Effects of PreOperative radiotherapy in a preclinical glioblastoma model: a paradigm-shift approach.

PURPOSE: PreOperative radiotherapy (RT) is commonly used in the treatment of brain metastasis and different cancer types but has never been used in primary glioblastoma (GBM). Here, we aim to establish, describe, and validate the use of PreOperative RT for the treatment of GBM in a preclinical model. METHODS: Rat brains were locally irradiated with 30-Gy, hypofractionated in five doses 2 weeks before or after the resection of intracranial GBM. Kaplan-Meier analysis determined survival. Hematoxylin-eosin staining was performed, and nuclei size and p21 senescence marker were measured in both resected and recurrent rodent tumors. Immunohistochemistry assessed microglia/macrophage markers, and RNAseq analyzed gene expression changes in recurrent tumors. Akoya Multiplex Staining on two human patients from our ongoing Phase I/IIa trial served as proof of principle. RESULTS: PreOperative RT group median survival was significantly higher than PostOperative RT (p < 0.05). Radiation enlarged cytoplasm and nuclei in PreOperative RT resected tumors (p < 0.001) and induced senescence in PostOperative RT recurrent tumors (p < 0.05). Gene Set Enrichment Analysis (GSEA) suggested a more proliferative profile in PreOperative RT group. PreOperative RT showed lower macrophage/microglia recruitment in recurrent tumors (p < 0.01) compared to PostOperative RT. Akoya Multiplex results indicated TGF-ß accumulation in the cytoplasm of TAMs and CD4 + lymphocyte predominance in PostOperative group. CONCLUSIONS: This is the first preclinical study showing feasibility and longer overall survival using neoadjuvant radiotherapy before GBM resection in a mammalian model. This suggests strong superiority for new clinical radiation strategies. Further studies and trials are required to confirm our results.

Living arrangements and socioeconomic-based health disparities in Mexico.

OBJECTIVE: To investigate the role living arrangements play in the co-dynamics of socioeconomic position and health in the latter part of life. MATERIALS AND METHODS: Based on longitudinal data from the Mexican Health and Aging Study (MHAS), latent class analysis (LCA) and locally weighted regressions, in this article we estimate age trajectories to examine the degree to which wealth and health-related outcomes correlate with typical living arrangement dynamics. RESULTS: Main results suggest a complex dynamic relationship between living arrangements and social inequalities in health, with important differences by sex, unlike mortality trends as they appear to diverge with differences in wealth regardless of household structure. CONCLUSIONS: Our methodological approach provides new insights regarding the likely effect household structure plays when analyzing the dynamics of social inequality. To date, this is the first longitudinal analysis to offer this kind of empirical evidence for the region.

Anti-inflammatory mechanisms of fruits and by-products from Mauritia flexuosa, an exotic plant with functional benefits.

Mauritia flexuosa L., traditionally known as "buriti", exhibits chemoprotective properties including antioxidant, antithrombotic, and nutritional actions. The aim of this study was to examine the oral anti-inflammatory activity of epicarp, mesocarp and endocarp obtained from M. flexuosa fruits using in vivo models to verify physiological benefits. The anti-edematogenic action was determined using phlogistic agents to induce paw edema and peritonitis. Pro-inflammatory cytokines, cell migration of peritoneal cells, histological changes, and abdominal swelling induced by acetic acid were also investigated. Carrageenan-induced edema was found to be decreased in mice pre-treated with epicarp by 50.8%, 53.7% and 39.2% and mesocarp by 41.8%, 65.3% and 71.9% after 2, 3, and 4 hr stimuli, respectively. Edema initiated by specific agents such as compound 48/80, histamine, serotonin, and prostaglandin E2 were also reduced, and better outcomes were found against histamine-induced edema, as evidenced by the decline at all times analyzed (30-120 min) with both doses of water extract of mesocarp (500 or 1000 mg/kg). Mesocarp-pre-treatment reduced inflammatory tissue parameters such as number of peritoneal leukocytes and TNF-α levels, but only epicarp diminished abdominal pain. In summary, M. flexuosa fruits, especially mesocarp, exhibited oral physiological benefits and capacity to modify biochemical and cellular steps in the inflammatory cascade, indicating that dietary supplements containing these fruits may be combined with pharmacological tools to ameliorate or prevent diseases of inflammatory origin.

The peroxisome proliferator-activated receptor-ß/δ antagonist GSK0660 mitigates retinal cell inflammation and leukostasis.

Diabetic retinopathy (DR) is triggered by retinal cell damage stimulated by the diabetic milieu, including increased levels of intraocular free fatty acids. Free fatty acids may serve as an initiator of inflammatory cytokine release from Müller cells, and the resulting cytokines are potent stimulators of retinal endothelial pathology, such as leukostasis, vascular permeability, and basement membrane thickening. Our previous studies have elucidated a role for peroxisome proliferator-activated receptor-ß/δ (PPARß/δ) in promoting several steps in the pathologic cascade in DR, including angiogenesis and expression of inflammatory mediators. Furthermore, PPARß/δ is a known target of lipid signaling, suggesting a potential role for this transcription factor in fatty acid-induced retinal inflammation. Therefore, we hypothesized that PPARß/δ stimulates both the induction of inflammatory mediators by Müller cells as well the paracrine induction of leukostasis in endothelial cells (EC) by Müller cell inflammatory products. To test this, we used the PPARß/δ inhibitor, GSK0660, in primary human Müller cells (HMC), human retinal microvascular endothelial cells (HRMEC) and mouse retina. We found that palmitic acid (PA) activation of PPARß/δ in HMC leads to the production of pro-angiogenic and/or inflammatory cytokines that may constitute DR-relevant upstream paracrine inflammatory signals to EC and other retinal cells. Downstream, EC transduce these signals and increase their synthesis and release of chemokines such as CCL8 and CXCL10 that regulate leukostasis and other cellular events related to vascular inflammation in DR. Our results indicate that PPARß/δ inhibition mitigates these upstream (MC) as well as downstream (EC) inflammatory signaling events elicited by metabolic stimuli and inflammatory cytokines. Therefore, our data suggest that PPARß/δ inhibition is a potential therapeutic strategy against early DR pathology.

The EPAC-Rap1 pathway prevents and reverses cytokine-induced retinal vascular permeability.

Increased retinal vascular permeability contributes to macular edema, a leading cause of vision loss in eye pathologies such as diabetic retinopathy, age-related macular degeneration, and central retinal vein occlusions. Pathological changes in vascular permeability are driven by growth factors such as VEGF and pro-inflammatory cytokines such as TNF-α. Identifying the pro-barrier mechanisms that block vascular permeability and restore the blood-retinal barrier (BRB) may lead to new therapies. The cAMP-dependent guanine nucleotide exchange factor (EPAC) exchange-protein directly activated by cAMP promotes exchange of GTP in the small GTPase Rap1. Rap1 enhances barrier properties in human umbilical endothelial cells by promoting adherens junction assembly. We hypothesized that the EPAC-Rap1 signaling pathway may regulate the tight junction complex of the BRB and may restore barrier properties after cytokine-induced permeability. Here, we show that stimulating EPAC or Rap1 activation can prevent or reverse VEGF- or TNF-α-induced permeability in cell culture and in vivo Moreover, EPAC activation inhibited VEGF receptor (VEGFR) signaling through the Ras/MEK/ERK pathway. We also found that Rap1B knockdown or an EPAC antagonist increases endothelial permeability and that VEGF has no additive effect, suggesting a common pathway. Furthermore, GTP-bound Rap1 promoted tight junction assembly, and loss of Rap1B led to loss of junctional border organization. Collectively, our results indicate that the EPAC-Rap1 pathway helps maintain basal barrier properties in the retinal vascular endothelium and activation of the EPAC-Rap1 pathway may therefore represent a potential therapeutic strategy to restore the BRB.

Verteporfin-Loaded Polymeric Microparticles for Intratumoral Treatment of Brain Cancer.

Glioblastoma (GBMs) is the most common and aggressive type of primary brain tumor in adults with dismal prognosis despite radical surgical resection coupled with chemo- and radiotherapy. Recent studies have proposed the use of small-molecule inhibitors, including verteporfin (VP), to target oncogenic networks in cancers. Here we report efficient encapsulation of water-insoluble VP in poly(lactic- co-glycolic acid) microparticles (PLGA MP) of ∼1.5 µm in diameter that allows tunable, sustained release. Treatment with naked VP and released VP from PLGA MP decreased cell viability of patient-derived primary GBM cells in vitro by ∼70%. Moreover, naked VP treatment significantly increased radiosensitivity of GBM cells, thereby enhancing overall tumor cell killing ability by nearly 85%. Our in vivo study demonstrated that two intratumoral administrations of sustained slow-releasing VP-loaded PLGA MPs separated by two weeks significantly attenuated tumor growth by ∼67% in tumor volume in a subcutaneous patient-derived GBM xenograft model over 26 d. Additionally, our in vitro data indicate broader utility of VP for treatment for other solid cancers, including chordoma, malignant meningioma, and various noncentral nervous system-derived carcinomas. Collectively, our work suggests that the use of VP-loaded PLGA MP may be an effective local therapeutic strategy for a variety of solid cancers, including unresectable and orphan tumors, which may decrease tumor burden and ultimately improve patient prognosis.

Airborne microorganisms associated with packaging glass sorting facilities.

In recent years, efforts have been undertaken to reduce the volume of residual waste through sorting and recycling. The waste management and recycling sector is thriving and the number of workers there is increasing. In this context, prior knowledge of the risks to which workers may be exposed is of crucial importance, and preventive measures need to be put in place to accurately identify and quantify those risks. This study aimed to assess occupational risk of exposure to biological agents (viable bacteria and fungi) in a Portuguese waste packaging glass sorting plant. Air samples were collected from selected locations in waste sorting cabins (critical area, CA), administrative services (noncritical area, NCA) and outdoors (control point, CP). Duplicate air samples were collected through an impaction method. The investigation was carried out over an 8-mo period with two collection periods, autumn/winter (AW) and spring/summer (SS), in order to access the influence of any seasonal variation. In the 36 air samples collected, 319 bacterial and 196 mold identifications were performed. Air samples revealed existence of high environmental contamination by bacteria (1.6 × 10(4) colony forming units [cfu]/m(3)) and fungi (1.5 × 10(4) cfu/m(3)). The predominant bacterial genus was Staphylococcus (coagulase negative) with values ranging from 29.6 to 60% of the total count of bacteria. Genera Bacillus, Micrococcus, and Staphylococcus (coagulase negative) were also present at all sampling sites, regardless of the season. However, the counts of these genera, in the CA, were higher in warmer seasons. The genus Penicillium was the most frequent genus present with an approximate value of 95% of total fungal count in the CA. Seasonal variation was a significant factor for total bacteria and fungi, except for NCA versus CP. Overall, the highest levels of bacterial and fungal species (10(4) cfu/m(3)) were found in the waste sorting cabin (CA). These results highlight the importance of proper design and risk evaluation when planning a new waste facility, such that working conditions minimize proliferation of biological agents in the workplace.

The shear bond strength of self-adhesive resin cements to dentin and enamel: an in vitro study.

STATEMENT OF PROBLEM: Clinicians continue to search for ways to simplify bonding procedures without compromising clinical efficacy. PURPOSE: The purpose of this study was to evaluate the shear strength of self-adhesive cements RelyX U100 and RelyX U200, and conventional resin cement RelyX ARC to enamel and dentin after different surface treatments. MATERIAL AND METHODS: The crowns of 120 bovine incisor teeth were separated from the roots and embedded in epoxy resin in polyvinyl chloride tubes. In each tooth, the area to be cemented was delimited with central holed adhesive tape. The teeth were distributed into 12 groups (n=10) according to the substrate; etched or not with 37% phosphoric acid; and cement type of enamel-U100, enamel-phosphoric acid-U100, enamel-U200, enamel-phosphoric acid-U200, enamel-ARC, enamel-phosphoric acid-ARC, dentin-U100, dentin-phosphoric acid-U100, dentin-U200, dentin-phosphoric acid-U200, dentin-ARC, and dentin-phosphoric acid-ARC. After 7 days of storage in artificial saliva, shear strength tests were performed by using a universal testing machine (0.5 mm/min). The data were analyzed with 3-way ANOVA and the Tukey test (α=.05). Fracture analysis was performed with a light microscope. Two specimens from each group were analyzed with a scanning electron microscope. RESULTS: In enamel, ARC (9.96 MPa) had higher shear strength (P=.038) than U100 (5.14 MPa); however, after surface etching, U100 (17.81 MPa) and U200 (17.52 MPa) had higher shear strength (P<.001). With dentin, no significant differences were observed (P=.999), except for dentin-ARC (0.34 MPa) (P=.001). Most fractures were of the adhesive type. CONCLUSIONS: U200 self-adhesive cement had similar bond strength to the ARC in enamel, but the combination with phosphoric acid had the best bond strength. For dentin, self-adhesive resin cements are equally effective alternatives to conventional resin cement.

A cellular model for sporadic ALS using patient-derived induced pluripotent stem cells.

Development of therapeutics for genetically complex neurodegenerative diseases such as sporadic amyotrophic lateral sclerosis (ALS) has largely been hampered by lack of relevant disease models. Reprogramming of sporadic ALS patients' fibroblasts into induced pluripotent stem cells (iPSC) and differentiation into affected neurons that show a disease phenotype could provide a cellular model for disease mechanism studies and drug discovery. Here we report the reprogramming to pluripotency of fibroblasts from a large cohort of healthy controls and ALS patients and their differentiation into motor neurons. We demonstrate that motor neurons derived from three sALS patients show de novo TDP-43 aggregation and that the aggregates recapitulate pathology in postmortem tissue from one of the same patients from which the iPSC were derived. We configured a high-content chemical screen using the TDP-43 aggregate endpoint both in lower motor neurons and upper motor neuron like cells and identified FDA-approved small molecule modulators including Digoxin demonstrating the feasibility of patient-derived iPSC-based disease modeling for drug screening.

Bond strength and Raman analysis of the zirconia-feldspathic porcelain interface.

STATEMENT OF PROBLEM: Zirconia has the best mechanical properties of the available ceramic systems. However, the stability of the zirconia-feldspathic porcelain interface may be jeopardized by the presence of the chipping and debonding of the feldspathic porcelain. PURPOSE: The purpose of this study is to evaluate the shear bond strength of 3 cold isostatic pressed zirconia materials and a feldspathic veneer by analyzing their interface with micro-Raman spectroscopy. MATERIAL AND METHODS: The test groups were experimental zirconia, Zirkonzahn zirconia, and Schuetz zirconia. Blocks of partially sintered zirconia were cut into disks (n=20) and then veneered with a feldspathic porcelain. Half of the specimens from each group (n=10) were incubated in 37°C water for 24 hours, and the other half were thermocycled. All the specimens were then subjected to shear testing. The fractured areas were analyzed with optical stereomicroscopy and classified as adhesive, cohesive, or an adhesive-cohesive failure. Spectral patterns were examined to detect bands related to the zirconia and feldspathic porcelain phases. The shear strength data were submitted to 2-way ANOVA. RESULTS: No significant differences in shear bond strength were observed among the 3 groups, regardless of whether or not the specimens were thermocycled. Adhesive failures were the most prevalent types of failure (70%). Raman spectra were clearly distinguished for all the materials, which showed the presence of tetragonal and monoclinic phases. CONCLUSIONS: The controlled production of the experimental zirconia did not influence the results of the bond strength. Raman analysis suggested a process of interdiffusion by the presence of peaks associated with the zirconia and feldspathic ceramics.

Nursing care for chimeric antigen receptor T cell therapy survivors: A literature review.

Chimeric antigen receptor T cell (CAR-T) therapy is an immunotherapy that involves genetically modifying the patient's own T cells to express a chimeric antigen receptor, enabling them to recognize and destroy cancer cells. This treatment has revolutionized the prognosis and management of hematological malignancies, leading to a significant increase in long-term survivors. However, there is limited evidence regarding late sequelae and post-treatment care due to the recent emergence of this therapy. The rapid advancement of CAR-T therapies has created opportunities for advanced practice nurses to play a crucial role in coordinating care, providing education, and ensuring the ongoing well-being of survivors. This article provides an overview of the physical, psychosocial, and financial challenges faced by long-term survivors of CAR-T therapy and proposes a comprehensive nursing care plan to address these issues.

Mexican Multicenter Experience of Metastatic Spinal Disease.

Background Spinal metastatic disease is a silent progressive cancer complication with an increasing prevalence worldwide. The spine is the third most common site where solid tumors metastasize. Complications involved in spinal metastasis include root or spinal cord compression, progressing to a declining quality of life as patient autonomy reduces and pain increases. The main objective of this study is to report the incidence of patients and typology of spinal metastases in three reference centers in Mexico. Methodology Retrospective cohorts of patients diagnosed with spinal metastases from January 2010 to February 2017 at the National Cancer Institute, National Rehabilitation Institute, and the Traumatology and Orthopedics Hospital "Lomas Verdes" in Mexico City were analyzed. Results A total of 326 patients (56% males) with spinal metastases were reported. The mean age was 58.06 ± 14.05 years. The main sources of spinal metastases were tumors of unknown origin in 53 (16.25%) cases, breast cancer in 67 (20.5%) cases, prostate cancer in 59 (18%) cases, myeloma in 24 (7.4%) cases, and lung cancer in 23 (7.1%) cases. Conclusions The data obtained in this analysis delivers an updated standpoint on Mexico, providing the opportunity to distinguish the current data from global references. Collecting more epidemiological information for better recording of cancer and its associated complications, as well as further studies on them, is necessary.

The effects of hypertension on the cerebral circulation.

Maintenance of brain function depends on a constant blood supply. Deficits in cerebral blood flow are linked to cognitive decline, and they have detrimental effects on the outcome of ischemia. Hypertension causes alterations in cerebral artery structure and function that can impair blood flow, particularly during an ischemic insult or during periods of low arterial pressure. This review will focus on the historical discoveries, novel developments, and knowledge gaps in 1) hypertensive cerebral artery remodeling, 2) vascular function with emphasis on myogenic reactivity and endothelium-dependent dilation, and 3) blood-brain barrier function. Hypertensive artery remodeling results in reduction in the lumen diameter and an increase in the wall-to-lumen ratio in most cerebral arteries; this is linked to reduced blood flow postischemia and increased ischemic damage. Many factors that are increased in hypertension stimulate remodeling; these include the renin-angiotensin-aldosterone system and reactive oxygen species levels. Endothelial function, vital for endothelium-mediated dilation and regulation of myogenic reactivity, is impaired in hypertension. This is a consequence of alterations in vasodilator mechanisms involving nitric oxide, epoxyeicosatrienoic acids, and ion channels, including calcium-activated potassium channels and transient receptor potential vanilloid channel 4. Hypertension causes blood-brain barrier breakdown by mechanisms involving inflammation, oxidative stress, and vasoactive circulating molecules. This exposes neurons to cytotoxic molecules, leading to neuronal loss, cognitive decline, and impaired recovery from ischemia. As the population ages and the incidence of hypertension, stroke, and dementia increases, it is imperative that we gain a better understanding of the control of cerebral artery function in health and disease.

Elucidating glial responses to products of diabetes-associated systemic dyshomeostasis.

Diabetic retinopathy (DR) is a leading cause of blindness in working age adults. DR has non-proliferative stages, characterized in part by retinal neuroinflammation and ischemia, and proliferative stages, characterized by retinal angiogenesis. Several systemic factors, including poor glycemic control, hypertension, and hyperlipidemia, increase the risk of DR progression to vision-threatening stages. Identification of cellular or molecular targets in early DR events could allow more prompt interventions pre-empting DR progression to vision-threatening stages. Glia mediate homeostasis and repair. They contribute to immune surveillance and defense, cytokine and growth factor production and secretion, ion and neurotransmitter balance, neuroprotection, and, potentially, regeneration. Therefore, it is likely that glia orchestrate events throughout the development and progression of retinopathy. Understanding glial responses to products of diabetes-associated systemic dyshomeostasis may reveal novel insights into the pathophysiology of DR and guide the development of novel therapies for this potentially blinding condition. In this article, first, we review normal glial functions and their putative roles in the development of DR. We then describe glial transcriptome alterations in response to systemic circulating factors that are upregulated in patients with diabetes and diabetes-related comorbidities; namely glucose in hyperglycemia, angiotensin II in hypertension, and the free fatty acid palmitic acid in hyperlipidemia. Finally, we discuss potential benefits and challenges associated with studying glia as targets of DR therapeutic interventions. In vitro stimulation of glia with glucose, angiotensin II and palmitic acid suggests that: 1) astrocytes may be more responsive than other glia to these products of systemic dyshomeostasis; 2) the effects of hyperglycemia on glia are likely to be largely osmotic; 3) fatty acid accumulation may compound DR pathophysiology by promoting predominantly proinflammatory and proangiogenic transcriptional alterations of macro and microglia; and 4) cell-targeted therapies may offer safer and more effective avenues for DR treatment as they may circumvent the complication of pleiotropism in retinal cell responses. Although several molecules previously implicated in DR pathophysiology are validated in this review, some less explored molecules emerge as potential therapeutic targets. Whereas much is known regarding glial cell activation, future studies characterizing the role of glia in DR and how their activation is regulated and sustained (independently or as part of retinal cell networks) may help elucidate mechanisms of DR pathogenesis and identify novel drug targets for this blinding disease.

Real-time PCR in the diagnosis of congenital toxoplasmosis.

The diagnosis of congenital toxoplasmosis presents limitations and therefore new options are necessary. The analysis of amniotic fluid by real-time PCR has already proved effective for confirmation of fetal infection. However, its performance in other biological samples is not clear yet. The aim of this study is to better understand the role of real-time PCR in the blood of the mother and newborn as well as in the amniotic fluid and placenta in the diagnosis of congenital toxoplasmosis. This is a descriptive cohort study of pregnant women with toxoplasmosis followed up in Rio de Janeiro, Brazil. Real-time PCR was performed in samples of maternal blood, amniotic fluid, placenta, and blood of newborns. In addition, histopathological examination of placentas was performed, and data collected from babies were collected. 116 pregnant women were followed up and 298 samples were analyzed. One (0.9%) pregnant woman presented positive PCR in the blood, 3 (3.5%) in the amniotic fluid, 1 (2.3%) in the placenta and no newborn had positive PCR in the blood. Histopathological study was suggestive of toxoplasmosis infection in 24 (49%) placentas. Six (5.2%) newborns were diagnosed with congenital toxoplasmosis, and only cases with positive PCR in the amniotic fluid had correlation of the PCR result with the diagnosis of congenital infection. Both maternal and blood samples of newborns and placenta did not prove to be promising in the diagnosis of congenital toxoplasmosis. Further studies are needed to evaluate the real role of molecular diagnosis in other biological materials rather than the amniotic fluid.

Single Dose of Tranexamic Acid Effectively Reduces Blood Loss in Patients Undergoing Spine Surgery: A Prospective Randomized Controlled Trial.

OBJECTIVE: To evaluate the efficacy of oral administration of tranexamic acid (TXA) in spine surgery to achieve blood loss reduction. METHODS: Sixty patients undergoing major surgery of the spine were randomly assigned into 2 groups. Group 1 was assigned as the control group and the other group comprised patients who received oral administration of TXA 2 hours before surgery. Outcome measures included intraoperative blood loss, postoperative blood loss, hematologic parameters, blood transfusion needed, and surgical complications. RESULTS: Sixty patients linked up with the inclusion criteria. Intraoperative blood loss was significantly lower in the TXA oral group than in the control group; total blood loss in the TXA group was 930.66 ± 614 mL, which was lower than in the control group, with 1075.66 ± 956.11 mL. The mean reduction of hemoglobin was almost the same in both groups. Similarly, the total transfusion package received was lower, and the number of complications and length of stay were akin in both groups. A logistic regression model was performed with patients who had blood loss >1000 mL and surgery time >230 minutes. This result was related to the risk of bleeding, with an odds ratio of 1.31, 95% confidence interval, 1.004-1.023, P = 0.004, independent of the group. CONCLUSIONS: Oral TXA is as an effective measure for reducing total blood loss among patients undergoing elective spine surgery.

Virulence Potential and Antibiotic Susceptibility of S. aureus Strains Isolated from Food Handlers.

Staphylococcus spp. are common members of the normal human flora. However, some Staphylococcus species are recognised as human pathogens due to the production of several virulence factors and enterotoxins that are particularly worrisome in food poisoning. Since many of Staphylococcal food poisoning outbreaks are typically associated with cross-contamination, the detection of S. aureus on food handlers was performed. Hand swabs from 167 food handlers were analysed for the presence of S. aureus. More than 11% of the samples were positive for S. aureus. All S. aureus strains were isolated and analysed for the presence of virulence and enterotoxin genes, namely, sea, seb, sec, sed, seg, sei, tsst-1 and pvl. The same strains were phenotypically characterised in terms of antibiotic susceptibility using the disc diffusion method and antimicrobial agents from 12 different classes. A low prevalence of antibiotic-resistant strains was found, with 55.6% of the strains being sensitive to all of the antimicrobial agents tested. However, a high prevalence of resistance to macrolides was found, with 44.4% of the strains showing resistance to erythromycin. At least one of the virulence or toxin genes was detected in 61.1% of the strains, and seg was the most prevalent toxin gene, being detected in 44.4% of the strains.

The Matrix Effect in the RT-PCR Detection of SARS-CoV-2 Using Saliva without RNA Extraction.

The present work focuses on the detection of SARS-CoV-2 in saliva, contributing to understanding the inhibition effect of the matrix and its influence on the results. Detection of viral genes ORF1ab, N, and E was performed by RT-PCR using saliva directly in the reaction without RNA extraction. Different amounts of saliva were spiked with increasing amounts of viral RNA from COVID-19 patients and subjected to RT-PCR detection. In parallel, 64 saliva samples from confirmed COVID-19 patients were used in two different amounts directly in the RT-PCR reaction and their results compared. The presence of saliva in the RT-PCR always causes a positive shift of the Ct values, but a very high between-person variability of its magnitude was obtained, with increases ranging from 0.93 to 11.36. Viral targets are also affected differently depending on the initial number of viral particles. Due to inhibitors present in saliva, the duplication of sample volume causes only 48 to 61% of the expected Ct value decrease depending on the viral target gene. The use of saliva has advantages, but also limitations, due to potential inhibitors present in the matrix. However, the choice of the target and the right amount of sample may significantly influence the results.

Biological Activity of NHC-Gold-Alkynyl Complexes Derived from 3-Hydroxyflavones.

In this paper we describe the synthesis of new N-heterocyclic carbene (NHC) gold(I) derivatives with flavone-derived ligands with a propargyl ether group. The compounds were screened for their antimicrobial and anticancer activities, showing greater activity against bacteria than against colon cancer cells (Caco-2). Complexes [Au(L2b)(IMe)] (1b) and [Au(L2b)(IPr)] (2b) were found to be active against both Gram-positive and Gram-negative strains. The mechanism of action of 1b was evaluated by measurement of thioredoxin reductase (TrxR) and dihydrofolate reductase (DHFR) activity, besides scanning electron microscopy (SEM). Inhibition of the enzyme thioredoxin reductase is not observed in either Escherichia Coli or Caco-2 cells; however, DHFR activity is compromised after incubation of E. coli cells with complex 1b. Moreover, loss of structural integrity and change in bacterial shape is observed in the images obtained from scanning electron microscopy (SEM) after treatment E. coli cells with complex 1b.

Scientometric Analysis of Publications from 2004-2021 in the Spine Surgery Field: A Latin American Perspective.

OBJECTIVE: To determine characteristics of Latin American (LA) productivity in spine surgery published worldwide between 2004 and 2021 compared between periods and global literature. METHODS: A comprehensive search about LA productivity in the field of spine surgery using the Scopus and PubMed databases was performed in February 2022. The results were limited to articles published in indexed journals from 2004 to 2021. RESULTS: A total of 1447 publications were identified in the study period. The number of publications has increased across evaluated decades, with 583 between 2004 and 2013 (58.3/year) and 864 between 2014 and 2021 (108/year), and a yearly increase was demonstrated (P = 0.0001). Comparing the most productive year in the first (2012) and last decade (2020), a 1.79-fold increase was demonstrated. Brazil ranked first in productivity (51.14%), followed by Mexico (26.40%) and Argentina (8.64%). Coluna/Columna published the largest number, with 309 articles (21.35%). The top 10 institutions published at least 475 (32.82%) and the most productive was the University of Campinas (Brazil, 74). CONCLUSIONS: This scientometric study is one of the first regional evaluations worldwide. The number of publications in the spine surgery field in Latin America has continued to increase over evaluated decades from 58.3 per year to 108, and a 1.79-fold increase between the most productive years for each decade. Brazil is still the greatest contributor (51.14%), with Mexico (26.40%) and Argentina (8.64%) as growing contributor countries. Most publications were classified as Level of Evidence 4, and this result reflects the importance of continuous research development in the quality of research for our region.