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Pseudomonas aeruginosa, a versatile Gram-negative bacterium, poses a serious threat due to its adeptness at developing resistance mechanisms. Metallo-beta-lactamases produced by P. aeruginosa are pivotal in conferring resistance to beta-lactam antibiotics, compromising treatment effectiveness. The bacterium’s proficiency in forming biofilms further enhances its persistence, especially in clinical settings. In this study conducted at Krishna Hospital and Medical Research Center, Karad, 205 clinical isolates of Pseudomonas aeruginosa were investigated for their metallo-beta-lactamase (MBL) production and biofilm-forming capabilities. The phenotypic detection of MBL production was carried out using the Imipenem-EDTA combination disc test, while biofilm formation was assessed through the microtiter plate technique. Genotypic detection involved conventional polymerase chain reaction targeting MBL and biofilm genes. Results showed that 28.29% of isolates produced MBL phenotypically, with 16.59% possessing MBL genes, notably the blaNDM-1 gene in 15.12% of isolates. Regarding biofilm production, 85.85% of isolates were biofilm producers, and biofilm-encoding genes were present in 80.49% of isolates. The most frequently encoded genes were algD (79.51%), pelF (58.0%), and pslD (46.34%). Comparing phenotypic and genotypic methods for MBL detection, a statistically significant average agreement was observed. While there was an increasing trend in biofilm genotypic positive patterns with stronger biofilm phenotypic patterns, the correlation was not statistically significant. The study concludes that every resistant clinical isolate should be screened for MBL and biofilm production using simple phenotypic tests, with confirmation by PCR if possible. This comprehensive analysis provides insights into the prevalence and genetic basis of MBL and biofilm in P. aeruginosa clinical isolates, contributing to strategies for combating antibiotic resistance.

Background: Postural orthostatic tachycardia syndrome (POTS) is a chronic form of orthostatic intolerance that primarily affects female patients. Despite the severity of POTS, there are no approved medications for use in patients with this disorder. Compression garments are a commonly prescribed nonpharmacological treatment, but little is known about the patient experience with compression. In this study we aimed to evaluate the patient experience with compression garments using a structured survey and semistructured telephone interviews. Methods: A focused survey was designed as a component of a larger clinical trial on compression garment use in patients diagnosed with POTS. Building on the survey, semistructured telephone interviews were conducted with POTS patients. Recorded interviews were transcribed and coded in a thematic analysis using a descriptive-interpretive approach. Results: A total of 27 participants completed the survey, and 20 participants completed the telephone interview. Patient experiences with compression were variable, with some participants experiencing significant benefits, and others reporting minimal to no benefits. Six themes that influenced garment use were identified: the potential benefit of the garment to improve symptoms, specific activities patients will be undertaking, environmental conditions, garment attributes, psychological and cognitive aspects, and financial considerations. Conclusions: Participants engage in a daily cost-benefit analysis when making decisions to use a compression garment. Clinicians should be aware of the benefits of and factors that limit use of compression garments as a treatment for POTS. Résumé: Contexte: Le syndrome de tachycardie orthostatique posturale (STOP) est une forme chronique d’intolérance orthostatique qui touche principalement les femmes. Malgré la gravité de ce syndrome, il n’existe aucun médicament approuvé pour traiter les patients qui en sont atteints. Les vêtements de compression constituent souvent le seul traitement non pharmacologique prescrit, mais il existe peu d’information sur l’expérience des patients avec ces vêtements. Dans cette étude, nous avons cherché à évaluer l’expérience des patients utilisant des vêtements de compression par le biais d’un sondage structuré et d’entrevues téléphoniques semi-structurées. Méthodologie: Un sondage ciblé constituait une composante d’une étude clinique plus vaste sur l’utilisation de vêtements de compression par des patients atteints du STOP. À partir du sondage, des entrevues téléphoniques semi-structurées des patients ont été réalisées. Ces entrevues ont été enregistrées, retranscrites et codées au moyen d’une analyse thématique utilisant une approche descriptive et interprétative. Résultats: Au total, 27 participants ont répondu au sondage et 20, à l’entrevue téléphonique. L’expérience des patients avec les vêtements de compression était variable, certains y trouvant des avantages significatifs tandis que d’autres en tiraient peu d’avantages, voire aucun. Six thèmes influant sur l’emploi de vêtements de compression ont été relevés : effet positif potentiel des vêtements de compression sur les symptômes, activités spécifiques projetées par les patients, conditions environnementales, attributs des vêtements, aspects psychologiques et cognitifs et considérations financières. Conclusions: Les participants devaient effectuer chaque jour une analyse du coût et des avantages avant de décider s’ils allaient utiliser un vêtement de compression. Les cliniciens doivent être conscients des bénéfices et des contraintes associés à l’utilisation des vêtements de compression dans le traitement du STOP.

Abstract The purpose of this study was biogenic synthesis of silver nanoparticles using aqueous leaf extract of Cissus woodrowii (CW-AgNPs) and exploration of their role in inhibition cell proliferation of breast cancer cells. Inhibitory effect of biogenic CW-AgNPs on cell proliferation of MCF-7 cells was determined by MTT assay. Apoptotic cell death was demonstrated by caspase-3 assay, DNA fragmentation assay, Annexin-V-FITC/PI staining assay and cell cycle arrest assay by flow cytometry. Expression of apoptosis-related genes including caspase-3, p53 and Bcl2 was studied by western blot analysis and semi-quantitative RT-PCR. Results of UV–Vis spectrum of colloidal solution of CW-AgNPs showed surface plasmon resonance peak at 430 nm. TEM and XRD results confirmed spherical shaped, 20–30 nm sized nanoparticles. Cell proliferation results showed inhibitory effects of CW-AgNPs on MCF-7 with IC50 (24 h) 8.48 µg/mL and (48 h) 7.11 µg/mL. The CW-AgNPs altered cell morphology of MCF-7 cells and induced apoptosis significantly which was evidenced through caspase-3 activation and nuclear DNA fragmentation. The results were supported by the observation of Annexin-V-FITC/PI staining and cell cycle arrest assays. The up-regulated expression of both p53 and caspase-3 genes and down-regulation of Bcl2 at both protein and mRNA level supported their role in induction of apoptosis in MCF-7 cells in response to CW-AgNPs. The findings obtained in current study supported the role of biogenic CW-AgNPs in inhibition of cell proliferation in breast cancer cells through induction of apoptosis. Graphical Abstract

Background: In recent years, biosynthesized nanoparticles has shown a promise as alternative avenue for improving the effectiveness of conventional chemotherapy. Despite, there is a significant gap in existing literature concerning the comprehensive study of biogenic silver nanoparticles derived from terrestrial fern species and their potential effects on cancer cells. This study is aiming to investigate effects of biogenic silver nanoparticles synthesized using aqueous extract of bracken fern Pteridium revolutum on inhibiting cell proliferation and inducing apoptosis in HCT-15 cells. Methods: Biogenic silver nanoparticles synthesized using aqueous extract of Pteridum revolutum followed by their characterization (UV–Visible spectroscopy, TEM, XRD and FTIR). The impact on cell proliferation of HCT-15 cells was assessed by MTT assay while induction of apoptosis was demonstrated via DNA fragmentation, caspase-3 assay, cell cycle arrest, FITC V- Annexin assay and evaluation of expression of apoptotic genes using real time PCR and western blotting techniques. Results: Results of UV–Vis spectrum of colloidal solution of CW-AgNPs showed surface plasmon resonance peak at 430 nm. TEM and XRD results confirmed synthesis of spherical shaped, 20–40 nm sized nanoparticles. The results elucidate cytotoxic effect of PR-AgNPs against HCT-15 cells in time and dose dependent manner with IC50 observed at 5.79 ± 0.58 µg /mL after 24 h of exposure. Furthermore, PR-AgNPs induce significant alterations in cellular morphology, elevate DNA DNA fragmentation and enhance expression of p53 and caspase-3 in HCT10 cells. Conclusion: The findings from this study address the noteworthy antiproliferative effects of PR-AgNPs in cancer cells primarily mediated through activation of intrinsic apoptosis pathway by inducing p53 and caspase-3 genes.

Klebsiella pneumoniae is one of the most common bacteria among all biofilm-producing as well as the beta-lactamase producing strains, which is responsible for multi-drug resistance. For better therapeutic applications, it is important to detect the biofilm production by Klebsiella pneumoniae and their antibiogram along with the ability to produce ESBL, MBL, and AmpC β-lactamases. The aim of the study was to determine the prevalence of biofilm formation and ESBL, MBL, AmpC β-lactamase phenotypes in K. pneumoniae as well as the antibiogram of all (biofilm and MBL-producing and non-producing) isolates of K. pneumoniae. Isolates of K. pneumoniae were tested for biofilm formation by the Congo-red agar method. ESBL, MBL, and AmpC β-lactamase detection were done by both screening and confirmatory tests as per CLSI guidelines. The antibiogram was obtained by the Kirby-Bauer disc diffusion method. Among the total 100 isolates of K. pneumoniae, 40% were biofilm-producing. Most of them were from urine specimens. Out of biofilm-producing isolates, ESBL – 28%, MBL- 47% and AmpC β-lactamase- 25.8% producers were observed. K. pneumoniae isolates were seen to have maximum resistance to ceftazidime and maximum sensitivity to nitrofurantoin. Study findings suggest the importance of assessment of biofilm formation for better treatment. The scenario further worsens if such biofilm-producing isolates are also MBL-positive leading to limited therapeutic options.

The present experimental work is carried out on SAE 420 steel to optimize process parameters of low-power laser hardening to improve surface micro-hardness and wear resistance for dry sliding for bio-medical applications. Laser power is the most significant factor for micro-hardening and wear resistance. Rank two for scanning speed and three for standoff distance, respectively. The experiments show that the surface micro-hardness of treated samples varies from 711 to 833 Vickers Pyramid Number by optimized process parameters such as laser beam power of 300 W, laser scan speed of 1.0 mm/s, and standoff distance of 225 mm. In comparison, the base material micro-hardness is 208 Vickers Pyramid Number as the predictive equation generated for finding micro-hardness value for the above three laser hardening process parameters. The dry sliding wear test is conducted on all laser-treated samples and a comparison is made with the untreated sample. A significant improvement in wear resistance was observed for treated as compared to untreated samples. The wear of laser hardened sample of SAE 420 steel was 3.67 x10-9 g/cm compared to untreated base metal wear rate of 139.00 x 10-9 g/cm at an applied load of 30 N and sliding speed of 300 revolutions per minute. The scanning electron microscopy analysis of wear samples (untreated, treated maximum, and minimum hardness) is observed for investigating material removal patterns.

Background: Antibiotic resistance in common pathogenic bacteria is linked with the genetic makeup. The genetic basis of antibiotic resistance may vary in different species or pathophysiological conditions. Objectives: We studied the antibiotic resistance in Klebsiella pneumonia isolates from DFU in the western Indian population. We also studied the presence of ESBL and MBL mechanisms of antibiotic resistance along with the prevalence of the genes involved in ESBL (TEMESBL, SHVESBL, and CTX-MESBL) and MBL (NDM-1bla, KPCbla, OXA-48bla, and VIMbla) production. Results: A total of 161 K. pneumoniae isolates were analyzed; among which 50.93% were positive for ESBL and 45.96% were positive for MBL production. Most of the isolates were resistant to antibiotics used in the present study and partially resistant to Imipenem and Amikacin. There was no relation between the antibiotic resistance of the isolates and the production of ESBL or MBL mechanism of antibiotic resistance. Further, TEMESBL was the most prevalent gene in K. pneumoniae isolates followed by CTX-MESBL, NDM-1bla, SHVESBL, and KPCbla. VIMbla was the least prevalent gene found in K. pneumoniae isolates. There was no difference in the prevalence of the genes with respect to the presence or absence of ESBL and MBL mechanism of resistance. Further, there was no relation between the prevalence of the genes and antibiotic resistance in K. pneumoniae isolates. Conclusion: These results along with the literature review suggest that the prevalence of the genes involved in antibiotic resistance mechanisms are widespread in India and their distribution varies in different studies.

Abstract Postural orthostatic tachycardia syndrome (POTS) is characterized by an excessive heart rate (HR) response upon standing and symptoms indicative of inadequate cerebral perfusion. We tested the hypothesis that during lower body negative pressure (LBNP), individuals with POTS would have larger decreases in cardiac and cerebrovascular function measured using magnetic resonance (MR) imaging. Eleven patients with POTS and 10 healthy controls were studied at rest and during 20 min of −25 mmHg LBNP. Biventricular volumes, stroke volume (SV), cardiac output (Qc), and HR were determined by cardiac MR. Cerebral oxygen uptake (VO2) in the superior sagittal sinus was calculated from cerebral blood flow (CBF; MR phase contrast), venous O2 saturation (SvO2; susceptometry‐based oximetry), and arterial O2 saturation (pulse oximeter). Regional cerebral perfusion was determined using arterial spin labelling. HR increased in response to LBNP (p

Deregulation of the DNA damage response (DDR) plays a critical role in the pathogenesis and progression of many cancers. The dependency of certain cancers on DDR pathways has enabled exploitation of such through synthetically lethal relationships e.g., Poly ADP-Ribose Polymerase (PARP) inhibitors for BRCA deficient ovarian cancers. Though lagging behind that of solid cancers, DDR inhibitors (DDRi) are being clinically developed for haematological cancers. Furthermore, a high proliferative index characterize many such cancers, suggesting a rationale for combinatorial strategies targeting DDR and replicative stress. In this review, we summarize pre-clinical and clinical data on DDR inhibition in haematological malignancies and highlight distinct haematological cancer subtypes with activity of DDR agents as single agents or in combination with chemotherapeutics and targeted agents. We aim to provide a framework to guide the design of future clinical trials involving haematological cancers for this important class of drugs.

Abstract Remote monitoring is beneficial for the management of patients with cardiovascular implantable electronic devices by impacting morbidity and mortality. With increasing numbers of patients using remote monitoring, keeping up with higher volume of remote monitoring transmissions creates challenges for device clinic staff. This international multidisciplinary document is intended to guide cardiac electrophysiologists, allied professionals, and hospital administrators in managing remote monitoring clinics. This includes guidance for remote monitoring clinic staffing, appropriate clinic workflows, patient education, and alert management. This expert consensus statement also addresses other topics such as communication of transmission results, use of third‐party resources, manufacturer responsibilities, and programming concerns. The goal is to provide evidence‐based recommendations impacting all aspects of remote monitoring services. Gaps in current knowledge and guidance for future research directions are also identified.

Background Rapidly consuming water may offer practical orthostatic hypotension therapy. However, its efficacy across disorders remains uncertain. This study aims to assess the impact of rapid 350‐ to 500‐mL water intake on systolic and diastolic blood pressure (BP) and heart rate (HR) through a systematic review and meta‐analysis. Methods and Results We systematically reviewed MEDLINE and Embase up to June 2023, including randomized controlled trials and prospective cohort studies. Using random‐effects meta‐analysis, we calculated pooled mean differences (MDs) for maximum hemodynamic effects of rapid 350‐ to 500‐mL water bolus consumption. Participants with orthostatic hypotension experienced increased systolic BP (MD, 24.18 [95% CI, 15.48–32.88]) and diastolic BP (MD, 11.98 [95% CI, 8.87–15.09]) with decreased HR (MD, −3.46 [95% CI, −5.21 to −1.71]). Similar results were observed in multiple system atrophy and pure autonomic failure subgroup analysis. Healthy participants showed modest increases in systolic BP (MD, 2.33 [95% CI, 1.02–3.64]) and diastolic BP (MD, 2.73 [95% CI, 1.15–4.30]), but HR changes were not significant (MD, −2.06 [95% CI, −5.25 to 1.13]). Water had no significant hemodynamic effects in patients with seated or supine postural tachycardia syndrome, although standing effects were unassessed. Our data do not exclude water's potential standing effect in postural tachycardia syndrome. Conclusions In patients with orthostatic hypotension, rapid water intake elevated short‐term systolic BP and diastolic BP, with mild HR reduction when seated or supine. Healthy participants exhibited similar but milder effects. However, patients with postural tachycardia syndrome did not experience these changes in seated or supine positions. Further research is needed to evaluate the promising impact of rapid water ingestion on patients with postural tachycardia syndrome in a standing position, which was not addressed in our study.

Approximately 30% to 70% of patients with cirrhosis have QT interval prolongation. In patients without cirrhosis, QT prolongation is associated with an increased risk of ventricular arrhythmias, such as torsade de pointes (TdP). In cirrhotic patients, there is likely a significant association between the corrected QT (QTc) interval and the severity of liver disease, and possibly with increased mortality. We present a stepwise overview of the pathophysiology and management of acquired long QT syndrome in cirrhosis. The QT interval is mainly determined by ventricular repolarization. To compare the QT interval in time it should be corrected for heart rate (QTc), preferably by the Fridericia method. A QTc interval >450 ms in males and >470 ms in females is considered prolonged. The pathophysiological mechanism remains incompletely understood, but may include metabolic, autonomic or hormonal imbalances, cirrhotic heart failure and/or genetic predisposition. Additional external risk factors for QTc prolongation include medication (IKr blockade and altered cytochrome P450 activity), bradycardia, electrolyte abnormalities, underlying cardiomyopathy and acute illness. In patients with cirrhosis, multiple hits and cardiac-hepatic interactions are often required to sufficiently erode the repolarization reserve before long QT syndrome and TdP can occur. While some risk factors are unavoidable, overall risk can be mitigated by electrocardiogram monitoring and avoiding drug interactions and electrolyte and acidbase disturbances. In cirrhotic patients with prolonged QTc interval, a joint effort by cardiologists and hepatologists may be useful and significantly improve the clinical course and outcome.

In atrial arrhythmias, amiodarone is usually given either intravenously for acute management, requiring in-hospital monitoring, or orally for chronic control, as doses given 60 times per half-life, requiring weeks to reach full effect. A high-risk, 245-kg male with heart failure exacerbated by atrial flutter was successfully cardioverted using an atypically large, 8000-mg oral amiodarone dose. The only adverse effect was transient sinus arrest, which did not require intervention, only 24 hours of inpatient monitoring. Amiodarone’s unique pharmacokinetics, including its long elimination half-life and its extensive distribution into a large volume of adipose tissue, make high-dose oral amiodarone boluses a reasonable strategy for cardioversion of atrial arrhythmias. Résumé: En présence d’arythmie auriculaire, l’amiodarone est généralement administrée par voie intraveineuse dans la phase aiguë de la prise en charge, ce qui nécessite une surveillance du patient en milieu hospitalier, ou encore par voie orale dans le cadre d’un traitement au long cours à des doses représentant 60 fois la demi-vie, le plein effet du médicament n’étant obtenu qu’au bout de plusieurs semaines. Un homme de 245 kg à haut risque souffrant d’insuffisance cardiaque aggravée par un flutter auriculaire a subi avec succès une cardioversion médicamenteuse faisant appel à une dose exceptionnellement élevée d’amiodarone – 8000 mg – administrée par voie orale. Le seul effet indésirable a été une pause sinusale n'ayant pas nécessité d'intervention, seulement 24 heures de surveillance en milieu hospitalier. Vu la pharmacocinétique particulière de l’amiodarone, notamment sa longue demi-vie d’élimination et sa distribution étendue dans un grand volume de tissu adipeux, l’administration perorale de ce médicament en dose de charge constitue une stratégie raisonnable de cardioversion en cas d’arythmie auriculaire.

Background: The Syncope: Pacing or Recording in the Later Years (SPRITELY) trial reported that a strategy of empiric permanent pacing in patients with syncope and bifascicular block reduces major adverse events more effectively than acting on the results of an implantable cardiac monitor (ICM). Our objective was to determine the cost-effectiveness of using the ICM, compared with a pacemaker (PM), in the management of older adults (age > 50 years) with bifascicular block and syncope enrolled in the SPRITELY trial. Methods: SPRITELY was a pragmatic, open-label randomized controlled trial with a median follow-up of 33 months. The primary outcome of this analysis is the cost per additional quality-adjusted life-year (QALY). Resource utilization and utility data were collected prospectively, and outcomes at 2 years were compared between the 2 arms. A decision analytic model simulated a 3-year time horizon. Results: The mean cost incurred by participants randomized to the PM arm was $9918, compared to $15,416 (both in Canadian dollars) for participants randomized to the ICM arm. The ICM strategy resulted in 0.167 QALYs fewer than the PM strategy. Cost and QALY outcomes are sensitive to the proportion of participants randomized to the ICM arm who subsequently required PM insertion. In 40,000 iterations of probabilistic sensitivity analysis, the PM strategy resulted in cost-savings in 99.7% of iterations, compared with the ICM strategy. Conclusions: The PM strategy was dominant—that is, less costly and estimated to result in a greater number of QALYs. For patients with unexplained syncope, bifascicular block, and age > 50 years, a PM is more likely to be cost-effective than an ICM. Résumé: Contexte: L’essai SPRITELY (Syncope: Pacing or Recording in the Later Years) a été mené auprès de patients ayant subi une syncope et un bloc bifasciculaire. Elle a montré qu’une méthode de stimulation électrique permanente et empirique du cœur permet de réduire les événements indésirables majeurs plus efficacement qu’une méthode reposant sur les résultats d’un moniteur cardiaque implantable. Notre objectif était de déterminer le rapport coût-efficacité de l’utilisation du moniteur cardiaque implantable par rapport à un stimulateur cardiaque dans la prise en charge de personnes âgées de plus de 50 ans présentant un bloc bifasciculaire et une syncope, inscrits à l’essai SPRITELY. Méthodologie: SPRITELY était un essai contrôlé ouvert et pragmatique à répartition aléatoire, dont le suivi médian était de 33 mois. Le paramètre d’évaluation principal de cette analyse était le coût supplémentaire par année de vie ajustée en fonction de la qualité (AVAQ). Les données sur l’utilisation des ressources et l’utilité ont été recueillies de manière prospective, et les résultats à deux ans ont été comparés entre les deux groupes. Un modèle décisionnel analytique a été utilisé pour simuler un horizon temporel de trois ans. Résultats: Le coût moyen pour les participants répartis aléatoirement dans le groupe utilisant un stimulateur cardiaque était de 9 918 $ CAN comparativement à 15 416 $ CAN pour ceux utilisant un moniteur cardiaque implantable. La stratégie du moniteur cardiaque implantable s’est traduite par une réduction de 0,167 du nombre d’AVAQ par rapport à la stratégie reposant sur le stimulateur cardiaque. Les résultats relatifs aux coûts et aux AVAQ sont sensibles à la proportion de participants répartis aléatoirement dans le groupe du moniteur cardiaque implantable qui ont par la suite dû recevoir un stimulateur cardiaque. Sur 40 000 itérations de l’analyse de sensibilité probabiliste, la stratégie du stimulateur cardiaque a occasionné des économies dans 99,7 % des itérations comparativement à la stratégie du moniteur cardiaque implantable. Conclusions: La stratégie du stimulateur cardiaque était dominante, autrement dit moins coûteuse et, selon les estimations, entraînerait un plus grand nombre d’AVAQ. Pour les patients de plus de 50 ans présentant une syncope idiopathique et un bloc bifasciculaire, un stimulateur cardiaque est plus susceptible d’être moins coûteux qu’un moniteur cardiaque implantable.

An increase in digitization is giving rise to cybercrimes. The existing network protocols are insufficient for collecting the required digital evidence of cybercrime, which eventually makes the process of forensic investigation difficult. In the current scenario of network forensics, the investigator with current capabilities can reach only up to the ISP. This is not primary evidence. Currently, available tools work only at the network layer. In this work, we propose a protocol that ensures tracking up to the true source by collecting beforehand forensically sound evidence. The proposed protocol can collect target data from the device in the form of a device fingerprint with the help of an agent process. The proposed methodology will help in proving non-repudiation, which is a well-known challenge in forensic cases. The fingerprint evidence generated by the proposed method has the capability of not getting obsolete even if the criminal tries to destroy evidence. The fingerprinting technique deployed uses a hash tree and generates evidence in such a way that this fingerprint can act as legal evidence. The security validation of the proposed system is done using the BAN logic. Formal verification is performed using the AVISPA tool. The system has been implemented as a prototype and hosted on AWS.

Abstract Inaccuracies in intraoperative and preoperative measurements and estimations may lead to adverse outcomes such as patient-prosthesis mismatch. We aim to measure the relation between different dimensions of the atrioventricular valve complex in explanted porcine heart models. After a detailed physical morphology study, a cast of the explanted heart models was made using silicon-based materials. Digital models were obtained from three-dimensional scanning of the casts, showing the measured annulopapillary distance was 2.50 ± 0.18 cm, and 2.75 ± 0.36 cm for anterior and posterior papillary muscles of left ventricle, respectively. There was a significant linear association between the mitral annular circumference to anterior–posterior distance (p = 0.003, 95% CI 0.78–3.06), mitral annular circumference to interpapillary distance (p = 0.009, 95% CI 0.38–2.20), anterior–posterior distance to interpapillary distance (p = 0.02, 95% CI 0.10–0.78). Anterior–posterior distance appeared to be the most important predictor of mitral annular circumference compared to other measured distances. The mean length of the perpendicular distance of the tricuspid annulus, a, was 2.65 ± 0.54 cm; b was 1.77 ± 0.60 cm, and c was 3.06 ± 0.55 cm. Distance c was the most significant predictor for tricuspid annular circumference (p = 0.006, 95% CI 0.28–2.84). The anterior–posterior distance measured by three-dimensional scanning can safely be used to predict the annular circumference of the mitral valve. For the tricuspid valve, the strongest predictor for the circumference is the c-distance. Other measurements made from the positively correlated parameters may be extrapolated to their respective correlated parameters. They can aid surgeons in selecting the optimal prosthesis for the patients and improve procedural planning.

This paper proposes an integration of renewable energy sources based on a modular multi-input bidirectional DC/DC buck-boost converter. The proposed four-port converter is realized with a reduced component count and simplified control strategy, which makes the converter more reliable and cost-effective. Also, this converter exhibits bidirectional power flow functionality, making it suitable for charging the battery during regenerative braking of an electric vehicle or hybrid electric vehicle. Photovoltaic (PV) panel, battery, and ultra-capacitor are the three different energy sources for the suggested topology. Dynamic modeling is derived, and the steady-state performance of the converter is well analyzed in the MATLAB/Simulink platform. Experimental results obtained from a 100 W prototype model validate the performance of the proposed four-port bidirectional buck/boost (FPB3C) DC/DC converter.

Introduction The use of gender-affirming oestrogen therapy (GAOT) is an integral part of the gender-affirming transition process for transgender women (assigned male at birth who identify as women) and gender-diverse individuals. However, its use may present significant cardiovascular implications, which may be influenced by systemic oestradiol levels. Therefore, we aim to establish the association between serum oestradiol levels and incidence of adverse cardiovascular events in individuals using GAOT.Methods and analysis We will conduct a systematic review addressing the association between serum oestradiol levels and risk of adverse cardiovascular events in individuals using GAOT. Our primary outcome is the incidence of adverse cardiovascular events, our secondary outcome is the incidence of cardiovascular-related mortality and our tertiary outcome is cardiovascular-related risk factors. Electronic databases (Cochrane Central Register of Controlled Trials, Embase, MEDLINE and Web of Science) will be searched from inception until September 2022. Two investigators will independently complete screening to determine appropriateness of inclusion. Extracted data will include information on serum sex hormone levels (oestradiol and testosterone), participants, GAOT (route of administration, formulations, dosages and duration of exposure), incidence of cardiovascular outcomes, study quality and risk of bias. Inter-reviewer reliability will be calculated at both phases. Data will be presented both descriptively and meta-analysed using a random effects model, if appropriate. Heterogeneity will be explored and meta-regressed if noted.Ethics and dissemination Ethics approval is not needed. We will disseminate findings through international conferences, distributions to transgender and gender-diverse support organisations, decision-makers and key stakeholders. The final systematic review will be published in a peer-reviewed journal.Trial registration number CRD42021247717.

ABSTRACT Prenyldiphosphate synthases catalyze the reaction of allylic diphosphates with one or more isopentenyl diphosphate molecules to form compounds such as farnesyl diphosphate, used in, e.g., sterol biosynthesis and protein prenylation, as well as longer “polyprenyl” diphosphates, used in ubiquinone and menaquinone biosynthesis. Quinones play an essential role in electron transport and are associated with the inner mitochondrial membrane due to the presence of the polyprenyl group. In this work, we investigated the synthesis of the polyprenyl diphosphate that alkylates the ubiquinone ring precursor in Toxoplasma gondii, an opportunistic pathogen that causes serious disease in immunocompromised patients and the unborn fetus. The enzyme that catalyzes this early step of the ubiquinone synthesis is Coq1 (TgCoq1), and we show that it produces the C35 species heptaprenyl diphosphate. TgCoq1 localizes to the mitochondrion and is essential for in vitro T. gondii growth. We demonstrate that the growth defect of a T. gondii TgCoq1 mutant is rescued by complementation with a homologous TgCoq1 gene or with a (C45) solanesyl diphosphate synthase from Trypanosoma cruzi (TcSPPS). We find that a lipophilic bisphosphonate (BPH-1218) inhibits T. gondii growth at low-nanomolar concentrations, while overexpression of the TgCoq1 enzyme dramatically reduced growth inhibition by the bisphosphonate. Both the severe growth defect of the mutant and the inhibition by BPH-1218 were rescued by supplementation with a long-chain (C30) ubiquinone (UQ6). Importantly, BPH-1218 also protected mice against a lethal T. gondii infection. TgCoq1 thus represents a potential drug target that could be exploited for improved chemotherapy of toxoplasmosis. IMPORTANCE Millions of people are infected with Toxoplasma gondii, and the available treatment for toxoplasmosis is not ideal. Most of the drugs currently used are only effective for the acute infection, and treatment can trigger serious side effects requiring changes in the therapeutic approach. There is, therefore, a compelling need for safe and effective treatments for toxoplasmosis. In this work, we characterize an enzyme of the mitochondrion of T. gondii that can be inhibited by an isoprenoid pathway inhibitor. We present evidence that demonstrates that inhibition of the enzyme is linked to parasite death. In addition, the inhibitor can protect mice against a lethal dose of T. gondii. Our results thus reveal a promising chemotherapeutic target for the development of new medicines for toxoplasmosis.

BackgroundSleep syncope is a subtype of vasovagal syncope in which patients experience syncope after awakening from their sleep. The aim was to investigate the association of clinical characteristics and gastrointestinal symptoms with syncope, as well as the body position in which symptoms began.MethodsA systematic search of studies was performed in MEDLINE and EMBASE without language restrictions, from inception to 9 January 2022. Studies were included if they reported data on the proportion of patients who experienced symptoms (nausea, vomiting, abdominal pain, and diarrhea) associated with syncope.ResultsData were included for 116 patients in 13 studies. Patients were 46.9 ± 4.3 years and 61.4% were female. In 52.5% of patients, a supine body position at the time of syncope was reported. A history of phobias was reported by 67.6% of patients, and 96.5% of patients also had typical daytime vasovagal syncope. In the 5 studies reporting the results of head-up tilt testing (n = 77), 90.9% of patients had positive tests. Gastrointestinal symptoms were present in the majority of patients with reported rates of 65.6% for upper gastrointestinal symptoms and 86.0% for lower gastrointestinal symptoms.ConclusionPatients with sleep syncope patients are predominantly female with a history of daytime vasovagal syncope. Gastrointestinal symptoms are present in the majority of patients and is therefore an important feature of sleep syncope.

Background: Remote monitoring is used to supplement in-clinic follow-up for patients with cardiac implantable electronic devices (CIEDs) every 6-12 months. There is a need to optimize remote management for CIEDs because of the consistent increases in CIED implants over the past decade. The objective of this study was to investigate real and perceived barriers to the use of remote patient management strategies in Canada and to better understand how remote models of care can be optimized. Methods: We surveyed 512 CIED patients and practitioners in 22 device clinics in Canada. Results: Device clinic surveys highlighted significant variation and inconsistency in follow-up care for in-clinic and remote visits across and within clinics. This survey showed that funding policies and management of additional workflow are barriers to optimal use and uptake. Despite this, device clinics perceive remote follow-up as a valuable resource and an efficient way to manage patient follow-up. Patients were broadly satisfied with their CIED follow-up care but identified barriers related to coordination of care, visit logistics, and information needs. Views varied as a function of clinical or sociodemographic characteristics. Most patients (n = 228; 91%) expressed a desire to receive a phone call from their device clinic after a remote transmission has been received. Conclusions: Lack of a unified, guideline-supported approach to follow-up after CIED implant, and discrepant funding policies across jurisdictions, are significant barriers to the use of remote patient management strategies in Canada. Efforts to increase or expand use of remote follow-up must recognize these barriers and the needs of specific subgroups of patients. Résumé: Introduction: La télésurveillance sert de complément à la consultation en clinique des patients porteurs d’un dispositif cardiaque électronique implantable (DCEI) tous les 6 à 12 mois. Il est nécessaire d’optimiser la prise en charge à distance des patients porteurs de DCEI en raison de la constante augmentation des implantations de DCEI au cours de la dernière décennie. L’objectif de la présente étude était d’examiner les obstacles réels et perçus à l’utilisation des stratégies de prise en charge à distance des patients du Canada et de mieux comprendre la façon d’optimiser les modèles de soins à distance. Méthodes: Nous avons interrogé 512 patients porteurs de DCEI et praticiens de 22 cliniques spécialisées en DCEI du Canada. Résultats: Les enquêtes des cliniques spécialisées en DCEI ont fait ressortir la variation importante et le manque d’uniformité dans les soins de suivi lors des consultations en clinique et à distance au sein de toutes les cliniques et entre elles. Cette enquête a montré que les politiques de financement et la gestion du flux de travail supplémentaire sont les obstacles qui empêchent l’utilisation optimale et l’adoption. Malgré cela, les cliniques spécialisées en DCEI perçoivent le suivi à distance comme une ressource très utile et un moyen efficace de prendre en charge le suivi du patient. Les patients étaient dans l’ensemble satisfaits de leurs soins de suivi relatifs à leur DCEI, mais relevaient des obstacles liés à la coordination des soins, à la logistique des consultations et à leurs besoins d’information. Les points de vue variaient en fonction des caractéristiques cliniques et sociodémographiques. La plupart des patients (n = 228 ; 91 %) ont fait part de leur souhait de recevoir un appel téléphonique de leur clinique spécialisée en DCEI après la réception de la transmission à distance. Conclusions: L’absence d’une approche unifiée et fondée sur les lignes directrices qui porte sur le suivi après l’implantation de DCEI, et la divergence des politiques de financement des provinces et territoires sont des obstacles importants à l’utilisation de stratégies de prise en charge à distance des patients au Canada. Les efforts visant à accroître ou à étendre l’utilisation du suivi à distance doivent tenir compte de ces obstacles et des besoins des sous-groupes particuliers de patients.

Abstract Background Nanomedicine has evolved as precision medicine in novel therapeutic approach of cancer management. The present study investigated the efficacy of biogenic gold nanoparticles synthesized using Argemone mexicana L. aqueous extract (AM-AuNPs) against the human colon cancer cell line, HCT-15. Results Biosynthesis of AM-AuNPs was determined by ultraviolet-visible spectroscopy and further characterized by transmission electron microscopy, X-ray diffraction, and Fourier transition infrared spectroscopy analysis. The cytotoxic activity of AM-AuNPs was assessed by the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay, whereas genotoxicity was evaluated by the DNA fragmentation assay. The expression of apoptosis regulatory genes such as p53 and caspase-3 was explored through semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR) and western blotting to evidence apoptotic cell death in HCT-15 cells. Biogenic AM-AuNPs inhibited cell proliferation in HCT-15 cell line with a half maximal inhibitory concentration (IC50) of 20.53 μg/mL at 24 h and 12.03 μg/mL at 48 h of exposure. The altered cell morphology and increased apoptosis due to AM-AuNPs were also evidenced through nuclear DNA fragmentation and upregulated expression of p53 and caspase-3 in HCT-15 cells. Conclusion The AM-AuNPs may exert antiproliferative and genotoxic effects on HCT-15 cells by cell growth suppression and induction of apoptosis mediated by activation of p53 and caspase-3 genes.

Background: Implantable cardioverter defibrillator (ICD) acceptance and shock anxiety are issues that clinicians should address to improve quality of life among device recipients. Previous findings have indicated that younger patients experience poorer device adjustment. The purpose of this study was to examine age and ICD-specific quality-of-life outcomes in a large sample of Canadian ICD patients. We tested the hypothesis that patient age is related to device acceptance and shock anxiety in an Alberta (Canada) ICD population. Methods: The Florida Patient Acceptance Survey (FPAS) and Florida Shock Acceptance Survey (FSAS) were completed by ICD patients attending the Cardiac Implantable Electrical Device Clinics in Alberta. The population was dichotomized into those aged ≤ 65 years (younger) and those aged > 65 years (older). Sex, ICD shock history, and remote monitoring use were also examined. Results: Surveys were completed by 126 younger (53 ± 11 years; 79% male) and 216 older (74 ± 6 years; 85% male) patients. Younger, compared with older, patients had greater device-related distress (P < 0.001) and more body-image concerns (P < 0.001), but no differences in return to function or positive appraisal. Younger patients reported lower total device acceptance (P = 0.001) and greater total shock anxiety (P < 0.001) compared with older patients. Conclusions: ICD patients aged ≤ 65 years reported poorer device acceptance and greater shock anxiety than older patients. Younger patients may require targeted interventions addressing adjustment to the ICD, and impact of the ICD on body image. Moreover, education about the relatively low probability of shocks may alleviate shock anxiety in younger patients. Résumé: Contexte: L’acceptation d’un défibrillateur cardioverteur implantable (DCI) et la crainte des chocs de DCI sont des problèmes auxquels les cliniciens devraient s’attaquer pour améliorer la qualité de vie des patients qui sont porteurs d’un DCI. Selon des observations antérieures, les plus jeunes patients ont davantage de mal à s’adapter au dispositif. L’étude avait pour objet l’examen des paramètres de la qualité de vie particuliers à l’âge et au port d’un DCI dans un vaste échantillon de patients canadiens porteurs de ce dispositif. Nous avons testé l’hypothèse voulant que l’âge du patient soit lié à l’acceptation du dispositif et à la crainte des chocs chez des Albertains porteurs d’un DCI. Méthodologie: Les patients des cliniques de l'Alberta (Canada) des dispositifs cardiaques électroniques implantables qui étaient porteurs d’un DCI ont rempli les questionnaires FPAS (Florida Patient Acceptance Survey) et FSAS (Florida Shock Acceptance Survey). Les patients ont été partagés en deux groupes selon leur âge, soit ceux de 65 ans et moins (plus jeunes patients) et ceux de plus de 65 ans (patients âgés). Nous avons aussi examiné les facteurs suivants : sexe, chocs de DCI antérieurs et utilisation d’une télésurveillance. Résultats: Les questionnaires ont été remplis par 126 plus jeunes patients (53 ± 11 ans; 79 % d’hommes) et 216 patients âgés (74 ± 6 ans; 85 % d’hommes). Chez les plus jeunes patients, par rapport aux patients âgés, la détresse causée par le dispositif était plus grande (p < 0,001) et il y avait davantage de préoccupations liées à l’image corporelle (p < 0001), mais il n’y avait pas de différences pour ce qui est de la reprise des activités ou de l’évaluation positive du dispositif. Chez les plus jeunes patients, l’acceptation totale du dispositif était moindre (p = 0,001) et la crainte des chocs était plus grande (p < 0,001) que chez les patients âgés. Conclusions: Chez les porteurs d’un DCI de 65 ans et moins, le dispositif était moins bien accepté, et la crainte des chocs était plus grande que chez les patients âgés. Chez les plus jeunes patients, des interventions ciblées axées sur l’adaptation au DCI et les répercussions du DCI sur l’image corporelle pourraient être nécessaires. De plus, l’éducation à propos de la probabilité relativement faible de subir des chocs pourrait réduire cette crainte chez les plus jeunes patients.

Background: Syncope is a common presentation to the emergency department (ED), yet little is known regarding patient mode of arrival. Methods: We identified patients ≥20 years old who presented to the ED with a primary diagnosis of syncope in Alberta and Ontario, Canada, between 2010 and 2016. Outcomes included 30-day in-hospital mortality, ED revisits, and rehospitalizations according to mode of arrival and discharge status. The estimated cost for ambulance use was calculated based on the provincial rates (Alberta CAD$385 and Ontario $240). Results: A total of 271,601 syncope presentations to the ED were identified and 60.7% arrived by ambulance. A total of 76.3% (n = 125,793) of ambulance users and 87.0% of self-presenters (n = 92,845) were discharged from the ED. Regardless of mode of arrival, discharged patients were younger with fewer comorbidities. Compared with ambulance users admitted, those discharged had lower in-hospital mortality (0.2% vs 3.5%, P < 0.001), ED revisits (4.4% vs 10.4%, P < 0.001), and rehospitalizations (3.6% vs 10.7%, P < 0.001). Discharged self-presenters also had significantly lower outcomes (P < 0.001, for each outcome) compared with admitted self-presenters. The estimated cost for ambulance use among patients discharged from the ED was $33,137,735. Conclusion: A majority of syncope patients arrived to the ED by ambulance, and over 3 quarters were directly discharged home. Although discharged patients had a favourable short-term prognosis, they incurred high transportation costs. Strategies aimed at preventing unnecessary ambulance use are needed. Résumé: Contexte: La syncope est une manifestation courante chez les patients qui se présentent au service des urgences; pourtant, on en sait peu sur la façon dont ces patients arrivent à l’hôpital. Méthodologie: Nous avons examiné les dossiers de patients âgés de 20 ans ou plus qui se sont présentés au service des urgences d’hôpitaux de l’Alberta et de l’Ontario, au Canada, et qui ont reçu un diagnostic de syncope entre 2010 et 2016. Les issues évaluées comprenaient la mortalité hospitalière à 30 jours, les nouvelles visites au service des urgences et les réadmissions à l’hôpital en fonction du mode d’arrivée et du statut au moment de la sortie de l’hôpital. Le coût estimatif des services d’ambulance a été calculé à partir des tarifs provinciaux (385 $ en Alberta et 240 $ en Ontario). Résultats: En tout, 271 601 cas de syncope ont été recensés dans les services des urgences; dans 60,7 % des cas, le patient est arrivé en ambulance. Au total, 76,3 % (n = 125 793) des patients arrivés en ambulance et 87,0 % des patients qui se sont présentés d’eux-mêmes (n = 92 845) ont reçu leur congé du service des urgences. Quel que soit leur mode d’arrivée, les patients qui ont reçu leur congé étaient plus jeunes et présentaient moins d’affections concomitantes. Chez les patients arrivés en ambulance, ceux qui ont reçu leur congé ont affiché des résultats inférieurs à ceux qui ont été admis à l’hôpital quant à la mortalité hospitalière (0,2 % vs 3,5 %, p < 0,001), aux nouvelles visites au service des urgences (4,4 % vs 10,4 %, p < 0,001) et aux réadmissions à l’hôpital (3,6 % vs 10,7 %, p < 0,001). Dans le cas des patients qui se sont présentés d’eux-mêmes, l’incidence des issues évaluées était aussi plus faible chez ceux qui ont reçu leur congé (p < 0,001 pour chaque issue) que chez ceux qui ont été admis à l’hôpital. Le coût estimatif du recours aux services d’ambulance par les patients qui ont reçu leur congé du service des urgences se chiffrait à 33 137 735 $. Conclusion: La majorité des patients subissant une syncope sont arrivés au service des urgences en ambulance, et plus des trois quarts ont reçu directement leur congé à la maison. Bien que le pronostic à court terme des patients ayant reçu leur congé du service des urgences ait été favorable, ces patients ont dû payer des frais de transport élevés. Des stratégies visant à prévenir le recours inutile aux services d’ambulance s’imposent.

Abstract Young women with chronic kidney disease (CKD) have disproportionately increased risk of cardiovascular mortality. Reduced anti‐Müllerian hormone (AMH) is linked to poor cardiovascular outcomes in the general population, but whether AMH is associated with increased cardiovascular risk in the high‐risk CKD population is unknown. This study examined the association between AMH and vascular function, validated markers of cardiovascular risk, in women with CKD. An exploratory cross‐sectional study was performed in 47 young women with CKD. Laboratory measurements of AMH were collected. Using standardized protocols, endothelial function was measured with brachial artery flow‐mediated dilation and hyperemic velocity time integral. Arterial stiffness was measured with aortic augmentation index and pulse wave velocity. Multivariate linear regression analyses were utilized to evaluate the association between AMH levels and each measure of vascular health. Forty women (36 ± 7 years) with non‐dialysis‐dependent CKD and 7 women (38 ± 6 years) with dialysis‐dependent CKD participated. AMH levels were inversely associated with age (p = 0.01) but not associated with eGFR (p = 0.59) or dialysis status (p = 0.97). AMH was associated with brachial artery flow‐mediated dilation (R2 = 0.21 [p = 0.03]) and aortic augmentation index (R2 = 0.20 [p = 0.04]) in the non‐dialysis‐dependent participants, and with aortic augmentation index in all participants (R2 = 0.18 [p = 0.03]). No association between AMH and any measure of vascular function was demonstrated in the dialysis‐dependent participants. AMH levels are associated with impaired vascular function in young women with CKD and may be an important marker of future cardiovascular risk. Further investigation into this female‐specific cardiovascular risk factor is warranted in this high‐risk population.

The unpredictable noise in received signal strength indicator (RSSI) measurements in indoor environments practically causes very high estimation errors in target localization. Dealing with high noise in RSSI measurements and ensuring high target-localization accuracy with RSSI-based localization systems is a very popular research trend nowadays. This paper proposed two range-free target-localization schemes in wireless sensor networks (WSN) for an indoor setup: first with a plain support vector regression (SVR)-based model and second with the fusion of SVR and kalman filter (KF). The fusion-based model is named as the SVR+KF algorithm. The proposed localization solutions do not require computing distances using field measurements; rather, they need only three RSSI measurements to locate the mobile target. This paper also discussed the energy consumption associated with traditional Trilateration and the proposed SVR-based target-localization approaches. The impact of four kernel functions, namely, linear, sigmoid, RBF, and polynomial were evaluated with the proposed SVR-based schemes on the target-localization accuracy. The simulation results showed that the proposed schemes with linear and polynomial kernel functions were highly superior to trilateration-based schemes.

Background: Postural orthostatic tachycardia syndrome (POTS) is a chronic form of orthostatic intolerance that primarily impacts female patients of childbearing age. The role of sex differences in POTS is not well understood. We sought to identify sex differences in diagnosis, symptoms, comorbidities, and treatments in female and male patients diagnosed with POTS. Methods: A comprehensive survey was designed in partnership by Dysautonomia International (East Moriches, NY) and Vanderbilt University Medical Center (Nashville, TN). Patients were recruited through Dysautonomia International’s website and social media channels. The survey was delivered online through a secure research data capture database. Responses were analyzed according to biological sex. Continuous variables are presented as median (25th percentile-75th percentile), and categorical variables are presented as number and proportion of participants. Results: A total of 8919 patients reported a physician diagnosis of POTS and were included in this analysis. The majority of respondents were female (93.7%). Female and male patients experienced misdiagnosis at similar rates (76.2% vs 74.9%, P = 0.5) and saw a similar number of doctors before diagnosis (5 [3-8] vs 5 [3-8], P = 0.9). Despite these similarities, diagnostic delay was longer for female, compared with male, patients (1.50 [0.25-5.25] years vs 0.92 [0.08-2.91] years, P < 0.001). Conclusions: Despite the primarily female demographic of POTS patients, female patients experience more challenges with diagnosis than male patients. Increased awareness and recognition of POTS may help to reduce the diagnostic challenges in both female and male patients, and improve treatment and management for individuals living with this debilitating disorder. Résumé: Contexte: Le syndrome de tachycardie orthostatique posturale (STOP) est une forme chronique d’intolérance orthostatique qui touche principalement les femmes en âge de procréer. L’incidence du sexe sur le STOP n’est pas bien comprise. Nous avons cherché à déterminer les différences entre les sexes en ce qui a trait au diagnostic, aux symptômes, aux comorbidités et aux traitements chez les patients féminins et masculins ayant reçu un diagnostic de STOP. Méthodologie: Une enquête exhaustive a été conçue en partenariat par Dysautonomia International (East Moriches, NY, États-Unis) et le Vanderbilt University Medical Center (Nashville, TN, États-Unis). Les patients ont été recrutés par l’entremise du site Web de Dysautonomia International et des médias sociaux. L’enquête a été réalisée en ligne au moyen d’une base de données sécurisée de saisie de données de recherche. Les réponses ont été analysées en fonction du sexe biologique. Les variables continues sont présentées sous forme de médiane (25e percentile-75e percentile), et les variables nominales sont présentées sous forme de nombre et de proportion de participants. Résultats: Au total, 8 919 patients ont signalé un diagnostic de STOP établi par un médecin et ont été inclus dans cette analyse. La majorité des répondants étaient des femmes (93,7 %). Les patients de sexe féminin et masculin ont été mal diagnostiqués dans des proportions similaires (76,2 % vs 74,9 %, p = 0,5) et ont vu un nombre similaire de médecins avant le diagnostic (5 [3-8] vs 5 [3-8], p = 0,9). Malgré ces similitudes, le retard de diagnostic était plus long chez les femmes que chez les hommes (1,50 [0,25-5,25] an contre 0,92 [0,08-2,91] an, p < 0,001). Conclusions: Même si les patients atteints de STOP sont principalement des femmes, ces dernières ont plus de difficultés à recevoir un diagnostic que les hommes. Une meilleure connaissance et reconnaissance du STOP peut contribuer à réduire les problèmes liés au diagnostic chez les patients féminins et masculins, et à améliorer le traitement et la prise en charge des personnes atteintes de ce trouble débilitant.

Location awareness is the key to success to many location-based services applications such as indoor navigation, elderly tracking, emergency management, and so on. Trilateration-based localization using received signal strength measurements is widely used in wireless sensor network–based localization and tracking systems due to its simplicity and low computational cost. However, localization accuracy obtained with the trilateration technique is generally very poor because of fluctuating nature of received signal strength measurements. The reason behind such notorious behavior of received signal strength is dynamicity in target motion and surrounding environment. In addition, the significant localization error is induced during each iteration step during trilateration, which gets propagated in the next iterations. To address this problem, this article presents an improved trilateration-based architecture named Trilateration Centroid Generalized Regression Neural Network. The proposed Trilateration Centroid Generalized Regression Neural Network–based localization algorithm inherits the simplicity and efficiency of three concepts namely trilateration, centroid, and Generalized Regression Neural Network. The extensive simulation results indicate that the proposed Trilateration Centroid Generalized Regression Neural Network algorithm demonstrates superior localization performance as compared to trilateration, and Generalized Regression Neural Network algorithm.

The Indian Ocean Dipole is a leading phenomenon of climate variability in the tropics, which affects the global climate. However, the best lead prediction skill for the Indian Ocean Dipole, until recently, has been limited to ~6 months before the occurrence of the event. Here, we show that multi-year prediction has made considerable advancement such that, for the first time, two general circulation models have significant prediction skills for the Indian Ocean Dipole for at least 2 years after initialization. This skill is present despite ENSO having a lead prediction skill of only 1 year. Our analysis of observed/reanalyzed ocean datasets shows that the source of this multi-year predictability lies in sub-surface signals that propagate from the Southern Ocean into the Indian Ocean. Prediction skill for a prominent climate driver like the Indian Ocean Dipole has wide-ranging benefits for climate science and society.

Background: Implantable cardioverter defibrillator (ICD) therapy is lifesaving; however, real-world data regarding the proportion of patients eligible for a primary prevention ICD and subsequent use remain sparse. This study evaluated rates of primary prevention ICD eligibility and use among patients in heart function clinics (HFCs) and to identify reasons for nonimplantation. Methods: A retrospective study was performed of patients seen at HFCs in Alberta, Canada, from 2013 to 2015. Demographics, comorbidities, clinical indications, and reasons for nonimplantation were abstracted. Eligibility was defined according to the 2008 American College of Cardiology/American Heart Association/Heart Rhythm Society ICD, 2012 American College of Cardiology/American Heart Association/Heart Rhythm Society Focused Update, and 2013 Canadian Cardiovascular Society Cardiac Resynchronization Therapy guidelines. Logistic regression was used to calculate an odds ratio (OR) and 95% confidence interval (CI) for predictors of nonimplantation. Results: Among 1239 patients in HFCs, the median age was 70 years (interquartile range, 59-80), 67% were male, and the median left ventricular ejection fraction was 0.40 (interquartile range, 0.28-0.53). Overall, 45% of patients (n = 553) met guideline criteria for an ICD, and of those, 36% (n = 198) received a device. Among device nonrecipients, 52% (n = 185) had no documented reason for nonimplantation. The most common reason for nonimplantation among nonrecipients was patient preference (48%). Predictors associated with nonimplantation were age more than 75 years (OR, 1.92; 95% CI, 1.31-2.82) and history of cancer (OR, 2.26; 95% CI, 1.07-4.78). At 3 years follow-up, 27% of nonrecipients were deceased. Conclusions: We found that one-third of patients who met guideline criteria received an ICD and that documentation for nonimplantation was poor. Résumé: Contexte: Le défibrillateur cardioverteur implantable (DCI) sauve des vies. Or, les données recueillies dans la pratique réelle concernant le pourcentage de patients admissibles à l’implantation d’un tel dispositif en prévention primaire et l’utilisation subséquente de ce dispositif sont très limitées. Cette étude a évalué le taux de patients admissibles à la pose d’un DCI en prévention primaire et le taux d’utilisation de ce dispositif chez des patients traités en clinique de cardiologie. Elle a également recensé les motifs de non-implantation. Méthodologie: Une étude rétrospective a été réalisée chez des patients traités de 2013 à 2015 dans plusieurs cliniques de cardiologie de l’Alberta, au Canada. Les données relatives aux caractéristiques démographiques, aux comorbidités, aux indications cliniques et aux motifs de la non-implantation ont été extraites. L’admissibilité était définie en fonction des lignes directrices de 2008 de l’American College of Cardiology, de l’American Heart Association et de la Heart Rhythm Society sur le DCI, de leur mise à jour ciblée en 2012 et des lignes directrices de 2013 de la Société canadienne de cardiologie sur la thérapie de resynchronisation cardiaque. Une régression logistique a été utilisée pour calculer le risque relatif approché (RRA) et l’intervalle de confiance (IC) à 95 % associés aux facteurs de prédiction de la non-implantation. Résultats: L’âge médian des 1 239 patients traités en clinique de cardiologie était de 70 ans (plage interquartile : 59 – 80 ans); 67 % d’entre eux étaient des hommes, et la fraction d’éjection ventriculaire gauche médiane était de 0,40 (plage interquartile : 0,28 – 0,53). D’une manière générale, 45 % des patients (n = 553) répondaient aux critères énoncés dans les lignes directrices pour la pose d’un DCI, et 36 % d’entre eux (n = 198) ont reçu un dispositif. Parmi les patients qui n’ont pas reçu de dispositif, aucun motif justifiant la non-implantation n’a été documenté chez 52 % des patients (n = 185); chez les 48 % des patients restants, le motif le plus courant pour justifier la non-implantation a été la préférence du patient. Les facteurs de prédiction associés à la non-implantation ont été l’âge (plus de 75 ans; RRA : 1,92; IC à 95 % : 1,31 – 2,82) et les antécédents de cancer (RRA : 2,26; IC à 95 % : 1,07 – 4,78). Après 3 ans de suivi, 27 % des patients qui n’avaient pas reçu de dispositif étaient décédés. Conclusions: Nous avons constaté que le tiers des patients qui répondaient aux critères énoncés dans les lignes directrices ont reçu un DCI et que les motifs justifiant la non-implantation étaient mal documentés.

Abstract Background Historically, the majority of insertable cardiac monitor (ICM) procedures were performed in the cardiac catheterization (cath) lab, electrophysiology (EP) lab, or operating room (OR). The miniaturization of ICMs allows the procedure to be relocated within the hospital without compromising patient safety. We sought to estimate the rate of untoward events associated with procedures performed within the hospital but outside the traditional settings and to characterize resource utilization, procedure time intervals, and physician experience. Methods The Reveal LINQ in-Office 2 (RIO 2) International study was a single arm, multicenter, prospective study. Patients indicated for an ICM and willing to undergo device insertion outside the cath/EP lab or OR were eligible and followed for 90 days after insertion. Results A total of 191 patients (45.5% female aged 63.8 ± 26.9 years) underwent successful Reveal LINQ ICM insertion at 17 centers in Europe, Canada and Australia. The median total visit duration was 106 min (interquartile range [IQR]: 55–61). Patient preparation and patient education accounted for 10 min (IQR: 5–20) and 10 min (IQR: 8–15) of total visit duration, respectively. Preparation and education occurred in the procedure room for 90.6 and 60.2% of patients, respectively. There were no untoward events (0.0, 95% CI: 0.0–2.1%) though four patients presented with procedure-related adverse events that did not require invasive intervention. Physicians rated procedure location as convenient or very convenient. Conclusions The Reveal LINQ™ ICM insertion can be safely and efficiently performed in the hospital outside the cath/EP lab or OR. Trial registration ClinicalTrials.gov identifier NCT02412488; registered on April 9, 2015.

Background: The purpose of this article is to examine the systemic circulation and left ventricular (LV) performance by alternative, nonconventional approaches: systemic vascular conductance (GSV) and the head-capacity relation (ie, the relation between LV pressure and cardiac output), respectively; in so doing, we aspired to present a novel and improved interpretation of integrated cardiovascular function. Methods: In 16 open-chest, anaesthetized pigs, we measured LV pressure (PLV), central aortic pressure (PAo), and central venous pressure (PCV) and aortic flow (QAo). We calculated heart rate (HR), stroke volume, cardiac index (CI = cardiac output/body weight), mean PLV (P¯LV), and the average arteriovenous pressure difference (ΔP=P¯Ao−P¯CV); GSV = CI/(P¯Ao−P¯CV). We studied the effects of changing loading conditions with the administration of phenylephrine (ΔP¯Ao ≥ +25 mm Hg), isoproterenol (ΔHR ∼+25%), sodium nitroprusside (ΔP¯Ao ≥ −25 mm Hg), and proximal aortic constriction (to maximize developed PLV and minimize QAo). Results: Sodium nitroprusside and isoproterenol increased GSV compared with phenylephrine and constriction. A maximum head-capacity curve was derived from pooled data using nonlinear regression on the maximum P¯LV values in QAo bins 12.5 mL/min/kg wide. The head-capacity relation and the plots of conductance were combined using CI as a common axis, which illustrated that CI is the output of the heart and the input of the circulation. Conclusions: Thus, at a given CI, GSV determines the driving pressure and, thereby, PAo. We also demonstrated how decreases in GSV compensate for arterial hypotension by restoring the arteriovenous pressure difference and arterial pressure. Résumé: Contexte: Le présent article examine l’efficacité de la circulation générale et la fonction ventriculaire gauche à l’aide de paramètres de rechange non conventionnels, soit la conductance vasculaire systémique (GVS) pour l’une et la relation pression-volume (c.-à-d. la relation entre la pression ventriculaire gauche et le débit cardiaque) pour l’autre, dans le but de présenter une interprétation nouvelle et améliorée de la fonction cardiovasculaire intégrée. Méthodologie: Chez 16 porcs anesthésiés, nous avons mesuré à thorax ouvert la pression ventriculaire gauche (PVG), la pression aortique centrale (PAC), la pression veineuse centrale (PVC) et le flux aortique (QA). Nous avons établi la fréquence cardiaque (FC), le volume d’éjection systolique, l’index cardiaque (IC; rapport entre le débit cardiaque et le poids corporel), la PVG moyenne (P¯VG) et la différence de pression artérioveineuse moyenne (ΔP=P¯AC−P¯VC); GVS = IC/(P¯AC−P¯VC). Nous avons aussi étudié les effets d’une modification des conditions de charge cardiaque provoquée par l’administration de phényléphrine (ΔP¯AC ≥ + 25 mmHg), d’isoprotérénol (ΔFC d’environ + 25 %) ou de nitroprussiate de sodium (ΔP¯AC ≥ − 25 mmHg) et par la constriction de l’aorte proximale (pour maximiser la PVG développée et réduire le plus possible le QA). Résultats: Le nitroprussiate de sodium et l’isoprotérénol ont augmenté la GVS comparativement à la phényléphrine et à la constriction. Une courbe de la relation pression-volume maximale a été dérivée à partir des données groupées, au moyen d’une régression non linéaire sur les valeurs maximales de la P¯VG réparties dans des classes de QA de 12,5 ml/min/kg d’amplitude. La courbe de la relation pression-volume et le tracé de la conductance ont été superposés en utilisant l’IC comme axe commun, ce qui a permis de constater que l’IC correspond au débit cardiaque et au volume entrant dans la circulation. Conclusions: Pour un IC donné, la GVS détermine la pression motrice et donc, la PAC. Nous avons aussi démontré comment une diminution de la GVS compense l’hypotension artérielle en rétablissant la différence de pression artérioveineuse et la pression artérielle.

Background: Rampant and injudicious use of broad spectrum antibiotic in hospitalized patients has increased the incidence of Clostridium difficile Associated Diarrhea (CDAD). In recent years, Clostridium difficile Infection (CDI) has become more frequent, severe, and difficult to treat. Aim and Objective: A prospective, study was conducted to isolate C. difficile in Antibiotic-associated Diarrhoea (AAD) and to detect toxin producing strains of C. difficile from faecal samples of patients suspected to have CDI. Material and Methods: A total of 111 hospitalized patients who developed diarrhoea after >72 hours of admission and suspected of CDI were enrolled for investigation. The samples were subjected to anaerobic culture and toxin assay. Results: The total sample size of the study was 111 patients who were having antibiotic associated diarrhoea. Majority of the patients were from the age group 21-30 years and 41-50 years i.e., 23 (20.7%). Males 64 (57.7%) were affected more as compared to females 47 (42.3%). Third generation cephalosporins were the most common group of antibiotics associated with both AAD 36 (32.4%) and CDAD 9 (42.85%) cases, followed by carbapenem fluroquinolones in combination 3 (12.5%). Culture positivity was seen in 12 (10.81%) of the 111 stool samples and 39 (35.13%) were toxin producers. Conclusion: The use of several medications was found to be associated with an increased risk of CDAD. The only way to reduce Cl. difficile infection is to judiciously use antibiotics, strictly adhere to antibiotic policy and to give prime importance to strict infection control measures.

AimsArrhythmia mechanisms in hypertrophic cardiomyopathy remain uncertain. Preclinical models suggest hypertrophic cardiomyopathy-linked mutations perturb sarcomere length-dependent activation, alter cardiac repolarization in rate-dependent fashion and potentiate triggered electrical activity. This study was designed to assess rate-dependence of clinical surrogates of contractility and repolarization in humans with hypertrophic cardiomyopathy.MethodsAll participants had a cardiac implantable device capable of atrial pacing. Cases had clinical diagnosis of hypertrophic cardiomyopathy, controls were age-matched. Continuous electrocardiogram and blood pressure were recorded during and immediately after 30 second pacing trains delivered at increasing rates.ResultsNine hypertrophic cardiomyopathy patients and 10 controls were enrolled (47% female, median 55 years), with similar baseline QRS duration, QT interval and blood pressure. Median septal thickness in hypertrophic cardiomyopathy patients was 18mm; 33% of hypertrophic cardiomyopathy patients had peak sub-aortic velocity >50mmHg. Ventricular ectopy occurred during or immediately after pacing trains in 4/9 hypertrophic cardiomyopathy patients and 0/10 controls (P = 0.03). During delivery of steady rate pacing across a range of cycle lengths, the QT-RR relationship was not statistically different between HCM and control groups; no differences were seen in subgroup analysis of patients with or without intact AV node conduction. Similarly, there was no difference between groups in the QT interval of the first post-pause recovery beat after pacing trains. No statistically significant differences were seen in surrogate measures for cardiac contractility.ConclusionRapid pacing trains triggered ventricular ectopy in hypertrophic cardiomyopathy patients, but not controls. This finding aligns with pre-clinical descriptions of excessive cardiomyocyte calcium loading during rapid pacing, increased post-pause sarcoplasmic reticulum calcium release, and subsequent calcium-triggered activity. Normal contractility at all diastolic intervals argues against clinical significance of altered length-dependent myofilament activation.

Background Splanchnic venous pooling induced by upright posture triggers a compensatory increase in heart rate (HR), a response that is exaggerated in patients with postural tachycardia syndrome. To assess whether abdominal compression attenuates orthostatic tachycardia and improves symptoms, 18 postural tachycardia syndrome patients (32±2 years) were randomized to receive either abdominal compression (40 mm Hg applied with an inflatable binder ≈2 minutes before standing) or propranolol (20 mg) in a placebo‐controlled, crossover study. Methods and Results Systolic blood pressure, HR, and symptoms were assessed while seated and standing, before and 2 hours postdrug. As expected, propranolol decreased standing HR compared with placebo (81±2 versus 98±4 beats per minute; P

SQ109 is an anti-tubercular drug candidate that has completed Phase IIb/III clinical trials for tuberculosis and has also been shown to exhibit potent in vitro efficacy against protozoan parasites including Leishmania and Trypanosoma cruzi spp. However, its in vivo efficacy against protozoa has not been reported. Here, we evaluated the activity of SQ109 in mouse models of Leishmania, Trypanosoma spp. as well as Toxoplasma infection. In the T. cruzi mouse model, 80% of SQ109-treated mice survived at 40 days post-infection. Even though SQ109 did not cure all mice, these results are of interest since they provide a basis for future testing of combination therapies with the azole posaconazole, which acts synergistically with SQ109 in vitro. We also found that SQ109 inhibited the growth of Toxoplasma gondii in vitro with an IC50 of 1.82 µM and there was an 80% survival in mice treated with SQ109, whereas all untreated animals died 10 days post-infection. Results with Trypanosoma brucei and Leishmania donovani infected mice were not promising with only moderate efficacy. Since SQ109 is known to be extensively metabolized in animals, we investigated the activity in vitro of SQ109 metabolites. Among 16 metabolites, six mono-oxygenated forms were found active across the tested protozoan parasites, and there was a ~6× average decrease in activity of the metabolites as compared to SQ109 which is smaller than the ~25× found with mycobacteria.

Trilateration-based target localization using received signal strength (RSS) in a wireless sensor network (WSN) generally yields inaccurate location estimates due to high fluctuations in RSS measurements in indoor environments. Improving the localization accuracy in RSS-based systems has long been the focus of a substantial amount of research. This paper proposes two range-free algorithms based on RSS measurements, namely support vector regression (SVR) and SVR + Kalman filter (KF). Unlike trilateration, the proposed SVR-based localization scheme can directly estimate target locations using field measurements without relying on the computation of distances. Unlike other state-of-the-art localization and tracking (L&T) schemes such as the generalized regression neural network (GRNN), SVR localization architecture needs only three RSS measurements to locate a mobile target. Furthermore, the SVR based localization scheme was fused with a KF in order to gain further refinement in target location estimates. Rigorous simulations were carried out to test the localization efficacy of the proposed algorithms for noisy radio frequency (RF) channels and a dynamic target motion model. Benefiting from the good generalization ability of SVR, simulation results showed that the presented SVR-based localization algorithms demonstrate superior performance compared to trilateration- and GRNN-based localization schemes in terms of indoor localization performance.

Background: Activating autoantibodies (AAb) to adrenergic receptors (AR) have previously been reported in patients with postural tachycardia syndrome (POTS). These AAb may contribute to a final common pathway for overlapping disease processes, reflecting a possible autoimmune contribution to POTS pathophysiology. In prior studies, measurement of AAb activity was inferred from costly, low-throughput, and laborious physiological assays. In the present study, we developed and validated an alternative cell-based bioassay for measuring AAb activity in serum by means of pre-treatment with monoamine oxidase (MAO). Methods: A total of 37 POTS patients and 61 sex-matched healthy control participants were included. Serum was pre-treated with MAO to remove endogenous catecholamines that could falsely inflate AR activation by AAb. A receptor-transfected cell-based bioassay was used to detect presence of α1AR-AAb and β1AR-AAb in serum. Results: MAO effectively degraded catecholamines as demonstrated by suppression of norepinephrine-induced α1AR activation in POTS (6.4 ​± ​0.7 vs. 5.5 ​± ​0.9; P ​= ​0.044) and in controls (4.1 ​± ​0.5 vs. 3.9 ​± ​0.6; P ​= ​0.001). Mean activity values were greater in the POTS vs. Controls for α1AR-AAb (6.2 ​± ​1.2 vs. 5.3 ​± ​1.0; P ​

Aneurysms of ascending aorta are rarely seen in pediatric age group. Only few cases with Marfans syndrome have been reported in the literature. Preferred treatment for these children has been the standard Bentall procedure (aortic root replacement with composite graft prosthesis). We report a 4-year-old male child with huge aneurysm of ascending aorta and aortic root dilation with severe aortic regurgitation, having phenotypic features of Loeys-Dietz syndrome type I. He underwent Bentall procedure with a novel modification (medial trap-door technique for coronary reimplantation). Short-term result of this procedure is encouraging and he is asymptomatic for the last 14 months of follow-up.

Introduction: Carbapenems have become one of the last resort of antimicrobials. But in last few years, Carbapenem Resistant Enterobacteriaceae (CRE) have been reported worldwide. Various phenotypic tests have been proposed for detection of carbapenemase activity including the newer modified Carbapenem Inactivation Method (mCIM) as advised by Clinical Laboratory Standard Institute (CLSI) 2017 guidelines. Aim: Detection of CRE from clinical specimens with new mCIM method and its comparative evaluation with phenotypic and genotypic methods. Materials and Methods: Study was conducted between January 2017 and December 2017 at KIMS, Karad. Total 66 CRE, isolated from 1634 clinical specimens and identified by VITEK 2 (Biomerieux, France) were included in the study. Phenotype screening was done by mCIM (CLSI 2017) method and was compared with Modified Hodge test (MHT) and Combined Disc Test (CDT) methods. Klebsiella pneumoniae ATCC BAA-1705 and Klebsiella pneumoniae ATCC BAA-1706 were used as positive and negative controls respectively. Molecular confirmation of these isolates for carbapenemase producing genes blaNDM-1, blaOXA-48, blaKPC was done by multiplex Polymerase Chain Reaction (PCR) study. Results: Klebsiella pneumoniae (n=35) outnumbered the other bacterial species among 66 CRE included in the study. mCIM was positive for 65 (98.48%) out of 66 isolates while MHT and CDT was positive for 50 (75.75%) and 59 (89.39%) of CRE isolates respectively. All the CRE isolates showed presence of at least one carbapenemase producing gene. Conclusion: The mCIM method is simple, less subjective, cost effective, reproducible and most sensitive method and plays important role in detection and prevention of spread of CRE, thereby, reducing morbidity and mortality, especially where there is lack of automation and molecular diagnostic facility.

BackgroundBoth the adrenergic and renin‐angiotensin systems contribute to orthostatic circulatory homeostasis, which is impaired in postural orthostatic tachycardia syndrome (POTS). Activating autoantibodies to the α1‐adrenergic and β1/2‐adrenergic receptors have previously been found in sera from patients with POTS. We hypothesized that patients with POTS might also harbor activating autoantibodies to the angiotensin II type 1 receptor (AT1R) independently of antiadrenergic autoimmunity. This study examines a possible pathophysiological role for AT1R autoantibodies in POTS. Methods and ResultsSerum immunoglobulin G from 17 patients with POTS, 6 patients with recurrent vasovagal syncope, and 10 normal controls was analyzed for the ability to activate AT1R and alter AT1R ligand responsiveness in transfected cells in vitro. Of 17 subjects with POTS, 12 demonstrated significant AT1R antibody activity in immunoglobulin G purified from their serum. No significant AT1R antibody activity was found in the subjects with vasovagal syncope or healthy subjects. AT1R activation by POTS immunoglobulin G was specifically blocked by the AT1R blocker losartan. Moreover, POTS immunoglobulin G significantly shifted the angiotensin II dosage response curve to the right, consistent with an inhibitory effect. All subjects with POTS were positive for one or both autoantibodies to the AT1R and α1‐adrenergic receptor. ConclusionsMost patients with POTS harbor AT1R antibody activity. This supports the concept that AT1R autoantibodies and antiadrenergic autoantibodies, acting separately or together, may exert a significant impact on the cardiovascular pathophysiological characteristics in POTS.

Background: Adolescence is a significant period of human growth and maturation. The reference values are central to the growth monitoring. Aims and Objectives: This study was carried out to develop the mean, standard deviation and percentile curves for height, weight, and BMI of studied population and to compare them with the national and international studies. Material and Methods: A cross-sectional, High School based study was conducted. A total 2025 adolescents (1222 boys and 803 girls) from 8 Tahsils of Satara districts were included in the study. Results: When compared with 1977 NCHS and 2007 WHO reference standards, boys and girls 50th percentile values of height of present study were comparable. th Mean and 50 percentile values of our study were considerably greater than ICMR values at all ages and th th for both the sexes. In the present study 85 and 95 percentile values for boys were comparable with WHO th 2007 reference values. For girls 85 percentile values were comparable with this reference values up to 13.5 years of age. Conclusions: The present physical growth standards can be recommended for monitoring of growth of High School going children from Satara district.