Current diagnostic standards involve severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) detection in nasopharyngeal swabs (NPS), but saliva is an attractive and noninvasive option for ...diagnosis. The objectives were to determine the performance of saliva in comparison with NPS for detecting SARS‐CoV‐2 and to compare the optimized home brew reverse‐transcription polymerase chain reaction (RT‐PCR) with a commercial RT‐PCR. Paired NPS and saliva specimens were prospectively collected and tested by RT‐PCR from patients presenting at an emergency room with signs and symptoms compatible with coronavirus disease‐2019. A total of 348 samples from 174 patients were tested by RT‐PCR assays. Among 174 patients with symptoms, 63 (36%) were SARS‐CoV‐2 positive in NPS using the optimized home‐brew PCR. Of these 63 patients, 61 (98%) were also positive in saliva. An additional positive SARS‐CoV‐2 saliva was detected in a patient with pneumonia. Kappa Cohen's coefficient agreement between NPS and saliva was 0.96 (95% confidence interval CI, 0.90–0.99). Median Ct values in NPS versus saliva were 18.88 (interquartile range IQR, 15.60–23.58; range, 11.97–38.10) versus 26.10 (IQR, 22.75–30.06; range, 13.78–39.22), respectively (p < .0001). The optimized home‐brew RT‐PCR demonstrated higher analytical and clinical sensitivity compared with the commercial RT‐PCR assay. A high sensitivity (98%) and agreement (kappa 0.96) in saliva samples compared to NPS was demonstrated when using an optimized home‐brew PCR even when the viral load in saliva was lower than in NPS. This noninvasive sample is easy to collect, requires less consumable and avoids discomfort to patients. Importantly, self‐collection of saliva can diminish exposure to healthcare personnel.
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•Fine detail of gene expression in each cell is achievable by single-cell (sc)RNA-seq.•scRNA-seq has generated gene expression cell atlases for helminth species.•Host cell responses ...to infection can be profiled at the single-cell level.•Organoids provide an in vitro system for helminth research.
How parasites develop and survive, and how they stimulate or modulate host immune responses are important in understanding disease pathology and for the design of new control strategies. Microarray analysis and bulk RNA sequencing have provided a wealth of data on gene expression as parasites develop through different life-cycle stages and on host cell responses to infection. These techniques have enabled gene expression in the whole organism or host tissue to be detailed, but do not take account of the heterogeneity between cells of different types or developmental stages, nor the spatial organisation of these cells. Single-cell RNA-seq (scRNA-seq) adds a new dimension to studying parasite biology and host immunity by enabling gene profiling at the individual cell level. Here we review the application of scRNA-seq to establish gene expression cell atlases for multicellular helminths and to explore the expansion and molecular profile of individual host cell types involved in parasite immunity and tissue repair. Studying host-parasite interactions in vivo is challenging and we conclude this review by briefly discussing the applications of organoids (stem-cell derived mini-tissues) to examine host-parasite interactions at the local level, and as a potential system to study parasite development in vitro. Organoid technology and its applications have developed rapidly, and the elegant studies performed to date support the use of organoids as an alternative in vitro system for research on helminth parasites.
Abstract
BACKGROUND
Nocturnal hypertension (NH) is a potent cardiovascular risk factor described frequently in people with HIV (PWH). Isolated NH (INH) is less well reported in PWH because of the ...need for ambulatory blood pressure monitoring (ABPM) in office normotensive patients. We aim to document the prevalence of NH and INH and the clinical factors associated with these phenotypes.
METHODS
Cross-sectional study from an HIV program in Argentina. Office and ABPM measurements, as well as clinical and laboratory exploration, were performed. We defined INH as NH with daytime normotension in patients with office normotension.
RESULTS
We obtained ABPM in 66 PWH, 60% male, aged 44.7 (IQR 27–69) years; 87% receiving antiretroviral therapy, and 86.2% virologically suppressed. ABPM-based hypertension prevalence was 54.7% (95% CI: 42.5–66.3). The prevalence of NH was 48.5% (32/66), while the INH prevalence was 19.7% (95% CI: 11.7–30.9). No differences were found regarding sex, HIV viral load, CD4+ T lymphocytes count, or years of infection between normotensive and INH patients. Multiple linear regression model adjusted for sex and age determined that body mass index (β = 0.93, P < 0.01), plasma uric acid (β = 0.25, P = 0.04), plasma potassium (β = −10.1, P = 0.01), and high-sensitivity C-reactive protein (hs-CRP) (β = 0.78, P = 0.02) independently predicted nocturnal systolic blood pressure (BP) in PWH. In a multiple logistic regression model adjusted for age and sex, the presence of sedentariness, plasma potassium <4 mEq/L, BMI, and hs-CRP levels were predictors of INH.
CONCLUSION
INH is highly prevalent in PWH. Metabolic and inflammatory markers predict nocturnal SBP in PWH.
Graphical Abstract
Graphical Abstract
Abstract The aim of this work was to determine Echinococcus granulosus sensu lato species and genotypes in intermediate and definitive hosts and in human isolates from endemic regions of Argentina ...and Brazil including those where no molecular data is available by a combination of classical and alternative molecular tools. A total of 227 samples were isolated from humans, natural intermediate and definitive hosts. Amplification of cytochrome c oxidase subunit I gene fragment was performed and a combination of Alu I digestion assay, High Resolution Melting analysis (HRM) assay and DNA sequencing was implemented for Echinococcus species/genotype determination. E. granulosus sensu stricto (G1) was found in sheep (n = 35), cattle (n = 67) and dogs (n = 5); E. ortleppi (G5) in humans (n = 3) and cattle (n = 108); E. canadensis (G6) in humans (n = 2) and E. canadensis (G7) in pigs (n = 7). We reported for the first time the presence of E. ortleppi (G5) and E. canadensis (G6) in humans from San Juan and Catamarca Argentinean provinces and E. canadensis (G7) in pigs from Cordoba Argentinean province. In this work, we widened molecular epidemiology studies of E. granulosus s. l. in South America by analyzing several isolates from definitive and intermediate hosts, including humans from endemic regions were such information was scarce or unavailable. The presence of different species/genotypes in the same region and host species reinforce the need of rapid and specific techniques for accurate determination of Echinococcus species such as the ones proposed in this work.
We describe a case of complete nasal agenesis and absence of the nasal fossae, without alterations in the central nervous system. The physical and intellectual development of the infant to date has ...been absolutely normal. Opening of the nasal respiratory passage was not required in our patient as he did not show respiratory problems during deglutition. - Microphthalmia in the right eye with iridoretinal coloboma and right cryptorchidism were also noted. When the child was 9 months old a right orbital asymmetry became evident due to a growth deficit of the microphthalmic eye. This improved after placement of an expandable prosthesis in the orbit to stimulate its growth. - When the child is 4 years old, he will start to use a nasal prosthesis supported by implantology. Final reconstruction of the nasal pyramid will take place after he is 15 years of age.
The mechanisms by which poikilothermic organisms ensure that biological processes are robust to temperature changes are largely unknown. Temperature compensation, the ability of circadian rhythms to ...maintain a relatively constant period over the broad range of temperatures resulting from seasonal fluctuations in environmental conditions, is a defining property of circadian networks. Temperature affects the alternative splicing (AS) of several clock genes in fungi, plants, and flies, but the splicing factors that modulate these effects to ensure clock accuracy throughout the year remain to be identified. Here we show that GEMIN2, a spliceosomal small nuclear ribonucleoprotein assembly factor conserved from yeast to humans, modulates low temperature effects on a large subset of pre-mRNA splicing events. In particular, GEMIN2 controls the AS of several clock genes and attenuates the effects of temperature on the circadian period in Arabidopsis thaliana . We conclude that GEMIN2 is a key component of a posttranscriptional regulatory mechanism that ensures the appropriate acclimation of plants to daily and seasonal changes in temperature conditions.
RNA processing, an important step in the regulation of gene expression, is mediated by proteins and RNA molecules that are highly sensitive to variations in temperature conditions. Most organisms do not control their own body temperature. Therefore, molecular mechanisms must have evolved that ensure that biological processes are robust to temperature changes. Here we identify a protein that buffers the effect of temperature on biological timing by enhancing the assembly of the spliceosome, a large ribonucleoprotein complex involved in RNA processing in organisms ranging from yeast to humans, and thereby controlling the alternative splicing of clock genes.
Background Chronic granulomatous disease (CGD) is a rare primary immunodeficiency caused by inborn errors of the phagocyte nicotinamide adenine dinucleotide phosphate oxidase complex. From the first ...year of life onward, most affected patients display multiple, severe, and recurrent infections caused by bacteria and fungi. Mycobacterial infections have also been reported in some patients. Objective Our objective was to assess the effect of mycobacterial disease in patients with CGD. Methods We analyzed retrospectively the clinical features of mycobacterial disease in 71 patients with CGD. Tuberculosis and BCG disease were diagnosed on the basis of microbiological, pathological, and/or clinical criteria. Results Thirty-one (44%) patients had tuberculosis, and 53 (75%) presented with adverse effects of BCG vaccination; 13 (18%) had both tuberculosis and BCG infections. None of these patients displayed clinical disease caused by environmental mycobacteria, Mycobacterium leprae , or Mycobacterium ulcerans . Most patients (76%) also had other pyogenic and fungal infections, but 24% presented solely with mycobacterial disease. Most patients presented a single localized episode of mycobacterial disease (37%), but recurrence (18%), disseminated disease (27%), and even death (18%) were also observed. One common feature in these patients was an early age at presentation for BCG disease. Mycobacterial disease was the first clinical manifestation of CGD in 60% of these patients. Conclusion Mycobacterial disease is relatively common in patients with CGD living in countries in which tuberculosis is endemic, BCG vaccine is mandatory, or both. Adverse reactions to BCG and severe forms of tuberculosis should lead to a suspicion of CGD. BCG vaccine is contraindicated in patients with CGD.
The first fossil remains of vertebrates, invertebrates, plants and palynomorphs of the Chorrillo Formation (Austral Basin), about 30km to the SW of the town of El Calafate (Province of Santa Cruz), ...are described. Fossils include the elasmarian (basal Iguanodontia) Isasicursor santacrucensis gen. et sp. nov., the large titanosaur Nullotitan glaciaris gen. et sp. nov., both large and small Megaraptoridae indet., and fragments of sauropod and theropod eggshells. The list of vertebrates is also composed by the Neognathae Kookne yeutensis gen. et sp. nov., two isolated caudal vertebrae of Mammalia indet., and isolated teeth of a large mosasaur. Remains of fishes, anurans, turtles, and snakes are represented by fragmentary material of low taxonomical value, with the exception of remains belonging to Calyptocephalellidae. On the other hand, a remarkable diversity of terrestrial and freshwater gastropods has been documented, as well as fossil woods and palinological assemblages. The Chorrillo Formation continues south, in the Las Chinas River valley, southern Chile, where it is called Dorotea Formation. Both units share in their lower two thirds abundant materials of titanosaurs, whose remains cease to appear in the upper third, registering only elasmarians (Chorrillo Formation) and hadrosaurs (Dorotea Formation). Above both units there are levels with remains of invertebrates and marine reptiles. It is striking that the dinosaurs of the lower two thirds of the Chorrillo and Dorotea formations are represented by large basal titanosaurs and Megaraptoridae coelurosaurs, being the Saltasaurinae and Aeolosaurinae sauropods and Abelisauridae theropods totally absent. In contrast, these taxa are dominant components in sedimentary units of central and northern Patagonia (e.g., Allen, Los Alamitos, La Colonia formations). Such differences could reflect, in part, a greater antiquity (i.e., late Campanian-early Maastrichtian) for the Chorrillo fossils, or, more probably, different environmental conditions. Thus, knowledge of the biota of the southern tip of Patagonia is expanded, particularly those temporarily close to the K-Pg boundary.
Current genetic evidence in mice indicates that SIRT1 has potent tumor suppressor activity in a variety of cancer models, with no evidence yet for SIRT1 oncogenic activity in vivo. We report here ...that transgenic Sirt1 expression is oncogenic in murine thyroid and prostate carcinogenesis initiated by Pten-deficiency. Based on mRNA expression analyses of pre-tumoral murine thyroids, we find that SIRT1 increases c-MYC transcriptional programs. Moreover, we show higher c-MYC protein levels in murine thyroid cancers from Sirt1 transgenic mice. Similarly, SIRT1 is overexpressed in human thyroid cancers and it is positively correlated with c-MYC protein levels. Finally, we show in cultured thyroid cancer cells that SIRT1 stabilizes c-MYC protein. These results implicate SIRT1 as a new candidate target for the treatment of thyroid carcinomas.
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