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The article explores the factors associated with applying for and receiving offers for urology training in the UK, focusing on demographic, socioeconomic, and educational aspects. It reveals that while gender was associated with receiving an offer, other factors like age, ethnicity, and socioeconomic status did not impact the likelihood of obtaining a post. The study, based on data from the UK Medical Education Database, highlights the need for diversity and inclusion initiatives in surgical training to create a more diverse senior workforce. [Extracted from the article]

Various fluorescence imaging agents are currently under clinical studies. Despite significant benefits, phototoxicity is a barrier to the clinical translation of fluorophores. Current regulatory guidelines on medication‐based phototoxicity focus on skin effects during sun exposure. However, with systemic and local administration of fluorophores and targeted illumination, there is now possibility of photochemical damage to deeper tissues during intraoperative imaging procedures. Hence, independent knowledge regarding phototoxicity is required to facilitate the development of fluorescence imaging products. Previously, we studied a cell‐free assay for initial screening of reactive molecular species generation from fluorophores. The current work addresses a safety test method based on cell viability as an adjunct and a comparator with the cell‐free assay. Our goal is to modify and implement an approach based on the in vitro 3T3 neutral red uptake assay of the Organization for Economic Co‐Operation and Development Test Guideline 432 (OECD TG432) to evaluate the photocytotoxicity of clinically relevant fluorophores. These included indocyanine green (ICG), proflavine, methylene blue (MB), and IRDye800, as well as control photosensitizers, benzoporphyrin derivative (BPD) and rose bengal (RB). We performed measurements at agent concentrations and illumination parameters used for clinic imaging. Our results aligned with prior studies, indicating photocytotoxicity in RB and BPD and an absence of reactivity for ICG and IRDye800. DNA interactive agents, proflavine and MB, exhibited drug/light dose–response curves like photosensitizers. This study provides evidence and insights into practices useful for testing the photochemical safety of fluorescence imaging products. [ABSTRACT FROM AUTHOR]

While surgical resection is a mainstay of cancer treatment, many tumors are unresectable due to stage, location, or comorbidities. Ablative therapies, which cause local destruction of tumors, are effective alternatives to surgical excision in several settings. Ethanol ablation is one such ablative treatment modality in which ethanol is directly injected into tumor nodules. Ethanol, however, tends to leak out of the tumor and into adjacent tissue structures, and its biodistribution is difficult to monitor in vivo. To address these challenges, this study presents a cutting‐edge technology known as Light‐Activatable Sustained‐Exposure Ethanol Injection Technology (LASEIT). LASEIT comprises a three‐part formulation: (1) ethanol, (2) benzoporphyrin derivative, which enables fluorescence‐based tracking of drug distribution and the potential application of photodynamic therapy, and (3) ethyl cellulose, which forms a gel upon injection into tissue to facilitate drug retention. In vitro drug release studies showed that ethyl cellulose slowed the rate of release in LASEIT by 7×. Injections in liver tissues demonstrated a 6× improvement in volume distribution when using LASEIT compared to controls. In vivo experiments in a mouse pancreatic cancer xenograft model showed LASEIT exhibited significantly stronger average radiant efficiency than controls and persisted in tumors for up to 7 days compared to controls, which only persisted for less than 24 h. In summary, this study introduced LASEIT as a novel technology that enabled real‐time fluorescence monitoring of drug distribution both ex vivo and in vivo. Further research exploring the efficacy of LASEIT is strongly warranted. [ABSTRACT FROM AUTHOR]

Microplastics have been found in large quantities in agricultural soil and now become a major global issue. Different types of microplastic have adverse effects on agricultural soil. The most widely used method for the extraction of microplastics in agricultural soil is the density floatation method by using saturated NaCl solution. This method includes the pre‐digestion of soil samples with H2O2 to remove all the organic matter present in the soil. Different types of microplastic particles were extracted and identified by using ATR‐FTIR viz polypropylene, polybutylene tetrapthalate, polyethylene, polystyrene, and polyethylene tetrapthalate. The crystalline nature of extracted microplastic was checked by employing XRD analytical technique. Floatation with higher density saturated sodium chloride (NaCl) solution recovered approximately 80% MPs from soil. Floatation methods were found to be effective for extracting microplastics from soils. [ABSTRACT FROM AUTHOR]

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The influence of the initial surface roughness of TiAl6V4 samples on the orientation and periodicity of the resulting laser‐induced periodic surface structures (LIPSS), as well as the surface wettability and chemistry is reported here. Before LIPSS fabrication, initial sample surface roughness is adjusted by variations of finial polishing steps with polishing grain sizes of 18.3, 8.4, 5, and 0.5 µm. A 3 × 3 irradiation matrix was defined and lasered on all samples by changing the laser power and distance between consecutive laser scans. The resulting structures were characterized by scanning electron microscopy (SEM), atomic force microscopy, Raman spectroscopy, and contact angle measurements. As a further step, three representative generated structures were chosen to explore their bone implant viability by resazurin assays, alkaline phosphatase activity, and direct SEM imaging of the induced cells (MG63) and bacteria (Escherichia coli and Staphylococcus aureus). Results show that initial surface roughness has big influence on the wettability of the resulting surface, as well as inducing small variations on the orientation of the generated LIPSS. Structures generated with a higher integrated fluence have also shown to enhance cell differentiation while reducing bacterial activity, making them a great candidate for improved bone implant compatibility and durability. [ABSTRACT FROM AUTHOR]

Nearly half of the persons receiving dialysis in the United States are aged 65 years or older. Kidney failure occurs most frequently in older adults, and typically triggers a discussion regarding dialysis treatment. In this Special Article, we describe the journey of Mr. Howard Russell, an older adult who experienced kidney failure and underwent dialysis. Using the experience of Mr. Russell, we illustrate the complexity of dialysis decision‐making, including how disease trajectory and health policy can potentially impede older adults from achieving "what matters." Our intent is to provide guidance regarding these barriers and support to clinicians who are sharing similar journeys with older adults making decisions about dialysis. Based on Mr. Russell's journey, we suggest that when discussing dialysis with an older adult, four points be considered: (1) recognize if dialysis is needed long‐term; (2) understand what matters for the older adult; (3) sync the treatment plan when what matters changes; and (4) set up with resources for kidney failure, which is limited but evolving. [ABSTRACT FROM AUTHOR]

Radiotherapy is an important aspect of oncological treatment in several childhood cancers. However, radiotherapy is known to have numerous side effects, including detrimental effects on growth, neurocognitive impairment, and the development of secondary malignancies. One less studied long‐term side effect of pediatric radiotherapy treatment is chronic pain. While the short‐term toxicities of radiotherapy resolve over a few weeks to months, the chronic pain caused by radiotherapy‐induced tissue damage can significantly affect children's quality of life. As long‐term childhood cancer survivors age into adulthood, they are typically followed up by a wide variety of doctors, not all of whom may be familiar with radiotherapy‐induced chronic pain and its management. The aim of this review is to discuss the various common manifestations of radiotherapy‐related pain in children, as well as ways to identify and manage these. Common radiotherapy‐related side effects leading to chronic pain symptoms include radiation fibrosis, enteritis, dermatitis, lymphedema, neuropathic pain, and effects on bone development. The pathophysiology, evaluation and management of these are briefly summarized in this review. This is followed by an overview of radiotherapy techniques that allow greater sparing of normal tissue, minimizing future painful side effects. Finally, the assessment of pain in children is described, as well as strategies for management, and red flag symptoms that should prompt urgent specialist referral. In conclusion, a good understanding of the long‐term side effects of radiotherapy treatment in children is essential for the various medical professionals that follow‐up the child in the years after treatment. For young children, the evaluation of pain is in itself a challenge, and effects on growth, development, and learning are crucial. For older children, social and psychological factors become increasingly important. As radiation therapy techniques continue to advance, the spectrum and incidence of chronic pain syndromes may change over time. [ABSTRACT FROM AUTHOR]

Objective: To report a case of a woman who continued erenumab for migraine prophylaxis throughout her pregnancy and to review the literature for pregnancy safety data for the calcitonin gene‐related peptide (CGRP) receptor and ligand‐directed therapies currently approved for migraine prophylaxis in the United States. Background: Migraine is a common headache disorder that can be significantly disabling. Many people experiencing migraine seek out preventative therapies to improve their quality of life. Unfortunately, currently approved prophylactic agents may not be safe to use during pregnancy, potentially limiting the use of these agents in women of childbearing potential. As the newest class of prophylactic agents for migraine, CGRP agents have limited pregnancy safety data in humans. Methods: A review of the literature was conducted through the PubMed database using the terms pregnancy and either erenumab, fremanezumab, galcanezumab, eptinezumab, rimegepant, or atogepant. Additional sources of information such as prescribing information, assessment reports submitted to the European Medicines Agency (EMA), and manufacturer data were sought. Results: One case report was found in the literature documenting a human pregnancy with no adverse effects in the baby after exposure to erenumab. However, the last dose was administered in the second week of pregnancy and discontinued thereafter. The evaluation of 92 safety reports describing maternal exposure prior to or during pregnancy to either erenumab, galcanezumab, or fremanezumab was located. Incidence of miscarriage and congenital anomalies appear to be similar to rates in the general population. Conclusions: The use of erenumab during pregnancy in our patient resulted in no known harm to the child. This case is unique in that the mother continued to receive erenumab throughout the pregnancy. Safety data is lacking regarding the use of these agents during pregnancy, despite their frequent use in women of childbearing potential. [ABSTRACT FROM AUTHOR]

In the age of the fourth industrial revolution, the metaverse is creating new waves in the world of internet technology and is promising to provide even better and more immersive ways to interact with other people. Metaverse will further lead to the intertwining of the physical and virtual lives. It will create a virtual environment that allows users to interact in virtual spaces and allow the selling and purchasing of virtual goods. These transformations will pose new challenges and risks for the users, players, and owners of the metaverse platforms. This would require the regulators and policymakers to look closely at the issues such as intellectual property rights (IPRs). The main objective of this study is to research the opportunities and challenges that the metaverse will present for IPRs and to examine the IPRs issues related to the metaverse in the Indian context. [ABSTRACT FROM AUTHOR]

The benefits of contrast‐enhancing imaging probes have become apparent over the past decade. However, there is a gap in the literature when it comes to the assessment of the phototoxic potential of imaging probes and systems emitting visible and/or near‐infrared radiation. The primary mechanism of fluorescent agent phototoxicity is thought to involve the production of reactive molecular species (RMS), yet little has been published on the best practices for safety evaluation of RMS production levels for clinical products. We have proposed methods involving a cell‐free assay to quantify singlet oxygen [(SO) a known RMS] generation of imaging probes, and performed testing of Indocyanine Green (ICG), Proflavine, Methylene Blue, IR700 and IR800 at clinically relevant concentrations and radiant exposures. Results indicated that SO production from IR800 and ICG were more than two orders of magnitude below that of the known SO generator Rose Bengal. Methylene Blue and IR700 produced much higher SO levels than ICG and IR800. These results were in good agreement with data from the literature. While agents that exhibit spectral overlap with the assay may be more prone to errors, our tests for one of these agents (Proflavine) appeared robust. Overall, our results indicate that this methodology shows promise for assessing the phototoxic potential of fluorophores due to SO production. [ABSTRACT FROM AUTHOR]

Genetic counselors, like many other healthcare providers, play a vital role in genomic health care. As a profession, we, along with our colleagues and students, have recognized the need to improve and incorporate diversity, equity, inclusion, and justice (DEIJ) within our daily ways of practice to help create access to genomic technologies. In order to create systemic change and focus on unity, open communication, and transparency, we introduce a suggested framework called ERA (Education, Recruitment, Retainment, Research, and Active Outreach). This framework would benefit a genetic counselor throughout various stages of their career, from student to practicing genetic counselor, and can be broadly applied to all specialties of genomic medicine. Different iterations of DEIJ efforts have arisen in the National Society of Genetic Counselors (NSGC), from the D&I (Diversity and Inclusion) Task Force to the J.E.D.I (justice, equity, diversity, and inclusion) committee. The lack of recorded history of these previous efforts and the lack of communication between current DEIJ organizations is one of the many reasons the ERA framework demands unity and transparency to achieve sustainable positive change. Genetic counselors must unite and work collaboratively to conduct and promote DEIJ efforts, so the benefits of genomic medicine can be realized by all. [ABSTRACT FROM AUTHOR]

Introduction: We sought to examine a magnetic resonance imaging (MRI)‐based marker of neurodegeneration from the AT(N) (amyloid/tau/neurodegeneration) framework among a multi‐ethnic, community‐dwelling cohort. Methods: Community‐dwelling Mexican Americans and non‐Hispanic White adults and elders were recruited. All participants underwent comprehensive assessments including an interview, functional exam, clinical labs, informant interview, neuropsychological testing and 3T MRI of the brain. A neurodegeneration MRI meta‐region of interest (ROI) biomarker for the AT(N) framework was calculated. Results: Data were examined from n = 1305 participants. Mexican Americans experienced N at significantly younger ages. The N biomarker was significantly associated with cognitive outcomes. N was significantly impacted by cardiovascular factors (e.g., total cholesterol, low‐density lipoprotein) among non‐Hispanic Whites whereas diabetes (glucose, HbA1c, duration of diabetes) and sociocultural (household income, acculturation) factors were strongly associated with N among Mexican Americans. Discussion: The prevalence, progression, timing, and sequence of the AT(N) biomarkers must be examined across diverse populations. [ABSTRACT FROM AUTHOR]

Hydrogels are polymeric materials widely used in medicine due to their similarity with the biological components of the body. Hydrogels are biocompatible materials that have the potential to promote cell proliferation and tissue support because of their hydrophilic nature, porous structure, and elastic mechanical properties. In this work, we demonstrate the microwave‐assisted synthesis of three molecular weight varieties of poly(ethylene glycol) dimethacrylate (PEGDMA) with different mechanical and thermal properties and the rapid photo of them using 1‐hydroxy‐cyclohexyl‐phenyl‐ketone (Irgacure 184) as UV photoinitiator. The effects of the poly(ethylene glycol) molecular weight and degree of acrylation on swelling, mechanical, and rheological properties of hydrogels were investigated. The biodegradability of the PEGDMA hydrogels, as well as the ability to grow and proliferate cells, was examined for its viability as a scaffold in tissue engineering. Altogether, the biomaterial hydrogel properties open the way for applications in the field of regenerative medicine for functional scaffolds and tissues. [ABSTRACT FROM AUTHOR]

Gelatin and chitosan polysaccharides were chemically modified to get methacrylate functionality to obtain biocompatible hydrogels for use as tissue engineering scaffolds. The methacrylation reaction was verified by 1H‐NMR. The degree of methacrylation was varied from 7% to 40% by changing the molar ratio of polysaccharide to methacrylic anhydride and the type of polysaccharide utilized. After the modification, polysaccharide‐based hydrogels were prepared by free‐radical polymerization in the presence of UV light and Irgacure 184 as a photoinitiator. The physical, chemical, and mechanical performances of the hydrogels were further characterized. Also, the biodegradability and the viability of the polysaccharide hydrogels were investigated using fibroblast cells. These cells were seeded directly onto the hydrogel surface, populated the entirety of the hydrogel, and remained viable for up to 1 week. Altogether, the modified polysaccharides exhibit the properties which make them crucial for applications in the field of regenerative medicine. [ABSTRACT FROM AUTHOR]

In the pre‐COVID period, the restaurant industry had significantly grown in India in the past decade due to rapid urbanization and modernization. In the post‐COVID period, the small restaurant entrepreneurs are fighting for their survival due to the lack of funds, a shift in the consumers' behaviour and perception, and negative cash flows. It has led to the closure of restaurants, loss of employment, and adversely affected the allied industries. The small restaurant entrepreneurs are exploring some new opportunities amid the crisis and adopting innovative approaches, technological and digital interventions to meet the consumers' need for a contact‐less dining experience. However, a joint effort on the part of entrepreneurs and government bodies will facilitate and fuel the restaurant industry's growth again. [ABSTRACT FROM AUTHOR]

Image fusion has emerged as a major area of research in the past few decades due to its extended applications. While progressing in the field of image fusion, a large number of techniques‐based image transforms and spatial filters have been devised for both general and specific sets of images. The primary criterion of image fusion technique is to deliver high‐quality visual perception besides giving a considerable objective evaluation rate. In this study, an information fusion rate‐based study is done on recent, most researched, and high‐performing state‐of‐the‐art techniques using visible and infrared image datasets. These techniques have been chosen carefully, owing to their superiority in performance on both objective and subjective scales of evaluation and have been discussed in terms of their respective advantages and disadvantages. It is clearly evident that some rather primitive techniques can perform well as well as techniques based on a hybrid of various domains can significantly boost the information fusion rate. [ABSTRACT FROM AUTHOR]

Image fusion in neuro diagnosis is intimidating due to its complexity. The heterogeneous natures of the original brain images make intermodal transmission difficult during fusion. Medical image fusion using complementary modalities results in loss of vital salient information. Poor fusion, colour deficiencies result due to similar processing for both the modalities. A dual technique is proposed using discrete fractional wavelet transform (FRWT) and non‐subsampled directional filter banks for better extraction of salient image elements for improved diagnosis. The sparsity character of the coefficients FRWT is controlled by optimising the parity operator using Grey Wolf optimisation algorithm. Four sets of neurological multimodal magnetic resonance imaging and single photon emission computed tomography (CT) brain images are used from benchmark database for validation. The objective evaluation has been conducted using five metrics. The main values obtained from objective metrics based on the proposed technique are 6.3213 for Shannon entropy, mutual information is computed to be 2.7582, fusion factor is 1.9095, standard deviation is 0.1310, and edge strength is 0.76122 indicating improved diagnostic information and superior image quality. Subjective evaluation by a medico validates the findings with finer visual output and enhanced contrast in comparison with recent and state‐of‐the‐art methods. [ABSTRACT FROM AUTHOR]

He underwent surgical drainage of the abscess, and both blood and abscess cultures grew I Streptococcus intermedius i . Through this case, we wish to highlight the importance of maintaining good personal hygiene in adolescents to prevent deep-seated life-threatening infections such as brain abscesses. Brain abscess is a rare life-threatening infection in children. [Extracted from the article]

Squamous cell carcinoma (SCC) is the most common periocular cancer in horses and the second most common tumor of the horse overall. A missense mutation in damage-specific DNA-binding protein 2 (DDB2, c.1012 C>T, p.Thr338Met) was previously found to be strongly associated with ocular SCC in Haflinger and Belgian horses, explaining 76% of cases across both breeds. To determine if this same variant in DDB2 contributes to risk for ocular SCC in the Arabian, Appaloosa, and Percheron breeds and to determine if the variant contributes to risk for oral or urogenital SCC, histologically confirmed SCC cases were genotyped for the DDB2 variant and associations were investigated. Horses with urogenital SCC that were heterozygous for the DDB2 risk allele were identified in the Appaloosa breed, but a significant association between the DDB2 variant and SCC occurring at any location in this breed was not detected. The risk allele was not identified in Arabians, and no Percherons were homozygous for the risk allele. High-throughput sequencing data from six Haflingers were analyzed to ascertain if any other variant from the previously associated 483 kb locus on ECA12 was more concordant with the SCC phenotype than the DDB2 variant. Sixty polymorphisms were prioritized for evaluation, and no other variant from this locus explained the genetic risk better than the DDB2 allele (P=3.39×10−17, n=118). These data provide further support of the DDB2 variant contributing to risk for ocular SCC, specifically in the Haflinger and Belgian breeds. [ABSTRACT FROM AUTHOR]

Keywords: virtual; conference; trainee; feedback EN virtual conference trainee feedback 263 265 3 02/09/21 20210201 NES 210201 Almost all medical conferences in 2020 were cancelled or converted to a virtual format. Free-text answers gave richer details on this outcome with trainees describing the conference as "less intimidating... due to it being trainee led", "easier to attend", but with "less opportunity to network" or "no networking" (Table 1). Further analysis of virtual conferences and trainee perspectives in general are necessary to gain a better understanding of trainee perspectives and to inform future conference design. [Extracted from the article]

Summary: The Functional Annotation of Animal Genomes (FAANG) project aims to identify genomic regulatory elements in both sexes across multiple stages of development in domesticated animals. This study represents the first stage of the FAANG project for the horse, Equus caballus. A biobank of 80 tissue samples, two cell lines and six body fluids was created from two adult Thoroughbred mares. Ante‐mortem assessments included full physical examinations, lameness, ophthalmologic and neurologic evaluations. Complete blood counts and serum biochemistries were also performed. At necropsy, in addition to tissue samples, aliquots of serum, ethylenediaminetetraacetic acid (EDTA) plasma, heparinized plasma, cerebrospinal fluid, synovial fluid, urine and microbiome samples from all regions of the gastrointestinal and urogenital tracts were collected. Epidermal keratinocytes and dermal fibroblasts were cultured from skin samples. All tissues were grossly and histologically evaluated by a board‐certified veterinary pathologist. The results of the clinical and pathological evaluations identified subclinical eosinophilic and lymphocytic infiltration throughout the length of the gastrointestinal tract as well as a mild clinical lameness in both animals. Each sample was cryo‐preserved in multiple ways, and nuclei were extracted from selected tissues. These samples represent the first published systemically healthy equine‐specific biobank with extensive clinical phenotyping ante‐ and post‐mortem. The tissues in the biobank are intended for community‐wide use in the functional annotation of the equine genome. The use of the biobank will improve the quality of the reference annotation and allow all equine researchers to elucidate unknown genomic and epigenomic causes of disease. [ABSTRACT FROM AUTHOR]

Summary: Squamous cell carcinoma (SCC) is the most common cancer affecting the equine eye, with a higher incidence documented in Haflinger horses. Recently, a missense variant in the gene damage specific DNA binding protein 2 (DDB2, p.Thr338Met) on ECA12 was identified as a risk factor for the development of limbal SCC in Haflinger horses. SCC also occurs on the nictitating membrane; therefore, investigating the role of this missense variant in nictitating membrane SCC is warranted. In this study, a common ancestor was identified among Haflinger horses affected with limbal SCC or with nictitating membrane SCC, thus supporting a recessive risk factor for the development of cancer at both ocular locations. Analysis of genotype data from Haflinger horses with and without nictitating membrane SCC revealed that the same region on ECA12 associated with limbal SCC was also associated with nictitating membrane SCC (P < 2.04 × 10−5). Fine mapping of this locus using 25 cases and 49 controls supported the hypothesis that DDB2:c.1013C>T, p.Thr338Met, is a risk factor for nictitating membrane SCC, as 88% of our cases were homozygous for this variant and no other polymorphism was more strongly associated (P = 4.13 × 10−14). These data indicate that the genetic risk is the same for the development of both limbal and nictitating membrane SCC in Haflinger horses and validates utilization of genetic testing of the DDB2 variant for both clinical management and the guidance of mating decisions. [ABSTRACT FROM AUTHOR]

Ciliopathies, a growing pleotropic class of diseases due to mutations in genes that play an important role in primary cilia function. These highly conserved organelles are key to cell signaling. We now know, that mutations in one gene may lead to more than one ciliopathy phenotype and that one ciliopathy phenotype may be due to mutations in more than one gene. We studied the case of a female child with a novel ciliopathy phenotype and identified two novel mutations in the gene IFT80. Previously, mutations in IFT80 have been associated with a very narrow rib cage and failure of the lungs. Bone anomalies are also part of this IFT80‐condition but with no vision problems documented. Our case had none of the features known to be associated with IFT80 mutations and had retinal degeneration (RD). This work broadens the IFT80‐phenotype spectrum and also shows RD can be a feature of many ciliopathies. [ABSTRACT FROM AUTHOR]

Sign language recognition system classifies signs made by hand gestures. An adequate number of features are required to represent the shape variations of sign language. As compared to individual feature set, a combination of features can be effective due to the fact that a particular feature set represents different shape information. A simple concatenation results in large feature vector size and increases the classification computational complexity. Discriminant correlation analysis (DCA)-based unimodal feature-level fusion has been applied on uniform as well as complex background Indian sign language datasets. DCA is a feature-level fusion technique that takes into account the class associations while combining the feature sets. It maximises the inter-class separability of two feature sets and also minimises the intra-class separability while performing the feature fusion. The objective of DCA-based unimodal feature fusion technique is to combine different feature sets into a single feature vector with more discriminative power. The performance of proposed framework is compared with individual orthogonal moment-based feature sets and canonical correlation analysis (CCA)-based feature fusion technique. Results show that in comparison to individual features and CCA-based fused features, DCA is an effective technique in terms of improved accuracy, reduced feature vector size and smaller classification time. [ABSTRACT FROM AUTHOR]

Abstract: Background & Aims: Cholestatic liver injury is mediated by bile acid‐induced inflammatory responses. We hypothesized that superior therapeutic effects might be achieved by combining treatments that reduce the bile acid pool size with one that blocks inflammation. Methods: Bile duct‐ligated (BDL) rats and Mdr2(Abcb4)−/− mice were treated with all‐trans retinoic acid (atRA), a potent inhibitor of bile acid synthesis, 5 mg/kg/d by gavage, or Cenicriviroc (CVC), a known antagonist of CCR2 and CCR5, 50 mg/kg/d alone or in combination for 14 days and 1 month respectively. Results: All‐trans retinoic acid alone reduced bile acid pool size and liver necrosis in BDL rats. However, the combination with CVC further reduced liver to body weight ratio, bile acid pool size, plasma liver enzyme, bilirubin, liver necrosis and fibrosis when compared to the atRA treatment. The assessment of hepatic hydroxyproline content further confirmed the reduced liver injury concurrent with reduction of pro‐inflammatory cytokines emphasizing the synergistic effects of these two agents. Profiling of hepatic inflammatory cells revealed that combination therapy reduced neutrophils and T cells but not macrophages. The superior therapeutic effects of combination treatment were also confirmed in Mdr2−/− mice where a significant reduction in plasma liver enzymes, bilirubin, liver fibrosis, bile duct proliferation and hepatic infiltration of neutrophils and T cells and expression of cytokines were found. Conclusions: Multitargeted therapy is an important paradigm for treating cholestatic liver injury. The combination of CVC with atRA or other FXR activators may warrant a clinical trial in patients with cholestatic liver disease. [ABSTRACT FROM AUTHOR]

Accurate muscular force estimation (from upper arm muscles) based on surface electromyogram forms an important issue in upper limb prosthetic design applications. The whole system consists of surface electrodes, signal acquisition protocols, and signal conditioning at different levels. Labview soft scope was used to acquire the surface electromyogram signal from the designed hardware. The study is concerned with the estimation of characteristics of recorded signals, and for that, statistical techniques of PCA were exercised for verifying the effectiveness of the processed signal against different upper arm motions before its classification. Thereafter, artificial neural network classifier was implemented for the classification surface electromyogram signals with best classification rate of 89.30%. Finally, the processing technique was used to significantly ( p < .05) improve classification rate, without much loss of information. [ABSTRACT FROM AUTHOR]

Objectives: An association between isolated, increased nuchal translucency thickness (NT) and pathogenic findings on chromosomal microarray analysis (CMA) has been reported. A recent meta-analysis reported that most studies use a NT cut-off value of 3.5 mm. However, considering NT distribution and the commonly accepted 5% false-positive rate in maternal serum screening, NT cut-off levels should be reconsidered. The aim of this study was to assess different NT cut-off levels as indication for CMA and to determine whether CMA should be recommended for mildly increased NT of 3.0-3.4 mm.Methods: This was a retrospective, multicenter study of singleton pregnancies with CMA results and either normal NT and no other finding or with increased NT as the only medical indication for CMA at the time of an invasive procedure (increased NT was considered an isolated finding in cases of advanced maternal age). Women with normal fetal NT who underwent CMA did so at their own request. A single laboratory performed all genetic analyses. Comparative genomic hybridization microarray analysis or single nucleotide polymorphism array technology was used for CMA. If combined first-trimester screening (NT and biochemistry) indicated increased risk for common aneuploidies, the case was excluded. NT was used to divide cases into three groups (≤ 2.9 mm, 3.0-3.4 mm and ≥ 3.5 mm) and their CMA results were compared.Results: CMA results were recorded in 1588 pregnancies, among which 770 fetuses had either normal NT with no other finding or isolated increased NT. Of these, 462 had NT ≤ 2.9 mm, 170 had NT of 3.0-3.4 mm and 138 had NT ≥ 3.5 mm. Pathogenic copy number variants were found in 1.7%, 6.5% and 13.8% of cases, respectively.Conclusion: Our results suggest that CMA should be recommended when fetuses have isolated, mildly increased NT (3.0-3.4 mm). Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the association between aberrant right subclavian artery (ARSA), with or without additional risk factors for aneuploidy or ultrasound abnormality, and results of chromosomal microarray analysis (CMA).Methods: This was a multicenter study of fetuses diagnosed with ARSA that underwent genetic analysis by CMA, all samples being analyzed in the same laboratory. Clinical investigation included nuchal translucency measurement, first- and second-trimester maternal serum screening, early and late second-trimester fetal anatomy scans and fetal echocardiography. Comparative genomic hybridization microarray analysis or single-nucleotide polymorphism array technology was used for CMA of DNA samples obtained from amniotic fluid.Results: CMA results were available for 63 fetuses with ARSA. In 36 fetuses, ARSA was an isolated finding, and no pathogenic variant was found. Additional ultrasound findings and/or risk factors for aneuploidy were present in 27 fetuses, five of which had pathogenic CMA results. Of these five, trisomy 21 was detected in a fetus with echogenic intracardiac focus (EIF), 22q11 deletion was detected in a fetus with EIF and an increased risk of trisomy 21 of 1:230 from maternal serum screening, 22q11 duplication was detected in a fetus with hypoplastic right kidney and choroid plexus cyst and 22q11 deletion was detected in a fetus with right aortic arch and clubfoot. The fifth fetus had increased nuchal translucency thickness (4 mm) and a ventricular septal defect, and CMA identified both 22q11 deletion and 1q21 duplication.Conclusions: In fetuses with isolated ARSA, an invasive procedure for CMA is not indicated. However, CMA is recommended when additional ultrasound abnormalities or risk factors for aneuploidy are observed. The chromosomal findings in four of the five cases with an abnormal CMA result in our study would not have been detected by standard fetal chromosomal testing. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Respiratory syncytial virus (RSV) causes severe acute lower respiratory tract disease leading to numerous hospitalizations and deaths among the infant and elderly populations worldwide. There is no vaccine or a less effective drug available against RSV infections. Natural RSV infection stimulates the Th1 immune response and activates the production of neutralizing antibodies, while earlier vaccine trials that used UV-inactivated RSV exacerbated the disease due to the activation of the allergic Th2 response. With a focus on Th1 immunity, we developed a DNA vaccine containing the native RSV fusion (RSV F) protein and studied its immune response in BALB/c mice. High levels of RSV specific antibodies were induced during subsequent immunizations. The serum antibodies were able to neutralize RSV in vitro. The RSV inhibition by sera was also shown by immunofluorescence analyses. Antibody response of the RSV F DNA vaccine showed a strong Th1 response. Also, sera from RSV F immunized and RSV infected mice reduced the RSV infection by 50% and 80%, respectively. Our data evidently showed that the RSV F DNA vaccine activated the Th1 biased immune response and led to the production of neutralizing antibodies, which is the desired immune response required for protection from RSV infections. [ABSTRACT FROM AUTHOR]

Objectives: Despite similar mandibular growth to that of humans, pigs lack a chin projection as shown in most humans. To understand whether this divergence is contributed to differences in local symphyseal growth, this project characterized bone modeling activities at the symphyseal surfaces of juvenile pigs.Material and Methods: Symphyseal specimens from two age groups (4- and 6-month-old, n = 10) were processed into histological sections with and without decalcification, which were assessed for surface mineral apposition and bone resorption, respectively. In a blinded fashion, measurements of four parameters (MAR: mineral apposition rate, MAZ: mineral apposition zone, ES/BS: eroded surface and OC.N/BS: osteoclast number) were obtained and tested by a multivariate two-way mixed-model analyses of variance (manova) for the differences between symphyseal regions and ages.Results: Qualitatively, pig symphyseal labial and lingual surfaces were horizontally oriented and characterized by mineral apposition and bone resorption, respectively. Quantitatively, labial mineral apposition tended to be greater rostrally than caudally at 4 months, which became greater caudally than rostrally at 6 months (region/age interactions: p = 0.127 for MAR, p = 0.012 for MAZ). Lingual bone resorption tended to be greater caudally than rostrally, but only ES/BS measurements were significant (p = 0.039) regardless of age, while OC.N/BS measurements varied with ages and regions (age/region interaction, p = 0.087).Conclusions: Insufficient differential in symphyseal surface modeling between the labial-caudal and labial-rostral regions contributes to the lack of chin projection in the pig. [ABSTRACT FROM AUTHOR]

It is increasingly recognised that phenotypic plasticity, apparently driven by epigenetic mechanisms, plays a key role in tumour behaviour and markedly influences the important processes of therapeutic survival and metastasis. An important source of plasticity in malignancy is epithelial-to-mesenchymal transition (EMT), a common epigenetically controlled event that results in transition of malignant cells between different phenotypic states that confer motility and enhance survival. In this review, we discuss the importance of phenotypic plasticity and its contribution to cellular heterogeneity in oral squamous cell carcinoma with emphasis on aspects of drug resistance and EMT. [ABSTRACT FROM AUTHOR]

Structured Abstract Objectives 1) To determine the concordance among surgeons on subjective assessments of nasolabial esthetics in children with repaired cleft lip; and 2) to evaluate longitudinal changes in nasolabial esthetics in relation to cleft lip revision surgery. Setting and Sample Population School of Dentistry at University of North Carolina, Chapel Hill. Children with repaired unilateral cleft lip: 32 had lip revision surgery and 27 did not have surgery. Materials and Methods Retrospective observational study from a non-randomized clinical trial. Ratings of nasolabial esthetics performed by six surgeons using the Asher-McDade scale at baseline and 12-month follow-up. Results Concordance among surgeons ranged from poor to acceptable. Nasolabial ratings at follow-up were better in the Revision group than in the Non-Revision group, although differences were small. The most prevalent change in the Revision Group was improvement in one or more units on the scale, while 'no change' was most prevalent in the Non-Revision group. Participants in the Revision group were more likely to receive a 'no' in relation to the need for lip or nose revision at the follow-up visit. Conclusion There were mild esthetic improvements observed in relation to lip revision surgery, which should be interpreted with caution given the subjectivity of the rating method used. [ABSTRACT FROM AUTHOR]

Spinocerebellar ataxia-1 (SCA1) is a neurodegenerative disease that primarily targets Purkinje cells (PCs) of the cerebellum. The exact mechanism of PC degeneration is unknown, however, it is widely believed that mutant ataxin-1 becomes toxic because of the phosphorylation of its serine 776 (S776) residue by cAMP-dependent protein kinase A (PKA). Therefore, to directly modulate mutant ATXN1 S776 phosphorylation and aggregation, we designed a therapeutic polypeptide to inhibit PKA. This polypeptide comprised of a thermally responsive elastin-like peptide (ELP) carrier, which increases peptide half-life, a PKA inhibitory peptide (PKI), and a cell-penetrating peptide (Synb1). We observed that our therapeutic polypeptide, Synb1-ELP-PKI, inhibited PKA activity at concentrations similar to the PKI peptide. Additionally, Synb1-ELP-PKI significantly suppressed mutant ATXN1 S776 phosphorylation and intranuclear inclusion formation in cell culture. Further, Synb1-ELP-PKI treatment improved SCA1 PC morphology in cerebellar slice cultures. Furthermore, the Synb1-ELP peptide carrier crossed the blood-brain barrier and localized to the cerebellum via the i.p. or intranasal route. Here, we show the intranasal delivery of ELP-based peptides to the brain as a novel delivery strategy. We also demonstrate that our therapeutic polypeptide has a great potential to target the neurotoxic S776 phosphorylation pathway in the SCA1 disease. [ABSTRACT FROM AUTHOR]

For robots operating in outdoor environments, a number of factors, including weather, time of day, rough terrain, high speeds, and hardware limitations, make performing vision-based simultaneous localization and mapping with current techniques infeasible due to factors such as image blur and/or underexposure, especially on smaller platforms and low-cost hardware. In this paper, we present novel visual place-recognition and odometry techniques that address the challenges posed by low lighting, perceptual change, and low-cost cameras. Our primary contribution is a novel two-step algorithm that combines fast low-resolution whole image matching with a higher-resolution patch-verification step, as well as image saliency methods that simultaneously improve performance and decrease computing time. The algorithms are demonstrated using consumer cameras mounted on a small vehicle in a mixed urban and vegetated environment and a car traversing highway and suburban streets, at different times of day and night and in various weather conditions. The algorithms achieve reliable mapping over the course of a day, both when incrementally incorporating new visual scenes from different times of day into an existing map, and when using a static map comprising visual scenes captured at only one point in time. Using the two-step place-recognition process, we demonstrate for the first time single-image, error-free place recognition at recall rates above 50% across a day-night dataset without prior training or utilization of image sequences. This place-recognition performance enables topologically correct mapping across day-night cycles. [ABSTRACT FROM AUTHOR]

Butanol and hexane leaves extracts of Parkinsonia aculeata L. (Fabaceae) were assessed for its antioxidant potential by in vitro methods. Phytochemical analysis and antioxidant activity of plant extracts were studied using different in vitro assays. UPLC analysis of extracts was carried out for the identification of chemical constituents. The total phenolic contents of the butanol and hexane leaf extract were 42mgGAE/g and 34mgGAE/g whereas flavonoid contents of these extracts were found to be 0.044mgRE/g and 0.005mgRE/g, respectively. Among both extracts, butanol extract shows maximum inhibition (%) of 93.88%, 80.02%, 52.06%, 94.68%, and 69.37% in DPPH, non-site-specific and site-specific, FTC, and TBA assays and absorbance of 0.852 and 0.522 in reducing power and CUPRAC assay at the highest concentration tested. The FRAP and TAC values of butanol extract were found to be 678 μM Fe(II)/g and 36mgAAE/100mg. UPLC analysis of extracts revealed the presence of various polyphenols. The tested plant extracts were found to possess potent antioxidant and free radical scavenging activity which may be due to the presence of flavonoids and polyphenols. [ABSTRACT FROM AUTHOR]

Respiratory syncytial virus (RSV) primarily causes bronchiolitis and pneumonia in infants. In spite of intense research, no safe and effective vaccine has been developed yet. For understanding its pathogenesis and development of anti-RSV drugs/therapeutics, it is indispensable to study the RSV-host interaction. Although, there are limited studies using electron microscopy to elucidate the infection process of RSV, to our knowledge, no study has reported the morphological impact of RSV infection using atomic force microscopy. We report the cytoplasmic and nuclear changes in human epidermoid cell line type 2 using atomic force microscopy. Human epidermoid cell line type 2 cells, grown on cover slips, were infected with RSV and fixed after various time periods, processed and observed for morphological changes using atomic force microscopy. RSV infected cells showed loss of membrane integrity, with degeneration in the cellular content and cytoskeleton. Nuclear membrane was disintegrated and nuclear volume was decreased. The chromatin of the RSV infected cells was condensed, progressing towards degeneration via pyknosis and apoptosis. Membrane protrusions of ∼150-200 nm diameter were observed on RSV infected cells after 6 h, suggestive of prospective RSV budding sites. To our knowledge, this is the first study of RSV infection process using atomic force microscopy. Such morphological studies could help explore viral infection process aiding the development of anti-RSV therapies. [ABSTRACT FROM AUTHOR]

Increasing demand for genetic services has resulted in the need to evaluate current service delivery models (SDMs) and consider approaches that improve access to and efficiency of genetic counseling (GC). This study aimed to describe SDMs currently used by the GC community. The NSGC membership was surveyed regarding the use of four SDMs: in-person GC, telephone GC, group GC, and telegenetics GC. Variables related to access and components of use were also surveyed, including: appointment availability, time-per-patient, number of patients seen, billing, and geographic accessiblity. Seven hundred one usable responses were received. Of these, 54.7 % reported using an in-person SDM exclusively. The remainder (45.3 %) reported using multiple SDMs. Telephone, group and telegenetics GC were used often or always by 8.0 %, 3.2 % and 2.2 % of respondents, respectively. Those using an in-person SDM reported the ability to see the highest number of patients per week ( p < 0.0001) and were the most likely to bill in some manner ( p < 0.0001). Those using telegenetic and telephone GC served patients who lived the furthest away, with 48.3 % and 35.8 %% respectively providing GC to patients who live >4 h away. This study shows that genetic counselors are incorporating SDMs other than traditional in-person genetic counseling, and are utilizing more than one model. These adaptations show a trend toward shorter wait time and shorter length of appointments. Further study is indicated to analyze benefits and limitations of each individual model and factors influencing the choice to adopt particular models into practice. [ABSTRACT FROM AUTHOR]

Objectives To evaluate exclusion of persons with cognitive impairment from research in geriatrics by determining its frequency, method, and rationale and treatment in the resulting publications. Design All original research articles published in 2008 and 2009 in the Journal of the American Geriatrics Society (n = 434) were reviewed using a structured data collection tool. Setting The Journal of the American Geriatrics Society. Participants There were no participants in this study. Measurements Data captured included recruitment method, explicit criterion for exclusion of persons with cognitive impairment, justification of exclusion criterion, reason given for exclusion, percentage of individuals excluded, and mention of exclusion as a possible limitation. Results Of 434 articles examined, 16% used recruitment methods likely to reduce participation by persons with cognitive impairment. At least 29% of studies (n = 127) employed explicit exclusion criteria. Half used the Folstein Mini-Mental State Examination ( MMSE), with variable cut points (10, 12, 17, 18, 23, 26), and 19% excluded individuals for 'having dementia' without specifying how this was determined. Few (6%) provided any justification for exclusion criteria used, only 43% gave any reason for exclusion, and only 14% discussed exclusion as a possible limitation. Conclusion Persons with cognitive impairment are frequently excluded from research, often without rationale or mention of exclusion as a limitation or any discussion of its potential effect on the evidence base in geriatrics. When necessary, exclusion should be done thoughtfully and with awareness that this may reduce the clinical utility of study findings. [ABSTRACT FROM AUTHOR]

J. Neurochem. (2010) 114, 706–716. Spinocerebellar ataxia 1 (SCA1) is a dominantly inherited neurodegenerative disease associated with progressive ataxia resulting from the loss of cerebellar Purkinje cells (PCs) and neurons in the brainstem. In PCs of SCA1 transgenic mice, the disease causing ataxin-1 protein mediates the formation of S100B containing cytoplasmic vacuoles and further self-aggregates to form intranuclear inclusions. The exact function of the ataxin-1 protein is not fully understood. However, the aggregation and neurotoxicity of the mutant ataxin-1 protein is dependent on the phosphorylation at serine 776 (S776). Although protein kinase A (PKA) has been implicated as the S776 kinase, the mechanism of PKA/ataxin-1 regulation in SCA1 is still not clear. We propose that a dopamine D2 receptor (D2R)/S100B pathway may be involved in modulating PKA activity in PCs. Using a D2R/S100B HEK stable cell line transiently transfected with GFP-ataxin-1[82Q], we demonstrate that stimulation of the D2R/S100B pathway caused a reduction in mutant ataxin-1 S776 phosphorylation and ataxin-1 aggregation. Activation of PKA by forskolin resulted in an enhanced S776 phosphorylation and increased ataxin-1 nuclear aggregation, which was suppressed by treatment with D2R agonist bromocriptine and PKA inhibitor H89. Furthermore, treating SCA1 transgenic PC slice cultures with forskolin induced neurodegenerative morphological abnormalities in PC dendrites consistent with those observed in vivo. Taken together our data support a mechanism where PKA dependent mutant ataxin-1 phosphorylation and aggregation can be regulated by D2R/S100B signaling. [ABSTRACT FROM AUTHOR]

Objective To assess long-term trends in disparities for prenatal diagnosis of Down syndrome in relation to policy changes. Design Population-based observational study. Setting Paris. Population Residents of Paris who gave birth or had a termination of pregnancy in Paris during 1983–2003 (approximately 23 000 births per year). Methods Using population-based data from the Paris Registry of Congenital Malformations on 1934 cases of Down syndrome, we assessed differences in prenatal diagnosis proportions by maternal profession and geographical origin for the years 1983–2003. Analyses included locally weighted scatter plot smoother curves and binomial regression. Main outcome measure Trends in proportion of Down syndrome cases diagnosed prior to birth for different maternal occupation groups and women of different geographical origins. Results The proportion of prenatally diagnosed cases increased substantially, reaching to about 85–90% of cases in 2003 for most socio-economic groups. This increase was accompanied by a significant decrease in disparities in prenatal diagnosis. Nonetheless, the proportion of prenatally diagnosed cases remained 12% lower for women without a profession compared with those in the highest occupational category (maternal age-adjusted risk difference −12.0%, 95% CI −17.1 to −6.9). Conclusions Together with the implementation of policies aimed at providing access to prenatal screening for all women, socio-economic differences in prenatal diagnosis of Down syndrome decreased over time. These trends need to be monitored, particularly in light of technical advances and alternative strategies for prenatal testing. However, while monitoring the proportion of cases with prenatal diagnosis is important, the ideal evaluation of prenatal testing programmes should also include measures of informed choice. [ABSTRACT FROM AUTHOR]