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1.
Quintessence Int ; 55(3): 212-222, 2024 Mar 27.
Article in English | MEDLINE | ID: mdl-37975644

ABSTRACT

OBJECTIVES: This systematic review aimed to search the literature for the answer to the following questions. In human studies: Does the osseodensification technique increase the resonance frequency analysis given in implant stability quotient value and the insertion torque value compared to the conventional technique? In animal studies: Does the osseodensification technique increase implant stability quotient, bone-to-implant contact, and bone area fraction occupancy values over the conventional technique? DATA SOURCES: A search for studies was carried out in eight databases until August 2021. Out of the 447 publications found, 11 were included. RESULTS: In human studies, osseodensification technique showed better results for implant stability quotient values with a summarized median difference of 8.57. As for secondary stability, there was no significant difference, with summarized median difference of 4.49 in favor of the osseodensification technique. In animal studies, all results were favorable to the osseodensification technique. Regarding insertion torque, bone-to-implant contact, and bone area fraction occupancy between counterclockwise osseodensification technique vs conventional, the mean difference was 46.79 for insertion torque, 2.17 for bone-to-implant contact, and 2.11 for bone area fraction occupancy. High heterogeneity was observed between the studies. The risk of bias in humans was moderate in three studies and low in one; and in animal studies, four presented moderate risk, two low risk, and one high risk. The certainty of evidence ranged from low to moderate. CONCLUSION: The osseodensification technique showed improvement concerning the resonance frequency and the insertion torque value of implants in human studies. In addition, it increased the values of bone-to-implant contact, bone area fraction occupancy, and implant stability quotient in animal studies, when compared to the conventional technique.


Subject(s)
Dental Implants , Osseointegration , Animals , Humans , Dental Implantation, Endosseous/methods , Osteotomy/methods , Torque
2.
J Dent ; 138: 104728, 2023 11.
Article in English | MEDLINE | ID: mdl-37783372

ABSTRACT

OBJECTIVES: We aimed to compare subjective (S) selective carious tissue removal using hand instruments versus objective (O) removal using a self-limiting polymer bur in a single-blind cluster-randomized controlled superiority trial. METHODS: 115 children (aged 7-8 years) with ≥1 vital primary molar with a deep dentin lesion (>1/2 dentin depth) were included and randomized (60 S/55 O); all eligible molars in a child were treated identically (91 S/86 O). Cavities were prepared and carious tissue on pulpal walls selectively removed using hand instruments (S) or a self-limiting polymer bur (Polybur P1, Komet), followed by restoration using a glass hybrid material (Equia Forte, GC). Treatment time and satisfaction data have been reported in a 1-year-interim report. We here report on 2 year survival (tooth retained with or without further retreatments being needed, or tooth exfoliated), analyzed using multi-level Cox-regression analysis, as well as success (ART criteria 0/1, no pulpal complications, no re-intervention needed, or tooth extraction). RESULTS: 71 restorations in S and 65 in O were examined after a mean (SD, range) of 22 (11; 3-31) months, of which 50 S and 48 O restorations were successful and 70 S and 65 O survived. The majority of failures were restorative, not pulpal, and distribution of ART codes was not significant different between groups. Risk of failure was not significantly associated with the removal protocol (HR; 95 % CI: 0.95; 0.51-1.78), and also not age, sex or dental arch, while single surfaced restorations showed significantly lower hazard (0.14; 0.06-0.37). CONCLUSION: There was no significant difference in success or survival between objective and subjective carious tissue removal. CLINICAL SIGNIFICANCE: In primary teeth, subjective selective excavation had no disadvantage compared with objective excavation, which required a separate instrument (polymer-based bur) for carious tissue removal. Polymer-based burs may be particularly useful when standardized excavation is needed.


Subject(s)
Dental Caries , Polymers , Child , Humans , Single-Blind Method , Dentin/pathology , Dental Pulp , Dental Caries/surgery , Dental Caries/pathology , Tooth, Deciduous , Dental Restoration, Permanent/methods
3.
Nucleic Acids Res ; 51(14): 7520-7540, 2023 08 11.
Article in English | MEDLINE | ID: mdl-37309887

ABSTRACT

Removal of the mRNA 5' cap primes transcripts for degradation and is central for regulating gene expression in eukaryotes. The canonical decapping enzyme Dcp2 is stringently controlled by assembly into a dynamic multi-protein complex together with the 5'-3'exoribonuclease Xrn1. Kinetoplastida lack Dcp2 orthologues but instead rely on the ApaH-like phosphatase ALPH1 for decapping. ALPH1 is composed of a catalytic domain flanked by C- and N-terminal extensions. We show that T. brucei ALPH1 is dimeric in vitro and functions within a complex composed of the trypanosome Xrn1 ortholog XRNA and four proteins unique to Kinetoplastida, including two RNA-binding proteins and a CMGC-family protein kinase. All ALPH1-associated proteins share a unique and dynamic localization to a structure at the posterior pole of the cell, anterior to the microtubule plus ends. XRNA affinity capture in T. cruzi recapitulates this interaction network. The ALPH1 N-terminus is not required for viability in culture, but essential for posterior pole localization. The C-terminus, in contrast, is required for localization to all RNA granule types, as well as for dimerization and interactions with XRNA and the CMGC kinase, suggesting possible regulatory mechanisms. Most significantly, the trypanosome decapping complex has a unique composition, differentiating the process from opisthokonts.


Subject(s)
Endoribonucleases , RNA Caps , Trypanosoma , Endoribonucleases/metabolism , RNA Caps/genetics , RNA Caps/metabolism , RNA Stability , RNA, Messenger/genetics , RNA, Messenger/metabolism , RNA-Binding Proteins/genetics , RNA-Binding Proteins/metabolism , Trypanosoma/genetics
4.
J Biol Chem ; 299(1): 102726, 2023 01.
Article in English | MEDLINE | ID: mdl-36410438

ABSTRACT

The characterization of protein-protein interactions (PPIs) is of high value for understanding protein function. Two strategies are popular for identification of PPIs direct from the cellular environment: affinity capture (pulldown) isolates the protein of interest with an immobilized matrix that specifically captures the target and potential partners, whereas in BioID, genetic fusion of biotin ligase facilitates proximity biotinylation, and labeled proteins are isolated with streptavidin. Whilst both methods provide valuable insights, they can reveal distinct PPIs, but the basis for these differences is less obvious. Here, we compare both methods using four different trypanosome proteins as baits: poly(A)-binding proteins PABP1 and PABP2, mRNA export receptor MEX67, and the nucleoporin NUP158. With BioID, we found that the population of candidate interacting proteins decreases with more confined bait protein localization, but the candidate population is less variable with affinity capture. BioID returned more likely false positives, in particular for proteins with less confined localization, and identified low molecular weight proteins less efficiently. Surprisingly, BioID for MEX67 identified exclusively proteins lining the inner channel of the nuclear pore complex (NPC), consistent with the function of MEX67, whereas the entire NPC was isolated by pulldown. Similarly, for NUP158, BioID returned surprisingly few PPIs within NPC outer rings that were by contrast detected with pulldown but instead returned a larger cohort of nuclear proteins. These rather significant differences highlight a clear issue with reliance on a single method to identify PPIs and suggest that BioID and affinity capture are complementary rather than alternative approaches.


Subject(s)
Proteins , Proteomics , Biotinylation , Nuclear Pore , Proteins/chemistry , Proteomics/methods , Streptavidin/chemistry
5.
Int J Mol Sci ; 23(23)2022 Nov 24.
Article in English | MEDLINE | ID: mdl-36498985

ABSTRACT

Ecto-nucleoside triphosphate diphosphohydrolases (NTPDases) are enzymes located on the surface of the T. cruzi plasma membrane, which hydrolyze a wide range of tri-/-diphosphate nucleosides. In this work, we used previously developed genetically modified strains of Trypanosoma cruzi (T. cruzi), hemi-knockout (KO +/−) and overexpressing (OE) the TcNTPDase-1 gene to evaluate the parasite infectivity profile in a mouse model of acute infection (n = 6 mice per group). Our results showed significantly higher parasitemia and mortality, and lower weight in animals infected with parasites OE TcNTPDase-1, as compared to the infection with the wild type (WT) parasites. On the other hand, animals infected with (KO +/−) parasites showed no mortality during the 30-day trial and mouse weight was more similar to the non-infected (NI) animals. In addition, they had low parasitemia (45.7 times lower) when compared with parasites overexpressing TcNTPDase-1 from the hemi-knockout (OE KO +/−) group. The hearts of animals infected with the OE KO +/− and OE parasites showed significantly larger regions of cardiac inflammation than those infected with the WT parasites (p < 0.001). Only animals infected with KO +/− did not show individual electrocardiographic changes during the period of experimentation. Together, our results expand the knowledge on the role of NTPDases in T. cruzi infectivity, reenforcing the potential of this enzyme as a chemotherapy target to treat Chagas disease (CD).


Subject(s)
Chagas Disease , Trypanosoma cruzi , Mice , Animals , Chagas Disease/genetics , Chagas Disease/parasitology , Heart , Disease Models, Animal
6.
Mar Pollut Bull ; 185(Pt B): 114364, 2022 Dec.
Article in English | MEDLINE | ID: mdl-36435019

ABSTRACT

Sea turtles are considered as bio-indicators for monitoring the efficiency of restoration measures to reduce marine litter impacts on health. However, the lack of extended and standardised empirical data has prevented the accurate analysis of the factors influencing litter ingestion and the relationships with individual health. Historic data collected from 1988 and standard data collected from 2016 were harmonised to enable such analyses on necropsied loggerhead turtles (Caretta caretta) in eight Mediterranean and North-East Atlantic countries. Litter was found in 69.24 % of the 1121 individuals, mostly single-use and fishing-related plastics. Spatial location, sex and life history stage explained a minor part of litter ingestion. While no relationships with health could be detected, indicating that all individuals can be integrated as bio-indicators, the mechanistic models published in literature suggest that the high proportion of plastics in the digestive contents (38.77 % per individual) could have long-term repercussions on population dynamics.


Subject(s)
Turtles , Animals , Plastics , Autopsy , Europe , Eating
7.
Indian J Hematol Blood Transfus ; 38(3): 492-498, 2022 Jul.
Article in English | MEDLINE | ID: mdl-35747568

ABSTRACT

Gastric mucosa-associated lymphoid tissue non-Hodgkin lymphoma (gMALT NHL) is the second most common gastrointestinal lymphoma (50% of all gastric lymphomas), being closely associated with Helicobacter pylori infection, justifying that antibiotic therapy is effective in over 75% of all cases. This is a retrospective study analyzing all adult gMALT NHL cases diagnosed and treated in a single center for 8 years, focusing on demographic features, treatment outcomes, and survival analysis. Sixty patients with a median age of 61 years (53.3% female gender) were analyzed. Most of the cases had localized disease (66.7% were Lugano stage I) and had low IPI scores (median: 1). There was a high prevalence of Helicobacter pylori infection (68.3%). Nearly 97% of the cases received treatment for the disease, a median of one line; 55% of the patients treated endured complete response after first-line therapy (mostly antibiotics). Median overall survival time and median progression-free survival time were not reached. The mean follow-up time was 81.8 months (95% CI: [73.3-90.3]). Thirty-six patients (60%) achieved a 3-year follow-up time; the mortality rate was 15% at the end of the study. Age superior to 65 years and transformation into DLBCL were statistically significant negative prognostic markers for survival in this study (p = 0.006 and p = 0.033, respectively). Our study confirms that gMALT NHL is an indolent disease with long-term survival. Many patients, however, are exposed to several treatment lines along their disease course.

8.
Microvasc Res ; 140: 104303, 2022 03.
Article in English | MEDLINE | ID: mdl-34914941

ABSTRACT

Systemic inflammatory response, as observed in sepsis and severe COVID-19, may lead to endothelial damage. Therefore, we aim to compare the extent of endothelial injury and its relationship to inflammation in both diseases. We included patients diagnosed with sepsis (SEPSIS group, n = 21), mild COVID-19 (MILD group, n = 31), and severe COVID-19 (SEVERE group, n = 24). Clinical and routine laboratory data were obtained, circulating cytokines (INF-γ, TNF-α, and IL-10) and endothelial injury markers (E-Selectin, Tissue Factor (TF) and von Willebrand factor (vWF)) were measured. Compared to the SEPSIS group, patients with severe COVID-19 present similar clinical and laboratory data, except for lower circulating IL-10 and E-Selectin levels. Compared to the MILD group, patients in the SEVERE group showed higher levels of TNF-α, IL-10, and TF. There was no clear relationship between cytokines and endothelial injury markers among the three studied groups; however, in SEVERE COVID-19 patients, there is a positive relationship between INF-γ with TF and a negative relationship between IL-10 and vWF. In conclusion, COVID-19 and septic patients have a similar pattern of cytokines and endothelial dysfunction markers. These findings highlight the importance of endothelium dysfunction in COVID-19 and suggest that endothelium should be better evaluated as a therapeutic target for the disease.


Subject(s)
COVID-19/pathology , Endothelium, Vascular/pathology , SARS-CoV-2 , Sepsis/pathology , Systemic Inflammatory Response Syndrome/blood , Aged , Aged, 80 and over , Biomarkers , Blood Cell Count , C-Reactive Protein/analysis , COVID-19/blood , COVID-19/complications , COVID-19/physiopathology , E-Selectin/blood , Female , Humans , Interferon-gamma/blood , Interleukin-10/blood , Male , Middle Aged , Retrospective Studies , Sepsis/blood , Sepsis/complications , Sepsis/physiopathology , Severity of Illness Index , Systemic Inflammatory Response Syndrome/etiology , Systemic Inflammatory Response Syndrome/physiopathology , Thromboplastin/analysis , Tumor Necrosis Factor-alpha/analysis , von Willebrand Factor/analysis
9.
Braz. dent. sci ; 25(1): 1-5, 2022. ilus
Article in English | LILACS, BBO - Dentistry | ID: biblio-1354241

ABSTRACT

The aim of this study is to report a clinical case of lesion sterilization and tissue repair in primary molar, with follow-up until the eruption of the permanent successor. A 6-year-old male patient came to the Pediatric Dentistry Clinic at Faculdade Sao Leopoldo Mandic in Campinas-SP, with his mother, complaining of "caries in several teeth". On clinical examination, it was found that tooth 85 had a severe carious lesion with pulp involvement and fistula. Radiographically, radiolucency was observed in the furcation region. It was then decided to perform lesion sterilization and tissue repair of the tooth with CTZ paste. After 6 months of the procedure, the tooth was clinically and radiographically normal and after 3 years it was observed that tooth 85 was in complete root resorption. After extraction, the permanent successor erupted naturally without clinical or radiographic alterations. It can be concluded that the present clinical case demonstrated success in the use of CTZ paste in the lesion sterilization and tissue repair of primary molars, until the complete eruption of the permanent successor. (AU)


O objetivo desse estudo é relatar o caso clínico de esterilização da lesão e reparação de tecidos em molar decíduo com pasta CTZ, com acompanhamento até a erupção do pré-molar sucessor. Paciente do sexo masculino, 6 anos de idade, apresentou-se à Clínica de Odontopediatria da Faculdade São Leopoldo Mandic em Campinas-SP, acompanhado de sua mãe, queixando-se de "cárie em vários dentes". Ao exame clínico, verificou-se que o dente 85 apresentava lesão de cárie severa com envolvimento pulpar e fístula. Radiograficamente, observou-se radiolucidez na região de furca. Optou-se, então, por realizar a esterilização da lesão e reparação de tecidos do dente com pasta CTZ. Após 6 meses da realização do procedimento, o dente apresentava-se clinica e radiograficamente normal e após 3 anos observou-se que o elemento 85 estava em rizólise completa. Feita a extração, o permanente sucessor erupcionou naturalmente sem alterações clínicas ou radiográficas. Pode-se concluir que o presente caso clínico demonstrou sucesso do emprego da pasta CTZ na esterilização da lesão e reparação de tecidos de molar decíduo, até completa erupção do permanente sucessor. (AU)


Subject(s)
Humans , Male , Child , Pulpectomy , Tooth, Deciduous , Pediatric Dentistry , Endodontics
10.
Epileptic Disord ; 23(5): 719-732, 2021 Oct 01.
Article in English | MEDLINE | ID: mdl-34612815

ABSTRACT

People with focal epilepsies are known to under-document their seizures, but there is no data on self-documentation in adults with genetic (idiopathic) generalized epilepsy (GGE/IGE). We assessed the accuracy of self-evaluation of typical absences (TA) or myoclonic seizures (MS) in adults with IGE based on home video-EEG telemetry (HVET). Patients' own estimates were compared to the objective count of definite TA and MS, performed visually. We considered definite TA as generalized spike-wave discharges (GSWD) that met any of the following criteria: 1) coinciding with clear behavioural arrest on video, 2) followed after a few seconds by positive indication that an absence occurred, or 3) in the absence of video, consistently coinciding with clear motor arrest, as evidenced by interruption of continuous muscle activity. For each patient, we also classified probable TA as GSWDs that were longer than those corresponding to the shortest definite TA on HVET or based on the most recent sleep-deprived EEG (SDEEG). From the first 300 consecutive adults who had HVET, 24 had IGE with TA and / or MS; 23 were women. Only one patient had newly diagnosed IGE. Erroneous self-assessment of TA and MS was noted in 16/24 patients (66.7%). Seizures were overestimated in nine (37.5%) and underestimated in seven (29.2%). Only one patient (4.2%) documented all her TA and MS without false-positive estimates. Overestimation (but not underestimation) of TA on HVET could be predicted when patients reported daily or multiple weekly TA and a recent SDEEG was either normal or contained only subclinical GSWD (p=0.0095). Under- and over-self-documentation of TA and MS occurred in two thirds of adults with GGE/IGE, with substantial impact on their outpatient management and treatment. Diagnostic HVET is a useful tool for the detection of erroneous self-evaluation in these patients.


Subject(s)
Epilepsy, Generalized , Adult , Diagnostic Self Evaluation , Electroencephalography , Epilepsies, Myoclonic/diagnosis , Epilepsies, Myoclonic/genetics , Epilepsy, Absence , Epilepsy, Generalized/diagnosis , Female , Humans , Immunoglobulin E , Male , Seizures/diagnosis , Self-Assessment , Telemetry
11.
Sci Rep ; 11(1): 15223, 2021 07 27.
Article in English | MEDLINE | ID: mdl-34315957

ABSTRACT

The role of innate immunity in COVID-19 is not completely understood. Therefore, this study explored the impact of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection on the expression of Pattern Recognition Receptors (PRRs) in peripheral blood cells and their correlated cytokines. Seventy-nine patients with severe COVID-19 on admission, according to World Health Organization (WHO) classification, were divided into two groups: patients who needed mechanical ventilation and/or deceased (SEVERE, n = 50) and patients who used supplementary oxygen but not mechanical ventilation and survived (MILD, n = 29); a control group (CONTROL, n = 17) was also enrolled. In the peripheral blood, gene expression (mRNA) of Toll-like receptors (TLRs) 3, 4, 7, 8, and 9, retinoic-acid inducible gene I (RIGI), NOD-like receptor family pyrin domain containing 3 (NLRP3), interferon alpha (IFN-α), interferon beta (IFN-ß), interferon gamma (IFN-γ), interferon lambda (IFN-λ), pro-interleukin(IL)-1ß (pro-IL-1ß), and IL-18 was determined on admission, between 5-9 days, and between 10-15 days. Circulating cytokines in plasma were also measured. When compared to the COVID-19 MILD group, the COVID-19 SEVERE group had lower expression of TLR3 and overexpression of TLR4.


Subject(s)
COVID-19/diagnosis , COVID-19/genetics , Gene Expression Regulation , Toll-Like Receptor 3/blood , Toll-Like Receptor 3/genetics , Aged , COVID-19/blood , COVID-19/therapy , Female , Humans , Male , Middle Aged , Prognosis , Respiration, Artificial
12.
Indian J Hematol Blood Transfus ; 37(3): 492-496, 2021 Jul.
Article in English | MEDLINE | ID: mdl-33424149

ABSTRACT

Gastric diffuse large B cell lymphoma (DLBCL) represents the majority of all gastric lymphomas. We report a series of gastric DLBCL diagnosed and treated in a single center, between 2010 and 2018 (included). We retrospectively analyzed the population demographic features, treatment outcomes and survival. One-hundred-and-one patients were studied, 50.5% males and median age of 64 years [23-94]. Lugano staging was I in 16.8%, II1 in 20.8%, II2 in 10.9%, IIE in 13.9% and IV in 34.7% of cases. Twenty percent had Helicobacter pylori infection. R-CHOP-like therapy was used as first line in 96.9% of the patients. A complete response was achieved in 80% after first line therapy. At 3-years of follow-up (FU), 54% were in complete remission. The mean FU time was 73.6 months. Median overall survival and median progression free survival were not reached. We identified seven factors with negative impact in survival: age above 65 years-old (p < 0.01), ECOG 2-3 (p < 0.01), B symptoms (p = 0.001), bulky disease (p = 0.003), IPI 3-4 (p = 0.001), more than 3 treatment lines (p < 0.01), absence of response to first line treatment (p < 0.01). This study demonstrates that gastric DLBCL is a potentially curable disease with R-CHOP-like therapy, entailing long term survival and comparing well with other published series.

13.
Curr Eye Res ; 46(1): 31-34, 2021 01.
Article in English | MEDLINE | ID: mdl-32482105

ABSTRACT

PURPOSE/AIM: Floppy eyelid syndrome (FES) is an ocular manifestation of obstructive sleep apnea (OSA), but no studies have analyzed whether it can be improved by nocturnal continuous positive airway pressure (CPAP) therapy. The aim of this study was to analyze the effect of CPAP on FES by comparing objective measurements before and after 6 months of CPAP therapy. MATERIALS AND METHODS: We conducted a prospective study of 47 patients (74.5% males) with newly diagnosed OSA at a secondary care Portuguese hospital who underwent objective diagnostic testing for FES (upper eyelid eversion for >6 seconds and tarsal conjunctival exposure and upper eyelid laxity ≥1.5 mm). Patients with hyperelastic eyelid or FES were re-evaluated by the same ophthalmologist (blinded to the patients' condition) after 6 months of CPAP therapy. RESULTS: Mean apnea hypopnea index (AHI), analyzed as number of events per hour, was 28.7 ± 18.6 overall and 42.8 ± 20.0 in the supine position. Thirty-four percent of patients had FES. Mean AHI in the supine position was significantly higher in patients with FES (p = .041) and was an independent predictor of FES (p = .034; OR = 0.48). Severe OSA was significantly associated with FES (p = .023). FES resolved in 53.8% of patients after CPAP therapy. Patients with non-reversible FES had more severe OSA and worse airway access according to the Mallampati classification (from class I: visualization of soft palate and entire uvula, to class IV: soft palate not visible). CONCLUSIONS: A higher AHI in the supine position may be predictive of FES. CPAP therapy might reverse FES and patients with non-reversible FES appear to have more severe OSA and a worse airway access.


Subject(s)
Continuous Positive Airway Pressure , Eyelid Diseases/physiopathology , Sleep Apnea, Obstructive/physiopathology , Sleep Apnea, Obstructive/therapy , Aged , Eyelid Diseases/diagnosis , Female , Humans , Male , Middle Aged , Polysomnography , Prospective Studies , Supine Position
15.
Clin Infect Dis ; 72(11): e736-e741, 2021 06 01.
Article in English | MEDLINE | ID: mdl-32964918

ABSTRACT

BACKGROUND: A local increase in angiotensin 2 after inactivation of angiotensin-converting enzyme 2 by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may induce a redox imbalance in alveolar epithelium cells, causing apoptosis, increased inflammation and, consequently, impaired gas exchange. We hypothesized that N-acetylcysteine (NAC) administration could restore this redox homeostasis and suppress unfavorable evolution in patients with coronavirus disease 2019 (COVID-19). METHODS: This was a double-blind, randomized, placebo-controlled, single-center trial conducted at the Emergency Department of Hospital das Clínicas, São Paulo, Brazil, to determine whether NAC in high doses can avoid respiratory failure in patients with COVID-19. We enrolled 135 patients with severe COVID-19 (confirmed or suspected), with an oxyhemoglobin saturation <94% or respiratory rate >24 breaths/minute. Patients were randomized to receive NAC 21 g (~300 mg/kg) for 20 hours or dextrose 5%. The primary endpoint was the need for mechanical ventilation. Secondary endpoints were time of mechanical ventilation, admission to the intensive care unit (ICU), time in ICU, and mortality. RESULTS: Baseline characteristics were similar between the 2 groups, with no significant differences in age, sex, comorbidities, medicines taken, and disease severity. Also, groups were similar in laboratory tests and chest computed tomography scan findings. Sixteen patients (23.9%) in the placebo group received endotracheal intubation and mechanical ventilation, compared with 14 patients (20.6%) in the NAC group (P = .675). No difference was observed in secondary endpoints. CONCLUSIONS: Administration of NAC in high doses did not affect the evolution of severe COVID-19. CLINICAL TRIALS REGISTRATION: Brazilian Registry of Clinical Trials (REBEC): U1111-1250-356 (http://www.ensaiosclinicos.gov.br/rg/RBR-8969zg/).


Subject(s)
COVID-19 Drug Treatment , Acetylcysteine/therapeutic use , Brazil , Double-Blind Method , Humans , Respiration, Artificial , SARS-CoV-2 , Treatment Outcome
16.
World J Hepatol ; 12(9): 661-671, 2020 Sep 27.
Article in English | MEDLINE | ID: mdl-33033571

ABSTRACT

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a major cause of liver disease worldwide. The diagnosis of nonalcoholic steatohepatitis (NASH), the most severe form of NAFLD, is crucial and has prognostic and therapeutic implications. However, currently this diagnosis is based on liver biopsy and has several limitations. AIM: To evaluate the performance of gadoxetic acid-enhanced magnetic resonance imaging (GA-MRI) in differentiating isolated steatosis from NASH in patients with NAFLD. METHODS: In this prospective study, 56 patients with NAFLD (18 with isolated steatosis and 38 with NASH) underwent GA-MRI. The contrast enhancement index (CEI) was calculated as the rate of increase of the liver-to-muscle signal intensity ratio from before and 20 min after intravenous GA administration. Between-group differences in mean CEI were examined using Student's t test. The area under the receiver operator characteristic curve and the diagnostic performance of gadoxetic acid-enhanced magnetic resonance imaging were evaluated. RESULTS: The mean CEI for all subjects was 1.82 ± 0.19. The mean CEI was significantly lower in patients with NASH than in those with isolated steatosis (P = 0.008). Two CEI cut-off points were used: < 1.66 (94% specificity) to characterize NASH and > 2.00 (89% sensitivity) to characterize isolated steatosis. CEI values between 1.66 and 2.00 indicated liver biopsy, and the procedure could be avoided in 40% of patients with NAFLD. CONCLUSION: GA-MRI is an effective noninvasive method that may be useful for the differentiation of NASH from isolated steatosis, and could help to avoid liver biopsy in patients with NAFLD.

17.
Front Microbiol ; 11: 434, 2020.
Article in English | MEDLINE | ID: mdl-32256481

ABSTRACT

Ecto-Nucleoside Triphosphate Diphosphohydrolases are enzymes that hydrolyze tri- and/or diphosphate nucleosides. Evidences pointed out to their participation in Trypanosoma cruzi virulence, infectivity, and purine acquisition. In this study, recombinant T. cruzi knocking out or overexpressing the TcNTPDase-1 gene were built, and the role of TcNTPDase-1 in the in vitro interaction with VERO cells was investigated. Results show that epimastigote forms of hemi-knockout parasites showed about 50% lower level of TcNTPDase-1 gene expression when compared to the wild type, while the T. cruzi overexpressing this gene reach 20 times higher gene expression. In trypomastigote forms, the same decreasing in TcNTPDase-1 gene expression was observed to the hemi-knockout parasites. The in vitro infection assays showed a reduction to 51.6 and 59.9% at the adhesion and to 25.2 and 26.4% at the endocytic indexes to the parasites knockout to one or other allele (Hygro and Neo hemi-knockouts), respectively. In contrast, the infection assays with T. cruzi overexpressing TcNTPDase-1 from the WT or Neo hemi-knockout parasites showed an opposite result, with the increasing to 287.7 and 271.1% at the adhesion and to 220.4 and 186.7% at the endocytic indexes, respectively. The parasitic load estimated in infected VERO cells by quantitative real time PCR corroborated these findings. Taken together, the partial silencing and overexpression of the TcNTPDase-1 gene generated viable parasites with low and high infectivity rates, respectively, corroborating that the enzyme encoded for this gene plays an important role to the T. cruzi infectivity.

18.
PeerJ ; 7: e7845, 2019.
Article in English | MEDLINE | ID: mdl-31660267

ABSTRACT

Intraspecific agonistic interactions are widespread across the animal kingdom, with many individual morphological and physiological characteristics playing important roles in the fate of disputes. Additionally, changes to environmental conditions can influence the outcomes of animal contests. The shore crab (Carcinus maenas) is a globally distributed species, present in numerous coastal and estuarine temperate systems around the world. Although shore crabs are highly tolerant to changes in temperature, this parameter has important physiological effects on the species' ecology, while its effects on behavior are not fully understood. Our study aims to investigate how different individual characteristics (such as sex, color morphotype, carapace and chela morphology) and temperature conditions affect the dyadic interactions between shore crabs when disputing food resources. In general, the differences in carapace width between opponents, their sexes, color morphotypes and the temperature conditions interacted and were important predictors of the contest fate. We found that the body size and color morphotype of C. maenas determined the fate of dyadic disputes. However, the higher temperatures disrupted the well-established dominance of the larger red color morphotype individuals. Overall, the agonistic contest results suggest higher plasticity than previously acknowledged.

19.
J Clin Oncol ; 37(14): 1188-1199, 2019 05 10.
Article in English | MEDLINE | ID: mdl-30897038

ABSTRACT

PURPOSE: Patients with indolent non-Hodgkin lymphoma typically respond well to first-line immunochemotherapy. At relapse, single-agent rituximab is commonly administered. Data suggest the immunomodulatory agent lenalidomide could increase the activity of rituximab. METHODS: A phase III, multicenter, randomized trial of lenalidomide plus rituximab versus placebo plus rituximab was conducted in patients with relapsed and/or refractory follicular or marginal zone lymphoma. Patients received lenalidomide or placebo for 12 cycles plus rituximab once per week for 4 weeks in cycle 1 and day 1 of cycles 2 through 5. The primary end point was progression-free survival per independent radiology review. RESULTS: A total of 358 patients were randomly assigned to lenalidomide plus rituximab (n = 178) or placebo plus rituximab (n = 180). Infections (63% v 49%), neutropenia (58% v 23%), and cutaneous reactions (32% v 12%) were more common with lenalidomide plus rituximab. Grade 3 or 4 neutropenia (50% v 13%) and leukopenia (7% v 2%) were higher with lenalidomide plus rituximab; no other grade 3 or 4 adverse event differed by 5% or more between groups. Progression-free survival was significantly improved for lenalidomide plus rituximab versus placebo plus rituximab, with a hazard ratio of 0.46 (95% CI, 0.34 to 0.62; P < .001) and median duration of 39.4 months (95% CI, 22.9 months to not reached) versus 14.1 months (95% CI, 11.4 to 16.7 months), respectively. CONCLUSION: Lenalidomide improved efficacy of rituximab in patients with recurrent indolent lymphoma, with an acceptable safety profile.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Lymphoma, B-Cell, Marginal Zone/drug therapy , Lymphoma, Follicular/drug therapy , Rituximab/therapeutic use , Adult , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Female , Humans , Lenalidomide/administration & dosage , Lenalidomide/adverse effects , Male , Middle Aged , Neoplasm Recurrence, Local/drug therapy , Placebos , Rituximab/adverse effects
20.
J Fish Biol ; 94(5): 725-731, 2019 May.
Article in English | MEDLINE | ID: mdl-30895622

ABSTRACT

Blue jack mackerel Trachurus picturatus collected at six sampling locations of the north-east Atlantic Ocean (Azores, Madeira, Canaries, and Matosinhos, Peniche and Portimão, mainland Portugal) and one location in the Mediterranean (Sicily), were used to examine the genetic structure of this species. Three mitochondrial gene regions (cytochrome c oxidase subunit I, cytochrome b and control region) were used to study the genetic structure of the species in Macaronesia, as well as to compare the genetic diversity of this region with published results from its eastern distribution. All markers indicated the absence of genetic structure among populations, with high indices of genetic diversity. These results suggest that the species went through a bottleneck event, followed by a recent population expansion. Moreover, the comparison with previously published results from the T. picturatus Mediterranean distribution suggests the existence of a single panmictic population throughout the species' full range. This was, however, an unexpected result since other methodologies have shown the presence of, at least, three different population-units in the NE Atlantic Ocean.


Subject(s)
Fish Proteins/genetics , Genetic Variation , Perciformes/genetics , Animal Distribution , Animals , Atlantic Ocean , Azores , Cytochromes b/genetics , DNA, Mitochondrial/chemistry , DNA, Mitochondrial/genetics , Electron Transport Complex IV/genetics , Genetics, Population , Haplotypes , Phylogeny , Portugal
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