrobianos , Insetos , Transdução de Sinais
14.
Natl J Maxillofac Surg ; 14(1): 47-54, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37273441

RESUMO

Study Design: Randomized Control Trial. Objective: A prospective, clinico-radiographic, comparative study was planned to evaluate the treatment outcome and postoperative complications in isolated mandibular angle fractures using 2.0-mm system single linear 4 hole with gap miniplate versus 4 hole rectangular grid plate, both stabilized with 4 8-mm monocortical screws. Methods: Thirty patients with isolated mandibular angle fractures were randomly categorized into two groups with 15 patients each. Group 1 patients were treated with single 2.0 mm × 4 hole linear miniplate along the superior border and Group 2 patients were treated with a 2.0 mm × 4 hole rectangular grid plate on lateral cortex of mandible. Pain, swelling, occlusion, bite force, maximum inter-incisal opening, intraoperative time, facial nerve injury, fracture stability, and postoperative complications were assessed and compared at regular intervals up to 12 months. Results: There was no major difference in terms of treatment outcome in both systems and both were equally effective without any statistically significant difference in any of the parameters. None of the patients presented with any of the complications except for postoperative infection which was reported by 1 patient from each group at 3 months postoperatively and were managed conservatively. Conclusion: Both plating systems are equally effective; however, the rectangular grid plate could be a safe and effective alternative to the single miniplate when adaptation and fixation is not possible along the external oblique ridge of the mandible (e.g., fracture with bone loss along the superior border).

15.
Proc Natl Acad Sci U S A ; 120(24): e2213241120, 2023 06 13.
Artigo em Inglês | MEDLINE | ID: mdl-37276406

RESUMO

The inner mitochondrial membrane (IMM), housing components of the electron transport chain (ETC), is the site for respiration. The ETC relies on mobile carriers; therefore, it has long been argued that the fluidity of the densely packed IMM can potentially influence ETC flux and cell physiology. However, it is unclear if cells temporally modulate IMM fluidity upon metabolic or other stimulation. Using a photostable, red-shifted, cell-permeable molecular-rotor, Mitorotor-1, we present a multiplexed approach for quantitatively mapping IMM fluidity in living cells. This reveals IMM fluidity to be linked to cellular-respiration and responsive to stimuli. Multiple approaches combining in vitro experiments and live-cell fluorescence (FLIM) lifetime imaging microscopy (FLIM) show Mitorotor-1 to robustly report IMM 'microviscosity'/fluidity through changes in molecular free volume. Interestingly, external osmotic stimuli cause controlled swelling/compaction of mitochondria, thereby revealing a graded Mitorotor-1 response to IMM microviscosity. Lateral diffusion measurements of IMM correlate with microviscosity reported via Mitorotor-1 FLIM-lifetime, showing convergence of independent approaches for measuring IMM local-order. Mitorotor-1 FLIM reveals mitochondrial heterogeneity in IMM fluidity; between-and-within cells and across single mitochondrion. Multiplexed FLIM lifetime imaging of Mitorotor-1 and NADH autofluorescence reveals that IMM fluidity positively correlates with respiration, across individual cells. Remarkably, we find that stimulating respiration, through nutrient deprivation or chemically, also leads to increase in IMM fluidity. These data suggest that modulating IMM fluidity supports enhanced respiratory flux. Our study presents a robust method for measuring IMM fluidity and suggests a dynamic regulatory paradigm of modulating IMM local order on changing metabolic demand.


Assuntos
Membranas Mitocondriais , Sondas Moleculares/química , Membranas Mitocondriais/química , Respiração Celular , Fluidez de Membrana , Pressão Osmótica , Difusão
16.
iScience ; 26(4): 106374, 2023 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-37096047

RESUMO

Two-photon lithography (TPL) is a versatile technology for additive manufacturing of 2D and 3D micro/nanostructures with sub-wavelength resolved features. Recent advancement in laser technology has enabled the application of TPL fabricated structures in several fields such as microelectronics, photonics, optoelectronics, microfluidics, and plasmonic devices. However, the lack of two-photon polymerizable resins (TPPRs) induces bottleneck to the growth of TPL to its true potential, and hence continuous research efforts are focused on developing efficient TPPRs. In this article, we review the recent advancements in PI and TPPR formulation and the impact of process parameters on fabrication of 2D and 3D structures for specific applications. The fundamentals of TPL are described, followed by techniques used for achieving improved resolution and functional micro/nanostructures. Finally, a critical outlook and future prospects of TPPR formulation for specific applications are presented.

17.
Clin Cosmet Investig Dermatol ; 16: 925-935, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37051586

RESUMO

Cutaneous squamous cell carcinoma (cSCC) has become a significant public health issue due to its rapidly rising incidence and an estimated 1.8 million newly diagnosed cases annually. As with other cancers, treatment decisions for patients with cSCC are based primarily on a patient's risk for poor outcomes. There has been improvement in clinicopathologic factor-based risk assessment approaches, either through informal methods or ever evolving staging approaches. However, these approaches misidentify patients who will eventually have disease progression as low-risk and conversely, over classify patients as high-risk who do not experience relapse. To improve the accuracy of risk assessment for patients with cSCC, the 40-gene expression profile (40-GEP) test has been validated to show statistically significant stratification of a high-risk cSCC patient's risk of nodal or distant metastasis, independent of currently available risk-assessment methods. The 40-GEP test allows for a more accurate classification of metastatic risk for high-risk cSCC patients, with the aim to influence appropriate allocation of clinician time and therapeutic resources to those patients who will most benefit. The objective of this article is to present a treatment algorithm in which clinicians can easily integrate the results of the 40-GEP test into their current treatment approaches to tailor patient care based on individual tumor biology. The following modalities were considered: surveillance imaging, sentinel lymph node biopsy (SLNB), adjuvant radiation therapy (ART), and clinical follow-up. The authors have contributed their own cases for discussion as to how they have seen the beneficial impact of 40-GEP test results in their own practice. Overall, clinicians can identify risk-aligned treatment pathway improvements with the use of the 40-GEP test for challenging to manage, high-risk cSCC patients.

19.
Chemphyschem ; 24(4): e202200421, 2023 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-36228089

RESUMO

Sulfated cyclodextrins have recently emerged as potential candidates for producing host-induced guest aggregation with properties better than p-sulfonatocalixarenes that have previously shown numerous applications involving the phenomena of host-induced guest aggregation. In the class of sulfated cyclodextrins (SCD), sulfated ß-cyclodextrin (ß-SCD) remains the most extensively investigated host molecule. Although it is assumed that the host-induced guest aggregation is predominantly an outcome of interaction of the guest molecule with the charges on the exterior of SCD cavity, it has not been deciphered whether the variation in the cavity size will make a difference in the efficiency of host-induced guest-aggregation process. In this investigation, we present a systematic study of host-induced guest aggregation of a cationic molecular rotor dye, Thioflavin T (ThT) with three different sulfated cyclodextrin molecules, α-SCD, ß-SCD and γ-SCD, which differ in their cavity size, using steady-state emission, ground-state absorption and time-resolved emission measurements. The obtained photophysical properties of ThT, upon interaction with different SCD molecules, indicate that the binding strength of ThT with different SCD molecules correlate with the cavity size of the host molecule, giving rise to the strongest complexation of ThT with the largest host molecule (γ-SCD). The binding affinity of ThT towards different host molecules has been supported by molecular docking calculations. The results obtained are further supported with the temperature and ionic strength dependent studies performed on the host-guest complex. Our results indicate that for host-induced guest aggregation, involving oppositely charged molecules, the size of the cavity also plays a crucial role beside the charge density on the exterior of host cavity.

20.
Methods Mol Biol ; 2600: 121-131, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36587094

RESUMO

Plant's roots grow in soils of different rigidities. Understanding how the stiffness of the surrounding environment impacts growth and cell fate of roots and root hair cells is an important and open question. Here, we describe a simple method to setup a microfluidic-like system (MLS) to tackle this question. This system enables to grow plantlets during weeks in microfluidic chips filled with gels of controlled stiffness and to image them under a microscope from a few minutes up to a few days. Furthermore, MLS keeps the numerous benefits of microfluidic chips, such as high-resolution imaging, precise control of the geometry of growth, and standardization of the measurements. In sum, MLS enables one to quantitatively test, even on long time scales, the effect of the rigidity and the geometry of the environment on the growth of roots and root hair cells, including mechanotransduction to the nucleus.


Assuntos
Arabidopsis , Microfluídica , Microfluídica/métodos , Mecanotransdução Celular , Raízes de Plantas , Estruturas da Membrana Celular
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