Do you know when the inhaler is empty?

BACKGROUND: Medication review is recommended at asthma appointments. The presence of propellant in the metered dose inhalers (MDIs) makes it challenging to identify when the inhaler is empty. The COVID-19 pandemic has resulted in move towards more virtual monitoring of care. We aimed to evaluate if patients identify when the inhaler is empty and the method of inhaler disposal. METHODS: Prospective, multicentre quality improvement project. Data collected from children with asthma and other respiratory conditions. OUTCOME MEASURES: Children/carers attending hospital were asked how they identify an empty salbutamol inhaler; dose counters in the preventer inhalers and disposal practices were reviewed. RESULTS: 157 patients recruited. 125 (73.5%) patients deemed an empty inhaler as either full/partially full. 12 of 66 (18.2%) preventer inhalers with a dose counter were empty. 83% disposed their inhalers in a dustbin. CONCLUSIONS: Patients cannot reliably identify when their MDI is empty. There is an urgent need for improving inhaler technology and providing appropriate guidance on how to identify when an MDI is empty.

Novel linezolid-based oxazolidinones as potent anticandidiasis and antitubercular agents.

The quest for new antifungal and antitubercular drugs is a need of the hour because of morbid co-pathogenesis and an increase in immunocompromised patients. One of the ways forward is to explore and repurpose the established pharmacophores for the desired application. Oxazolidinones are well-known antibacterial agents, with few investigations reported to exploit their antifungal properties. Herein, we report the design and synthesis of a series of linezolid-based oxazolidinones as potent anticandidiasis and antitubercular agents. Studies revealed that two of the novel oxazolidinones 2 and 3a exhibited excellent anticandidiasis activity against different Candida fungus strains, superior to standard drugs. Mechanistic and docking studies revealed that oxazolidinones were better inhibitors of the ergosterol biosynthesis pathway than the controls used. In addition, the oxazolidinones 2 and 3a also exhibited prominent inhibitory activity against M. tuberculosis H37Rv with MIC values of 1 and 2 µg/ml, respectively. Computational studies demonstrated the binding of the compounds to the transcriptional regulatory repressor protein, which was reinforced by the molecular dynamics simulations. The pharmacophore modeling experiments validated the molecular docking results in both the target proteins.

Unusual semiconductor-metal-semiconductor transitions in magnetite Fe3O4 nanoparticles.

Magnetite (Fe3O4) nanoparticles were successfully prepared by a co-precipitation method. Rietveld refinement on the X-ray diffraction pattern confirmed the development of a single-phase cubic spinel structure with space group Fd3̄m. However, 57Fe Mössbauer spectroscopy suggested the presence of Fe3+ and Fe2.5+ (mixed Fe3+ and Fe2+) ions at the tetrahedral and octahedral sites of the inverse spinel structure, respectively. Impedance spectroscopy measurements showed a discontinues variation in the temperature dependence of the sample's resistive behavior, indicating the appearance of semiconductor-metal-semiconductor like transitions between the temperature range of 293 and 373 K. A similar dual transition was also observed from the dielectric and conductivity measurements around the same temperature regions. The observed unusual transition is explained in term of the competitive effects among the hopping of localized/delocalized and short-range/long-range charge carriers present in the sample. Moreover, the prepared sample exhibits colossal dielectric permittivity (∼106), reduced tangent loss (∼0.2) and moderate conductivity (>10-6 S cm-1) values, making Fe3O4 nanoparticles a potential candidate for electromagnetic absorbing materials.

Phytochemical analysis and biological activities of ethanolic extract of Curcuma longa rhizome / Análise fitoquímica e atividades biológicas do extrato etanólico do rizoma de Curcuma longa

Abstract Curcuma longa is an important dietary plant which possess several pharmacological activities, including antioxidant, antimicrobial, anti-inflamatory, anticancer and anti clotting etc. The aim of the present study was to determine the phenolic profile of Curcuma longa and in vitro antioxidant and antidiabetic activities. In HPLC chromatogram of Curcuma longa rhizome extract 15 phenolic compounds were identified namely Digalloyl-hexoside, Caffeic acid hexoside, Curdione, Coumaric, Caffeic acid, Sinapic acid, Qurecetin-3-D-galactoside, Casuarinin, Bisdemethoxycurcumin, Curcuminol, Demethoxycurcumin, and Isorhamnetin, Valoneic acid bilactone, Curcumin, Curcumin-O-glucuronide respectively. The ethanolic extract displayed an IC50 value of 37.1±0.3 µg/ml against alpha glucosidase. The IC50 value of DPPH radical scavenging activity was 27.2 ± 1.1 μg/mL. It is concluded that ethanolic extract of Curcuma long is rich source of curcumin and contain several important phenolics. The in vitro antioxidant and alpha glucosidase inhibitory effect of the plant justifies its popular use in traditional medicine.

Resumo A Curcuma longa é uma importante planta presente na dieta da população, pois possui diversas atividades farmacológicas, incluindo antioxidante, antimicrobiana, anti-inflamatória, anticancerígena, anticoagulante etc. O objetivo do presente estudo foi elucidar o perfil fenólico da Curcuma longa e determinar as atividades antioxidante e antidiabética in vitro do extrato. No cromatograma por HPLC do extrato de rizoma de Curcuma longa, foram identificados 15 compostos fenólicos: digaloil-hexosídeo, hexosídeo de ácido cafeico, curdiona, cumárico, ácido cafeico, ácido sinápico, quercetina-3-D-galactosídeo, casuarinina, bisdemetoxicurcumina, curcuminol, demetoxicurcumina, isoramnetina, bilactona de ácido valônico, curcumina e curcumina-O-glicuronídeo. O extrato etanólico apresentou um valor de IC50 de 37,1 ± 0,3 µg / mL em relação à alfa-glucosidase. O valor de IC50 da atividade de eliminação de radicais DPPH foi de 27,2 ± 1,1 μg / mL. Conclui-se que o extrato etanólico de Curcuma longa é uma rica fonte de curcumina e contém várias substâncias fenólicas importantes. O efeito antioxidante in vitro e inibidor da alfa-glucosidase da planta justifica seu uso popular na medicina tradicional.

Evaluation of serum procalcitonin level as a biomarker for disease severity in COVID-19 patients.

The pandemic of coronavirus disease 2019 (COVID-19) has infected millions of individuals around the globe. Forecasting the COVID-19 severity is essential, and various biomarkers could be used to evaluate it. The current study was therefore aimed to evaluate the serum pro-calcitonin (PCT) level as a biomarker for bacterial co-infection and disease severity in COVID-19 patients. A total of 430 COVID-19 positive individuals were examined, in which 332 (77.2%) were male individuals while 98 (22.8%) were female individuals. Among the examined samples, 281 were classified as moderate (PCT value 0.07 ± 0.06 ng/mL), 95 were severe (PCT value 0.5 ± 0.4 ng/mL), and 54 were classified as critical (PCT value > 1 ng/mL) individuals. The increase in the total serum level of PCT was observed with the severity of the disease (p < 0.05). The statistical analysis represented no association of PCT value with gender (p 0.9650) while revealed a significant association (p < 0.001) with the age and PCT value in COVID-19 patients. It can be concluded that the serial PCT measurement could determine the prognosis of the disease and the presence of bacterial co-infection in COVID-19 patients. Further exploration of the topic is needed to evaluate the effect of different therapies on the PCT level and to prescribe specific treatment options for coinfection.

Getting the most out of MRI in perianal fistula: update on surgical techniques and radiological features that define surgical options.

Perianal fistulas affect approximately 2 in 10,000 people, causing symptoms such as pain and discharge, which can have a debilitating effect on a patient's quality of life. Surgical treatment, which can offer a potential cure or palliation of symptoms, must be considered carefully in cases with extensive sphincter involvement. In complex cases, the use of preoperative magnetic resonance imaging (MRI) can help to determine the best course of operative action. This review describes common and contemporary surgical procedures for perianal fistula, highlighting technical features, as well as important surgical considerations associated with each method and how these can be assessed radiologically. We focus on the anatomical features and MRI findings that take procedural elements into account and help determine the most appropriate method of treatment. The aim of this article is to provide a basis for informed and focused discussion between surgeons and radiologists to ensure the most appropriate procedure is selected for each case, with the ultimate aim of obtaining the most favourable outcomes for patients.

Heterogeneity in outcome selection, definition and measurement in studies assessing the treatment of cryptoglandular anal fistula: findings from a systematic review.

BACKGROUND: Treatment for cryptoglandular anal fistula (AF) is challenging and a lack of uniform outcomes in the literature prevents direct comparison of treatments. This can be addressed by developing a core outcome set, a standardised set of outcomes reported in all interventional studies for a specific condition. The aim of this systematic review is to assess the range of outcomes, their definitions, and the measurement instruments currently utilised in interventional studies for adult patients with AF. This will inform the development of an AF core outcome set. METHODS: Medline, Embase and The Cochrane Library were searched to identify all patient- and clinician-reported outcomes in studies assessing medical, surgical or combination treatment of adult patients with AF published from January 2008 to May 2020. The resulting outcomes were categorized according to the Core Outcome Measurement in Effectiveness Trials (COMET) taxonomy to better understand their distribution. RESULTS: In total, 155 studies were included, 552 outcomes were extracted, with a median of three outcomes (interquartile range 2-5) per study. Only 25% of studies demonstrated high-quality outcome reporting. The outcomes were merged into 52 unique outcomes and structured into four core areas and 14 domains, with the majority in the domain of physiological or clinical (gastrointestinal) outcomes. The most commonly reported outcomes were healing (77%), incontinence (63%), and recurrence (40%), with no single outcome assessed across all studies. There was a wide variation in outcome definitions and measurement instruments used. CONCLUSIONS: There is substantial heterogeneity in outcomes, definitions, and measurement instruments reported in interventional studies for cryptoglandular anal fistula. This emphasises the need for standardised outcome reporting and measurement.

BF3-OEt2 Catalyzed C3-Alkylation of Indole: Synthesis of Indolylsuccinimidesand Their Cytotoxicity Studies.

A simple and efficient BF3-OEt2 promoted C3-alkylation of indole has been developed to obtain3-indolylsuccinimidesfrom commercially available indoles and maleimides, with excellent yields under mild reaction conditions. Furthermore, anti-proliferative activity of these conjugates was evaluated against HT-29 (Colorectal), Hepg2 (Liver) and A549 (Lung) human cancer cell lines. One of the compounds, 3w, having N,N-Dimethylatedindolylsuccinimide is a potent congener amongst the series with IC50 value 0.02 µM and 0.8 µM against HT-29 and Hepg2 cell lines, respectively, and compound 3i was most active amongst the series with IC50 value 1.5 µM against A549 cells. Molecular docking study and mechanism of reaction have briefly beendiscussed. This method is better than previous reports in view of yield and substrate scope including electron deficient indoles.

Cabazitaxel versus abiraterone or enzalutamide in poor prognosis metastatic castration-resistant prostate cancer: a multicentre, randomised, open-label, phase II trial.

BACKGROUND: Treatment of poor prognosis metastatic castration-resistant prostate cancer (mCRPC) includes taxane chemotherapy and androgen receptor pathway inhibitors (ARPI). We sought to determine optimal treatment in this setting. PATIENTS AND METHODS: This multicentre, randomised, open-label, phase II trial recruited patients with ARPI-naive mCRPC and poor prognosis features (presence of liver metastases, progression to mCRPC after <12 months of androgen deprivation therapy, or ≥4 of 6 clinical criteria). Patients were randomly assigned 1 : 1 to receive cabazitaxel plus prednisone (group A) or physician's choice of enzalutamide or abiraterone plus prednisone (group B) at standard doses. Patients could cross over at progression. The primary endpoint was clinical benefit rate for first-line treatment (defined as prostate-specific antigen response ≥50%, radiographic response, or stable disease ≥12 weeks). RESULTS: Ninety-five patients were accrued (median follow-up 21.9 months). First-line clinical benefit rate was greater in group A versus group B (80% versus 62%, P = 0.039). Overall survival was not different between groups A and B (median 37.0 versus 15.5 months, hazard ratio (HR) = 0.58, P = 0.073) nor was time to progression (median 5.3 versus 2.8 months, HR = 0.87, P = 0.52). The most common first-line treatment-related grade ≥3 adverse events were neutropenia (cabazitaxel 32% versus ARPI 0%), diarrhoea (9% versus 0%), infection (9% versus 0%), and fatigue (7% versus 5%). Baseline circulating tumour DNA (ctDNA) fraction above the cohort median and on-treatment ctDNA increase were associated with shorter time to progression (HR = 2.38, P < 0.001; HR = 4.03, P < 0.001). Patients with >30% ctDNA fraction at baseline had markedly shorter overall survival than those with undetectable ctDNA (HR = 38.22, P < 0.001). CONCLUSIONS: Cabazitaxel was associated with a higher clinical benefit rate in patients with ARPI-naive poor prognosis mCRPC. ctDNA abundance was prognostic independent of clinical features, and holds promise as a stratification biomarker.

Phytochemical analysis and biological activities of ethanolic extract of Curcuma longa rhizome.

Curcuma longa is an important dietary plant which possess several pharmacological activities, including antioxidant, antimicrobial, anti-inflamatory, anticancer and anti clotting etc. The aim of the present study was to determine the phenolic profile of Curcuma longa and in vitro antioxidant and antidiabetic activities. In HPLC chromatogram of Curcuma longa rhizome extract 15 phenolic compounds were identified namely Digalloyl-hexoside, Caffeic acid hexoside, Curdione, Coumaric, Caffeic acid, Sinapic acid, Qurecetin-3-D-galactoside, Casuarinin, Bisdemethoxycurcumin, Curcuminol, Demethoxycurcumin, and Isorhamnetin, Valoneic acid bilactone, Curcumin, Curcumin-O-glucuronide respectively. The ethanolic extract displayed an IC50 value of 37.1±0.3 µg/ml against alpha glucosidase. The IC50 value of DPPH radical scavenging activity was 27.2 ± 1.1 µg/mL. It is concluded that ethanolic extract of Curcuma long is rich source of curcumin and contain several important phenolics. The in vitro antioxidant and alpha glucosidase inhibitory effect of the plant justifies its popular use in traditional medicine.

Phosphorus supplementation modulates nitric oxide biosynthesis and stabilizes the defence system to improve arsenic stress tolerance in mustard.

The interaction of mineral nutrients with metals/metalloids and signalling molecules is well known. In the present study, we investigated the effect of phosphorus (P) in mitigation of arsenic (As) stress in mustard (Brassica juncea L.). The study was conducted to investigate potential of 30 mg P·kg-1 soil P supplement (diammonium phosphate) to cope up with the adverse effects of As stress (24 mg As·kg-1 soil) in mustard plants Supplementation of P influenced nitric oxide (NO) generation, which up-regulated proline metabolism, ascorbate-glutathione system and glyoxalase system and alleviated the effects of on photosynthesis and growth. Arsenic stress generated ROS and methylglyoxal content was scavenged through P-mediated NO, and reduced As translocation from roots to leaves. The involvement of NO under P-mediated alleviation of As stress was substantiated with the use of cPTIO (NO biosynthesis inhibitor) and SNP (NO inducer). The reversal of P effects on photosynthesis under As stress with the use of cPTIO emphasized the role of P-mediated NO in mitigation of As stress and protection of photosynthesis The results suggested that P reversed As-induced oxidative stress by modulation of NO formation, which regulated antioxidant machinery. Thus, P-induced regulatory interaction between NO and reversal of As-induced oxidative stress for the protection of photosynthesis may be suggested for sustainable crops.

Characterizing Agreement in the Level of Interarm Blood Pressure Readings of Adults in the Emergency Department (CALIBRATE Study).

Background: Increased interarm systolic blood pressure difference (IASBPD) is one of the major predictors of cardiovascular disease. An IASBPD of >10 mmHg is of clinical significance. However, studies have reported a high number of patients visiting the emergency department (ED) with high IASBPD and varying correlation of IASBPD to age, ethnic background, and comorbidities such as hypertension and diabetes. Objective: The CALIBRATE study aimed to measure the IABPDs in the multiethnic patient population presenting to the ED in Qatar and to assess the distribution of IASBPD in this population. Methods: In a sitting position, two consecutive blood pressure (BP) measurements were recorded from the right and left arms for each participant using a calibrated automated machine and appropriate cuff sizes. The data were recorded using predefined data fields, including patient demographics, past medical, and social and family history. The continuous variables were reported as mean or median based on the distribution of data. The data were analyzed using Stata MP 14.0. Results: A total of 1800 patients, with a mean age of 34 (10) years, were prospectively recruited from the ED. The median absolute systolic BP difference (ΔSBP) between the right and left arms was 6 (3-10) mmHg, and it was the same for the first (ΔSBP1) and the second readings (ΔSBP2). The absolute average of ΔSBP1 and ΔSBP2 was 7 (4-10) mmHg. The difference in systolic BP difference (SBP) of < 20 mmHg for interarm blood pressure was seen in the 95th percentile of the population. No meaningful association could be detected between the IABPD and the study variables such as age, demographics, regions of interest, and risk factors. Conclusion: In population presenting to the ED, the IASBPD of at least 20 mmHg reached at the 95th percentile, validating the known significant difference. The utility of SBP difference can be improved further by taking the average of two individual readings.

The development of a cryptoglandular Anal Fistula Core Outcome Set (AFCOS): an international Delphi study protocol.

PURPOSE: Cryptoglandular anal fistula is a disorder with an incidence of around 1 per 5,000 people per year in European countries. Many studies have been conducted to evaluate the effectiveness of interventions for anal fistula. However, there is considerable heterogeneity in the outcomes assessed and reported in these studies. This limits research quality and complicates evidence synthesis. A solution for heterogeneity in outcome reporting is the development of a Core Outcome Set (COS). This paper describes the protocol for the development of a European COS for Anal Fistula (AFCOS). METHODS: The first step will be a systematic review of the literature to identify potential outcomes that may be included in the COS. Patient interviews will be conducted in The United Kingdom and The Netherlands to ensure that both clinician-important and patient-important outcomes are captured. The outcomes will be categorized using the COMET taxonomy and taken forward to a Delphi consensus exercise. In up to three web-based Delphi surveys the outcomes will be prioritized by patients, clinicians (surgeons, gastroenterologists, and radiologists), and (clinical) researchers. The responses will be summarized and reported anonymously in subsequent round(s) facilitating convergence to a consensus opinion. The final COS will be decided during a face-to-face consensus meeting with patients, clinicians, and (clinical) researchers. DISCUSSION: This study protocol describes the development of a European COS for anal fistula to improve research quality, evidence synthesis, and patient care.

Prevalence of Restless Legs Syndrome among Medical Students of Karachi: An Experience from a Developing Country.

BACKGROUND: Restless legs syndrome (RLS) is a neurological disorder characterized by an uncomfortable sensation in the legs which gets worse in the evening or night, relieved upon movement. The aim of this study was to specify the prevalence of RLS in the group of young medical students and to assess the effect of RLS on sleep, as sleep disturbance is one of the chief complaints of RLS patients. We also studied its association with smoking as it is considered an aggravating factor. METHOD: This was a cross-sectional study conducted from June 2017 to July 2018 in Karachi. A total of 300 students (220 females and 80 males) participated and were given questionnaires to detect RLS based on criteria proposed by the International Restless Legs Syndrome Study Group. Subjects who were positive for RLS were further asked questions about sleep by using the Epworth Sleepiness Scale and severity of RLS by using RLS Rating Scale. They were also asked about their smoking status. RESULTS: The frequency of RLS is 8% among young adults. Out of 300 medical students, 24 students were classified positive for RLS with a female preponderance (66.7% were females and 33.3% were males). The severity of RLS was more rated to be mild to moderate. The effect of RLS on sleep was in the mild range. The p value of smoking status comparing with gender came out to be <0.001, and p value of smoking status comparing with gender came out to be <0.001, and. CONCLUSION: It is concluded that we found RLS to be present significantly in our population that is without comorbidities. Our results showed female preponderance and a mild sleep disturbance in our study population. More attention is needed to recognize RLS and to manage the aggravating factors of RLS.

Correction to: Topical antimicrobial prophylaxis in colorectal surgery for the prevention of surgical wound infection: a systematic review and meta-analysis.

Unfortunately, an author name (Nuzhat Iqbal) was missed out in the original publication. The complete updated author list is given below.

Structural and binding studies of phosphopantetheine adenylyl transferase from Acinetobacter baumannii.

Phosphopantetheine adenylyltransferase (PPAT, EC. 2.7.7.3) catalyzes an essential step in the reaction that transfers an adenylyl group from adenosine tri phosphate (ATP) to 4'-phosphopantetheine (pPant) yielding 3'- dephospho-coenzyme A (dPCoA) and pyrophosphate (PP) in the coenzyme A (CoA) biosynthesis pathway. The enzyme PPAT from Acinetobacter baumannii (AbPPAT) was cloned, expressed and purified. The binding studies of AbPPAT were carried out with two compounds, tri­sodium citrate (TSC) and l-ascorbic acid (LAA, vitamin-C) using fluorescence spectroscopic (FS) and surface Plasmon resonance (SPR) methods. Both methods provided similar values of dissociation constants for TSC and LAA which were of the order of 10-8 M and 10-5 M respectively. The computer aided docking studies indicated fewer interactions of LAA with AbPPAT as compared to those of TSC. The freshly purified samples of AbPPAT were crystallized. The crystals of AbPPAT were soaked in the solutions containing TSC and LAA. However, the crystals of the complex of AbPPAT with LAA did not diffract well and hence the structure of the complex of AbPPAT with LAA could not be determined. On the other hand, the crystals of the complex of AbPPAT with TSC diffracted well and the structure was determined at 1.76 Šresolution. It showed that TSC bound to AbPPAT at the ATP binding site and formed several intermolecular contacts including 12 hydrogen bonds. The results of binding studies for both TSC and LAA and the structure of the complex of AbPPAT with TSC clearly indicated a potential role of TSC and LAA as antibacterial agents.

Radial forearm free flap as the last resort for oesophageal reconstruction.

Strategies for oesophageal reconstruction following resection vary according to the nature of the pathology encountered, patient factors and surgeon preference. However, reconstruction in patients with multiple previous failed attempts poses specific management challenges. We present the case of a 61-year-old man who underwent oesophageal reconstruction with a radial forearm flap as a last resort.