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Saliva, salivary glands, gingival crevicular fluid, and supragingival biofilms may harbor SARS‐CoV‐2 RNA. This observational study aimed to investigate the presence and load of SARS‐CoV‐2 RNA in supragingival, and subgingival biofilms obtained from intensive care unit (ICU) patients. A convenience sample, composed of 52 COVID‐19+ participants (48.6 ± 14.8 years, 26.9% females), were evaluated for pre‐existing comorbidities, number of teeth, and periodontal data [visible plaque (VPI), bleeding on probing (BOP), periodontal probing depth (PPD), and attachment loss (AL)]. Supragingival and subgingival samples (SubDeep: four sites with the deepest PPD; SubRemain: remaining shallower sites) were analyzed by RT‐qPCR with corresponding cycle quantification (Cq). Statistical analyses considered the individual (P= 5%). Twenty‐six participants tested positive for dental biofilms (Biofilm+) with 96.2% of them being positive for subgingival samples. Pre‐existing comorbidities, number of teeth examined, VPI, PPD, AL, and BOP were similar between Biofilm+ and Biofilm‐. SubDeep PPD (3.72 ± 0.86), AL (4.34 ± 1.33), and % of BOP (66.0 ± 31.1) values were significantly greater compared to SubRemain values (2.84 ± 0.48, 3.37 ± 0.34, and 20.4 ± 24.1, respectively). Biofilm+ Cqs showed no association with the periodontal condition. Cqs from Nasopharynx/Oropharynx (Naso/Oro; n = 36) were similar between Biofilm+ and Biofilm‐ participants. Length of time since ICU intake, last Naso/Oro RT‐qPCR readings, onset of COVID‐19 symptoms, and biofilm samplings were greater for Biofilm‐. ICU patients harbored SARS‐CoV‐2 RNA in supragingival and subgingival biofilms, irrespective of the periodontal condition, and systemic viral load. The high number of positive patients highlights the need to better understand this habit to provide adequate oral care.

The aim of the present study was to compare the neuromuscular, morphological, and functional responses to a high-velocity resistance training (HVRT) program between three cohorts: middle-aged adults (40–55 years, n= 18), healthy older adults (> 60 years, n= 18), and mobility-limited older adults (n= 8). Participants were tested before and after a 4-week control period and then assigned to a 12-week HVRT intervention. Investigated outcomes included ultrasound-derived muscle thickness and quality, maximal dynamic strength (1RM), maximal voluntary isometric contraction (MVIC), and muscle activation (sEMG), as well as muscle power and functional performance. After the intervention, quadriceps muscle thickness, 1RM, and sEMG improved in all three groups (all p< 0.05), whereas muscle quality improved only in middle-aged and older participants (p≤ 0.001), and MVIC only in middle-aged and mobility-limited older adults (p< 0.05). With a few exceptions, peak power improved in all groups from 30–90% 1RM (p< 0.05) both when tested relative to pre-training or post-training 1RM workloads (all p< 0.05). Both mobility-limited older adults and older adults improved their short physical performance battery score (p< 0.05). Chair stand, stair climb, maximal gait speed, and timed up-and-go performance, on the other hand, improved in all three groups (p< 0.05), but no change was observed for habitual gait speed and 6-min walk test performance. Overall, our results demonstrate that a HVRT intervention can build a stronger foundation in middle-aged individuals so that they can better deal with age-related impairments at the same time that it can mitigate already present physiological and functional impairments in older adults with and without mobility-limitation.

Background: Quality of life (QoL) is an important health index for older adults. Aim: The aim of this study was to compare the effects of 16 weeks of aerobic training to 8 weeks of aerobic followed by 8 weeks of combined (i.e., resistance and aerobic exercises) training, as well as to a control group on the QoL of older women exercising in the aquatic environment. Methods: 52 older women were first randomized to either aerobic training (n= 35) or a control group (n= 17). After 8 weeks of intervention, participants initially assigned to the aerobic training group were again randomized to either 8 additional weeks of aerobic (n= 17) or combined training (n= 18). Aerobic training was performed at the heart rate percentage associated with the anaerobic threshold, while resistance training sets were performed at maximal effort. The control group performed low-intensity water-based therapeutic exercises. QoL was assessed before (week 0) and after the intervention (week 17) using the WHOQOL-BREEF and WHOQOL-OLD questionnaires. Generalized Estimating Equations (GEE) and Bonferroni post hoc tests (α= 0.05) were used to compare time points and groups. Results: QoL improved significantly only in the training groups after the 16-week training intervention, whereas it remained unchanged in the control group. In addition, autonomy, environment, and present, past and future activities domains were more impacted after combined training. Conclusion: QoL improved only in the water-based training groups, and the addition of resistance exercises to the training program resulted in additional benefits to autonomy, environment, and past, present, and future activities domains. Trial registration: Clinical Trials NCT03892278.

About 4% to 7% of the non–small-cell lung cancer patients have anaplastic lymphoma kinase (ALK) rearrangements, and specific targeted therapies improve patients' outcomes significantly. ALKgene fusions are detected by immunohistochemistry or fluorescent in situhybridization as gold standards in South America. Next-generation sequencing–based assays are a reliable alternative, able to perform simultaneous detection of multiple events from a single sample. We analyzed 4240 non–small-cell lung cancer samples collected in 37 hospitals from Chile, Brazil, and Peru, where ALK rearrangements were determined as part of their standard of care (SofC) using either immunohistochemistry or fluorescent in situhybridization. A subset of 1450 samples was sequenced with the Oncomine Focus Assay (OFA), and the concordance with the SofC tests was measured. An orthogonal analysis was performed using a real-time quantitative PCR echinoderm microtubule-associated protein-like 4-ALK fusion detection kit. ALK fusion prevalence is similar for Chile (3.67%; N = 2142), Brazil (4.05%; N= 1013), and Peru (4.59%; N= 675). Although a comparison between OFA and SofC assays showed similar sensitivity, OFA had significantly higher specificity and higher positive predictive value, which opens new opportunities for a more specific determination of ALKgene rearrangements.

El neonato tiene un diámetro horizontal de la córnea, generalmente de hasta 10mm, con un crecimiento de hasta 2mm en los primeros 2 años de vida. Presentamos un caso de megalocórnea, un trastorno raro, recesivo, ligado al cromosoma X, en un niño de 3 meses de edad, buscando revisar lo que la literatura médica aporta como información sobre la enfermedad, así como los parámetros diagnósticos y de seguimiento de sus principales diagnósticos diferenciales.

Being part of the development of environmentally clean and safe sustainable technologies photocatalysis is attracting increasing attention. During the last decade, great attention has been paid to the synthesis of different photocatalysts possessing high photocatalytic activity, whereas fundamental studies concerning the underlying photocatalytic processes have rarely been executed. The knowledge of these processes is, however, of utmost importance for the understanding of the reaction mechanism and thus for a better design of photocatalytic systems. The transient absorption spectroscopy (TAS) is one widely used method to study such fundamental processes. The present review paper focuses on the application of TAS in the UV-Vis-IR regions to investigate the charge carrier dynamics in ultrafast and nano-to-millisecond time regime. Hereby, the photo induced processes occurring in different materials will be discussed. Moreover, further attention is also paid to nanocomposite-based systems, in which different materials are used concomitantly to promote more efficient photocatalytic processes.

To assess the incidence, costs, and mortality associated with chronic critical illness (CCI), and to identify clinical predictors of CCI in a general intensive care unit.

The objective of the current study was to evaluate the mechanism of absorption and metabolism of a PEGylated peptide, MRL-1 (46 kDa), after s.c. dosing in dogs and rats. Thoracic lymph duct-cannulated (LDC) dog and rat models were developed that allowed continuous collection of lymph for up to 8 days. When [3H]MRL-1 was administered s.c. to LDC dogs, ∼73% of the administered radioactivity was recovered in pooled lymph over a period of 120 hours, suggesting that lymphatic uptake is the major pathway of s.c. absorption for this peptide. In agreement with these data, the systemic exposure of radioactivity related to [3H]MRL-1 in LDC dogs was decreased proportionately when compared with that in noncannulated control dogs. After i.v. dosing with [3H]MRL-1 in LDC dogs, 20% of the administered radioactivity was recovered in pooled lymph over 168 hours, suggesting some level of recirculation of radioactivity related to [3H]MRL-1 from the plasma compartment into the lymphatic system. Experiments conducted in the LDC rat model also resulted in similar conclusions. Analysis of injection site s.c. tissue showed significant metabolism of [3H]MRL-1, which provides an explanation for the <100% bioavailability of therapeutic proteins and peptides after s.c. dosing. After s.c. dosing, the major circulating components in plasma were the parent peptide and the PEG-linker [3H]MRL-2. The metabolism profiles in lymph were similar to those in plasma, suggesting that the loss of peptide was minimal during lymphatic transport. After i.v. dosing in rats, [3H]MRL-1 was metabolized and excreted primarily in the urine as metabolites.

To assess the incidence, costs, and mortality associated with chronic critical illness (CCI), and to identify clinical predictors of CCI in a general intensive care unit.

The mechanism underlying subcutaneous absorption of macromolecules and factors that can influence this process were studied in rats using PEGylated erythropoietins (EPOs) as model compounds. Using a thoracic lymph duct cannulation (LDC) model, we showed that PEGylated EPO was absorbed from the subcutaneous injection site mainly via the lymphatic system in rats, which is similar to previous reports in sheep. After subcutaneous administration, the serum exposure was reduced by ∼70% in LDC animals compared with that in the control animals, and most of the systemically available dose was recovered in the lymph. In both LDC and intact rats, the total radioactivity recoveries in excreta after subcutaneous administration were high (70–80%), indicating that catabolism, not poor absorption, was the main cause for the observed low bioavailability (30–40%). Moreover, catabolism of PEGylated EPO was found with both rat subcutaneous tissue homogenate and lymph node cell suspensions, and a significant amount of dose-related breakdown fragments was found in the lymph of LDC rats. In addition, the bioavailability of PEGylated EPOs was shown to be 2- to 4-fold lower in “fat rats,” indicating that physiologic features pertinent to lymphatic transport can have a profound impact on subcutaneous absorption. Limited studies in dogs also suggested similar subcutaneous absorption mechanisms. Collectively, our results suggest that the lymphatic absorption mechanism for macromolecules is probably conserved among commonly used preclinical species, e.g., rats and dogs, and that mechanistic understanding of the subcutaneous absorption mechanism and associated determinants should be helpful in biologic drug discovery and development.

The mechanism underlying subcutaneous absorption of macromolecules and factors that can influence this process were studied in rats using PEGylated erythropoietins (EPOs) as model compounds. Using a thoracic lymph duct cannulation (LDC) model, we showed that PEGylated EPO was absorbed from the subcutaneous injection site mainly via the lymphatic system in rats, which is similar to previous reports in sheep. After subcutaneous administration, the serum exposure was reduced by ∼70% in LDC animals compared with that in the control animals, and most of the systemically available dose was recovered in the lymph. In both LDC and intact rats, the total radioactivity recoveries in excreta after subcutaneous administration were high (70–80%), indicating that catabolism, not poor absorption, was the main cause for the observed low bioavailability (30–40%). Moreover, catabolism of PEGylated EPO was found with both rat subcutaneous tissue homogenate and lymph node cell suspensions, and a significant amount of dose-related breakdown fragments was found in the lymph of LDC rats. In addition, the bioavailability of PEGylated EPOs was shown to be 2- to 4-fold lower in "fat rats," indicating that physiologic features pertinent to lymphatic transport can have a profound impact on subcutaneous absorption. Limited studies in dogs also suggested similar subcutaneous absorption mechanisms. Collectively, our results suggest that the lymphatic absorption mechanism for macromolecules is probably conserved among commonly used preclinical species, e.g., rats and dogs, and that mechanistic understanding of the subcutaneous absorption mechanism and associated determinants should be helpful in biologic drug discovery and development.

Low-molecular-weight organic acids with one or more carboxylic groups are ubiquitous. In soils, they can originate from leaching of plants, litter decomposition, plant-roots exudation, and microbial activity. Their presence in the soil may favor the formation of soluble organo-metallic complexes that improve the transport of Zn, Cu, Fe, and Mn to plant-root surfaces via diffusion. The current study sought to determine if some of the organic acids (OA) in soils and a cover-crop residue influence the diffusive flux (DF) of Zn, Cu, Mn, and Fe. Two OA were added to two Oxisols (Typic Haplustox): a clayey Dark Red Latosol (DRL) and a sandy-loam Red Yellow Latosol (RYL). Acetic and citric acid were added to achieve concentrations of 0, 250, 500, 1000, and 2000 mmol (m3 soil)–1. The effect of adding plant material (pearl millet) on the soil DF of the cationic micronutrients was also determined. Soil diffusive flux was evaluated by incubating positively charged and negatively charged exchange-resin membranes with the soil in PVC diffusion chambers for 15 d. Desorption of Zn, Cu, Fe, Mn, and OA from the resins was performed with 0.5 mol l–1 HCl. The results demonstrated that the DF of the cationic micronutrients increased with the addition of organic acid. The DF of Zn and Mn occurred mostly towards the cationic resin, whereas the diffusive flux of Cu and Fe occurred mostly towards the anionic resin. Apparently, the dissolution of oxides and/or complexation of micronutrients adsorbed to the solid phase or in the soil solution contributed to the obtained results. Citric acid was more efficient than acetic acid in maintaining a larger DF value for Zn, Cu, and Fe. The addition of millet plant material to the soil increased the DF in the following order: Mn > Cu > Fe > Zn; Mn moved towards the cationic resin, and the other micronutrients moved towards the anionic resin. These findings suggest that organic compounds play an important role in the short-distance transport of cationic micronutrients in highly weathered soils.

MTII, an agonist of melanocortinergic receptors, is a well-documented anorexigenic agent in rats. Many investigators have reported its effects on feeding without considering concurrent alterations in other behaviors. Accordingly, we performed studies to simultaneously measure nocturnal feeding, drinking, activity, and temperature of rats after intracerebroventricular (third ventricle) administration of a wide dose range of MTII (0.05–500 ng). We observed that MTII modulates these physiological parameters in a dose-dependent manner. Low doses of MTII (0.05 ng) caused reductions in feeding without alterations in body temperature, drinking, or activity. In contrast, hyperthermia and disrupted drinking patterns, along with food intake reductions, were evident at doses exceeding 50 ng. The fact that low doses altered only feeding, whereas higher doses affected a range of parameters, suggests that certain melanocortin-induced behavioral changes may be mediated by distinct populations of melanocortin receptors with varying affinities or that those changes seen at higher doses may be nonspecific in nature.

Data for 401 depressed outpatients with mood reactivity who participated in a randomized trial comparing placebo, imipramine, and phenelzine were analyzed for predictors of differential response by stepwise multiple regression techniques. Features of the Columbia criteria for atypical depression including oversleeping, overeating, severe anergy, and pathologic rejection sensitivity were each predictive of a poorer response to imipramine than to phenelzine onlywhen compared to those patients with none of the features. These features were not additive in their contribution to differential outcome. Lack of endogenous features was not predictive of a differential drug treatment response. Compared with patients who have no symptoms of atypical depression, patients with any of the four features had an inferior imipramine response rather than a superior phenelzine response. These analyses indicate that the clear differential responsivity to medication treatment in atypical depression is not simply related to any one defining symptom and that further correlates of this apparent biological heterogeneity need to be explored.

Vidigal, T. H. D. A., Spatz, L., Nunes, D. N., Simpson, A. J. G., Carvalho, O. S., and Dias Neto, E. 1998Biomphalaria spp:Identification of the intermediate snail hosts ofSchistosoma mansoniby polymerase chain reaction amplification and restriction enzyme digestion of the ribosomal RNA gene intergenic spacer.Experimental Parasitology89, 180–187. The intermediate hosts ofS. mansoniin South America,B. glabrata, B. tenagophila, andB. straminea, were identified by restriction fragment length polymorphism (RFLP) analysis of the internal transcribed spacer region of the rRNA gene. The restriction patterns obtained withDdeI were the most informative of the eight enzymes that were tried. The RFLP profiles obtained using this enzyme are highly distinctive and exhibit low levels of intraspecific polymorphism even between specimens collected from diverse regions of Brazil, Argentine, Paraguay, and Uruguay. The method proved useful for the identification of DNA extracted from eggs, permitting species identification while preserving the living adult specimens for further studies.

Human tumors exhibit two fundamentally important characteristics, extensive genetic alteration and clonality. Although it is still unclear to what extent tumors have an elevated mutational burden as compared with normal tissue, their clonality results in their ready detection. Thus, assaying tissues for clonal alterations at frequently mutated microsatellitelocirepresents a viable approach to cancer diagnosis. The most remarkable extension of this concept is that not only can cancer cells be detected in biological samples, but tumor DNA can also be directly detected in the serum or plasma of patients with some forms of cancer. This recent finding is currently being explored but may represent an important contribution to future diagnostic strategies.Copyright 1998 Academic Press

Gastric cancer (GC) is the fifth most common type of cancer worldwide with high incidences in Asia, Central, and South American countries. This patchy distribution means that GC studies are neglected by large research centers from developed countries. The need for further understanding of this complex disease, including the local importance of epidemiological factors and the rich ancestral admixture found in Brazil, stimulated the implementation of the GE4GAC project. GE4GAC aims to embrace epidemiological, clinical, molecular and microbiological data from Brazilian controls and patients with malignant and pre-malignant gastric disease. In this letter, we summarize the main goals of the project, including subject and sample accrual and current findings.