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Abstract The design of optimum filters constitutes a fundamental aspect within the realm of signal processing applications. The process entails the calculation of ideal coefficients for a filter in order to get a passband with a flat response and an unlimited level of attenuation in the stopband. The objective of this work is to solve the FIR filter design problem and to compare the optimal solutions obtained from evolutionary algorithms. The design of optimal FIR low pass (LP), high pass (HP), and band stop (BS) filters is achieved by the utilization of nature-inspired optimization approaches, namely gray wolf optimization ,cuckoo search, particle swarm optimization, and genetic algorithm. The filters are evaluated in terms of their stop band attenuation, pass band ripples, and departure from the anticipated response. In addition, this study compares the optimization strategies applied in the context of algorithm execution time which is achievement of global optimal outcomes for the design of digital finite impulse response (FIR) filters. The results indicate that when the Gray wolf algorithm is applied to the development of a finite impulse response (FIR) filter, it produces a higher level of performance than other approaches, as supported by enhanced design precision, decreased execution time, and achievement of an optimal solution.

Introduction: Endoscopic ultrasound (EUS)-guided lumen-apposing metal stents (LAMS) represent a novel tool in therapeutic endoscopy. However, the presence of LAMS may dissuade surgeons from operations with curative-intent. We report three clinical scenarios with deployment of LAMS in patients that subsequently underwent pancreaticoduodenectomy (PD). Methods: Six patients identified from our IRB-approved pancreas cancer database had EUS-LAMS placement prior to PD. Patient, tumor, treatment-related variables, and outcomes are herein reported. Results: Two patients underwent a LAMS gastrojejunostomy (GJ) for duodenal obstruction. Another patient underwent LAMS choledochoduodenostomy (CDS) for malignant biliary obstruction. In three patients, a LAMS gastrogastrostomy or jejunogastrostomy was deployed post Roux-en-Y gastric bypass (RYGB) for a EUS-directed transgastric ERCP (EDGE) procedure. The hospital length of stay after LAMS placement was 0–3 days without morbidity. Patients subsequently proceeded to either classic PD (n = 5) or PPPD (n = 1). Interval from LAMS insertion to surgery ranged from 28 to 194 days. Mean PD operative time and EBL were 513 minutes and 560 mL, respectively. Post-PD hospital length of stay was 4–17 days. Clavien-Dindo IIIb morbidity required percutaneous drainage of intra-abdominal collections in two patients. In cases involving LAMS-GJ and CDS, the LAMS directly impacted the surgeon's preference not to perform pylorus preservation. Conclusions: In this case series, PD following EUS-LAMS was feasible with acceptable morbidity. Additional studies with larger patient populations are needed to evaluate LAMS as a bridge to PD with curative-intent.

Anupam Trehan, Rachna Anand, Garima Chaudhary, Himanshi Garg, Manoj Kumar Verma Bright Lifecare Pvt. Ltd, Gurugram, Haryana, IndiaCorrespondence: Rachna Anand, Bright Lifecare Pvt. Ltd, The Presidency, Tower B, Second Floor, 46/4, M G Road, Sector-14, Opp. Girls College, Gurgaon, Haryana, 122001, India, Email rachna.anand@brightlifecare.comPurpose: Collagen supplements are rising in the market as collagen has been demonstrated to be an important protein in the human aging process. Also, it is safe and easily absorbed in the body. Hence the aim of this study was to examine the effectiveness and safety of a collagen and antioxidant-rich treatment compared to a placebo in relation to various skin and hair indicators in healthy adult human subjects.Patients and Methods: Forty healthy adult non-pregnant/non-lactating women (aged 38– 50 years) provided their informed consent in writing before their participation. Skin Radiance Collagen (SRC) treatment and a placebo were assessed for efficacy before application on Day 1, and post-application on Days 28 and 56, to measure changes in skin elasticity, hydration, brightness, pigmentation; texture, wrinkles, dryness, smoothness, fine lines, changes in the crow’s feet region; as well as hair strength and hair fall.Results: It was observed after 56 days that therapy with SRC, compared to placebo, produced a substantial effect on reduction of wrinkle depth and fine lines by 48.11% and 39%, respectively, with p-value < 0.01 in the test group. There was a 15.69% improvement in skin hydration observed and 28% reduction in hair fall with p-value < 0.01.Conclusion: SRC, a combination of collagen with hyaluronic acid (HA), biotin, and vitamins C and E, showed a significant improvement in skin and hair health, including improvements in skin elasticity, skin hydration, reduction in crow’s feet area wrinkles and fine lines, hair fall, and decrease in roughness, leading to improved skin texture. Vitamin C in the formulation also acts as a collagen builder for the body and helps in preventing oxidative stress in the body. The test treatment SRC was found to be efficacious and safe in healthy human adult subjects.Keywords: skin hydration, skin roughness, hair fall reduction, crow’s feet wrinkles, skin elasticity

Abstract Systems-level assessments of protein-protein interaction (PPI) network dysfunctions are currently out-of-reach because approaches enabling proteome-wide identification, analysis, and modulation of context-specific PPI changes in native (unengineered) cells and tissues are lacking. Herein, we take advantage of chemical binders of maladaptive scaffolding structures termed epichaperomes and develop an epichaperome-based ‘omics platform, epichaperomics, to identify PPI alterations in disease. We provide multiple lines of evidence, at both biochemical and functional levels, demonstrating the importance of these probes to identify and study PPI network dysfunctions and provide mechanistically and therapeutically relevant proteome-wide insights. As proof-of-principle, we derive systems-level insight into PPI dysfunctions of cancer cells which enabled the discovery of a context-dependent mechanism by which cancer cells enhance the fitness of mitotic protein networks. Importantly, our systems levels analyses support the use of epichaperome chemical binders as therapeutic strategies aimed at normalizing PPI networks.

It is unclear why hemorrhagic myocardial infarctions (hMI) are destined for adverse outcomes. Here, the authors show that hMI drives fatty degeneration of infarct territories and contributes to adverse remodeling of the heart, which can be mitigated via timely depletion of iron within the hMI zone.

Toll-like receptor 4 (TLR4) is an integral factor in the initiation of the innate immune response and plays an important role in cardiovascular diseases such as hypertension and myocardial infarction. Previous studies from our lab demonstrated that central TLR4 blockade reduced cardiac TLR4 expression, attenuated hypertension, and improved cardiac function. However, the contribution of cardiac specific TLR4 to the development of hypertension and cardiac remodeling is unknown. Therefore, we hypothesized that cardiomyocyte specific knockdown of TLR4 would have beneficial effects on hypertension, cardiac hypertrophy, and remodeling. To test this hypothesis, cardiomyocyte-specific TLR4 knockdown (cTLR4KO) mice were generated by crossing floxed TLR4 mice with Myh6-Cre mice, and subjected to angiotensin II (Ang II, 1 µg/kg/min or vehicle for 14 days) hypertension model. Blood pressure measurements using radio telemetry revealed no differences in baseline mean arterial pressure between control littermates and cTLR4KO mice (103 ± 2 vs. 105 ± 3 mmHg, p > 0.05). Ang II-induced hypertension (132 ± 2 vs. 151 ± 3 mmHg, p

Abstract Background Triptans are the first-line option for the acute treatment of migraine attacks; however, triptans are contraindicated in people with certain underlying cardiovascular risk factors and are associated with inadequate efficacy or poor tolerability in some individuals. Ubrogepant is an oral calcitonin gene–related peptide receptor antagonist approved for the acute treatment of migraine. Methods This post hoc analysis of the phase 3 ACHIEVE trials examined the impact of ubrogepant on the Functional Disability Scale (FDS), satisfaction with medication, and Patient Global Impression of Change (PGIC) in participants who were self-reported triptan insufficient responders (TIRs), defined as those who are unable to take triptans due to contraindications, tolerability issues, or insufficient efficacy. Responder definitions for the FDS, satisfaction measures, and PGIC were based on qualitative interpretation of the respective response options for the pooled ubrogepant 50 mg and placebo groups. Results In the pooled analysis population (n = 1799), 451 (25%) participants were TIRs, with most (80%) reporting insufficient efficacy with triptan use. A significantly higher proportion of TIRs treated with ubrogepant vs placebo reported being able to function normally from 2 to 8 h post dose (P

Since tragedies caused by nuclear disasters are always a concern, it is essential that nuclear power plants be monitored on a regular basis for any irregularities in ionising radiation levels. Irrespective of leakage proof measures being deployed in the plant, ensuring the safety of these measures is necessary. Given this scenario, the present study proposes the usage of unmanned aerial vehicles (UAVs) to ensure that radiation levels in nuclear plants remain within safe limits. The UAV deployed will map the entire environment following a unique path planning algorithm and monitor the environment with an onboard radiation sensor. If any irregularities are detected, the positional coordinates are flagged, and the A* algorithm is implemented to generate the shortest path between the starting point, and the flagged coordinates, which are considered as the destination coordinates. The UAV is made to traverse the shortest path together with maintaining stability of the system while traversing.

Background:. Infected Ventricular Assist Device (VAD)–associated wounds are common and associated with significant morbidity and mortality. The efficacy of hardware salvage utilizing flaps and negative pressure wound therapy (NPWT) remains understudied. We hypothesized that patients treated with flaps and/or NPWT would have higher hardware salvage rates compared with other surgical management strategies. Methods:. A meta-analysis study evaluating VAD-associated wounds was performed following PRISMA guidelines. Primary predictor variables were flap-reconstruction (FR), NPWT, no FR, and infection location (mediastinum versus driveline). Primary outcomes were hardware retention (salvage) versus explantation, infection recurrence, or death. Twenty-nine studies were included. Standard statistical methods included logistic regression analysis. Results:. Seventy-four subjects with nonsignificant demographic differences between cohorts were identified. Overall salvage was 59.5% in both driveline and mediastinum cohorts. Overall, NPWT significantly improved salvage compared with no NPWT [77.4% versus 46.5% respectively (P = 0.009)], and FR significantly improved salvage compared with no FR [68.6% versus 39.1% respectively (P = 0.022)]. Logistic regression analysis predicting odds of salvage by FR (area under curve = 0.631) was significantly three times higher (95% CI: 1.2–9.5) and predicting the odds for salvage by NPWT (area under curve = 0.656) was significantly four times higher (95% CI: 1.4–11.1) compared with other treatment. Conclusions:. NPWT or flap reconstruction for treatment of threatened VAD hardware was associated with a significantly improved device salvage compared with other surgical strategies. Further study should focus on subgroup analysis of flaps utilized and synergistic treatment benefits.

Background:. Current treatment for volumetric muscle loss is limited to muscle transfer or acellular collagen scaffold (ACS) therapies that are associated with donor site morbidity and nonfunctional fibrosis, respectively. The aim of this study is to assess the utility of amniotic membrane scaffold (AMS) for volumetric muscle loss treatment. Methods:. Murine quadriceps defects were created and randomized to three groups (n = 5/group): untreated controls, ACS, and AMS. In vivo muscle regeneration volume was quantified by MRI and microcomputed tomography. Muscle explants were analyzed using standard histology and whole-mount immunofluorescence at 8 weeks. Results:. The cross-sectional muscle regeneration ratio was 0.64 ± 0.3 for AMS, 0.48 ± 0.07 for ACS, and 0.4 0 ± 0.03 for controls as assessed by MRI (P = 0.09) and 0.61 ± 0.28 for AMS, 0.50 ± 0.06 for ACS, and 0.43 ± 0.04 for controls as assessed by microcomputed tomography (P = 0.2). Histologically, AMS demonstrated significantly higher cellular density (900 ± 2 70 nuclei/high powered field) than ACS (210 ± 36) and control (130 ± 4) groups (P = 0.05). Immunofluorescence for laminin (AMS 623 ± 11 versus ACS 339 ± 3 versus control 115 ± 7; P < 0.01) and myosin heavy chain (AMS 509 ± 7 versus ACS 288 ± 5 versus control 84 ± 5; P = 0.03) indicated greater organized muscle fiber formation with AMS. Conclusion:. AMS mediated muscle healing was characterized by increased cellular infiltration and organized muscle formation when compared with controls and ACS.

The DIY approach promotes small-scale digital manufacturing for the production of customized, fast moving consumer goods, including powder detergent. In this context, a machine was developed to manufacture a customized detergent according to the needs of the clients indicated on a digital platform connected to the machine. The detergent is produced by a mixing process of the formulation components carried out in a 3D mixer. Analysing the mixing performance of the process is essential to obtain a quality product. In this study, the mixing process of the powder detergent was modelled using the discrete element method. After validating it with experimental test, this model was utilized to study the mixing performance considering the allowable mass fraction range of every formulation component and a mixer speed of 45 rpm, and the dataset generated from this study was employed along with a machine learning algorithm to obtain a model to predict the mixing index. In this sense, twenty-five different combinations of the defined components were simulated and a mixing index of 0.98–0.99 was obtained in a time of 60 s, revealing that all the combinations were completely mixed. In addition, the developed model was validated with results obtained from the DEM model. The model predicts the mixing index in advance and with accuracy.

Background and Purpose: Cerebral small vessel disease (CSVD) markers have not been widely studied in relation to hematoma volume and growth in hypertensive intracerebral hemorrhage (ICH). The objectives to assess the relationship of white matter hyperintense lesions (WMHL), microbleeds (MBs), and cortical siderosis (CSS) with hematoma volume, hematoma expansion (HE), and 3 months outcome in patients with hypertensive ICH. Methods: All consecutive acute hypertensive supratentorial ICH presenting to the emergency were prospectively recruited. Baseline and 24 hours computed tomography (CT) to assess hematoma volume and magnetic resonance imaging (MRI) for CSVD markers were performed in all subjects. WMHL (graded using Fazekas's scale), MBs, and CSS were assessed and compared with baseline variables and outcomes. All the images were assessed by an experienced stroke neurologist/neuroradiologist. Results: One hundred and fifty-seven patients were screened and 60 were included. Mean age was 54.08 ± 11.57 years and 47 (78%) were males. Of 60, 19 (28.1%) had HE, 31 (51.6%) had major bleed (>30 ml), and 28 (47.46%) had poor 3 month outcome (mRS 4-6). On univariate analysis, high grade WMHL was associated with greater HE [odds ratio (OR): 2.65, confidence interval (CI) 1.48–4.72, P = 0.001), greater proportion with volume >30 ml (OR: 7.16, CI: 1.09–47.13, P = 0.001) and poor outcome (OR: 2.1, CI: 0.05–3.27, P = 0.001). MBs were associated with poor outcome (P = 0.029) but not with HE/volume. CSS was related to HE (P = 0.031), a large volume bleed (P = 0.023), and poor outcome (P = 0.021). On multivariate model, only WMHL independently predicted HE (P = 0.034), greater proportion with bleed volume >30 ml (P = 0.041), and poor outcome (P = 0.042). Conclusions: WMHL in MRI serves as a predictor of hematoma expansion, a large volume bleed, and poor outcome in hypertensive ICH and may be incorporated into existing prediction models.

Mammalian cells require iron to satisfy their metabolic needs and to accomplish specialized functions, such as hematopoiesis, mitochondrial biogenesis, energy metabolism, or oxygen transport. Iron homeostasis is balanced by the interplay of proteins responsible for iron import, storage, and export. A misbalance of iron homeostasis may cause either iron deficiencies or iron overload diseases. The clinical work-up of iron dysregulation is highly important, as severe symptoms and pathologies may arise. Treating iron overload or iron deficiency is important to avoid cellular damage and severe symptoms and improve patient outcomes. The impressive progress made in the past years in understanding mechanisms that maintain iron homeostasis has already changed clinical practice for treating iron-related diseases and is expected to improve patient management even further in the future.

There’s a lot of hope for phase change material (PCM) in applications like sustainable energy generation and retrieval of heat loss. Latent heat thermal energy storage (LHTES) systems containing hydrated salt (HS) at minimum-temperature have been the topic of much study, particularly with regards to their thermal behavior and charging-discharging properties. The PCM was prepared by adding sodium acetate trihydrate (SAT), a nucleation agent, and a thickness agent to the test tube. We monitored PCM’s temperature behavior and analyzed its thermal characteristics. Natural convection was the dominant way of heat transmission while the phase change material temperature was over the fusion threshold, whereas conduction was the dominant mode when liquid phase change material formed during the phase transition progression. Heat storage and release efficiency as a function of tube diameter and flow rate was analyzed. Internal stainless-steel fins and aluminium fins of varying thicknesses were added to the tube to increase heat transmission. The shape of the storing tube and fins was shown to have a significant impact on the heat transmission among the thermal fluid and the phase change material. Charging and discharging duration may be cut by 28 % and 25 %, respectively, because to the revised fins shape. Our findings from this study can serve as an experimental foundation for using the minimum-temperature hydrated salt LHTES system.

Gastrointestinal mucormycosis involving ileum is a very rare phenomenon. We present a case of 52-year-old male, known case of diabetes mellitus requiring extracorporeal membrane oxygenation (ECMO) for H1N1 pneumonia with severe acute respiratory distress syndrome (ARDS). The patient had small bowel obstruction with impending perforation requiring emergency bowel resection and ileostomy. The resected bowel segment histopathology showed mucormycosis. He was treated with conventional Amphotericin-B and later changed to Posaconazole. The patient responded very well and was gradually weaned from ventilator and successfully discharged home. This case report highlights rare site of mucormycosis. Early diagnosis and timely intervention can reduce mortality.

Background: Endovenous radiofrequency ablation is gaining popularity as an alternative to conventional surgical treatment of varicose veins. The initial experience with this treatment modality is presented along with review of literature. Methods: A prospective study of 31 consecutive patients with primary great saphenous vein varicosities was undertaken. The procedure was performed under spinal anesthesia using bipolar radiofrequency induced thermotherapy CELON (Olympus) system with continuous pull-back technique. Additionally, multiple stab phlebectomies were performed to deal with tributary varices. Post-operatively; at one, four, twelve and twenty four weeks, the patients were followed up in out-patient department with clinical examination and ultrasound duplex imaging. The occlusion of great saphenous vein trunk, length of residual patent proximal great saphenous vein and improvement in quality of life using revised Venous Clinical Severity Score and Aberdeen Varicose Vein Questionnaire were recorded and analysed using appropriate statistical methods. Results: The mean (SD) age of patients was 41.8 (14.1) years with an average BMI of 23.4 kg/m2. Ten patients had C2 disease, four C3, thirteen C4, and two each; C5 and C6 disease. Average length of great saphenous vein ablated was 41.9 cm with a mean ablation time of 62.3 (18.6) seconds. Post procedure total occlusion rate at 24 weeks follow-up, was 93.1% and the quality of life indices showed a statistically significant improvement. Conclusion: Endovenous radiofrequency ablation holds immense promise as a safe and effective modality for the treatment of varicose veins of lower limbs.

Permanent magnet motor drive is a widely used technology, offering many advantages, such as exceptional speed, torque control and greater flexibility. Improvement of reliability and efficiency has become a great research interest. Towards this direction and taking into account the major developments in permanent machine technology over the recent years, the use of energy recovery converters has been introduced in various industrial applications. In this paper, the effects of harmonics on a three-phase motor controlled by a drive are analysed, and the behaviours of the filter topology after adopting regenerative drives are studied. The main contribution of this study is a methodology to foresee the standards that can be achieved with the use of an active front end system topology with filters. Moreover, the use of an optimum filter that eases the power system distortion is presented. The analysis presented in this paper is validated experimentally.

The continuing cases of COVID-19 due to emerging strains of the SARS-CoV-2 virus underscore the urgent need to develop effective antiviral technologies. A crucial aspect of reducing transmission of the virus is through environmental disinfection. To this end, a nanotechnology-based antimicrobial platform utilizing engineered water nanostructures (EWNS) was utilized to challenge the human coronavirus 229E (HCoV-229E), a surrogate of SARS-CoV-2, on surfaces. The EWNS were synthesized using electrospray and ionization of aqueous solutions of antimicrobials, had a size in the nanoscale, and contained both antimicrobial agents and reactive oxygen species (ROS). Various EWNS were synthesized using single active ingredients (AI) as well as their combinations. The results of EWNS treatment indicate that EWNS produced with a cocktail of hydrogen peroxide, citric acid, lysozyme, nisin, and triethylene glycol was able to inactivate 3.8 logs of HCoV-229E, in 30 s of treatment. The delivered dose of antimicrobials to the surface was measured to be in pico to nanograms. These results indicate the efficacy of EWNS technology as a nano-carrier for delivering a minuscule dose while inactivating HCoV-229E, making this an attractive technology against SARS-CoV-2.

BackgroundIntramyocardial hemorrhage following reperfusion is strongly associated with major adverse cardiovascular events in myocardial infarction (MI) patients; yet the mechanisms contributing to these outcomes are not well understood. Large animal models have been used to investigate intramyocardial hemorrhage, but they are exorbitantly expensive and difficult to use for mechanistic studies. In contrast, rat models are widely used to investigate mechanistic aspects of cardiovascular physiology, but a rat model that consistently recapitulates the characteristics of an hemorrhagic MI does not exist. To bridge this gap, we investigated the physiological conditions of MI that would create intramyocardial hemorrhage in rats so that a reliable model of hemorrhagic MI would become available for basic research.Methods & resultsSprague-Dawley rats underwent either a 90-minute (90-min) ischemia and then reperfusion (I/R) (n = 22) or 30-minute (30-min) I/R (n = 18) of the left anterior descending coronary artery. Sham rats (n = 12) were used as controls. 90-min I/R consistently yielded hemorrhagic MI, while 30-min I/R consistently yielded non-hemorrhagic MI. Twenty-four hours post-reperfusion, ex-vivo late-gadolinium-enhancement (LGE) and T2* cardiac MRI performed on excised hearts from 90-min I/R rats revealed colocalization of iron deposits within the scarred tissue; however, in 30-min I/R rats scar was evident on LGE but no evidence of iron was found on T2* CMR. Histological studies verified tissue damage (H&E) detected on LGE and the presence of iron (Perl's stain) observed on T2*-CMR. At week 4 post-reperfusion, gene and protein expression of proinflammatory markers (TNF-α, IL-1β and MMP-9) were increased in the 90-min I/R group when compared to 30-min I/R groups. Further, transmission electron microscopy performed on 90-min I/R myocardium that were positive for iron on T2* CMR and Perl's stain showed accumulation of granular iron particles within the phagosomes.ConclusionIschemic time prior to reperfusion is a critical factor in determining whether a MI is hemorrhagic or non-hemorrhagic in rats. Specifically, a period of 90-min of ischemia prior to reperfusion can produce rat models of hemorrhagic MI, while 30-minutes of ischemia prior to reperfusion can ensure that the MIs are non-hemorrhagic. Hemorrhagic MIs in rats result in marked increase in iron deposition, proinflammatory burden and adverse left-ventricular remodeling compared to rats with non-hemorrhagic MIs.

Epithelial-to-mesenchymal transition (EMT) and maturation of a fibrillar tumor microenvironment play important roles in breast cancer progression. A better understanding of how these events promote cancer cell migration and invasion could help identify new strategies to curb metastasis. The nucleus and Golgi affect migration in a microenvironment-dependent manner. Nucleus size and mechanics influence the ability of a cell to squeeze through confined tumor microenvironments. Golgi positioning determines front-rear polarity necessary for migration. While the roles of individual attributes of nucleus and Golgi in migration are being clarified, how their manifold features are inter-related and work together remains to be understood at a systems level. Here, to elucidate relationships among nucleus and Golgi properties, we quantified twelve morphological and positional properties of these organelles during fibrillar migration of human mammary epithelial cells. Principal component analysis (PCA) reduced the twelve-dimensional space of measured properties to three principal components that capture 75% of the variations in organelle features. Unexpectedly, nucleus and Golgi properties that co-varied in a PCA model built with data from untreated cells were largely similar to co-variations identified using data from TGFβ-treated cells. Thus, while TGFβ-mediated EMT significantly alters gene expression and motile phenotype, it did not significantly affect the relationships among nucleus size, aspect ratio and orientation with migration direction and among Golgi size and nucleus-Golgi separation distance. Indeed, in a combined PCA model incorporating data from untreated and TGFβ-treated cells, scores of individual cells occupy overlapping regions in principal component space, indicating that TGFβ-mediated EMT does not promote a unique "Golgi-nucleus phenotype" during fibrillar migration. These results suggest that migration along spatially-confined fiber-like tracks employs a conserved nucleus-Golgi arrangement that is independent of EMT state.

Purpose: Recently we reported the use of renal nerve stimulation (RNS) during renal denervation (RDN) procedures. RNS induced changes in blood pressure (BP) and heart rate are not fully delineated yet. We hypothesized that electrical stimulation of the sympathetic nerve tissue in the renal artery would lead to an increase in BP and vagal stimulation would cause a decrease in BP. We report the different patterns of BP and heart rate responses elicited by RNS prior to RDN. Methods: 35 patients with drug-resistant hypertension were included. RNS was performed under general anesthesia at four sites in the right and left renal arteries, both before and immediately after RDN. RNS-induced BP and heart rate changes were monitored. Results: A total of 289 RNS sites in 35 patients were analyzed. An increase in systolic BP of >10 mmHg was regarded as a positive BP response to RNS. This pattern of response was observed in 180 sites (62%). 86 RNS sites (30%) showed an indifferent response with BP changes ≤10 mmHg. At 13 sites (4.5%) RNS elicited a decrease in BP up to −8 mmHg. However, 10 RNS sites (3.5%) showed a pronounced vagal response with hypotension and sinus cycle lengths ranging between 4224–10272 milliseconds. These sites were distributed among two patients. Conclusion: RNS identified sympathetic and parasympathetic nerve tissue in the renal arteries. RNS can be potentially used to map nerve bundles and guide selective ablation of sympathetic nerve fibers and prevent inadvertent ablation of parasympathetic nerve tissue during RDN.

Background: Haiti has the worst malnutrition rate in the Western hemisphere. In October 2010, a cholera epidemic erupted and spread rapidly throughout the country, straining Haiti’s already fragile health infrastructure across all levels of care. This study reviews data from an outpatient therapeutic feeding program (OTP) for acute childhood malnutrition at a clinic in rural Haiti with a focus on the effect of the 2010 cholera epidemic on program operations. Methods: A retrospective chart review was conducted for the complete set of patients who were enrolled in the OTP from its inception in March 2009 through January 2014. Findings: A total of 187 charts were retrieved representing 176 unique patients, of whom 5 were currently enrolled in care. At admission, 96 (51.3%) met criteria for severe acute malnutrition, 88 (47.1%) met criteria for moderate acute malnutrition, and 3 (1.6%) did not meet criteria for acute malnutrition. Of the 182 completed charts, 119 (65.4%) reached their target weight (≥–1 weight-for-height 'z'-score) by discharge (ie, were “cured”), 43 (23.6%) defaulted, 11 (6.0%) were discharged prematurely, 8 (4.4%) died, and 1 (0.5%) was hospitalized. A total of 11 patients (6.3%) who were initially admitted relapsed after discharge and were later readmitted. Data from 170 complete records (93.4%) were included in a multivariate logistic regression. Severe (vs moderate) acute malnutrition was negatively associated with likelihood of being cured when controlling for other patient- and care-related factors (OR = 0.261, 'P' = .002). Average cholera burden was negatively correlated with likelihood of OTP treatment cure when controlling for patient- and care-related variables (OR = 0.859, 'P' = .002) but was insignificant when controlling for year. Conclusions: Results from the study have been used to inform a restructuring of the clinic’s acute malnutrition program toward a more community-centered model of management, the context and implications of which are discussed in relation to the existing literature.

[This corrects the article DOI: 10.1371/journal.pbio.2006145.].

The circadian oscillator is a molecular feedback circuit whose orchestration involves posttranslational control of the activity and protein levels of its components. Although controlled proteolysis of circadian proteins is critical for oscillator function, our understanding of the underlying mechanisms remains incomplete. Here, we report that JmjC domain-containing protein 5 (JMJD5) interacts with CRYPTOCHROME 1 (CRY1) in an F-box/leucine-rich repeat protein 3 (FBXL3)-dependent manner and facilitates targeting of CRY1 to the proteasome. Genetic deletion of JMJD5 results in greater CRY1 stability, reduced CRY1 association with the proteasome, and disruption of circadian gene expression. We also report that in the absence of JMJD5, AMP-regulated protein kinase (AMPK)-induced CRY1 degradation is impaired, establishing JMJD5 as a key player in this mechanism. JMJD5 cooperates with CRY1 to repress circadian locomotor output cycles protein kaput (CLOCK)-brain and muscle ARNT-like protein 1 (BMAL1), thus linking CRY1 destabilization to repressive function. Finally, we find that ablation of JMJD5 impacts FBXL3- and CRY1-related functions beyond the oscillator.

Purpose: We hypothesized that pulmonary vein (PV) orientation influences tissue contact of the contact force (CF) sensing radiofrequency ablation catheter (CFC) and therefore atrial fibrillation (AF) free survival after pulmonary vein isolation (PVI). The aim of this study was to determine the association between PV orientation, CF and AF free survival in patients undergoing CFC PVI. Methods: Sixty consecutive patients undergoing CFC PVI were included. ECG-triggered cardiac CT scans were obtained in all patients before PVI, and the PV orientation was measured at the insertion in the LA for all PVs in both the transverse and frontal plane. PVs were assigned to 1 of 4 orientation groups: ventral–caudal, dorsal–caudal, ventral–cranial and dorsal–cranial. Results: Mean age was 59 years, 88% had paroxysmal AF. AF free survival off anti-arrhythmic drugs after a median follow-up of 12 months was 58% after a single PVI procedure. No association was found between PV orientation and CF. Furthermore, no association was found between PV orientation and AF free survival. In univariate analysis, the number of lesions with a mean CF of 10 g was associated with AF free survival. However, in multivariate analysis, only the AF duration was significantly associated with AF free survival. Conclusions: This study shows that in patients undergoing PVI with the CFC ablation system, PV orientation does not affect CF and is not associated with AF free survival. PV orientation assessment does not appear to be necessary in patients undergoing CFC PVI.

Background: Pulmonary vein isolation (PVI) for atrial fibrillation (AF) is performed with the endoscopically assisted laser balloon ablation system (EAS). We hypothesized that placement of a circular mapping catheter (CMC) in the pulmonary vein (PV) distal to the laser balloon during ablation is feasible and safe. Methods: Out of 58 included patients, 37 underwent mapping-guided EAS PVI, with the CMC inside the PV during laser ablation, and 21 patients underwent standard EAS PVI, with the CMC outside the PV during laser ablation. Results: Mean age was 56 years and 81% had paroxysmal AF. In the mapping-guided ablation group, 91% of PVs were isolated with the CMC in the PV during EAS ablation, isolation was completed in 9% of PVs after the CMC was removed from the PV. After passing a learning curve in 18 patients, a significant drop in unsuccessfully isolated PVs was observed in the mapping guided EAS PVI group (15% to 4%, P = 0.020). No major complications were seen in the mapping-guided EAS PVI group. However, in the standard EAS PVI group, laser ablation was complicated by a temporary phrenic nerve palsy in 1 patient. After a median follow-up of 16.7 months, there was no statistical difference in AF free survival among treatment groups (mapping-guided: 56% vs. 52%, P = 0.875). Conclusion: Mapping guided EAS PVI with a distal CMC in the PV during laser ablation is feasible and seems safe as the standard EAS PVI approach.

Aim: Septal rebound stretch (SRSsept) reflects an inefficient deformation of the septum during systole and is a potential new echocardiographic tool to predict response to Cardiac Resynchronization Therapy (CRT). However, there are only limited data on the potential predictive value of SRSsept on echocardiographic response. We evaluated the predictive value of SRSsept on echocardiographic response to CRT in a large population. Methods and results: A total of 138 consecutive patients with functional class II–IV heart failure who underwent CRT were studied. Echocardiography was performed at baseline and after a mean follow-up period of 22 ± 8 months. Echocardiographic response to CRT was defined as a reduction in LV end-systolic volume ≥15%. Receiver operating characteristic curve analysis was performed to define the optimal cut-off value for SRSsept. Multivariable analyses were performed to adjust for potential confounders. Mean age was 68 ± 8 years (30% female). Mean baseline LV ejection fraction was 26 ± 7%, 51% had ischemic etiology. LBBB or LBBB like morphology was present in 95% of patients. Mean SRSsept was 4.4 ± 3.2%, 56% of patients had SRSsept ≥4%. Ninety six patients (70%) were echocardiographic responders. Baseline SRSsept was significantly higher in responders compared to non-responders (5.1 ± 3.2 vs 3.0 ± 2.7, P 4% independently predicted the response to CRT. Conclusions: Baseline septal rebound stretch is independently associated with echocardiographic response to CRT.