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BACKGROUND: Increasing fruit and vegetable (FV) consumption is associated with reduced cardiovascular disease risk in observational studies but with little evidence from randomised controlled trials (RCTs). The impact of concurrent pharmacological therapy is unknown. OBJECTIVE: To pool data from six RCTs to examine the effect of increasing FV intake on blood pressure (BP) and lipid profile, also exploring whether effects differed by medication use. DESIGN: Across trials, dietary intake was assessed by diet diaries or histories, lipids by routine biochemical methods and BP by automated monitors. Linear regression provided an estimate of the change in lipid profile or BP associated with a one portion increase in self-reported daily FV intake, with interaction terms fitted for medication use. RESULTS: The pooled sample included a total of 554 participants (308 males and 246 females). Meta-analysis of regression coefficients revealed no significant change in either systolic or diastolic BP per portion FV increase, although there was significant heterogeneity across trials for systolic BP (I2 = 73%). Neither adjusting for change in body mass index, nor analysis according to use of anti-hypertensive medication altered the relationship. There was no significant change in lipid profile per portion FV increase, although there was a significant reduction in total cholesterol among those not on lipid-lowering therapy (P < 0.05 after Bonferroni correction). CONCLUSION: Pooled analysis of six individual FV trials showed no impact of increasing intake on BP or lipids, but there was a total cholesterol-lowering effect in those not on lipid-lowering therapy.
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Pressão Sanguínea , Frutas , Lipídeos , Ensaios Clínicos Controlados Aleatórios como Assunto , Verduras , Humanos , Pressão Sanguínea/efeitos dos fármacos , Masculino , Feminino , Pessoa de Meia-Idade , Lipídeos/sangue , Idoso , Dieta Saudável , Anti-Hipertensivos/uso terapêutico , Biomarcadores/sangueRESUMO
Azithromycin (AZM) is commonly used in Covid-19 patients based on low-quality evidence, increasing the risk of developing adverse events and antimicrobial resistance. The current systematic review and meta-analysis investigated the safety and efficacy of AZM in treating Covid-19 patients using published randomized controlled trials. Google Scholar, PubMed, Scopus, Cochrane Library, Clinical Trials.gov, MEDLINE, bioRxiv and medRxiv were searched for relevant studies. The random-effects model was used to pool estimates using the Paule-Mandel estimate for heterogeneity. The odds ratio and raw difference in medians were used for dichotomous and continuous outcomes, respectively. The analysis included seven studies with 8822 patients (median age, 55.8 years; 61% males). The risk of bias was assessed as 'low' for five of the seven mortality results and as 'some concerns' and 'high' in one trial each. There were 657/3100 (21.2%) and 1244/5654 (22%) deaths among patients randomized to AZM and standard of care, respectively. The use of AZM was not associated with mortality in Covid-19 patients (OR = 0.96, 95% CI 0.88-1.05, p = 0.317 based on the random-effect meta-analysis). The use of AZM was not associated with need for invasive mechanical ventilation (OR = 0.96, 95% CI 0.49-1.87, p = 0.85) and length of stay (Δ = 1.11, 95% CI -2.08 to 4.31, p = 0.49). The results show that using AZM as routine therapy in Covid-19 patients is not justified due to lack of efficacy and potential risk of bacterial resistance that is not met by an increased clinical benefit.
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Antibacterianos/uso terapêutico , Azitromicina/uso terapêutico , Tratamento Farmacológico da COVID-19 , Antibacterianos/efeitos adversos , Azitromicina/efeitos adversos , COVID-19/diagnóstico , Humanos , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , SARS-CoV-2RESUMO
BACKGROUND: In arterial line cannulation in children and adolescents, traditional methods of locating the artery include palpation and Doppler auditory assistance. It is unclear whether ultrasound guidance is superior to these methods. This is an update of a review originally published in 2016. OBJECTIVES: To evaluate the benefits and harms of ultrasound guidance compared with traditional techniques (palpation, Doppler auditory assistance) for assisting arterial line placement at all potential sites in children and adolescents. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, and Web of Science from inception to 30 October 2022. We also searched four trials registers for ongoing trials, and we checked the reference lists of included studies and relevant reviews for other potentially eligible trials. SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing ultrasound guidance versus other techniques (palpation or Doppler auditory assistance) to guide arterial line cannulation in children and adolescents (aged under 18 years). We planned to include quasi-RCTs and cluster-RCTs. For RCTs with both adult and paediatric populations, we planned to include only the paediatric population data. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the risk of bias of included trials and extracted data. We used standard Cochrane meta-analytical procedures, and we applied the GRADE method to assess the certainty of evidence. MAIN RESULTS: We included nine RCTs reporting 748 arterial cannulations in children and adolescents (under 18 years of age) undergoing different surgical procedures. Eight RCTs compared ultrasound with palpation, and one compared ultrasound with Doppler auditory assistance. Five studies reported the incidence of haematomas. Seven involved radial artery cannulation and two involved femoral artery cannulation. The people performing arterial cannulation were physicians with different levels of experience. The risk of bias varied across studies, with some studies lacking details of allocation concealment. It was not possible to blind practitioners in any case; this adds a performance bias that is inherent to the type of intervention studied in our review. Compared to traditional methods, ultrasound guidance probably causes a large increase in first-attempt success rates (risk ratio (RR) 2.01, 95% confidence interval (CI) 1.64 to 2.46; 8 RCTs, 708 participants; moderate-certainty evidence) and probably causes a large reduction in the risk of complications such as haematoma formation (RR 0.26, 95% CI 0.14 to 0.47; 5 RCTs, 420 participants; moderate-certainty evidence). No studies reported data about ischaemic damage. Ultrasound guidance probably improves success rates within two attempts (RR 1.78, 95% CI 1.25 to 2.51; 2 RCTs, 134 participants; moderate-certainty evidence) and overall rate of successful cannulation (RR 1.32, 95% CI 1.10 to 1.59; 6 RCTs, 374 participants; moderate-certainty evidence). In addition, ultrasound guidance probably reduces the number of attempts to successful cannulation (mean difference (MD) -0.99 attempts, 95% CI -1.15 to -0.83; 5 RCTs, 368 participants; moderate-certainty evidence) and duration of the cannulation procedure (MD -98.77 seconds, 95% CI -150.02 to -47.52, 5 RCTs, 402 participants; moderate-certainty evidence). More studies are needed to confirm whether the improvement in first-attempt success rates is more pronounced in neonates and younger children compared to older children and adolescents. AUTHORS' CONCLUSIONS: We identified moderate-certainty evidence that ultrasound guidance for arterial cannulation compared with palpation or Doppler auditory assistance improves first-attempt success rate, second-attempt success rate and overall success rate. We also found moderate-certainty evidence that ultrasound guidance reduces the incidence of complications, the number of attempts to successful cannulation and the duration of the cannulation procedure.
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Artérias , Hematoma , Adolescente , Adulto , Criança , Recém-Nascido , Humanos , Idoso , Ultrassonografia , Artérias/diagnóstico por imagem , Cateterismo , Ultrassonografia de IntervençãoRESUMO
Matrix metalloproteinases (MMPs) are identifiable members of proteolytic enzymes that can degrade a wide range of proteins in the extracellular matrix (ECM). MMPs can be categorized into six groups based on their substrate specificity and structural differences: collagenases, gelatinases, stromelysins, matrilysins, metalloelastase, and membrane-type MMPs. MMPs have been linked to a wide variety of biological processes, such as cell transformation and carcinogenesis. Over time, MMPs have been evaluated for their role in cancer progression, migration, and metastasis. Accordingly, various MMPs have become attractive therapeutic targets for anticancer drug development. The first generations of broad-spectrum MMP inhibitors displayed effective inhibitory activities but failed in clinical trials due to poor selectivity. Thanks to the evolution of X-ray crystallography, NMR analysis, and homology modeling studies, it has been possible to characterize the active sites of various MMPs and, consequently, to develop more selective, second-generation MMP inhibitors. In this review, we summarize the computational and synthesis approaches used in the development of MMP inhibitors and their evaluation as potential anticancer agents.
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Antineoplásicos , Neoplasias , Humanos , Inibidores de Metaloproteinases de Matriz/farmacologia , Inibidores de Metaloproteinases de Matriz/uso terapêutico , Neoplasias/metabolismo , Metaloproteinases da Matriz/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Antineoplásicos/metabolismo , Matriz Extracelular/metabolismoRESUMO
BACKGROUND: Resin composite restorations are highly esthetic restorations, which should have and maintain high surface polish. However, esthetic restorations are subjected to different beverages at variable temperatures, which may affect their surface roughness. This study aimed to evaluate the surface roughness of single-shade (Omnichroma) and multi-shade (Filtek Z350XT) composite materials, following aging by immersion and thermocycling in different beverages, simulating one year of clinical service. METHODS: Thirty specimens of each material were prepared and divided into 6 subgroups (n = 5). In each material, the grouping of the specimens was as follows: the first subgroup was the as-prepared specimens stored dry without immersion or thermocycling. The second, third, and fourth subgroups were immersed in saliva, tea, and red wine, respectively, for 12 days at 37 °C. The fifth and sixth subgroups were thermocycled for 10,000 cycles, in tea (the fifth between 37 and 57 °C) and in red wine (the sixth between 37 °C and12°C). The resultant surface roughness was measured by two different methods, stylus profilometer and atomic force microscopy (AFM). Intergroup comparison was performed using independent t test, while intragroup comparison was performed using one-way analysis of variance (ANOVA) followed by Tukey's post-hoc test. RESULTS: Intergroup comparison between both composites showed no statistically significant differences in all groups using the stylus profilometer roughness measurements (P>0.05), while the AFM measurements showed significant difference (P ≤ 0.05) within all storage media except the as-prepared control (P = 0.0645), where nanofilled Filtek Z350 XT showed lower nano-roughness. Intragroup comparison data were variable, depending on the material, aging conditions, and roughness assessment tool. However, the resultant average surface roughness (Ra) values in all groups did not exceed the threshold value of Ra 0.2 µm. CONCLUSIONS: Both resin composites attained and retained a clinically acceptable surface finish after immersion and thermocycling in different beverages.
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Resinas Compostas , Imersão , Humanos , Bebidas , Chá , Propriedades de Superfície , Teste de Materiais , CorRESUMO
BACKGROUND: Jordan has experienced several COVID-19 waves in the past 2 years. Cross-sectional studies have been conducted to evaluate distress in healthcare practitioners (HCPs), but there is limited evidence with regards to the impact of continuing pandemic waves on levels of distress in HCPs. We previously studied psychological distress in HCPs during the start of the pandemic (period 1, when cases were infrequent and the country was in lockdown), and demonstrated that HCPs were experiencing considerable stress, despite the country reporting low caseloads at the time. In this study, we sought to utilize the same methodology to reexamine levels of distress as COVID-19 peaked in the country and HCPs began managing large numbers of COVID-19 cases (period 2). METHODS: A cross-sectional online survey utilizing a tool previously used during period 1 was completed by HCPs working in various settings. Demographic, professional and psychological factors such as distress, anxiety, depression, burnout, sleep issues, exhaustion, and fear were assessed; and coping strategies also were measured. Items in the tool were assessed for reliability and validity. A multivariable regression was used to identify factors that continued to impact distress during period 2. RESULTS: Samples in both periods (n = 937, n = 876, respectively) were relatively comparable in demographic characteristics, but in period 2, a greater proportion of nurses and healthcare practitioners reported working in general hospitals. During the pandemic peak (period 2), 49.0% of HCPs reported high levels of distress (compared to 32% in period 1); anxiety and depression scores were approximately 21% higher in period 2; and 50.6% reported fatigue (compared to 34.3% in period 1). Variables significantly associated with greater distress in period 2 included experiencing burnout, experiencing sleep disturbances, being fatigued, having fatalistic fears, and having fears related to workload. Conversely, being male, reporting satisfaction at work, and using positive coping practices were associated with a significantly lower odds of being in distress. CONCLUSIONS: Between the two periods (early pandemic and first wave), COVID-19-related mental health continued to deteriorate among HCPs, highlighting the need to do more to support HCP front-liners facing COVID-19 surges.
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Esgotamento Profissional , COVID-19 , Angústia Psicológica , Esgotamento Profissional/epidemiologia , Esgotamento Profissional/psicologia , COVID-19/epidemiologia , Controle de Doenças Transmissíveis , Estudos Transversais , Depressão/epidemiologia , Pessoal de Saúde/psicologia , Humanos , Jordânia/epidemiologia , Masculino , Reprodutibilidade dos TestesRESUMO
BACKGROUND: Multiple sclerosis (MS) is a chronic inflammatory neurodegenerative disease of the central nervous system. Vasoactive and intestinal peptide (VIP) and pituitary adenylate cyclase-activating peptide (PACAP) are neuropeptides that play roles in anti-inflammation and neuroprotection in MS. In this study, we aimed to determine the serum levels of VIP and PACAP in MS patients versus healthy controls and to correlate them with demographics and clinical characteristics. METHODS: Serum samples were collected from MS patients (n = 145) and healthy controls (n = 73) to measure serum levels VIP and PACAP. RESULTS: VIP serum levels were lower in MS patients than healthy controls (p < 0.001). Serum PACAP levels were the same among the two groups. Gender-based analysis showed that VIP levels were lower in healthy females (1238.840 pg/ml) than healthy males (3300.105 pg/ml; p < 0.001), and PACAP serum levels were significantly lower in male MS patients (48,516.214 fg/ml) than female MS patients (62,466.400 fg/ml; p = 0.029). ROC curve suggested that serum VIP level can discriminate patients with MS from healthy controls. Relapsing-remitting MS, progressive-MS, and clinically isolated syndrome groups were different in age, MS disease duration, EDSS score, and VIP levels (p < 0.05). MS disease type and history of previous relapses in the preceding 24 months predicted serum VIP levels, while gender predicted PACAP levels. CONCLUSION: VIP serum levels are decreased in MS patients and can be used to differentiate between MS patients and healthy controls. Further studies with larger sample sizes are required to investigate VIP as a marker to reflect MS disease progression.
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Esclerose Múltipla , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase , Peptídeo Intestinal Vasoativo , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Esclerose Múltipla/sangue , Esclerose Múltipla/diagnóstico , Doenças Neurodegenerativas/sangue , Doenças Neurodegenerativas/diagnóstico , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/sangue , Peptídeo Intestinal Vasoativo/sangueRESUMO
Background: People perform sports for better health and wellbeing. However, the use of doping agents is emerging among young adults. This study investigated aspects related to doping agents. Methods: A reliable self-administered questionnaire (Cronbach's alpha =0.72, Pearson's r = 0.89) was used to assess knowledge, attitudes, and practicalities related to the use of doping agents. Results for pharmacists as health care providers (HCP, n=550) were compared with non-healthcare providers (Non-HCP, n=319). Results: Among pharmacists, 82.9% knew the definition of doping agents vs. 72.4% of non-HCP (P<0.001). However, 36.7% of pharmacists vs. 39.6% of non-HCP incorrectly classified doping agents (P=0.02). The majority of responders (89.8%) supported having an anti-doping authority, yet, only 15% were aware of the anti-doping organizations. The majority of responders (83%) did not receive an official education related to doping agents. Enhancing physical performance was perceived as a leading driver (82.1%) to use doping agents. More than 90% of responders supported awareness in the community. The perceived best tool for awareness was social media and TV sites, as suggested by pharmacists (95.0%) and non-HCP (92.1%, P=0.312). A total of 6.1% had ever used doping agents (3.6% pharmacist vs. 9.8% non-HCP, P<0.001). Almost half of the users utilized a diet or medication to counteract the side effects of doping agents. Within pharmacists, males received more requests to provide doping agents (41.9%) compared with females (23.8%, P<0.001). Conclusion: It is crucial to enhance professional and legal knowledge and public awareness about doping agents, not only for non-HCP but also for HCPs. Applying more restrictions on doping agents is strongly recommended.
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The long-term color stability and gloss retention of resin composites are among the crucial factors that affect the clinical longevity of esthetic restorations, especially in anterior teeth. This study evaluated the effect of artificial aging by immersion in different storage media and thermocycling on color and gloss of dental single-shade resin composite (Omnichroma) versus multi-shade one (Filtek Z350XT). One hundred resin-composite disc-shaped specimens were used, 50 from each group, Omnichroma and Filtek Z350XT. Ten specimens from each material acted as control group (incubated in saliva). For each material, 40 specimens were divided according to the artificial-aging protocol (immersion at 37 °C for 12 days or thermocycling for 10,000 cycles) and storage media (tea, red wine). Color and gloss were measured before and after artificial aging. Color difference (∆E00) was compared with perceptibility threshold and acceptability threshold. Data were statistically analyzed; independent t test was used to compare results between two tested materials, while two-way ANOVA was used to compare results among the different immersion media within the same material. Artificial aging (immersion or thermocycling) in tea and red wine led to significant color changes and gloss reduction in both materials (P < 0.05), in contrast to control group. Red wine produced highest color differences. Both dental resin-composites; the single-shade (Omnichroma) and multi-shade (Filtek Z350XT) displayed unacceptable discoloration and gloss reduction after artificial-aging in tea and red-wine by immersion or thermocycling simulating one-year clinical-service.
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Resinas Compostas , Chá , Cor , Humanos , Teste de Materiais , Propriedades de SuperfícieRESUMO
Matcha tea has been used as an adjunct in weight loss programs. The weight loss effects of matcha tea were evaluated in a prospective non-randomized open-label comparative study of overweight and obese individuals who followed a specified low-calorie diet (LCD) plan. A total of 40 participants were enrolled and assigned to either matcha tea or control groups. The matcha tea group followed a LCD plan and received matcha tea once daily, whereas the control group followed only the LCD diet plan. The study lasted 12 weeks. The main outcome measures included anthropometric measurements, fasting blood glucose, hemoglobin A1c (HbA1c), lipid profile, obesity-related hormone peptides, pro-inflammatory and anti-inflammatory cytokines, and oxidative stress biomarkers. Thirty-four participants had completed the study. The matcha tea and control groups showed significant reductions in body weight, body mass index, waist circumference, water content, minerals, and fat mass at week 12. The post-treatment body composition and anthropometric measurements were not significantly different between the two groups. The matcha tea group showed a potential increase in HDL-C, a potential decrease in blood glucose, and a potential increase in HbA1c. Furthermore, the study indicated a potential decrease in insulin and leptin levels, a potential increase in the activity of superoxide dismutase, and a potential decreased activity of glutathione peroxidase. IL-10 was increased by matcha tea consumption. The data suggest that matcha tea may have some potential effect on weight loss, along with anti-inflammatory properties. The findings of this study will be used to design a multicenter randomized clinical trial to examine the potential weight loss benefits of matcha tea.
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Sobrepeso , Chá , Antioxidantes , Glicemia , Índice de Massa Corporal , Hemoglobinas Glicadas , Humanos , Obesidade/tratamento farmacológico , Estudos Prospectivos , Chá/química , Redução de PesoRESUMO
Increased fruit and vegetable (FV) intake is associated with reduced blood pressure (BP). However, it is not clear whether the effect of FV on BP depends on the type of FV consumed. Furthermore, there is limited research regarding the comparative effect of juices or whole FV on BP. Baseline data from a prospective cohort study of 10 660 men aged 50-59 years examined not only the cross-sectional association between total FV intake but also specific types of FV and BP in France and Northern Ireland. BP was measured, and dietary intake assessed using FFQ. After adjusting for confounders, both systolic BP (SBP) and diastolic BP (DBP) were significantly inversely associated with total fruit, vegetable and fruit juice intake; however, when examined according to fruit or vegetable sub-type (citrus fruit, other fruit, fruit juices, cooked vegetables and raw vegetables), only the other fruit and raw vegetable categories were consistently associated with reduced SBP and DBP. In relation to the risk of hypertension based on SBP >140 mmHg, the OR for total fruit, vegetable and fruit juice intake (per fourth) was 0·95 (95 % CI 0·91, 1·00), with the same estimates being 0·98 (95 % CI 0·94, 1·02) for citrus fruit (per fourth), 1·02 (95 % CI 0·98, 1·06) for fruit juice (per fourth), 0·93 (95 % CI 0·89, 0·98) for other fruit (per fourth), 1·05 (95 % CI 0·99, 1·10) for cooked vegetable (per fourth) and 0·86 (95 % CI 0·80, 0·91) for raw vegetable intakes (per fourth). Similar results were obtained for DBP. In conclusion, a high overall intake of fruit, vegetables and fruit juice was inversely associated with SBP, DBP and risk of hypertension, but this differed by FV sub-type, suggesting that the strength of the association between FV sub-types and BP might be related to the type consumed, or to processing or cooking-related factors.
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Pressão Sanguínea , Dieta , Frutas , Infarto do Miocárdio/epidemiologia , Verduras , Citrus , Culinária , Estudos Transversais , França , Frutas/classificação , Sucos de Frutas e Vegetais , Humanos , Hipertensão/epidemiologia , Hipertensão/prevenção & controle , Masculino , Pessoa de Meia-Idade , Irlanda do Norte , Razão de Chances , Estudos Prospectivos , Verduras/classificaçãoRESUMO
Objective: Electronic cigarettes (ECIGs) are battery-powered devices that emit vaporized solutions for the user to inhale. ECIGs are marketed as a less harmful alternative to combustible cigarettes. The current study examined the effects of ECIG aerosol exposure on learning and memory, expression of brain derived neurotrophic factor (BDNF), and the activity of antioxidant enzymes in the hippocampus.Methods: Male Wistar rats were exposed to ECIG aerosol, by a whole-body exposure system, 1 h/day for 1 week, 4 weeks, and 12 weeks. Spatial learning and memory were tested using the Radial Arm Water Maze (RAWM). Hippocampal BDNF protein level, and oxidative stress biomarkers (GPx, SOD, GSH, GSSG, GSH/GSSG ratio) were also assessed.Results: ECIG aerosol exposure for 4 and 12 weeks impaired both short- and long- term memory and induced reductions in the hippocampus BDNF, SOD and GPx activities, and GSH/GSSG ratio (p < 0.05). No changes in any examined biomarkers were observed after 1-week exposure to ECIG aerosol (p > 0.05).Conclusions: ECIG aerosol exposure impaired functional memory and elicited changes in brain chemistry that are consistent with reduced function and oxidative stress.
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Fator Neurotrófico Derivado do Encéfalo/metabolismo , Sistemas Eletrônicos de Liberação de Nicotina , Aprendizagem em Labirinto/efeitos dos fármacos , Memória/efeitos dos fármacos , Nicotina/efeitos adversos , Estresse Oxidativo , Animais , Biomarcadores , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Masculino , Ratos , Ratos Wistar , Fatores de TempoRESUMO
OBJECTIVE: Paediatric patients are highly exposed to medication errors especially dosing errors. This study assessed the community pharmacists' knowledge about appropriate dosing of antibiotics among paediatric patients, factors affecting community pharmacists' knowledge and barriers that lead to inappropriate dosing of antibiotics. METHODS: A self-administered questionnaire was distributed to 1283 Jordanian pharmacists who worked in community pharmacies. Descriptive statistics and multivariate regression were conducted. RESULTS: The response rate was 87.1%. The majority of pharmacists (86.4%) were non-knowledgeable about appropriate dosing of antibiotics among paediatrics. The monthly income of the pharmacist was positively associated with pharmacists' knowledge. The case of azithromycin dosing in acute bacterial pharyngitis was answered correctly by the highest percentage of community pharmacists (55.8%) while the case of trimethoprim-sulfamethoxazole dosing in lower urinary tract infection was answered correctly by the lowest percentage (15.7%). Poor scientific knowledge about dose calculation was the most reported barrier by the participants (54.7%). CONCLUSION: Most community pharmacists were non-knowledgeable about appropriate dosing of antibiotics in paediatrics and the level of knowledge was affected by monthly income. Implementing adequate and appropriate educational programmes, constructing specific guidelines that regulate antibiotics practice among community pharmacists are highly recommended.
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Serviços Comunitários de Farmácia , Pediatria , Antibacterianos , Criança , Estudos Transversais , Humanos , Jordânia , FarmacêuticosRESUMO
BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiology of COVID-19 pandemic, resulted in significant harm to the affected countries in every aspect of life. The virus infected over 139 million patients and resulted in over 2.9 million deaths until April 16, 2021. New variants of this virus were identified that spread rapidly worldwide. SUMMARY: Remdesivir, a prodrug of adenosine nucleotide analog, is an antiviral with a broad spectrum of activity that was tested on SARS and Middle East respiratory syndrome infections. In vitro studies conducted on SARS-CoV-2 revealed that remdesivir inhibited viral replication with high selectivity index in cell cultures. In vivo studies showed that remdesivir reduced viral load in bronchoalveolar lavage fluid and attenuated pulmonary infiltrates in infected animals. Further, remdesivir showed promising results in terms of clinical improvement, shortening the recovery time, mortality rate, and the duration of oxygen need, despite that some clinical trials did not reveal significant effect on remdesivir use. Several studies showed positive results of remdesivir against the new variants. Key Messages: Remdesivir showed a promising beneficial effect against new variants of SARS-CoV-2, but more clinical evidence is needed to confirm this effect.
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Monofosfato de Adenosina/análogos & derivados , Alanina/análogos & derivados , Antivirais/farmacologia , Antivirais/uso terapêutico , Tratamento Farmacológico da COVID-19 , Monofosfato de Adenosina/farmacologia , Monofosfato de Adenosina/uso terapêutico , Alanina/farmacologia , Alanina/uso terapêutico , Animais , COVID-19/virologia , Humanos , Pandemias , Ensaios Clínicos Controlados Aleatórios como Assunto , SARS-CoV-2/efeitos dos fármacosRESUMO
We present a new, open source, computationally capable datalogger for collecting and analyzing high temporal resolution residential water use data. Using this device, execution of water end use disaggregation algorithms or other data analytics can be performed directly on existing, analog residential water meters without disrupting their operation, effectively transforming existing water meters into smart, edge computing devices. Computation of water use summaries and classified water end use events directly on the meter minimizes data transmission requirements, reduces requirements for centralized data storage and processing, and reduces latency between data collection and generation of decision-relevant information. The datalogger couples an Arduino microcontroller board for data acquisition with a Raspberry Pi computer that serves as a computational resource. The computational node was developed and calibrated at the Utah Water Research Laboratory (UWRL) and was deployed for testing on the water meter for a single-family residential home in Providence City, UT, USA. Results from field deployments are presented to demonstrate the data collection accuracy, computational functionality, power requirements, communication capabilities, and applicability of the system. The computational node's hardware design and software are open source, available for potential reuse, and can be adapted to specific research needs.
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Software , Água , Algoritmos , Computadores , Armazenamento e Recuperação da InformaçãoRESUMO
OBJECTIVES: To study the effect of artificial aging on color stability, translucency, and surface roughness of stained all-ceramic restorations. MATERIALS AND METHODS: Disc-shaped specimens were fabricated from six different all-ceramic materials: two glass ceramics (Vita Mark II and Empress CAD), two lithium disilicate based ceramics (e.max and Suprinity), and two zirconia-based materials (ZirCAD LT and ZirCAD MT Multi). The discs were stained using two universal stains; IPS Ivocolor stain or Vita Akzent stain. Color change (ΔE) and the translucency parameter (TP) were measured before and after artificial aging. The surface roughness (Ra) was evaluated using atomic force microscopy, while the surface microstructure was evaluated using scanning electron microscopy (SEM). Quantitative elemental analysis was performed using the energy dispersive X-ray (EDX). Leached ions were analyzed by inductively coupled plasma (ICP) (n = 12, α = 0.05). RESULTS: Artificial aging had significantly changed the color (ΔE) and decreased the translucency (TP) of all stained ceramics. The mean surface roughness (Ra) was significantly increased in all specimens, which was also confirmed in the SEM scans. EDX analysis revealed a decrease in the elemental composition of the stained surface as a result of ceramic degradation, except for Ca and Zn in IPS Ivocolor stain. Furthermore, the ICP analysis revealed that most compositional elements of stain and glaze were detected in the aging solution. CONCLUSIONS: Chemical aging had significantly affected the optical parameters and surface texture of stained monolithic ceramics. CLINICAL SIGNIFICANCE: Stained ceramics are liable to color degradation. Each type of stain should be used with its corresponding type of ceramic. Stained all-ceramic restorations are liable to color change and surface degradation during function.
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Cerâmica , Porcelana Dentária , Cor , Desenho Assistido por Computador , Teste de Materiais , Propriedades de SuperfícieRESUMO
Objective: To evaluate clinical and economic burden associated with respiratory tract infection (RTI)-induced asthma exacerbations and to identify risk factors associated with these exacerbations. Factors associated with these exacerbations are understudied and little information is available about consequent expenditures. Methods: In this retrospective case-control study, medical records and pharmacy data in King Abdullah University Hospital in Northern Jordan were reviewed for adults with asthma aged 40 years and older, over the period 2013-2016. Cases of RTI-induced asthma exacerbations were identified, and controls were selected randomly from asthmatic adults who did not experience any RTI-induced asthma exacerbation during the same period. Independent-samples t-tests and chi-square tests were conducted to compare patient characteristics of cases and controls. Predictors of RTI-induced asthma exacerbations and the resultant complications were evaluated using multivariable logistic regression. Multivariable regression on log-transformed charges was used to predict expenditures of these exacerbations. Results: A total of 137 cases and 548 controls were identified. Using inhaled corticosteroid + long-acting beta-agonists (ICS + LABA) was significantly associated with lower odds of RTI-induced asthma exacerbations (OR = 0.4; 95% CI, 0.21-0.77; p = 0.006), and lower odds of resultant serious complications (OR = 0.23; 95% CI, 0.07-0.69; p = 0.009), compared to being untreated with any asthma maintenance treatment. Asthma severity and co-morbidities were associated with increased susceptibility to these exacerbations. The average charges of RTI-induced asthma admissions and outpatient exacerbations were 1042.9 JD ($1471.0) and 81.1 JD ($114.4), respectively. Conclusions: ICS + LABA, asthma severity and co-morbidities appeared to affect the clinical and economic burden associated with RTI-induced asthma exacerbations. Efforts to prevent these exacerbations in patients with risk factors are warranted.
Assuntos
Antiasmáticos/uso terapêutico , Asma/epidemiologia , Efeitos Psicossociais da Doença , Infecções Respiratórias/epidemiologia , Exacerbação dos Sintomas , Administração por Inalação , Agonistas de Receptores Adrenérgicos beta 2/administração & dosagem , Idoso , Asma/tratamento farmacológico , Asma/economia , Asma/imunologia , Estudos de Casos e Controles , Comorbidade , Prescrições de Medicamentos/estatística & dados numéricos , Feminino , Glucocorticoides/administração & dosagem , Preços Hospitalares/estatística & dados numéricos , Hospitalização/economia , Hospitalização/estatística & dados numéricos , Humanos , Jordânia/epidemiologia , Masculino , Pessoa de Meia-Idade , Infecções Respiratórias/complicações , Infecções Respiratórias/economia , Infecções Respiratórias/imunologia , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de DoençaRESUMO
OBJECTIVE: The popularity of electronic cigarettes (E-Cigs) smoking is increasing worldwide including patients with asthma. In this study, the effects of E-Cigs aerosol exposure on airway inflammation in an allergen-driven murine model of asthma were investigated. MATERIALS AND METHODS: Balb/c mice were randomly assigned to; control group (received fresh air, Ovalbumin (Ova) sensitization and saline challenge), E-Cig group (received E-Cig aerosol, Ova sensitization, and saline challenge), Ova S/C group (received fresh air, Ova sensitization and Ova challenge) and E-Cig + Ova S/C group. Bronchoalveolar lavage fluid (BALF) and lung tissue were evaluated for inflammatory cells and inflammatory mediators, respectively. RESULTS: Exposure to E-Cig aerosol significantly increased the number of all types of inflammatory cells in BALF (p < 0.05). Further, E-Cig aerosol reduced levels of transforming growth factor (TGF)-ß1 and matrix metalloproteinase (MMP)-2 in lung tissue homogenate (p < 0.05). Combined E-Cig aerosol and Ova S/C increased the airway recruitment of inflammatory cells, especially neutrophils, eosinophils, and lymphocytes (p < 0.05), increased the level of interleukin (IL)-13, and reduced the level of TGF-ß1 (p < 0.05). CONCLUSIONS: E-Cig aerosol exposure induced airway inflammation in both control mice and allergen-driven murine model of asthma. The inflammatory response induced by E-Cig was slightly higher in allergen-driven murine model of asthma than in healthy animals.
Assuntos
Asma/imunologia , Sistemas Eletrônicos de Liberação de Nicotina , Administração por Inalação , Aerossóis , Alérgenos , Animais , Líquido da Lavagem Broncoalveolar/citologia , Líquido da Lavagem Broncoalveolar/imunologia , Modelos Animais de Doenças , Interleucina-13/imunologia , Leucócitos/imunologia , Pulmão/imunologia , Macrófagos/imunologia , Masculino , Metaloproteinase 2 da Matriz/imunologia , Camundongos Endogâmicos BALB C , Ovalbumina , Fator de Crescimento Transformador beta/imunologiaRESUMO
The mostly widely used bronchodilators in asthma therapy are ß2-adrenoreceptor (ß2AR) agonists, but their chronic use causes paradoxical adverse effects. We have previously determined that ß2AR activation is required for expression of the asthma phenotype in mice, but the cell types involved are unknown. We now demonstrate that ß2AR signaling in the airway epithelium is sufficient to mediate key features of the asthmatic responses to IL-13 in murine models. Our data show that inhibition of ß2AR signaling with an aerosolized antagonist attenuates airway hyperresponsiveness (AHR), eosinophilic inflammation, and mucus-production responses to IL-13, whereas treatment with an aerosolized agonist worsens these phenotypes, suggesting that ß2AR signaling on resident lung cells modulates the asthma phenotype. Labeling with a fluorescent ß2AR ligand shows the receptors are highly expressed in airway epithelium. In ß2AR-/- mice, transgenic expression of ß2ARs only in airway epithelium is sufficient to rescue IL-13-induced AHR, inflammation, and mucus production, and transgenic overexpression in WT mice exacerbates these phenotypes. Knockout of ß-arrestin-2 (ßarr-2-/-) attenuates the asthma phenotype as in ß2AR-/- mice. In contrast to eosinophilic inflammation, neutrophilic inflammation was not promoted by ß2AR signaling. Together, these results suggest ß2ARs on airway epithelial cells promote the asthma phenotype and that the proinflammatory pathway downstream of the ß2AR involves ßarr-2. These results identify ß2AR signaling in the airway epithelium as capable of controlling integrated responses to IL-13 and affecting the function of other cell types such as airway smooth muscle cells.
Assuntos
Asma/etiologia , Eosinófilos/patologia , Células Epiteliais/metabolismo , Pulmão/patologia , Receptores Adrenérgicos beta 2/metabolismo , Antagonistas de Receptores Adrenérgicos beta 2/farmacologia , Animais , Asma/patologia , Brônquios/citologia , Modelos Animais de Doenças , Epinefrina/farmacologia , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/patologia , Humanos , Inflamação/metabolismo , Inflamação/patologia , Interleucina-13/toxicidade , Pulmão/citologia , Metaplasia , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Pneumonia/induzido quimicamente , Pneumonia/metabolismo , Receptores Adrenérgicos beta 2/genética , Transdução de SinaisRESUMO
Bacterial diversity is an important factor controlling the functioning of aquatic ecosystems. With the critical sensitivity of the microbial community towards chemical and/or physical factors, this study aims to identify for the first time the microbiota of the Lebanese coastal Ibrahim River. Water and sediment samples were collected at the outlet of the river, between May 2016 and April 2017, covering a hydrological year. The main microbiological parameters were tested: total germs, total coliforms, fecal coliforms, Escherichia coli, and Enterococcus. A DNA extraction followed by NGS analysis was applied on both water and sediment samples, in order to investigate the bacterial diversity and the habitat specificity. The link between this microbial composition and seasonal variations was then investigated. Results showed fourteen different bacterial phyla, among which were major microorganisms, including a wide variety of pathogenic and commensal ones, frequently available in the aquatic ecosystem. Most of the detected water microbiota were mostly correlated to other freshwater samples, with the main dominance of 5 common phyla: Proteobacteria, Actinobacteria, Firmicutes, Bacteroidetes, and Acidobacteria with the average of 43%, 13%, 16%, 10%, and 4% respectively. Despite this overall similarity, multiple patterns were visible, confirming the influence of the temporal variations and the discharge influence on taxonomic diversity. Sediment samples contained the highest relative abundance of Proteobacteria, Firmicutes, and Bacteroidetes: with an average of 31%, 44%, and 22% respectively. Our study showed that the Ibrahim River outlet has a specific habitat clustering. The among-compartment bacterial community variation, which responded to changing environmental factors, approved the existence of a meaningful temporal heterogeneity.