This paper reports the development of a novel electrochemical platform based on graphite electrodes modified with copolymer poly(aniline-4-aminophenol) and anti-triiodothyronine, integrated into the ...design of an electrochemical immunosensor for thyroid hormone, allowing free triiodothyronine (T3) detection in real serum samples. The proposed copolymer showed synergistic characteristics among its original polymers, which led to good results in the biofunctionalization step. A specific antibody for T3 was immobilized on copolymer poly(aniline-4-aminophenol). In the presence of target T3, an immunological reaction occurs with anti-T3, being observed a current decrease proportional to T3 concentration. The decrease was monitored by differential pulse voltammetry, detecting up to 0.60 pg mL
−1
and showing good stability, maintaining 90% of its response after 60 days of storage. This platform shows linear relationship between the anodic current and T3 concentration with linear regression as
y
= 616.79 − 26.03
x
(
r
2
= 0.9976). The immunosensor shows suitable for detection of thyroid hormones in real serum samples, as well as potential for use in detection of other disease biomarkers.
Clinical features and outcomes of SARS-CoV-2 infections diverge in different countries. The aim of this study was to describe clinical characteristics and outcomes in a cohort of patients ...hospitalized with SARS-CoV-2 in Argentina. Multicenter prospective cohort study of greater than or equal to18 years-old patients with confirmed SARS-CoV-2 infection consecutively admitted to 19 hospitals in Argentina. Multivariable logistic regression models were used to identify variables associated with 30-day mortality and admission to intensive care unit (ICU). A total of 809 patients were analyzed. Median age was 53 years, 56% were males and 71% had at least one comorbidity. The most common comorbidities were hypertension (32%), obesity (23%) and diabetes (17%). Disease severity at admission was classified as mild 25%, moderate 51%, severe 17%, and critical 7%. Almost half of patients (49%) required supplemental oxygen, 18% ICU, and 12% invasive ventilation. Overall, 30-day mortality was 11%. Factors independently associated with ICU admission were male gender (OR 1.81; 95%CI 1.16-2.81), hypertension (OR 3.21; 95%CI 2.08-4.95), obesity (OR 2.38; 95%CI 1.51-3.7), oxygen saturation less than or equal to93% (OR 6.45; 95%CI 4.20-9.92) and lymphopenia (OR 3.21; 95%CI 2.08-4.95). Factors independently associated with 30-day mortality included age greater than or equal to60 years-old (OR 2.68; 95% CI 1.63-4.43), oxygen saturation less than or equal to93% (OR 3.19; 95%CI 1.97-5.16) and lymphopenia (OR 2.65; 95%CI 1.64-4.27). This cohort validates crucial clinical data on patients hospitalized with SARS-CoV-2 in Argentina.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The objective of this research was to provide longitudinal, corpus-based evidence of actual teacher behaviour with respect to the teaching of second language (L2) pronunciation in a communicative ...language learning context. The data involved 40 hours of videotaped lessons from three experienced teachers recorded four times at 100-hour increments during the 400-hour programme for grade six (11- to 12-year-olds) francophone learners in Quebec, Canada. The videotaped lessons were initially transcribed and coded for individual pronunciation teaching episodes, then analysed in terms of their type, linguistic target and impact. Results demonstrated that pronunciation teaching episodes were infrequent (accounting for 10% of all language-related episodes), that pronunciation teaching targeted individual sounds (to the exclusion of other aspects of pronunciation) and that most pronunciation teaching episodes were not incorporated into lesson plans but instead involved various kinds of corrective feedback in response to individual student errors. These findings, which clarify results of previous survey-based studies of teachers' in-class behaviour, provide evidence that might be used to address teachers' concerns regarding the place, scope and role of pronunciation instruction in L2 teaching and teacher training.
Matrix metalloproteinases have been implicated in diabetic microvascular complications. However, little is known about the pathophysiological links between MMP-10 and the renin-angiotensin system ...(RAS) in diabetic kidney disease (DKD). We tested the hypothesis that MMP-10 may be up-regulated in early stage DKD, and could be down-regulated by angiotensin II receptor blockade (telmisartan). Serum MMP-10 and TIMP-1 levels were measured in 268 type 2 diabetic subjects and 111 controls. Furthermore, histological and molecular analyses were performed to evaluate the renal expression of Mmp10 and Timp1 in a murine model of early type 2 DKD (db/db) after telmisartan treatment. MMP-10 (473 ± 274 pg/ml vs. 332 ± 151; p = 0.02) and TIMP-1 (573 ± 296 ng/ml vs. 375 ± 317; p < 0.001) levels were significantly increased in diabetic patients as compared to controls. An early increase in MMP-10 and TIMP-1 was observed and a further progressive elevation was found as DKD progressed to end-stage renal disease. Diabetic mice had 4-fold greater glomerular Mmp10 expression and significant albuminuria compared to wild-type, which was prevented by telmisartan. MMP-10 and TIMP-1 are increased from the early stages of type 2 diabetes. Prevention of MMP-10 upregulation observed in diabetic mice could be another protective mechanism of RAS blockade in DKD.
This study's design was a cross-cultural validation of the Neck Disability Index and Neck Pain and Disability Scale.
This study's objective was to translate, culturally adapt, and validate a ...Brazilian Portuguese version of the Neck Disability Index (NDI-BR) and the Neck Pain and Disability Scale (NPDS-BR).
Although several valid measures exist for measurement of neck pain and functional impairment, these measures have yet been validated in Brazilian Portuguese. Successful linguistic and cultural translation may allow appropriate cross-cultural comparison for clinical and laboratory research analysis.
The NDI-BR and NPAD-BR were culturally and linguistically translated from English into Brazilian Portuguese. The translated version of the instrument was administered to 203 patients at a midsize hospital in southern Brazil. Psychometric evaluation included factor analysis, internal reliability measures, test-retest reliability at 1 and 7 days, and criterion validity comparison with the Brazilian version of the SF-36.
Factor analyses demonstrated a single-factor subscale for the NDI-BR and three subscales for the NPDS-BR. An item analysis showed a high degree of internal consistency for the NDI-BR (r = 0.74) and the three subscales of the NPDS-BR (subscale 1, r = 0.89; subscale 2, r = 0.81; subscale 3, r = 0.72). Test-retest reliability was also acceptable at for the NDI-BR (0.98 at baseline and 0.48 at 7 days) and subset one (0.96 at baseline and 0.91 at 7 days), subset 2 (0.96 at baseline and 0.62 at 7 days), and subset 3 (0.52 at baseline and 0.45 at 7 days) of the NPDS-BR. Construct validity was established during comparison of the Brazilian version of the SF-36. Only items associated with physical role, bodily pain, and emotional role failed significant correlation.
A reliable and valid Portuguese version of the Neck Disability Index and Neck Pain and DisabilityScale was developed, which will facilitate the examination of functional performance within a large patient population, as well as cross-cultural comparisons.
Abstract
STUDY QUESTION
Can maternal plasma cell-free DNA (cfDNA) detect chromosomal anomalies in early pregnancy loss (EPL) and recurrent pregnancy loss (RPL)?
SUMMARY ANSWER
Genome-wide cfDNA ...testing can serve as an alternative to cytogenetic analysis in products of conception (POCs) in RPLs and can guide further management.
WHAT IS KNOWN ALREADY
Random chromosomal anomalies are the single most common cause for EPL and RPL. Cytogenetic analysis in POCs may be used to direct management in RPL because the detection of random chromosomal anomalies can eliminate further unwarranted testing.
STUDY DESIGN, SIZE, DURATION
This was a prospective diagnostic test study from March 2018 to January 2019 of 109 patients experiencing pregnancy loss before 14 weeks gestation at a tertiary-care academic medical center.
PARTICIPANTS/MATERIALS, SETTING, METHODS
Blood samples were drawn for genome-wide cfDNA testing prior to chorionic villous sampling for cytogenetic analysis of POCs with both short-term cultures (STCs) and long-term cultures (LTCs). Final analysis included 86 patients with non-mosaic cytogenetic results in POCs and available cfDNA results. Aneuploidy detection rates by cfDNA testing and POC cytogenetic analysis were compared. The first 50 samples served as the Training Set to establish pregnancy loss-specific log-likelihood ratio (LLR) thresholds using receiver-operator characteristic (ROC)-like analyses. These were then used for the entire cohort.
MAIN RESULTS AND THE ROLE OF CHANCE
Seventy-eight samples (71.5%) had results available from both STC and LTC; 12 samples (11%) had a result from STC only, and 7 samples (6.4%) had a result from LTC only. A chromosomal anomaly was detected in 55/86 (64%). The rates of chromosomal anomalies were 61, 72, 73 and 44% in patients undergoing their first, second, third and ≥4th pregnancy losses, respectively. The median cfDNA fetal fraction was 5%. With standard LLR thresholds used for noninvasive prenatal screening, the sensitivity of cfDNA in detecting aneuploidy was 55% (30/55) and with a specificity of 100% (31/31). Using pregnancy loss-specific LLR thresholds, the sensitivity of cfDNA in detecting aneuploidy was 82% (45/55), with a specificity of 90% (28/31). The positive and negative likelihood ratios were 8.46 and 0.20, respectively. Fetal sex was correctly assigned in all cases.
LIMITATIONS, REASONS FOR CAUTION
Cases with a false-positive result by cfDNA analysis would not receive the indicated RPL workup. Specificity could be improved by using a fetal fraction (FF) cutoff of 4%, but this would result in exclusion of more than a quarter of cases.
WIDER IMPLICATIONS OF THE FINDINGS
cfDNA-based testing can serve as an alternative to POC cytogenetic analysis and can guide further RPL management: if cfDNA demonstrates aneuploidy, no further action is taken and if no abnormality is detected, the recommended RPL workup is performed.
STUDY FUNDING/COMPETING INTEREST(S)
Cell-free DNA testing was funded by Illumina, Inc., San Diego, CA. Y.Y. is a member of Illumina’s Clinical Expert Panel and has received travel grants. A.B. has received travel grants from Illumina. All authors have no competing interest to declare.
Cutaneous and mucocutaneous leishmaniasis are parasitic diseases characterized by skin manifestations. In Brazil, Leishmania (Leishmania) amazonensis is one of the etiological agents of cutaneous ...leishmaniasis. The therapeutic arsenal routinely employed to treat infected patients is unsatisfactory, especially for pentavalent antimonials, as they are often highly toxic, poorly tolerated and of variable effectiveness. This study aimed to evaluate in vitro the leishmanicidal activity of toxins isolated from Crotalus durissus terrificus venom as a new approach for the treatment of leishmaniasis.
The comparative effects of crotamine, crotoxin, gyrotoxin, convulxin and PLA2 on bone marrow-derived macrophages infected with L. (L.) amazonensis as well as the release of TGF-β from the treated macrophages were studied.
Crotamine had the strongest inhibitory effect on parasite growth rate (IC50: 25.65±0.52 μg/mL), while convulxin showed the weakest inhibitory effect (IC50: 52.7±2.21 μg/mL). In addition, TGF-β was significantly reduced after the treatment with all toxins evaluated.
The Crotalus durissus terrificus toxins used in this study displayed significant activity against L. (L.) amazonensis, indicating that all of them could be a potential alternative for the treatment of cutaneous leishmaniasis.
The detection of distribution patterns of genetic diversity of plant and animal species has contributed to the understanding of biodiversity and evolutionary history of the Atlantic Forest. We used ...microsatellite markers to access the genetic diversity and structure of 26 populations and 527 adult individuals of Euterpe edulis, a native palm which is an important food resource for fauna and is intensively exploited due to economic reasons. We found high genetic diversity and inbreeding in all populations analyzed. We report highest rates of inbreeding for this species, which could reflect the anthropic impacts of selective cutting, fragmentation, and change in foraging behavior from pollinators and less availability and mobility of large dispersers. We detected by STRUCTURE, two genetic groups, Northern and Southern, which divide the Brazilian Atlantic Forest geographically. These groups have low genetic admixtures, but we found a region of lineage hybridization in the contact zone with low recent gene flow. Distribution pattern of this species corroborates results from previous studies reporting the Last Glacial Maximum (LGM) have shaped the structuring of the species through movements of forests' expansion and contraction. The STRUCTURE analysis of each group revealed the presence of genetic subgroups with low rates of recurrent gene flow. Southern subgroups have higher rates of admixtures than the Northern subgroups, revealing greater historical connectivity of forests in this region.
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•The first structures of septin coiled coils are described.•Two overlapping helical interfaces permit both parallel and antiparallel arrangements.•The antiparallel structures are ...stabilized by polar residues in a positions.•Modelling and NMR data imply that both arrangements are energetically viable.•Antiparallel homodimeric coiled coils are expected to mediate filament pairing.
Septins are an example of subtle molecular recognition whereby different paralogues must correctly assemble into functional filaments important for essential cellular events such as cytokinesis. Most possess C-terminal domains capable of forming coiled coils which are believed to be involved in filament formation and bundling. Here, we report an integrated structural approach which aims to unravel their architectural diversity and in so doing provide direct structural information for the coiled-coil regions of five human septins. Unexpectedly, we encounter dimeric structures presenting both parallel and antiparallel arrangements which are in consonance with molecular modelling suggesting that both are energetically accessible. These sequences therefore code for two metastable states of different orientations which employ different but overlapping interfaces. The antiparallel structures present a mixed coiled-coil interface, one side of which is dominated by a continuous chain of core hydrophilic residues. This unusual type of coiled coil could be used to expand the toolkit currently available to the protein engineer for the design of previously unforeseen coiled-coil based assemblies. Within a physiological context, our data provide the first atomic details related to the assumption that the parallel orientation is likely formed between septin monomers from the same filament whilst antiparallelism may participate in the widely described interfilament cross bridges necessary for higher order structures and thereby septin function.
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