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Abstract Objective This study aimed to evaluate the association of dynamic contrast enhancement (DCE) with clinically significant prostate cancer (csPCa, Gleason Grade Group ≥2) and compare biparametric magnetic resonance imaging (bpMRI) and multiparametric MRI (mpMRI) nomograms. Subjects/patients and methods We identified a retrospective cohort of biopsy naïve patients who underwent pre‐biopsy MRI separated by individual MRI series from 2018 to 2022. csPCa detection rates were calculated for patients with peripheral zone (PZ) lesions scored 3–5 on diffusion weighted imaging (DWI) with available DCE (annotated as − or +). bpMRI Prostate Imaging Reporting and Data System (PIRADS) (3 = 3−, 3+; 4 = 4−, 4+; 5 = 5−, 5+) and mpMRI PIRADS (3 = 3−; 4 = 3+, 4−, 4+; 5 = 5−, 5+) approaches were compared in multivariable logistic regression models. Nomograms for detection of csPCa and ≥GG3 PCa incorporating all biopsy naïve patients who underwent prostate MRI were generated based on available serum biomarkers [PHI, % free prostate‐specific antigen (PSA), or total PSA] and validated with an independent cohort. Results Patients (n = 1010) with highest PIRADS lesion in PZ were included in initial analysis with 127 (12.6%) classified as PIRADS 3+ (PIRADS 3 on bpMRI but PIRADS 4 on mpMRI). On multivariable analysis, PIRADS 3+ lesions were associated with higher csPCa rates compared to PIRADS 3− (3+ vs. 3−: OR 1.86, p = 0.024), but lower csPCa rates compared to PIRADS DWI 4 lesions (4 vs. 3+: OR 2.39, p

Introduction The gummy smile (GS) or excessive gum visibility (EGV) is an aesthetic concern that affects an individual’s attractiveness and personality. Treatment Planning Lip Repositioning surgery (LRP) is a less invasive surgery that can be attributed to treating EGV due to hypermobile lip muscles or mild-to-moderate vertical maxillary excess (VME). Three patients went through LRP surgery by stripping overlying mucosa from the buccal vestibule, followed by suturing the lip mucosa to the mucogingival junction (MGJ), creating shallow vestibule and restricted muscle pull and reducing gingival visibility (GV) during a smile. Follow-up Three months of follow-up showed a satisfactory result with 3.67 ± 0.58 mm mean reduction in GV.

Abstract We executed this study to determine if chemerin‐like receptor 1 (CMKLR1), a Gi/o protein‐coupled receptor expressed by leukocytes and non‐leukocytes, contributes to the development of phenotypic features of non‐atopic asthma, including airway hyperresponsiveness (AHR) to acetyl‐β‐methylcholine chloride, lung hyperpermeability, airway epithelial cell desquamation, and lung inflammation. Accordingly, we quantified sequelae of non‐atopic asthma in wild‐type mice and mice incapable of expressing CMKLR1 (CMKLR1‐deficient mice) following cessation of acute inhalation exposure to either filtered room air (air) or ozone (O3), a criteria pollutant and non‐atopic asthma stimulus. Following exposure to air, lung elastic recoil and airway responsiveness were greater while the quantity of adiponectin, a multi‐functional adipocytokine, in bronchoalveolar lavage (BAL) fluid was lower in CMKLR1‐deficient as compared to wild‐type mice. Regardless of genotype, exposure to O3 caused AHR, lung hyperpermeability, airway epithelial cell desquamation, and lung inflammation. Nevertheless, except for minimal genotype‐related effects on lung hyperpermeability and BAL adiponectin, we observed no other genotype‐related differences following O3 exposure. In summary, we demonstrate that CMKLR1 limits the severity of innate airway responsiveness and lung elastic recoil but has a nominal effect on lung pathophysiology induced by acute exposure to O3.

JET, the world’s largest operating tokamak with unique Be/W wall and tritium handling capability, completed a Deuterium-Tritium (D-T) campaign in 2021 (Maggi et al 29th Fusion Energy Conf. ) following a decade of preparatory experiments, dedicated enhancements, technical rehearsals and training (Horton et al 2016 Fusion Eng. Des. 109–111 925). Operation with tritium raises significant technical, safety and scientific challenges not encountered in standard protium or deuterium operation. This contribution describes the tritium operational requirements, pulses and technical preparations, new operating procedures, lessons learned and details on the achieved operational availability and performance. The preparation and execution of the recent JET tritium experiments benefitted from the previous experience in 1991 (Preliminary Tritium Experiment), 1997 (DTE1 campaign) and 2003 (Trace Tritium Campaigns) and consisted of the following five phases: technical rehearsals and scenario preparation, tritium commissioning, 100% tritium campaign, D-T campaign (DTE2), tritium clean-up. Following the clean-up JET resumed normal operation and is currently undertaking a further D-T campaign (DTE3).

Background: Under and over-nutrition-related health conditions are highly prevalent in Pakistan. Dietary data are required to understand the challenges of over and undernutrition in Pakistan. Objective: The purpose of the study was to develop and validate a FoodEapp application (FoodEapp) for field staff with no formal education in nutrition (unskilled) to accurately collect 24-hour (24HR) dietary recall (DR) data to assess the dietary intake of adults in Karachi, Pakistan. Method: We designed a novel FoodEapp application for unskilled data collectors to collect 24HR DR data. We validated the FoodEapp against the conventional 24HR DR method in rural and urban Karachi. We compared the mean intake of total energy (kcal), macronutrients, and micronutrients, reported through both methods using Pearson Correlation and Intraclass Correlation (ICC). We also used Bland Altman analysis to assess the agreement between the methods. Results: We found a high correlation between the two methods for total energy (ρ = 0.88, p-value

Abstract Background Apps have been shown to be an effective tool in changing patients’ behaviours in orthodontics and can be used to improve their compliance with treatment. The Behaviour Change Techniques (BCTs) and quality (using MARS) within these apps have previously not been published. Objectives 1. To evaluate the quality of these apps aiming to change behaviour. 2. To assess BCTs used in patient focused orthodontic apps. Methods The UK Google Play and Apple App Stores were searched to identify all orthodontic apps and 305 apps were identified. All 305 apps were assessed for the presence of BCTs using an accepted taxonomy of BCTs (Behaviour Change Wheel (BCW)), widely utilised in healthcare. Of those containing BCTs, the quality was assessed using the Mobile App Rating Scale (MARS), a validated and multi-dimensional tool which rates apps according to 19 objective criteria. Data collection was carried out by two calibrated, independent assessors and repeated after 6 weeks for 25% of the apps by both assessors. Results BCTs were found in 31 apps, although only 18 of them were analysed for quality and 13 apps were excluded. Six different BCTs were identified: these were most commonly ‘prompts/cues’, and ‘information about health consequences’. All apps were shown to be of moderate quality (range 3.1–3.7/5). Inter-rater and intra-rater reliability for BCT and quality assessment were excellent. Conclusions The current availability of orthodontic apps of sufficient quality to recommend to patients is very limited. There is therefore a need for high-quality orthodontic apps with appropriate BCTs to be created, which may be utilised to improve patients’ compliance with treatment.

Background: Graphene-based nanomaterials possess unique optical, physicochemical and biomedical properties which make them potential tools for imaging and therapy. Manganese oxide nanoparticles are attractive candidates for contrast agents in magnetic resonance imagint (MRI). We used manganese oxide (Mn3O4) and highly reduced graphene oxide (HRG) to synthesize hybrid nanoparticles (HRG-Mn3O4) and tested their efficacy for photodynamic therapy (PDT) in breast cancer cells. Methods: The newly synthesized nanoparticles were characterized by transmission electron microscopy (TEM), energy-dispersive X-ray (EDX) spectroscopy, UV-visible spectroscopy, Fourier-transform infrared (FT-IR) spectroscopy, thermogravimetry, and X-ray diffraction (XRD) analyses. We used standard protocols of cytotoxicity and PDT after exposing A549 cells to various concentrations of hybrid nanoparticles (HRG-Mn3O4). We also performed fluorescence microscopy for live/dead cellular analysis. A549 cells were incubated with nanoparticles for 24 h and stained with fluorescein diacetate (green emission for live cells) and propidium iodide (red emission for dead cells) to visualize live and dead cells, respectively. Results: The cell viability analysis showed that more than 98% of A549 cells survived even after the exposure of a high concentration (100 μg/mL) of nanomaterials. These results confirmed that the HRG-Mn3O4 nanoparticles are nontoxic and biocompatible at physiological conditions. When the cell viability analysis was performed after laser irradiation, we observed significant and concentration-dependent cytotoxicity of HRG-Mn3O4 as compared to Mn3O4 nanoparticles. Fluorescence microscopy showed that almost 100% cells were viable when treated with phosphate buffered saline or Mn3O4 while only few dead cells were detected after exposure of HRG-Mn3O4 nanoparticles. However, laser irradiation resulted in massive cellular damage by HRG-Mn3O4 nanoparticles which was directly related to the generation of reactive oxygen species (ROS). Conclusions: HRG-Mn3O4 hybrid nanoparticles are stable, biocompatible, nontoxic, and possess therapeutic potential for photodynamic therapy of cancer. Further studies are warranted to explore the MRI imaging ability of these nanomaterials using animal models of cancer.

Abstract The objective of the present study was to analyse the bioactive compounds of the leaves of Conocarpus lancifolius (C. lancifolius). The GC-MS analysis of the hot methanolic extract of the leaves (HMEL) of C. lancifolius exhibited the bioactive compounds such as 1-(3-Methoxy-2-nitrobenzyl) iso quinoline, morphin-4-ol-6,7-dione, 1-bromo-N-methyl-, phytol, hexadecanoic acid, 2,3-dihydroxypropyl ester, 2,2':4',2”-terthiophene, ethyl iso-allocholate, caryophyllene oxide, campesterol, epiglobulol, cholestan-3-ol, 2-methylene-, (3á,5à)-, dasycarpidan-1-methanol, acetate (ester) and oleic acid, eicosyl ester. The FT-IR analysis of HMEL of C. lancifolius showed a unique peak at 3184, 2413, 1657 cm-1 representing coumaric acid, chlorogenic acid and ferulic acid. The HMEL of C. lancifolius was actively inhibiting the proliferation of breast cancer cells MCF-7 ATCC at the concentration of 72.66 ± 8.21 µg/ml as IC50 value. The HMEL of C. lancifolius also revealed a good spectrum of activity against Gram-positive and Gram-negative bacterial cultures screened in this work. The activity observed has shown more or less similar effects against screened bacteria. However, the magnitude of potentiality was significantly lesser compared to standard ciprofloxacin disc at p< 0.001 level (99% confidence intervals). Furthermore, the study demonstrating the bioactive compounds can be isolated from the leaves of C. lancifolius.

The nanomaterials synthesis is an intensifying research field due to their wide applications. The high surface-to-volume ratio of nanoparticles and quick interaction capacity with different particles make them as an attractive tool in different areas. Conventional physical and chemical procedures for development of metal nanoparticles become outmoded due to extensive production method, energy expenditure and generation of toxic by-products which causes significant risks to the human health and environment. Hence, there is a growing requirement to search substitute, non-expensive, reliable, biocompatible and environmental friendly methods for development of nanoparticles. The nanoparticles synthesis by microorganisms has gained significant interest due to their potential to synthesize nanoparticles in various sizes, shape and composition with different physico-chemical properties. Microbes can be widely applied for nanoparticles production due to easy handling and processing, requirement of low-cost medium such as agro-wastes, simple scaling up, economic viability with the ability of adsorbing and reducing metal ions into nanoparticles through metabolic processes. Biogenic synthesis of nanoparticles offers clean, non-toxic, environmentally benign and sustainable approach in which renewable materials can be used for metal reduction and nanoparticle stabilization. Nanomaterials synthesized through microbes can be used as a pollution abatement tool as they also contain multiple functional groups that can easily target pollutants for efficient bioremediation and promotes environmental cleanup. The objective of the present review is to highlight the significance of micro-organisms like bacteria, actinomycetes, filamentous fungi, yeast, algae and viruses for nanoparticles synthesis and advantages of microbial approaches for elimination of heavy metals, dyes and wastewater treatment.

The development of a myocardial infarction ventricular septal rupture is a rare fatal complication, and the surgical repair is the treatment of choice. In most of the scenarios, the operation will be done as an emergency procedure that carries high mortality. Prognosis of these patients depends on prompt echocardiographic diagnosis and the proactive medical and surgical therapy. More recently, various options have been put forward including the timing for surgery, percutaneous closure devices, and the improved outcome with initial stabilization with medical treatment including mechanical support. In this retrospective case series, we are presenting the management of these patients who presented us in different clinical scenarios and trying to identify the risks for the poor outcome and to formulate a strategy to improve the outcome.

Introduction In April 2019, 14 children were diagnosed with HIV infection by a private healthcare provider in Larkana district, Sindh province, Pakistan. Over the next 3 months, 930 individuals were diagnosed with HIV, >80% below 16 years, the largest ever outbreak of HIV in children in Pakistan. In this protocol paper, we describe research methods for assessing likely modes of HIV transmission in this outbreak and investigate spatial and molecular epidemiology.Methods and analysis A matched case–control study will be conducted with 406 cases recruited. Cases will be children aged below 16 years registered for care at the HIV treatment centre at Shaikh Zayed Children Hospital in Larkana City. Controls will be children who are HIV-uninfected (confirmed by a rapid HIV test) matched 1:1 by age (within 1 year), sex and neighbourhood. Following written informed consent from the guardian, a structured questionnaire will be administered to collect data on sociodemographic indices and exposure to risk factors for parenteral, vertical and sexual (only among those aged above 10 years) HIV transmission. A blood sample will be collected for hepatitis B and C serology (cases and controls) and HIV lineage studies (cases only). Mothers of participants will be tested for HIV to investigate the possibility of mother-to-child transmission. Conditional logistic regression will be used to investigate the association of a priori defined risk factors with HIV infection. Phylogenetic analyses will be conducted. Global positioning system coordinates of participants’ addresses will be collected to investigate concordance between the genetic and spatial epidemiology.Ethics and dissemination Ethical approval was granted by the Ethics Review Committee of the Aga Khan University, Karachi. Study results will be shared with Sindh and National AIDS Control Programs, relevant governmental and non-governmental organisations, presented at national and international research conferences and published in international peer-reviewed scientific journals.

Objective: The management of Heparin resistance in patients undergoing ECMO is still uncertain. We sought to assess the efficacy and safety of Fresh frozen plasma to optimize the anticoagulation in these patients. Methods: We studied 42 adults undergoing VA-ECMO. Heparin infusion was increased incrementally to achieve target ACT in HG group and plasma administered in FFPG group in heparin resistance (HR) patients. Statistical comparison was performed between these two groups and results compared with non-heparin resistance (Non-HR) patients. Results: Overall 36% survived and 64% suffered bleeding complications. There was no difference in age (p = 0.118) or average ECMO duration (p = 0.393). The heparin requirement was significantly less in FFPG (p = 0.008) and average ACT difference of 159.2 (20.3) was highly significant (p

Abstract Background The seroprevalence of human cytomegalovirus (HCMV) infection ranges from 30 to 90 % in developed countries. Reliable estimates of HCMV seroprevalence are not available for Pakistan. This study determined the seroprevalence and sociodemographic factors associated with HCMV infection in adult populations of Karachi, Pakistan. Methods A seroprevalence survey was conducted on 1000 adults, including residents of two semi-urban communities, and visitors to a government and a private hospital. Questionnaire-based interviews were conducted. Sera were analysed for HCMV-specific IgG and IgM. Chi-square or Fisher’s exact test was used for comparing sociodemographic variables against seropositivity of HCMV-IgG or IgM. Multiple logistic regression modeling was performed for IgG seroprevalence and adjusted odds ratios were computed. Results The seroprevalence of HCMV-IgG and IgM was 93.2 and 4.3 % respectively. 95.3 % of individuals who were IgM seropositive were also seropositive for IgG. Around 6 % (15/250) of women of childbearing age remained uninfected and were therefore susceptible to primary infection. HCMV-IgG seroprevalence was associated with being female (p = 0.001), increasing age (p = 0.002) and crowding index (p = 0.003) and also with lower levels of both education (p

[This corrects the article DOI: 10.1371/journal.pone.0210024.].

ObjectivesThe objectives of this study were to determine incidence and risk factors of glucose intolerance one year after delivery in a sub-cohort of Riyadh Mother and Baby Cohort Study (RAHMA) study.MethodsThis is a follow-up study of a sub-cohort from RAHMA study from King Khalid University Hospital (KKUH). All women from RAHMA database who completed one year since delivery at KKUH were contacted by phone to participate in the study. Previously collected data from RAHMA registry for each participant were linked to this study data. Clinical data measured for each participant included current weight and height to calculate the BMI and waist circumference. Blood tests done for each participant were fasting blood glucose (FPG) and HbA1c. Based on the blood tests results, participants were classified into three groups; diabetic, pre-diabetic and normal. The incidence of diabetes and prediabetes was calculated for the whole cohort. Clinical, biochemical, and sociodemographic predictors of glucose intolerance were compared between the three groups. Risk factors with P-value less than 0.05 were tested in multivariate regression model with bootstrapping to calculate the relative risk (RR) and its 95% Bias corrected Confidence Interval (C.I.).ResultsFrom the sub-cohort, 407 women fulfilled the inclusion criteria and agreed to participate in the study. From the study participants; 250 (61.4%) women were normoglycemic, 142 (35%) women had prediabetes and 15 (3.6%) women were diabetic. Following multivariable regression analysis only history of gestational diabetes mellitus (GDM), (RR 1.74, 95% CI (1.06 to 2.84), P = 0.01), obesity (RR 1.69, 95% CI (1.01-3.11), P = 0.04) and diastolic blood pressure, (RR 1.04, 95% CI (1.01-1.09), P = 0.03) remained as predictors of postpartum glucose intolerance.ConclusionThe incidence of postpartum glucose intolerance (diabetes and prediabetes) is very high in Saudi women. Both GDM and obesity are strong predictors of glucose intolerance.

BCG sepsis is rarely seen with modern intravesical therapy and therefore its presentation may not be apparent to recently trained urologists. We describe BCG sepsis occurring in a patient treated with combined intravesical and intraurethral BCG which resulted in lung consolidation with acid-fast bacilli requiring cessation of BCG and initiation of systemic antibiotic therapy.