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1.
Biochim Biophys Acta Biomembr ; 1864(1): 183749, 2022 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-34506795

RESUMO

Gangliosides induced a smelting process in nanostructured amyloid fibril-like films throughout the surface properties contributed by glycosphingolipids when mixed with 1-palmitoyl-2-oleoyl-phosphatidylcholine (POPC)/Aß(1-40) amyloid peptide. We observed a dynamical smelting process when pre-formed amyloid/phospholipid mixture is laterally mixed with gangliosides. This particular environment, gangliosides/phospholipid/Aß(1-40) peptide mixed interfaces, showed complex miscibility behavior depending on gangliosides content. At 0% of ganglioside covered surface respect to POPC, Aß(1-40) peptide forms fibril-like structure. In between 5 and 15% of gangliosides, the fibrils dissolve into irregular domains and they disappear when the proportion of gangliosides reach the 20%. The amyloid interfacial dissolving effect of gangliosides is taken place at lateral pressure equivalent to the organization of biological membranes. Domains formed at the interface are clearly evidenced by Brewster Angle Microscopy and Atomic Force Microscopy when the films are transferred onto a mica support. The domains are thioflavin T (ThT) positive when observed by fluorescence microscopy. We postulated that the smelting process of amyloids fibrils-like structure at the membrane surface provoked by gangliosides is a direct result of a new interfacial environment imposed by the complex glycosphingolipids. We add experimental evidence, for the first time, how a change in the lipid environment (increase in ganglioside proportion) induces a rapid loss of the asymmetric structure of amyloid fibrils by a simple modification of the membrane condition (a more physiological situation).


Assuntos
Peptídeos beta-Amiloides/química , Gangliosídeos/química , Glicoesfingolipídeos/química , Lipídeos de Membrana/química , Nanoestruturas/química , Fragmentos de Peptídeos/química , Amiloide/química , Peptídeos beta-Amiloides/ultraestrutura , Microscopia de Força Atômica , Nanoestruturas/ultraestrutura , Fragmentos de Peptídeos/ultraestrutura , Fosfatidilcolinas/química , Propriedades de Superfície
2.
Cochrane Database Syst Rev ; 12: CD013720, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34850383

RESUMO

BACKGROUND: Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder characterised by progressive muscle weakness beginning in early childhood. Respiratory failure and weak cough develop in all patients as a consequence of muscle weakness leading to a risk of atelectasis, pneumonia, or the need for ventilatory support. There is no curative treatment for DMD. Corticosteroids are the only pharmacological intervention proven to delay the onset and progression of muscle weakness and thus respiratory decline in DMD. Antioxidant treatment has been proposed to try to reduce muscle weakness in general, and respiratory decline in particular.  OBJECTIVES: To assess the effects of antioxidant agents on preventing respiratory decline in people with Duchenne muscular dystrophy during the respiratory decline phase of the condition.  SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, and two trials registers to 23 March 2021, together with reference checking, citation searching, and contact with study authors to identify additional studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi-RCTs that met our inclusion criteria. We included male patients with a diagnosis of DMD who had respiratory decline evidenced by a forced vital capacity (FVC%) less than 80% but greater than 30% of predicted values, receiving any antioxidant agent compared with other therapies for the management of DMD or placebo.  DATA COLLECTION AND ANALYSIS: Two review authors screened studies for eligibility, assessed risk of bias of studies, and extracted data. We used standard methods expected by Cochrane. We assessed the certainty of the evidence using the GRADE approach. The primary outcomes were FVC and hospitalisation due to respiratory infections. Secondary outcomes were quality of life, adverse events, change in muscle function, forced expiratory volume in the first second (FEV1), and peak expiratory flow (PEF).  MAIN RESULTS: We included one study with 66 participants who were not co-treated with corticosteroids, which was the only study to contribute data to our main analysis. We also included a study that enrolled 255 participants treated with corticosteroids, which was only available as a press release without numerical results. The studies were parallel-group RCTs that assessed the effect of idebenone on respiratory function compared to placebo. The trial that contributed numerical data included patients with a mean (standard deviation) age of 14.3 (2.7) years at the time of inclusion, with a documented diagnosis of DMD or severe dystrophinopathy with clinical features consistent with typical DMD. The overall risk of bias across most outcomes was similar and judged as 'low'.  Idebenone may result in a slightly less of a decline in FVC from baseline to one year compared to placebo (mean difference (MD) 3.28%, 95% confidence interval (CI) -0.41 to 6.97; 64 participants; low-certainty evidence), and probably has little or no effect on change in quality of life (MD -3.80, 95% CI -10.09 to 2.49; 63 participants; moderate-certainty evidence) (Pediatric Quality of Life Inventory (PedsQL), range 0 to 100, 0 = worst, 100 = best quality of life). As a related but secondary outcome, idebenone may result in less of a decline from baseline in FEV1 (MD 8.28%, 95% CI 0.89 to 15.67; 53 participants) and PEF (MD 6.27%, 95% CI 0.61 to 11.93; 1 trial, 64 participants) compared to placebo. Idebenone was associated with fewer serious adverse events (RR 0.42, 95% CI 0.09 to 2.04; 66 participants; low-certainty evidence) and little to no difference in non-serious adverse events (RR 1.00, 95% CI 0.88 to 1.13; 66 participants; low-certainty evidence) compared to placebo. Idebenone may result in little to no difference in change in arm muscle function (MD -2.45 N, 95% CI -8.60 to 3.70 for elbow flexors and MD -1.06 N, 95% CI -6.77 to 4.65 for elbow extensors; both 52 participants) compared to placebo. We found no studies evaluating the outcome hospitalisation due to respiratory infection.  The second trial, involving 255 participants, for which data were available only as a press release without numerical data, was prematurely discontinued due to futility after an interim efficacy analysis based on FVC. There were no safety concerns. The certainty of the evidence was low for most outcomes due to imprecision and publication bias (the lack of a full report of the larger trial, which was prematurely terminated). AUTHORS' CONCLUSIONS: Idebenone is the only antioxidant agent tested in RCTs for preventing respiratory decline in people with DMD for which evidence was available for assessment. Idebenone may result in slightly less of a decline in FVC and less of a decline in FEV1 and PEF, but probably has little to no measurable effect on change in quality of life. Idebenone is associated with fewer serious adverse events than placebo. Idebenone may result in little to no difference in change in muscle function. Discontinuation due to the futility of the SIDEROS trial and its expanded access programmes may indicate that idebenone research in this condition is no longer needed, but we await the trial data. Further research is needed to establish the effect of different antioxidant agents on preventing respiratory decline in people with DMD during the respiratory decline phase of the condition.

3.
Chest ; 160(6): e639-e643, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34872678

RESUMO

CASE PRESENTATION: A 31-year-old man was admitted to our hospital with a recent history of generalized seizures. Three months earlier, he started with intermittent hemoptysis. CT scan showed a cavitary lung lesion in the upper segment of the right inferior lobe (RIL). Because of his job as a social worker in a high-risk population, he started treatment for Mycobacterium TB; however, the BAL culture result was negative. At the time of his current admission, he has continued taking rifampicin, isoniazid, pyrazinamide, and levofloxacin. He denied the use of any illicit drugs or alcohol. He had no history of smoking. One year earlier, he visited Southeast Asia, Oceania, and South Africa for several months. He reported a weight loss of 7 kg since then. Except for a recurrent oral candidiasis, he did not have a relevant medical history. His family history was notable for mother with lupus, and brother with sarcoidosis.

4.
Molecules ; 26(23)2021 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-34885718

RESUMO

Spinal cord injury (SCI) refers to the damage suffered in the spinal cord by any trauma or pathology. The purpose of this work was to determine whether 99mTc-GA-5, a radiotracer targeting Glial Fibrillary Acidic Protein (GFAP), can reveal in vivo the reactivation of astrocytes in a murine model with SCI. A method for the 99mTc radiolabeling of the mouse anti-GFAP monoclonal antibody GA-5 was implemented. Radiochemical characterization was performed, and radioimmunohistochemistry assays were used to evaluate the integrity of 99mTc-GA-5. MicroSPECT/CT was used for in vivo imaging to trace SCI in the rats. No alterations in the GA-5's recognition/specificity ability were observed after the radiolabeling. The GA-5's radiolabeling procedure implemented in this work offers a practical method to allow the in vivo following of this monoclonal antibody to evaluate its biodistribution and specificity for GFAP receptors using SPECT/CT molecular imaging.

5.
J Intensive Care Med ; : 8850666211066799, 2021 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-34898320

RESUMO

OBJECTIVE: To determine whether high-dose dexamethasone increases the number of ventilator-free days (VFD) among patients with acute respiratory distress syndrome (ARDS) caused by COVID-19. DESIGN: Multicenter, randomized, open-label, clinical trial. PARTICIPANTS: Consecutive patients with confirmed COVID-19-related ARDS were enrolled from June 17, 2020, to March 27, 2021, in four intensive care units (ICUs) in Argentina. INTERVENTION: 16 mg of dexamethasone intravenously daily for five days followed by 8 mg of dexamethasone daily for five days or 6 mg of dexamethasone intravenously daily for 10 days. MAIN OUTCOME AND MEASURES: The primary outcome was ventilator-free days during the first 28 days. The secondary outcomes were all-cause mortality at 28 and 90 days, infection rate, muscle weakness, and glycemic control in the first 28 days. RESULTS: Data from 98 patients who received at least one dose of dexamethasone were analyzed. The trial was prematurely terminated due to low enrollment rate. At 28 days after randomization, there was no difference between high- and low-dose dexamethasone groups in VFD (median, 0 [interquartile range [IQR] 0-14] vs. 0 [IQR 0-1] days; P = .231), or in the mean duration of mechanical ventilation (19 ± 18 vs. 25 ± 22 days; P = .078). The cumulative hazard of successful discontinuation from mechanical ventilation was increased by the high-dose treatment (adjusted sub-distribution hazard ratio: 1.84; 95% CI: 1.31 to 2.5; P < .001). None of the prespecified secondary and safety outcomes showed a significant difference between treatment arms. CONCLUSIONS: Among patients with ARDS due to COVID-19, the use of higher doses of dexamethasone compared with the recommended low-dose treatment did not show an increase in VFD. However, the higher dose significantly improved the time required to liberate them from the ventilator.

6.
Front Psychol ; 12: 783781, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34899536

RESUMO

Sports management is booming, thanks to society's growing interest in sports in general. This work provides an exhaustive review of the scientific literature of one of the variables most coveted by managers: loyalty. Antecedents positively related to loyalty are also conceptualized in this paper. The scientific literature search was limited to the last 15years to achieve a better fit with today's context. The Web of Science database was the main search method used, along with other, secondary resources, for a total of 328 scientific articles obtained as a base for this review. The results of this study bring together the most representative data in a systematic review of the loyalty variable in the field of sports management: the antecedents of loyalty, the terms with the greatest presence in the theory, the most representative authors and sources of this topic, and so on. One of the most significant results obtained from the review of these 300 bibliographical references is that the factors to be borne in mind for marketing strategies in sports organizations are satisfaction, commitment, trust, and service quality. The literature reflects that these variables, present in studies on loyalty in general, can also be found in the literature on sports management - in particular, satisfaction and service quality. However, few papers include all these antecedents at once, making this an interesting field for future research.

7.
Viruses ; 13(12)2021 12 06.
Artigo em Inglês | MEDLINE | ID: mdl-34960714

RESUMO

Mid-regional pro-adrenomedullin (MR-proADM), methemoglobin (MetHb), and carboxyhemoglobin (COHb) levels have been associated with sepsis. In this study, we assessed the role of this potential biomarkers in critically ill COVID-19 patients. Outcomes were mortality and a combined event (mortality, venous or arterial thrombosis, and orotracheal intubation (OTI)) during a 30-day follow-up. A total of 95 consecutive patients were included, 51.6% required OTI, 12.6% patients died, 8.4% developed VTE, and 3.1% developed arterial thrombosis. MetHb and COHb levels were not associated with mortality nor combined event. Higher MR-proADM levels were found in patients with mortality (median of 1.21 [interquartile range-IQR-0.84;2.33] nmol/L vs. 0.76 [IQR 0.60;1.03] nmol/L, p = 0.011) and combined event (median of 0.91 [IQR 0.66;1.39] nmol/L vs. 0.70 [IQR 0.51;0.82] nmol/L, p < 0.001); the positive likelihood ratio (LR+) and negative likelihood ratio (LR-) for mortality were 2.40 and 0.46, respectively. The LR+ and LR- for combined event were 3.16 and 0.63, respectively. MR-proADM ≥1 nmol/L was the optimal cut-off for mortality and combined event prediction. The predictive capacity of MR-proADM showed an area under the ROC curve of 0.73 (95% CI, 0.62-0.81) and 0.72 (95% CI, 0.62-0.81) for mortality and combined event, respectively. In conclusion, elevated on-admission MR-proADM levels were associated with higher risk of 30-day mortality and 30-day poor outcomes in a cohort of critically ill patients with COVID-19.

8.
Viruses ; 13(11)2021 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-34835085

RESUMO

INTRODUCTION: Hospitalized patients with COVID-19 are at increased risk for venous thromboembolism (VTE), but also for bleeding. We previously derived a prognostic score including four variables (elevated D-dimer, elevated ferritin, critical illness, and therapeutic-dose anticoagulation) that identified those at increased risk for major bleeding. METHODS: We aimed to validate the score in a subsequent cohort of hospitalized patients with COVID-19 receiving standard-, intermediate- or therapeutic doses of VTE prophylaxis. We evaluated its capacity to predict major bleeding, non-major bleeding, and bleeding-related death. RESULTS: The cohort included 972 patients from 29 hospitals, of whom 280 (29%) received standard-; 412 (42%) intermediate-, 157 (16%) therapeutic doses of VTE prophylaxis and 123 (13%) other drugs. Median duration of prophylaxis was 14.7 ± 10.3 days. Major bleeding occurred in 65 patients (6.7%) and non-major bleeding in 67 (6.9%). Thirty patients with major bleeding (46%) died within the first 30 days after bleeding. The prognostic score identified 203 patients (21%) at very low risk, 285 (29%) at low risk, 263 (27%) intermediate-risk and 221 (23%) at high risk for bleeding. Major bleeding occurred in 1.0%, 2.1%, 8.7% and 15.4% of the patients, respectively. Non-major bleeding occurred in 0.5%, 3.5%, 9.5% and 14.2%, respectively. The c-statistics was: 0.74 (95% confidence intervals [CI]: 0.68-0.79) for major bleeding, 0.73 (95% CI: 0.67-0.78) for non-major bleeding and 0.82 (95% CI: 0.76-0.87) for bleeding-related death. CONCLUSIONS: In hospitalized patients with COVID-19, we validated that a prognostic score including 4 easily available items may identify those at increased risk for bleeding.

9.
Cochrane Database Syst Rev ; 11: CD013720, 2021 11 08.
Artigo em Inglês | MEDLINE | ID: mdl-34748221

RESUMO

BACKGROUND: Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder characterised by progressive muscle weakness beginning in early childhood. Respiratory failure and weak cough develop in all patients as a consequence of muscle weakness leading to a risk of atelectasis, pneumonia, or the need for ventilatory support. There is no curative treatment for DMD. Corticosteroids are the only pharmacological intervention proven to delay the onset and progression of muscle weakness and thus respiratory decline in DMD. Antioxidant treatment has been proposed to try to reduce muscle weakness in general, and respiratory decline in particular.  OBJECTIVES: To assess the effects of antioxidant agents on preventing respiratory decline in people with Duchenne muscular dystrophy during the respiratory decline phase of the condition.  SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, and two trials registers to 23 March 2021, together with reference checking, citation searching, and contact with study authors to identify additional studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi-RCTs that met our inclusion criteria. We included male patients with a diagnosis of DMD who had respiratory decline evidenced by a forced vital capacity (FVC%) less than 80% but greater than 30% of predicted values, receiving any antioxidant agent compared with other therapies for the management of DMD or placebo.  DATA COLLECTION AND ANALYSIS: Two review authors screened studies for eligibility, assessed risk of bias of studies, and extracted data. We used standard methods expected by Cochrane. We assessed the certainty of the evidence using the GRADE approach. The primary outcomes were FVC and hospitalisation due to respiratory infections. Secondary outcomes were quality of life, adverse events, change in muscle function, forced expiratory volume in the first second (FEV1), and peak expiratory flow (PEF).  MAIN RESULTS: We included one study with 66 participants who were not co-treated with corticosteroids, which was the only study to contribute data to our main analysis. We also included a study that enrolled 255 participants treated with corticosteroids, which was only available as a press release without numerical results. The studies were parallel-group RCTs that assessed the effect of idebenone on respiratory function compared to placebo. The trial that contributed numerical data included patients with a mean (standard deviation) age of 14.3 (2.7) years at the time of inclusion, with a documented diagnosis of DMD or severe dystrophinopathy with clinical features consistent with typical DMD. The overall risk of bias across most outcomes was similar and judged as 'low'.  Idebenone may result in a slightly less of a decline in FVC from baseline to one year compared to placebo (mean difference (MD) 3.28%, 95% confidence interval (CI) -0.41 to 6.97; 64 participants; low-certainty evidence), and probably has little or no effect on change in quality of life (MD -3.80, 95% CI -10.09 to 2.49; 63 participants; moderate-certainty evidence) (Pediatric Quality of Life Inventory (PedsQL), range 0 to 100, 0 = worst, 100 = best quality of life). As a related but secondary outcome, idebenone may result in less of a decline from baseline in FEV1 (MD 8.28%, 95% CI 0.89 to 15.67; 53 participants) and PEF (MD 6.27%, 95% CI 0.61 to 11.93; 1 trial, 64 participants) compared to placebo. Idebenone was associated with fewer serious adverse events (RR 0.42, 95% CI 0.09 to 2.04; 66 participants; low-certainty evidence) and little to no difference in non-serious adverse events (RR 1.00, 95% CI 0.88 to 1.13; 66 participants; low-certainty evidence) compared to placebo. Idebenone may result in little to no difference in change in arm muscle function (MD -2.45 N, 95% CI -8.60 to 3.70 for elbow flexors and MD -1.06 N, 95% CI -6.77 to 4.65 for elbow extensors; both 52 participants) compared to placebo. We found no studies evaluating the outcome hospitalisation due to respiratory infection.  The second trial, involving 255 participants, for which data were available only as a press release without numerical data, was prematurely discontinued due to futility after an interim efficacy analysis based on FVC. There were no safety concerns. The certainty of the evidence was low for most outcomes due to imprecision and publication bias (the lack of a full report of the larger trial, which was prematurely terminated). AUTHORS' CONCLUSIONS: Idebenone is the only antioxidant agent tested in RCTs for preventing respiratory decline in people with DMD for which evidence was available for assessment. Idebenone may result in slightly less of a decline in FVC and less of a decline in FEV1 and PEF, but probably has little to no measurable effect on change in quality of life. Idebenone is associated with fewer serious adverse events than placebo. Idebenone may result in little to no difference in change in muscle function. Discontinuation due to the futility of the SIDEROS trial and its expanded access programmes may indicate that idebenone research in this condition is no longer needed, but we await the trial data. Further research is needed to establish the effect of different antioxidant agents on preventing respiratory decline in people with DMD during the respiratory decline phase of the condition.

10.
Transplant Proc ; 2021 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-34774310

RESUMO

Renal retransplant patients have decreased graft survival compared with primary renal transplant patients. Alemtuzumab induction is often used at the time of retransplant; however, the literature surrounding alemtuzumab induction in renal retransplant patients is limited. In this single-center, retrospective, observational study, we aimed to determine the 1-year incidence of infections and transplant outcomes in renal retransplant patients who received alemtuzumab induction. Thirty-four patients who received alemtuzumab met inclusion criteria and were included in the final analysis. Twenty-two (64.7%) of these patients acquired infections. Of these, 7 patients (31.8%) acquired infections that resulted in hospitalization or intravenous antibiotics. The most common infections were urinary tract infections (n = 10; 29.4%), cytomegalovirus DNAemia (n = 7; 20.6%), and BK virus (n = 6; 17.6%). The use of steroid maintenance therapy after alemtuzumab induction did not increase the number of infections compared with patients with a steroid-free interval after alemtuzumab induction. The number of patients who developed de novo donor-specific antibodies (DSA) was 11 (32.4%) with only 1 of these patients having DSA before retransplantation. The incidence of acute cellular rejection was 2.9% (n = 1). There was no graft loss, and patient survival was 97% (n = 33). There were no significant differences in infection rate or DSA development between alemtuzumab and the other induction agents, antithymocyte globulin and basiliximab, among retransplanted patients. Alemtuzumab induction in renal retransplant patients resulted in similar bacterial and viral infection rates as previously reported in the literature and did not negatively impact graft and patient survival.

11.
Cochrane Database Syst Rev ; 11: CD013757, 2021 11 16.
Artigo em Inglês | MEDLINE | ID: mdl-34783356

RESUMO

BACKGROUND: Respiratory viruses are the leading cause of lower respiratory tract infection (LRTI) and hospitalisation in infants and young children. Respiratory syncytial virus (RSV) is the main infectious agent in this population. Palivizumab is administered intramuscularly every month during five months in the first RSV season to prevent serious RSV LRTI in children. Given its high cost, it is essential to know if palivizumab continues to be effective in preventing severe RSV disease in children. OBJECTIVES: To assess the effects of palivizumab for preventing severe RSV infection in children. SEARCH METHODS: We searched CENTRAL, MEDLINE, three other databases and two trials registers to 14 October 2021, together with reference checking, citation searching and contact with study authors to identify additional studies. We searched Embase to October 2020, as we did not have access to this database for 2021. SELECTION CRITERIA: We included randomised controlled trials (RCTs), including cluster-RCTs, comparing palivizumab given at a dose of 15 mg/kg once a month (maximum five doses) with placebo, no intervention or standard care in children 0 to 24 months of age from both genders, regardless of RSV infection history.  DATA COLLECTION AND ANALYSIS: We used Cochrane's Screen4Me workflow to help assess the search results. Two review authors screened studies for selection, assessed risk of bias and extracted data. We used standard Cochrane methods. We used GRADE to assess the certainty of the evidence. The primary outcomes were hospitalisation due to RSV infection, all-cause mortality and adverse events. Secondary outcomes were hospitalisation due to respiratory-related illness, length of hospital stay, RSV infection, number of wheezing days, days of supplemental oxygen, intensive care unit length of stay and mechanical ventilation days. MAIN RESULTS: We included five studies with  a total of 3343 participants. All studies were parallel RCTs, assessing the effects of 15 mg/kg of palivizumab every month up to five months compared to placebo or no intervention in an outpatient setting, although one study also included hospitalised infants. Most of the included studies were conducted in children with a high risk of RSV infection due to comorbidities like bronchopulmonary dysplasia and congenital heart disease. The risk of bias of outcomes across all studies was similar and predominately low.  Palivizumab reduces hospitalisation due to RSV infection at two years' follow-up (risk ratio (RR) 0.44, 95% confidence interval (CI) 0.30 to 0.64; 5 studies, 3343 participants; high certainty evidence). Based on 98 hospitalisations per 1000 participants in the placebo group, this corresponds to 43 (29 to 62) per 1000 participants in the palivizumab group. Palivizumab probably results in little to no difference in mortality at two years' follow-up (RR 0.69, 95% CI 0.42 to 1.15; 5 studies, 3343 participants; moderate certainty evidence). Based on 23 deaths per 1000 participants in the placebo group, this corresponds to 16 (10 to 27) per 1000 participants in the palivizumab group. Palivizumab probably results in little to no difference in adverse events at 150 days' follow-up (RR 1.09, 95% CI 0.85 to 1.39; 3 studies, 2831 participants; moderate certainty evidence). Based on 84 cases per 1000 participants in the placebo group, this corresponds to 91 (71 to 117) per 1000 participants in the palivizumab group. Palivizumab probably results in a slight reduction in hospitalisation due to respiratory-related illness at two years' follow-up (RR 0.78, 95% CI 0.62 to 0.97; 5 studies, 3343 participants; moderate certainty evidence). Palivizumab may result in a large reduction in RSV infection at two years' follow-up (RR 0.33, 95% CI 0.20 to 0.55; 3 studies, 554 participants; low certainty evidence). Based on 195 cases of RSV infection per 1000 participants in the placebo group, this corresponds to 64 (39 to 107) per 1000 participants in the palivizumab group. Palivizumab also reduces the number of wheezing days at one year's follow-up (RR 0.39, 95% CI 0.35 to 0.44; 1 study, 429 participants; high certainty evidence). AUTHORS' CONCLUSIONS: The available evidence suggests that prophylaxis with palivizumab reduces hospitalisation due to RSV infection and results in little to no difference in mortality or adverse events. Moreover, palivizumab results in a slight reduction in hospitalisation due to respiratory-related illness and may result in a large reduction in RSV infections. Palivizumab also reduces the number of wheezing days. These results may be applicable to children with a high risk of RSV infection due to comorbidities. Further research is needed to establish the effect of palivizumab on children with other comorbidities known as risk factors for severe RSV disease (e.g. immune deficiencies) and other social determinants of the disease, including children living in low- and middle-income countries, tropical regions, children lacking breastfeeding, living in poverty, or members of families in overcrowded situations.

12.
Syst Biol ; 2021 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-34672346

RESUMO

Species are crucial to most branches of biological research, yet remain controversial in terms of definition, delimitation and reality. The difficulty of resolving the "species problem" stems from the tension between their theoretical concept as groups of evolving and highly variable organisms and the practical need for a stable and comparable unit of biology. Here we suggest that treating species as a heuristic can be consistent with a theoretical definition of what species are and with the practical means by which they are identified and delimited. Specifically, we suggest that theoretically species are heuristic since they comprise clusters of closely related individuals responding in a similar manner to comparable sets of evolutionary and ecological forces, whilst they are practically heuristic because they are identifiable by the congruence of contingent properties indicative of those forces. This reconciliation of the theoretical basis of species with their practical applications in biological research allows for a loose but relatively consistent definition of species based on the strategic analysis and integration of genotypic, phenotypic and ecotypic data.

13.
Acta Odontol Latinoam ; 34(1): 166-172, 2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-34570162

RESUMO

Adhesively cemented fiber-reinforced composite posts are commonly used to reconstruct endodontically treated teeth. Adhesion to intraradicular dentin is complex, and close contact between the resin cements and the dentin is essential. The removal of the smear layer following post space preparation (secondary smear layer) can improve this integration. Different mechanical systems have been used to activate the irrigant inside the root canal. The purpose of this study was to compare, ex-vivo, the removal of the smear layer from the walls of the immediate post space preparation by the action of three mechanized instruments. Forty premolar specimens with a single root canal were selected, endodontically treated, and shaped for glass fiber post cementation with Peeso reamer #1 (Dentsply Sirona, Switzerland) and Macrolock finishing drill #3 (RTD, France). The specimens were randomly divided into 4 groups (n=10): Group C (control); Group PUI (passive ultrasonic irrigation); Group CEP (Rotoprox brush, Hager Werken, Germany) and Group XP (XP-endo Finisher, FKG Dentaire, Switzerland). Post space surfaces were cleaned with 3mL of distilled water; each specimen root split longitudinally to expose the root canals, and prepared for examination in a scanning electron microscope at magnification 350X. The results were analyzed using the Kruskal-Wallis and Friedman tests (p>0.05). RESULTS: Statistically significant differences (p<0.05) were found between Groups C and XP in all three root regions, but not between Groups C, CEP and PIU. Of these, Group CEP showed a better trend in the results of the coronary and middle thirds, without significant difference with Group XP. Although it was difficult to achieve a clean dentin surface after preparation for the fiberglass post, the XP-endo Finisher was the most efficient in removing secondary smear layer, followed by the Rotoprox conical brush.


Assuntos
Camada de Esfregaço , Dente Pré-Molar , Cavidade Pulpar , Dentina , Ácido Edético , Humanos , Microscopia Eletrônica de Varredura , Irrigantes do Canal Radicular , Preparo de Canal Radicular , Hipoclorito de Sódio
14.
Acta Odontol Latinoam ; 34(1): 188-194, 2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-34570165

RESUMO

In the field of anthropology, discrete traits are considered as minimal epigenetic variations. However, they can elicit complications in endodontic therapy. Thorough understanding of root canal morphology is essential to achieving predictable results in endodontic practice, and may be attained by using cone-beam computed tomography (CBCT) scans. The aim of the present study was to research the internal root anatomy of maxillary central and lateral incisors in vivo and quantify its variation in a population of the Autonomous City of Buenos Aires, Argentina. A total 697 CBCT scans from a pre-existing database were observed, and the configuration type for each tooth was determined according to Vertucci's classification. The data were described by absolute frequencies and percentages with 95% confidence intervals (CI). The CI was estimated by the Wilson Score method. Chi-square test (χ2) was used for comparing frequencies, with a 5% significance level. 238 CBCT scans met the inclusion criteria, resulting in 761 teeth assessed. Vertucci Type I configuration was observed in 760 teeth (99.9%) and the Type II was found in only one tooth (0.1%), in which the anatomy was compatible with dens in dente. When differences were analyzed according to sex, all the teeth in all women had Vertucci Type I configuration. In men, all maxillary central incisors were Vertucci Type I. Of 151 maxillary lateral incisors, 150 had Vertucci Type I configuration (99.3%) and 1 had Type II (0.7%). Conclusions: Maxillary incisor internal root anatomy prevalence was estimated from CBCT scans for the first time in an Argentine population. 99.9% of the sample presented Vertucci Type I configuration, and 0.1% had Vertucci Type II configuration. The clinical finding of maxillary incisors with anatomical complexity should be considered as a possibility in endodontic practice.


Assuntos
Cavidade Pulpar , Incisivo , Argentina , Tomografia Computadorizada de Feixe Cônico , Feminino , Humanos , Incisivo/diagnóstico por imagem , Masculino , Raiz Dentária
15.
Br J Radiol ; : 20210683, 2021 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-34538073

RESUMO

OBJECTIVE: To determine morphological and biological control as well as toxicity and quality of life (QoL) of men with localized prostate cancer (PCa) treated with MRI-guided focal boost radiotherapy. MATERIAL AND METHODS: 30 patients with PCa and a visible dominant intraprostatic lesion (DIL) identified on mpMRI were included in a prospective Phase II trial. Matching point registration of planning CT and T2W, diffusion-weighted and a gradient-recalled echo (GRE) MRI images made in treatment position was used for prostate and tumour delineation. Treatment consisted on 35 daily fractions of 2.17 Gy with a concomitant focal boost to the DIL of 2.43 Gy using volumetric modulated arc therapy (VMAT) and image-guided radiation therapy (IGRT) with intraprostatic fiducial markers. Biochemical failure was analysed using PSA nadir +2 ng/mL criteria and local control using mpMRI evaluation at 6-9 months following RT. Acute and late toxicity were defined according to CTCAE v.4.0 and RTOG/EORTC scales and QoL was assessed using IPSS, EPIC short-form and UCLA-PCI questionnaires. RESULTS: The median radiation dose to the prostate was 77.6 Gy (IQR 77.3-78.1), and to the DIL was 85.5 Gy (IQR 85.0-86.0). With a median follow up of 30.0 months (IQR 25.5-40.27), all patients remain free of biochemical relapse. An mpMRI complete response was observed in 25 patients during the first post-treatment evaluation at 6 months. The remaining five patients achieved a complete disappearance of the DIL both on T2 and DWI on the second mpMRI performed at 9 months following treatment. Six out of 30 (20%) patients presented acute Grade 2 urinary toxicity with no Grade 3 acute complications. Acute rectal toxicity was only found in 2 (6.6%) patients (both Grade 1). Only late Grade 1 urinary and rectal complications were observed in 3/30 patients, respectively, with no Grade 2 or more late toxicity. The urinary, bowel and sexual bother EPIC scores were slightly and insignificantly increased in the first 3 months post-treatment, returning to normal afterwards. CONCLUSIONS: mpMRI-guided focal boost using VMAT hypofractionated technique is associated with an excellent morphological and functional response control and a safe toxicity profile. ADVANCES IN KNOWLEDGE: In the present trial, we examined the potential role of mpMRI for radiological assessment (functional and morphological) of treatment response in high-risk prostate cancer patients treated with MRI-guided focal radiotherapy dose intensification to dominant Intraprostatic lesion.

17.
Acta Odontol Latinoam ; 34(2): 166-172, 2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-34570865

RESUMO

Adhesively cemented fiber-reinforced composite posts are commonly used to reconstruct endodontically treated teeth. Adhesion to intraradicular dentin is complex, and close contact between the resin cements and the dentin is essential. The removal of the smear layer following post space preparation (secondary smear layer) can improve this integration. Different mechanical systems have been used to activate the irrigant inside the root canal. The purpose of this study was to compare, ex-vivo, the removal of the smear layer from the walls of the immediate post space preparation by the action of three mechanized instruments. Forty premolar specimens with a single root canal were selected, endodontically treated, and shaped for glass fiber post cementation with Peeso reamer #1 (Dentsply Sirona, Switzerland) and Macrolock finishing drill #3 (RTD, France). The specimens were randomly divided into 4 groups (n=10): Group C (control); Group PUI (passive ultrasonic irrigation); Group CEP (Rotoprox brush, Hager Werken, Germany) and Group XP (XP-endo Finisher, FKG Dentaire, Switzerland). Post space surfaces were cleaned with 3mL of distilled water; each specimen root split longitudinally to expose the root canals, and prepared for examination in a scanning electron microscope at magnification 350X. The results were analyzed using the Kruskal-Wallis and Friedman tests (p>0.05). RESULTS: Statistically significant differences (p<0.05) were found between Groups C and XP in all three root regions, but not between Groups C, CEP and PIU. Of these, Group CEP showed a better trend in the results of the coronary and middle thirds, without significant difference with Group XP. Although it was difficult to achieve a clean dentin surface after preparation for the fiberglass post, the XP-endo Finisher was the most efficient in removing secondary smear layer, followed by the Rotoprox conical brush.


Assuntos
Camada de Esfregaço , Dente Pré-Molar , Cavidade Pulpar , Dentina , Ácido Edético , Humanos , Microscopia Eletrônica de Varredura , Irrigantes do Canal Radicular , Preparo de Canal Radicular , Hipoclorito de Sódio
18.
Acta Odontol Latinoam ; 34(2): 188-194, 2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-34570868

RESUMO

In the field of anthropology, discrete traits are considered as minimal epigenetic variations. However, they can elicit complications in endodontic therapy. Thorough understanding of root canal morphology is essential to achieving predictable results in endodontic practice, and may be attained by using cone-beam computed tomography (CBCT) scans. The aim of the present study was to research the internal root anatomy of maxillary central and lateral incisors in vivo and quantify its variation in a population of the Autonomous City of Buenos Aires, Argentina. A total 697 CBCT scans from a pre-existing database were observed, and the configuration type for each tooth was determined according to Vertucci's classification. The data were described by absolute frequencies and percentages with 95% confidence intervals (CI). The CI was estimated by the Wilson Score method. Chi-square test (χ2) was used for comparing frequencies, with a 5% significance level. 238 CBCT scans met the inclusion criteria, resulting in 761 teeth assessed. Vertucci Type I configuration was observed in 760 teeth (99.9%) and the Type II was found in only one tooth (0.1%), in which the anatomy was compatible with dens in dente. When differences were analyzed according to sex, all the teeth in all women had Vertucci Type I configuration. In men, all maxillary central incisors were Vertucci Type I. Of 151 maxillary lateral incisors, 150 had Vertucci Type I configuration (99.3%) and 1 had Type II (0.7%). Conclusions: Maxillary incisor internal root anatomy prevalence was estimated from CBCT scans for the first time in an Argentine population. 99.9% of the sample presented Vertucci Type I configuration, and 0.1% had Vertucci Type II configuration. The clinical finding of maxillary incisors with anatomical complexity should be considered as a possibility in endodontic practice.


Assuntos
Cavidade Pulpar , Incisivo , Argentina , Tomografia Computadorizada de Feixe Cônico , Feminino , Humanos , Incisivo/diagnóstico por imagem , Masculino , Raiz Dentária
19.
J Environ Manage ; 296: 113411, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34351286

RESUMO

Uranium-containing effluents generated by nuclear energy industry must be efficiently remediated before release to the environment. Currently, numerous microbial-based strategies are being developed for this purpose. In particular, the bacterial strain Stenotrophomonas sp. Br8, isolated from U mill tailings porewaters, has been already shown to efficiently precipitate U(VI) as stable U phosphates mediated by phosphatase activity. However, the upscaling of this strategy should overcome some constraints regarding cell exposure to harsh environmental conditions. In the present study, the immobilization of Br8 biomass in an inorganic matrix was optimized to provide protection to the cells as well as to make the process more convenient for real-scale utilization. The use of biocompatible, highly porous alginate beads for Br8 cells immobilization resulted the best alternative when investigating by a multidisciplinary approach (High-Angle Annular Dark-Field Scanning Transmission Electron Microscopy (HAADF-STEM), Environmental Scanning Electron Microscopy (ESEM), Fourier Transform Infrared Spectroscopy with Attenuated Total Reflectance, etc.) several consolidated entrapment methods. This biomaterial was applied to complex real U mining porewaters (containing 47 mg/L U) in presence of an organic phosphate source (glycerol-2-phosphate) to produce reactive free orthophosphates through Br8 phosphatase activity. Uranium immobilization rates around 98 % were observed after one cycle of 72 h. In terms of U removal ability as a function of biomass, Br8-doped alginate beads were determined to remove up to 1199.5 mg U/g dry biomass over two treatment cycles. Additionally, optimized conditions for storing Br8-doped beads and for a correct application were assessed. Results for U accumulation kinetics and HAADF-STEM/ESEM analyses revealed that U removal by the immobilized cells is a biphasic process combining a first passive U sorption onto bead and/or cell surfaces and a second slow active biomineralization. This work provides new practical insights into the biological and physico-chemical parameters governing a high-efficient U bioremediation process based on the phosphatase activity of immobilized bacterial cells when applied to complex mining waters under laboratory conditions.


Assuntos
Urânio , Alginatos , Biodegradação Ambiental , Mineração , Stenotrophomonas , Urânio/análise
20.
Materials (Basel) ; 14(15)2021 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-34361536

RESUMO

The structure of FeCoNiCrAl1.8Cu0.5 high-entropy alloys (HEA) obtained by two different routes has been studied. The selection of the composition has followed the Hume-Rothery approach in terms of number of itinerant electrons (e/a) and average atomic radius to control the formation of specific phases. The alloys were obtained either from a mixture of elemental powders or from gas-atomised powders, being consolidated in both cases by uniaxial pressing and vacuum sintering at temperatures of 1200 °C and 1300 °C. The characterization performed in the sintered samples from both types of powder includes scanning electron microscopy, X-ray diffraction, differential thermal analysis, and density measurements. It was found that the powder production techniques give similar phases content. However, the sintering at 1300 °C destroys the achieved phase stability of the samples. The phases identified by all techniques and confirmed by Thermo-Calc calculations are the following: a major Co-Ni-Al-rich (P1) BCC phase, which stays stable after 1300 °C sintering and homogenising TT treatments; a complex Cr-Fe-rich (P2) B2 type phase, which transforms into a sigma phase after the 1300 °C sintering and homogenising TT treatments; and a very minor Al-Cu-rich (P3) FCC phase, which also transforms into Domain II and Domain III phases during the heating at 1300 °C and homogenising TT treatments.

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