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The Alberta moving beyond breast cancer (AMBER) cohort study: baseline description of the full cohort

Cancer Causes Control. 2022 Jan 22. doi: 10.1007/s10552-021-01539-6. Online ahead of print.

ABSTRACT

PURPOSE: The Alberta Moving Beyond Breast Cancer (AMBER) Study is an ongoing prospective cohort study investigating how direct measures of physical activity (PA), sedentary behavior (SB), and health-related fitness (HRF) are associated with survival after breast cancer.

METHODS: Women in Alberta with newly diagnosed stage I (≥ T1c) to IIIc breast cancer were recruited between 2012 and 2019. Baseline assessments were completed within 90 days of surgery. Measurements included accelerometers to measure PA and SB; a graded treadmill test with gas exchange analysis to measure cardiorespiratory fitness (VO2peak); upper and lower body muscular strength and endurance; dual-X-ray absorptiometry to measure body composition; and questionnaires to measure self-reported PA and SB.

RESULTS: At baseline, the 1528 participants’ mean age was 56 ± 11 years, 59% were post-menopausal, 62% had overweight/obesity, and 55% were diagnosed with stage II or III disease. Based on device measurements, study participants spent 8.9 ± 1.7 h/day sedentary, 4.4 ± 1.2 h/day in light-intensity activity, 0.9 ± 0.5 h/day in moderate-intensity activity, and 0.2 ± 0.2 h/day in vigorous-intensity activity. For those participants who reached VO2peak, the average aerobic fitness level was 26.6 ± 6 ml/kg/min. Average body fat was 43 ± 7.1%.

CONCLUSION: We have established a unique cohort of breast cancer survivors with a wealth of data on PA, SB, and HRF obtained through both direct and self-reported measurements. Study participants are being followed for at least ten years to assess all outcomes after breast cancer. These data will inform clinical and public health guidelines on PA, SB, and HRF for improving breast cancer outcomes.

PMID:35064432 | DOI:10.1007/s10552-021-01539-6

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Renin-angiotensin system modulation and outcomes in patients hospitalized for interstitial SARS-CoV2 pneumonia: a cohort study

Intern Emerg Med. 2022 Jan 21. doi: 10.1007/s11739-022-02929-7. Online ahead of print.

ABSTRACT

AIM: The role of cardiovascular (CV) pharmacotherapies in patients with severe COVID-19 pneumonia remains controversial. This study aims to assess the impact of renin-angiotensin system modulation (RASi) (either angiotensin-converting enzymes (ACEIs) or angiotensin-receptor blockers (ARBs)) on COVID-19 outcome.

METHODS: We performed a cohort study on consecutive patients admitted for COVID-19 pneumonia at the Internal Medicine Unit of Sant’Orsola-Malpighi Hospital in Bologna, Italy. Patients with a possible alternative cause of respiratory failure other than COVID-19 were excluded. Clinical, pharmacological and laboratory data at admission and during the hospitalization were collected. Patients were treated with intravenous dexamethasone, low molecular weight heparin and nasal flow or Venturi mask oxygen. Subjects were followed until discharge, Intensive Care Unit (ICU) admission or death. Severe cases were defined by acute respiratory distress syndrome (arterial oxygen partial pressure and the fraction of inhaled oxygen ratio (P/F) ≤ 100 mmHg/%, or P/F ≤ 150 mmHg/% and respiratory rate ≥ 26/min). Patients with chronic use of RAS modulation were compared with those without for the composite outcome of in-hospital mortality or ICU admission. Hazard ratios (HR) were obtained by Cox regression, adjusted for several clinical factors.

RESULTS: Of the 268 patients enrolled in the study, 93 (35%, mean age 68 ± 13 years, 67% males) were treated with RASi (58% ACEIs and 42% ARBs). There were no meaningful differences between the RASI and no RASI group regarding clinical and laboratory parameters at admission. As expected, patients in the RASi group had a higher prevalence of hypertension, diabetes mellitus, atrial fibrillation, and ischemic heart disease. One hundred eight patients (40%) were admitted to ICU during hospitalization due to severe respiratory failure, and 24 (9%) died. The risk of in-hospital death or ICU admission was lower in the RASI group than in the non-RASI group (age and sex-adjusted HR 0.57, 95% CI 0.37-0.8), even after adjustment for several comorbidities (fully adjusted HR 0.44, 95% CI 0.26-0.74). Seven (7.5%) patients died in the RASi group vs 17 (9.7%) in the non-RASi group, leading to a non-statistically significant mortality risk reduction (fully adjusted HR 0.69, 95% CI 0.18-1.90). The lower risk in the RASi group was primarily related to ARBs use compared to ACEIs (HR 0.5, 95% CI 0.28-0.92 and HR 0.82, 95% CI 0.51-1.32, respectively).

CONCLUSIONS: Our study showed an inverse association between the chronic use of RASi and COVID-19 pneumonia severity (either ICU admissions or in-hospital death), even when significant comorbidities are considered.

PMID:35064437 | DOI:10.1007/s11739-022-02929-7

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Thermal Cycling Effect on Locator System Retention and Metal Surface Roughness

J Prosthodont. 2022 Jan 21. doi: 10.1111/jopr.13481. Online ahead of print.

ABSTRACT

PURPOSE: To estimate the effects of the thermal cycling (TC) process on the metal surfaces of Locators, as well as retention loss, and the correlation between them.

MATERIALS AND METHODS: Twenty-five new Locator R-Tx were included in the study. Four areas were marked on each Locators’ patrix metal surface and scanned using a confocal scanner (μsurf explorer; NanoFocus). Three surface roughness parameters were measured in the scans: Sa (average distance of peaks from the central plain of the area), Vmp (volume of the peaks in the area), and Spc (mean curvature of the peaks describing the degree of their sharpness). Retention test was performed using Instron® 4500 compression tension tensile tester at a speed of 10 mm/min. The retention tests were done using a working model made of two acrylic blocks in which the Locator system parts were inserted. The surface parameters measurements and the retention tests were performed 2 times, one before and one after TC. The Locators were subjected to 15,000 TC cycles by investing them into 2 tubs with different water temperatures, 55˚ and 5˚ Celsius. During each 60 second cycle, the Locators were submerged in each tub for 20 seconds, with a 10 second transition time between the tubs. The post TC retention and surface parameters measurements were compared with those prior to TC and the prior to TC measurements served as controls. Changes in parameters before and after TC were analyzed by a two-way ANOVA nested model with random intercept and slope by restricted maximum likelihood method. Correlation between retention and surface parameters was quantified and examined using Kendall’s correlation test. The findings were considered statistically significant if p<0.05.

RESULTS: There was a significant decrease in retention of 16.6N at the second retention test (p <0.001). A significant statistical decrease in surface parameters were measured after TC process, Sa and Vmp (18 ×10-3 μm, p = 0.041 and 0.94 ×10-3 1/μm, p = 0.001 respectively). A significant statistical increase in Spc of 6.4 ×10-3 μm3 /μm2 (p = 0.023) was noticed. The correlation between retention decreases and surface changes was not statistically significant.

CONCLUSION: The TC process causes a substantial reduction in retention over time to the Locator system. In addition, TC causes significant but minor changes to Locator surface area. Most of the changes are in the horizontal dimension. This article is protected by copyright. All rights reserved.

PMID:35061925 | DOI:10.1111/jopr.13481

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Efficacy of fluorescent microscopy versus modified Fite-Faraco stain in skin biopsy specimens of leprosy cases – a comparative study

Int J Dermatol. 2022 Jan 21. doi: 10.1111/ijd.16046. Online ahead of print.

ABSTRACT

BACKGROUND: Histopathological examination of skin remains the cornerstone in the diagnosis of leprosy. At a few centers, fluorescent microscopy has been found to be useful in detecting more acid-fast bacilli (AFB) compared to modified Fite-Faraco staining but is sparsely documented. Hence, we studied the sensitivity of fluorescent microscopy and modified Fite-Faraco stain in the detection of Mycobacterium leprae in tissue sections.

METHODS: Patients attending our outpatient department during January 2019 to June 2020 with the clinical features of leprosy were examined, and the diagnosis was confirmed by histopathology after informed consent. Tissue sections were stained by fluorescent stain and modified Fite-Faraco stain. Bacillary index was calculated for each case.

RESULTS: Forty patients were recruited after following the inclusion and exclusion criteria. AFB were demonstrated in 20 patients by modified Fite-Faraco stain and in 27 patients with fluorescent stain. The sensitivity of fluorescent staining method (67.5%) was higher than modified Fite-Faraco stain (50%). Bacillary index was increased in 26 out of 40 cases by the fluorescent staining compared to the modified Fite-Faraco staining. Chi-square value was 69.3 and P value was 0.000, indicating a statistically significant correlation.

LIMITATIONS: Fluorescent microscope is expensive, and trained people are needed to identify the bacilli.

CONCLUSION: Fluorescent staining is more sensitive than modified Fite-Faraco staining in the detection of AFB in tissue sections. The bacilli detected per field were high with the fluorescent staining compared to the modified Fite-Faraco method.

PMID:35061916 | DOI:10.1111/ijd.16046

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Retrospective study of endodontic treatment performed by undergraduate students using reciprocating instrumentation and single-cone obturation

J Dent Educ. 2022 Jan 21. doi: 10.1002/jdd.12884. Online ahead of print.

ABSTRACT

OBJECTIVES: The aim of this cross-sectional retrospective study was to evaluate radiographically the technical quality of root canal treatment performed by undergraduate students using reciprocating NiTi instrumentation and single-cone obturation.

METHODS: Endodontic treatment on 1102 teeth performed by undergraduate students from the School of Dentistry of the University of Santa Cecilia (Brazil) was evaluated. All root canal preparations were performed using Reciproc files and were irrigated with 1% NaOCl. The root canal was filled with gutta-percha, along with AH Plus sealer, using the single-cone obturation technique. The technical quality of the root canal treatment was evaluated based on immediate postoperative radiographs. Distance between the end of the filling and the radiographic apex, the filling density, and the taper of the root filling was assessed. Inter-examiner agreement statistic (Kappa) and Chi-square statistic test were used for statistical evaluation of the results. Differences were considered statistically significant when p < 0.05.

RESULTS: Anterior teeth, maxillary premolars, and molars presented better results than mandibular premolars and molars (p < 0.05). Mandibular premolars presented a high incidence of a short length of obturation (33.34%) and mandibular molars presented a high incidence of overfilling (6.55%). The majority of the treatment analyzed (62.46%) fulfilled all the criteria showing acceptable working length, taper, and density of obturation. Instrument fractures occurred in eighteen root canals (0.81%).

CONCLUSIONS: The use of NiTi reciprocating instruments with the single-cone obturation technique provided an acceptable quality of endodontic treatment in the majority of the cases performed by undergraduate students.

PMID:35061917 | DOI:10.1002/jdd.12884

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Impact of combinations of clinically observed HIV integrase mutations on phenotypic resistance to integrase strand transfer inhibitors (INSTIs): a molecular study

J Antimicrob Chemother. 2022 Jan 21:dkab498. doi: 10.1093/jac/dkab498. Online ahead of print.

ABSTRACT

BACKGROUND: Routine HIV drug resistance genotyping identified an integrase sequence harbouring T97A, E138K, G140S and Q148H, with high predicted resistance to all integrase strand transfer inhibitors (INSTIs).

OBJECTIVES: To assess the impact of these substitutions alone and together on phenotypic INSTI susceptibility.

METHODS: We constructed recombinant NL4.3 viruses harbouring all mutation combinations in the autologous integrase sequence. Viruses were grown in GFP-reporter CD4+ T-cells in the presence of 0.01-1000 nM raltegravir, elvitegravir, dolutegravir, bictegravir, and cabotegravir. Infection was measured by imaging cytometry.

RESULTS: Q148H-containing viruses lacking G140S failed to propagate or mutated in vitro, consistent with fitness costs. Statistically significant reductions in INSTI susceptibility were observed for several mutation combinations, as follows. T97A or G140S alone conferred 3.6- to 5.6-fold decreased susceptibility to raltegravir and elvitegravir. Two-mutation combinations conferred low-to-moderate resistance to raltegravir and elvitegravir only, except G140S/Q148H which eliminated raltegravir and elvitegravir activity and conferred 24.6-, 7.9-, and 107.5-fold reduced susceptibility to dolutegravir, bictegravir and cabotegravir. Addition of E138K to G140S/Q148H conferred 35.5, 11.6 and 208-fold reduced susceptibility to dolutegravir, bictegravir, and cabotegravir, while addition of T97A to G140S/Q148H conferred 318, 121 and >1000-fold reduced susceptibility to these drugs. T97A/E138K/G140S/Q148H in the autologous backbone conferred >300-fold reduced susceptibility to all INSTIs. Notably, bictegravir EC50 was significantly lower when T97A/E138K/G140S/Q148H was introduced into NL4.3, suggesting that other mutations in the autologous sequence enhanced resistance.

CONCLUSIONS: High-level dolutegravir, bictegravir and cabotegravir resistance requires multiple integrase substitutions including compensatory mutations. T97A and E138K further enhance the resistance conferred by G140S/Q148H, yielding >300-fold decreased susceptibility to all INSTIs when all four mutations are present.

PMID:35061879 | DOI:10.1093/jac/dkab498

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Benchmarking of a Bayesian single cell RNAseq differential gene expression test for dose-response study designs

Nucleic Acids Res. 2022 Jan 21:gkac019. doi: 10.1093/nar/gkac019. Online ahead of print.

ABSTRACT

The application of single-cell RNA sequencing (scRNAseq) for the evaluation of chemicals, drugs, and food contaminants presents the opportunity to consider cellular heterogeneity in pharmacological and toxicological responses. Current differential gene expression analysis (DGEA) methods focus primarily on two group comparisons, not multi-group dose-response study designs used in safety assessments. To benchmark DGEA methods for dose-response scRNAseq experiments, we proposed a multiplicity corrected Bayesian testing approach and compare it against 8 other methods including two frequentist fit-for-purpose tests using simulated and experimental data. Our Bayesian test method outperformed all other tests for a broad range of accuracy metrics including control of false positive error rates. Most notable, the fit-for-purpose and standard multiple group DGEA methods were superior to the two group scRNAseq methods for dose-response study designs. Collectively, our benchmarking of DGEA methods demonstrates the importance in considering study design when determining the most appropriate test methods.

PMID:35061903 | DOI:10.1093/nar/gkac019

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Computed tomographic evaluation of pectus excavatum in 14 cats

PLoS One. 2022 Jan 21;17(1):e0262866. doi: 10.1371/journal.pone.0262866. eCollection 2022.

ABSTRACT

Pectus excavatum (PE) is one of the most frequently reported chest deformities. However, limited studies are available with regard to its CT scan findings in cats. In the present research computed tomographic images of the thoraxes of 14 cats diagnosed with PE has been reviewed. This is one of the first studies exploring the use of CT to characterise PE in animals. The aim of this study was to present characteristic CT features of PE in cats. The introduction of new criteria for better assessing thoracic wall deformity-a correction index (CI) and an asymmetry index (AI)-was also proposed. The study revealed a high variety of morphological features of PE in cats. It was demonstrated that among the 14 cats: cranial PE (an atypical location) occurred in seven cats while seven cats had typical (caudal) PE, long PE occurred in five cats, while short PE had nine cats. Of the 14 cats included in the study eight showed symmetric PE, and asymmetric PE was found insix. Thoracic asymmetry was found in six cats. Six cats had sternal torsion. Based on the Vertebral Index moderate or severe PE was revealed in 11 animals. In the group of cats studied the CI ranged from 12.20 to 32.11. The magnitude of AI did not exceed 10% in any of the cats studied. The study confirmed statistically significant differences in the CI values between groups of cats with different degrees of PE severity (p = 0.02). CT examination showed many PE features that have not been discussed so far. The main benefit of CT examination is its ability to reveal asymmetric PE, thoracic asymmetry and sternal torsion. CI and AI provided a clinically useful tool to quantify thoracic wall deformity in order to obtain comparable results between cats with PE.

PMID:35061860 | DOI:10.1371/journal.pone.0262866

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Effects of Internet-delivered cognitive behavioural therapy adapted for patients with cardiovascular disease and depression: a long-term follow-up of a randomized controlled trial at 6 and 12 months posttreatment

Eur J Cardiovasc Nurs. 2022 Jan 21:zvab131. doi: 10.1093/eurjcn/zvab131. Online ahead of print.

ABSTRACT

BACKGROUND: Internet-based cognitive behavioural treatment (iCBT) has shown positive short-term effects on depression in patients with cardiovascular disease (CVD). However, knowledge regarding long-term effects and factors that may impact the effect of iCBT is lacking.

AIMS: This study therefore sought (i) to evaluate the effect of iCBT on depression in CVD patients at 6- and 12-month follow-ups and (ii) to explore factors that might impact on the effect of iCBT on change in depression at 12-month follow-up.

METHODS AND RESULTS: A longitudinal follow-up study of a randomized controlled trial evaluating the effects of a 9-week iCBT programme compared to an online discussion forum (ODF) on depression in CVD patients (n = 144). After 9 weeks, those in the ODF group were offered the chance to take part in the iCBT programme. The Patient Health Questionnaire (PHQ-9) and the Montgomery-Åsberg Depression Rating Scale-self-rated version (MADRS-S) measured depression at baseline, 9 weeks, 6 months, and 12 months. Linear mixed model and multiple regression analysis were used for statistical computing. The iCBT programme significantly improved depression at 9-week follow-up and this was stable at 6- and 12-month follow-ups (PHQ-9 P = 0.001, MADRS-S P = 0.001). Higher levels of depression at baseline and a diagnosis of heart failure were factors found to impact the effect of iCBT on the change in depression.

CONCLUSION: A 9-week iCBT programme in CVD patients led to long-term improvement in depression. Higher levels of depression scores at baseline were associated with improvement in depression, whereas heart failure had opposite effect.

CLINICAL TRIAL: The trial is registered at ClinicalTrials.gov, NCT02778074.

PMID:35061868 | DOI:10.1093/eurjcn/zvab131

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Knowledge, attitude, and practice related to the COVID-19 pandemic among undergraduate medical students in Indonesia: A nationwide cross-sectional study

PLoS One. 2022 Jan 21;17(1):e0262827. doi: 10.1371/journal.pone.0262827. eCollection 2022.

ABSTRACT

INTRODUCTION: The potential role of medical students in raising awareness during public health emergencies has been acknowledged. To further explore their potentials as public educators and role models for the communities during the coronavirus disease 2019 (COVID-19) pandemic, this study aims to assess the knowledge, attitude, and practice of these students toward COVID-19.

METHODS: An online cross-sectional survey was conducted among undergraduate medical students in Indonesia. Socio-demographics characteristics, social interaction history, information-seeking behavior, as well as knowledge, attitude, and practice toward COVID-19 were collected through a self-reported questionnaire. A p-value of <0.05 indicated statistical significance.

RESULTS: Out of 4870 respondents, 64.9% had positive attitude and 51.5% had positive practice toward COVID-19, while only 29.8% had adequate knowledge. Knowledge was slightly positively correlated with attitude and practice (ρ = 0.074 and ρ = 0.054, respectively; both p<0.001), while attitude was weakly correlated with practice (ρ = 0.234, p<0.001). Several factors including age, sex, place of residence, institution type, academic level, family income, history of chronic illness, prior volunteering experience, and perceptual awareness on COVID-19 were significantly associated with either knowledge, attitude, and/or practice toward COVID-19. Furthermore, health institution’s and the government’s press releases, as well as health expert opinions were deemed as the most reliable sources of COVID-19-related information-yet trivially none of these sources were associated with knowledge, attitude, and practice in the study population.

CONCLUSION: Many undergraduate medical students in Indonesia had positive attitude and practice against COVID-19, yet only a few had adequate knowledge. This warrants further interventions to keep them updated with COVID-19 evidence to maximize their potentials in raising public awareness on COVID-19.

PMID:35061848 | DOI:10.1371/journal.pone.0262827