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Abstract Introduction We report a case of a 42-year-old man who had symptomatic hypothermia as a result of taking olanzapine for paranoid schizophrenia. According to published data, only a few cases of hypothermia associated with olanzapine have been reported since its introduction into clinical use. Case presentation A 42-year-old Sri Lankan man with schizophrenia who was being treated with a therapeutic dose of olanzapine presented with reduced level of consciousness. He had a core temperature of 32°C and was bradycardic. At the time of admission, the electrocardiogram showed sinus bradycardia with J waves. He did not have any risk factors for developing hypothermia except the use of olanzapine. There was improvement in his clinical condition with reversal of electrocardiogram changes following gradual rewarming and the omission of olanzapine. Conclusion Hypothermia induced by antipsychotic medications is not uncommon, but olanzapine-induced hypothermia is rare and occurrence has been reported during initiation or increasing the dose. But here the patient developed hypothermia without dose adjustment.

Abstract It has been consistently reported that vegetable oils including canola oil have a life shortening effect in Stroke-Prone Spontaneously Hypertensive Rats (SHRSP) and this toxic effect is not due to the fatty acid composition of the oil. Although it is possible that the phytosterol content or type of phytosterol present in vegetable oils may play some role in the life shortening effect observed in SHRSP rats this is still not completely resolved. Furthermore supercritical CO2 fractionation of canola oil with subsequent testing in SHRSP rats identified safe and toxic fractions however, the compounds responsible for life shortening effect were not characterised. The conventional approach to screen toxic substances in oils using rats takes more than six months and involves large number of animals. In this article we describe how rapid bioassay-guided screening could be used to identify toxic substances derived from vegetable oils and/or processed foods fortified with vegetable oils. The technique incorporates sequential fractionation of oils/processed foods and subsequent treatment of human cell lines that can be used in place of animal studies to determine cytotoxicity of the fractions with structural elucidation of compounds of interest determined via HPLC-MS and GC-MS. The rapid bioassay-guided screening proposed would require two weeks to test multiple fractions from oils, compared with six months if animal experiments were used to screen toxic effects. Fractionation of oil before bio-assay enhances the effectiveness of the detection of active compounds as fractionation increases the relative concentration of minor components.

The article presents a study to investigate the correlation between the histological finding that, increased intraepithelial lymphocytes (IEL) with normal villous morphology is the first and most sensitive marker of the effects of gluten on small bowel mucosa in duodenal biopsies and, clinical findings. Duodenal biopsies with the histological finding were retrieved and the IEL counts were reviewed using CD3 immunostain, including only cases with counts >40 IELs/100 enterocytes. Patient records were reviewed retrospectively.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a potential cancer therapeutic that induces apoptosis in cancer cells while sparing the non-malignant cells in preclinical models. However, its efficacy in clinical trials has been limited, suggesting unknown modulatory mechanisms responsible for the lack of TRAIL activity in patients. Here, we hypothesized that TRAIL treatment elicits transcriptional changes in triple negative breast cancer (TNBC) cells that alter the immune milieu. To test this, we performed an RNAseq analysis of MDA-MB-231 cells treated with TRAIL, followed by validation in additional TNBC cell lines. TRAIL significantly induces expression of multiple cytokines such as CXCLs 1, 2, 3, 8,11 and IL-6, which are known to modify neutrophil function. Mechanistically, the induction of these cytokines was predominantly mediated by death receptor 5, caspase 8 (but not caspase 8 enzymatic activity), and the non-canonical NFKB2 pathway. The cytokines produced by the TRAIL-treated TNBC cells enhanced chemotaxis of healthy human donor isolated neutrophils. In vivo , TRAIL treated TNBC murine xenograft tumors showed activation of the NFKB2 pathway, elevated production of CXCLs and IL-6, and increased neutrophil recruitment into the tumors. Moreover, donor isolated neutrophils preincubated in supernatants from TRAIL-treated TNBC cells exhibited impaired cytotoxic effect against TNBC cells. Transcriptomic analysis of neutrophils incubated with either TRAIL alone or supernatant of TRAIL-treated TNBC cells revealed increased expression of inflammatory cytokines, immune modulatory genes, immune checkpoint genes, and genes implicated in delayed neutrophil apoptosis. Functional studies with these neutrophils confirmed their suppressive effect on T cell proliferation and an increase in Treg suppressive phenotype. Collectively, our study demonstrates a novel role of TRAIL-induced NFKB2-dependent cytokine production that promotes neutrophil chemotaxis and immune suppression.

The suppression head impulse paradigm (SHIMP) involves suppression of the vestibulo-ocular reflex (VOR) and anticompensatory saccades generated thereof. SHIMP is gaining importance to understand vestibular compensation with its different parameters (VOR gain/peak saccadic velocity PSV/latency of saccades). SHIMP studies are emerging in adults, but pediatric studies have hardly been performed. This study is a retrospective case note audit over a period of 2 months in a tertiary pediatric vestibular center in the United Kingdom to investigate whether SHIMP is safe/robust to be used in children conforming to existing standards/norms in normal children and whether it yields any meaningful inferences in pediatric vestibular hypofunction. This is the largest pediatric SHIMP study to date. A total of 44 referred children (6-18 years, female children>male children) with a range of complaints from dizziness, imbalance, motor incoordination, postural instability, and hearing loss were included, and their SHIMP parameters were measured. All children underwent comprehensive functional/objective audiovestibular assessments. Two groups were defined-Group A with normal vestibular function and Group B with abnormal vestibular function. The normal population showed an average SHIMP VOR gain of 0.98+/-0.08 and latency of overt saccades at 215.68+/-46.16 milliseconds agreeing with published evidence. The PSV of overt saccades was 315.39+/-56.3 0 /s, and there was a gain asymmetry of 7.42+/-4.68 between the sides. Statistically significant differences with moderate/large effect sizes were observed between the groups in terms of VOR gain and PSV but not in saccade latencies. Covert saccades were rare in SHIMP, while overt saccades were observed in 100% of children. VOR gain difference between the head impulse paradigm (HIMP) and the SHIMP was significant as well. We observed statistically significant differences in side asymmetry of VOR gain between the groups. Furthermore, we identified a group of children with cerebellar lesions where overt saccades in SHIMP were rather low in number. Further research is recommended to investigate pediatric PSV, asymmetry, and inability to generate overt saccades that may suggest useful means to assess compensation and central function. We conclude that SHIMP yields valuable information and is a safe, easy to perform, and a reliable test that should be used in children to supplement HIMP., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Dasgupta, Crunkhorn, Wong, McMahon, Ratnayake and Manzari.)

Previous studies of the murine Ly49 and human KIR gene clusters implicated competing sense and antisense promoters in the control of variegated gene expression. In the current study, an examination of transcription factor genes defines an abundance of convergent and divergent sense/antisense promoter pairs, suggesting that competing promoters may control cell fate determination. Differentiation of CD34 + hematopoietic progenitors in vitro shows that cells with GATA1 antisense transcription have enhanced GATA2 transcription and a mast cell phenotype, whereas cells with GATA2 antisense transcription have increased GATA1 transcripts and an erythroblast phenotype. Detailed analyses of the AHR and RORC genes demonstrate the ability of competing promoters to act as binary switches and the association of antisense transcription with an immature/progenitor cell phenotype. These data indicate that alternative cell fates generated by promoter competition in lineage-determining transcription factors contribute to the programming of cell differentiation., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023. Published by Elsevier Inc.)

Aim: To explore how nurses and nursing knowledge contributed to the success of an Australian nurse-led medical hotel quarantine facility during the COVID-19 pandemic. The facility was established to accommodate returning travellers who were COVID-19 positive or at risk of becoming positive, to travellers requiring complex care and expanded to community members who could not quarantine at home., Design: This descriptive qualitative study explored how nurses and nursing knowledge in the quarantine facility contributed to the low transmission incidence of COVID-19 infection., Method: Twelve semi-structured interviews were conducted via ZOOM from February to May 2022 with all levels of nursing staff (nurse managers to assistants in nursing) who had worked in the facility for 3 months or more. The nurses were asked to describe their experiences, the challenges they faced and how they overcame them. The data were rich and were analysed using Braun and Clarke's six-step thematic analysis., Results: Four broad themes were generated demonstrating how nurses played a pivotal role in the success of the facility. First: nursing knowledge was evident through the development of policies, which minimized risks to nurses and patients. Second: a community of learning was developed as nurses supported upskilling and capacity building of staff, particularly new graduates with the facility. Third: a supportive management structure promoted teamwork and a positive workplace culture. And finally: the nurses were encouraged to develop techniques that promoted self-care which enabled them to develop resilience., Conclusion: This was a nurse-led service that developed strategies to manage care delivery and overcame unanticipated difficulties in a unique clinical setting., Reporting Method: The quality of the research design was ensured by using the Consolidated Criteria for Reporting Qualitative Studies (COREQ) checklist., Patient or Public Contribution: No patient or public contribution., (© 2023 John Wiley & Sons Ltd.)

Phytophthora sojae is a soil-borne oomycete and the causal agent of Phytophthora root and stem rot (PRR) in soybean (Glycine max [L.] Merrill). Yield losses attributed to P. sojae are devastating in disease-conducive environments, with global estimates surpassing 1.1 million tonnes annually. Historically, management of PRR has entailed host genetic resistance (both vertical and horizontal) complemented by disease-suppressive cultural practices (e.g., oomicide application). However, the vast expansion of complex and/or diverse P. sojae pathotypes necessitates developing novel technologies to attenuate PRR in field environments. Therefore, the objective of the present study was to couple high-throughput sequencing data and deep learning to elucidate molecular features in soybean following infection by P. sojae. In doing so, we generated transcriptomes to identify differentially expressed genes (DEGs) during compatible and incompatible interactions with P. sojae and a mock inoculation. The expression data were then used to select two defense-related transcription factors (TFs) belonging to WRKY and RAV families. DNA Affinity Purification and sequencing (DAP-seq) data were obtained for each TF, providing putative DNA binding sites in the soybean genome. These bound sites were used to train Deep Neural Networks with convolutional and recurrent layers to predict new target sites of WRKY and RAV family members in the DEG set. Moreover, we leveraged publicly available Arabidopsis (Arabidopsis thaliana) DAP-seq data for five TF families enriched in our transcriptome analysis to train similar models. These Arabidopsis data-based models were used for cross-species TF binding site prediction on soybean. Finally, we created a gene regulatory network depicting TF-target gene interactions that orchestrate an immune response against P. sojae. Information herein provides novel insight into molecular plant-pathogen interaction and may prove useful in developing soybean cultivars with more durable resistance to P. sojae., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Hale et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Competing Interests: Competing interests: We have read and understood BMJ policy on declaration of interests and declare SR is employed by the UK Council for Psychotherapy. The views expressed in this article are her personal views and not necessarily those of her employer.

Background: High throughput experiments in cancer and other areas of genomic research identify large numbers of sequence variants that need to be evaluated for phenotypic impact. While many tools exist to score the likely impact of single nucleotide polymorphisms (SNPs) based on sequence alone, the three-dimensional structural environment is essential for understanding the biological impact of a nonsynonymous mutation., Results: We present a program, 3DVizSNP, that enables the rapid visualization of nonsynonymous missense mutations extracted from a variant caller format file using the web-based iCn3D visualization platform. The program, written in Python, leverages REST APIs and can be run locally without installing any other software or databases, or from a webserver hosted by the National Cancer Institute. It automatically selects the appropriate experimental structure from the Protein Data Bank, if available, or the predicted structure from the AlphaFold database, enabling users to rapidly screen SNPs based on their local structural environment. 3DVizSNP leverages iCn3D annotations and its structural analysis functions to assess changes in structural contacts associated with mutations., Conclusions: This tool enables researchers to efficiently make use of 3D structural information to prioritize mutations for further computational and experimental impact assessment. The program is available as a webserver at https://analysistools.cancer.gov/3dvizsnp or as a standalone python program at https://github.com/CBIIT-CGBB/3DVizSNP ., (© 2023. The Author(s).)

Mobility and bioavailability of radionuclides in the environment strongly depend on their aqueous speciation, adsorption behavior and the solubility of relevant solid phases. In the present context, we focus on naturally occurring Th-232 at a location in central Sri Lanka presenting high background radiation levels. Four different soil samples were characterized using X-ray Absorption Spectroscopy (XAS) at the Th L 3 -edge (16.3 keV), Scanning Electron Microscopy (SEM) and Energy Dispersive X-ray (EDX) spectroscopy. X-ray Absorption Near Edge Structure (XANES) spectra are applied as a fingerprint indication for Th existing in different chemical environments. Linear combination fitting (LCF) of the Extended X-ray Absorption Fine Structure (EXAFS) data involving reference Th-monazite (phosphate) and thorianite (oxide) compounds suggested that Th is mostly present as Th-phosphate (76 ± 2%) and Th-oxide (24 ± 2%), even though minor amounts of thorite (silicate) were also detected by SEM-EDX. Further studies on selected individual particles using micro-focus X-ray Fluorescence (μ-XRF) and micro-X-ray Absorption Spectroscopy (μ-XAS) along with SEM-EDX elemental mapping provided information about the nature of Th-bearing mineral particles regarding mixed phases. This is the first study providing quantitative and XAS based speciation information on Th-mineral phases in soil samples from Sri Lanka., (© 2023. The Author(s).)

Tissue inhibitor of metalloproteinases (TIMPs/Timps) are an endogenous family of widely expressed matrisome-associated proteins that were initially identified as inhibitors of matrix metalloproteinase activity (Metzincin family proteases). Consequently, TIMPs are often considered simply as protease inhibitors by many investigators. However, an evolving list of new metalloproteinase-independent functions for TIMP family members suggests that this concept is outdated. These novel TIMP functions include direct agonism/antagonism of multiple transmembrane receptors, as well as functional interactions with matrisome targets. While the family was fully identified over two decades ago, there has yet to be an in-depth study describing the expression of TIMPs in normal tissues of adult mammals. An understanding of the tissues and cell-types that express TIMPs 1 through 4, in both normal and disease states are important to contextualize the growing functional capabilities of TIMP proteins, which are often dismissed as non-canonical. Using publicly available single cell RNA sequencing data from the Tabula Muris Consortium, we analyzed approximately 100,000 murine cells across eighteen tissues from non-diseased organs, representing seventy-three annotated cell types, to define the diversity in Timp gene expression across healthy tissues. We describe the unique expression profiles across tissues and organ-specific cell types that all four Timp genes display. Within annotated cell-types, we identify clear and discrete cluster-specific patterns of Timp expression, particularly in cells of stromal and endothelial origins. RNA in-situ hybridization across four organs expands on the scRNA sequencing analysis, revealing novel compartments associated with individual Timp expression. These analyses emphasize a need for specific studies investigating the functional significance of Timp expression in the identified tissues and cell sub-types. This understanding of the tissues, specific cell types and microenvironment conditions in which Timp genes are expressed adds important physiological context to the growing array of novel functions for TIMP proteins., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 Published by Elsevier B.V.)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has very rapidly become a global pandemic with millions of confirmed cases worldwide. In early 2021, viral encephalitis was the first neurological complication associated with COVID-19 and since then rise in cases has been reported with this association. A review highlighting 3 potential mechanisms linking a correlation between seizures and COVID-19 was previously reported. Herein described is a unique case of SARS-CoV2 infection that presented with focal seizure with impaired awareness., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Epidermal growth factor receptor (EGFR) signaling is frequently dysregulated in various cancers. The ubiquitin ligase Casitas B-lineage lymphoma proto-oncogene (Cbl) regulates degradation of activated EGFR through ubiquitination and acts as an adaptor to recruit proteins required for trafficking. Here, we used stable isotope labeling with amino acids in cell culture mass spectrometry to compare Cbl complexes with or without epidermal growth factor (EGF) stimulation. We identified over a hundred novel Cbl interactors, and a secondary siRNA screen found that knockdown of Flotillin-2 (FLOT2) led to increased phosphorylation and degradation of EGFR upon EGF stimulation in HeLa cells. In PC9 and H441 cells, FLOT2 knockdown increased EGF-stimulated EGFR phosphorylation, ubiquitination, and downstream signaling, reversible by EGFR inhibitor erlotinib. CRISPR knockout (KO) of FLOT2 in HeLa cells confirmed EGFR downregulation, increased signaling, and increased dimerization and endosomal trafficking. Furthermore, we determined that FLOT2 interacted with both Cbl and EGFR. EGFR downregulation upon FLOT2 loss was Cbl dependent, as coknockdown of Cbl and Cbl-b restored EGFR levels. In addition, FLOT2 overexpression decreased EGFR signaling and growth. Overexpression of wildtype (WT) FLOT2, but not the soluble G2A FLOT2 mutant, inhibited EGFR phosphorylation upon EGF stimulation in HEK293T cells. FLOT2 loss induced EGFR-dependent proliferation and anchorage-independent growth. Lastly, FLOT2 KO increased tumor formation and tumor volume in nude mice and NSG mice, respectively. Together, these data demonstrated that FLOT2 negatively regulated EGFR activation and dimerization, as well as its subsequent ubiquitination, endosomal trafficking, and degradation, leading to reduced proliferation in vitro and in vivo., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Published by Elsevier Inc.)

Mitochondria are multifaceted organelles which are important for bioenergetics, biosynthesis and signaling in metazoans. Mitochondrial functions are frequently altered in cancer to promote both the energy and the necessary metabolic intermediates for biosynthesis required for tumor growth. Cancer stem cells (CSCs) contribute to chemotherapy resistance, relapse, and metastasis. Recent studies have shown that while non-stem, bulk cancer cells utilize glycolysis, breast CSCs are more dependent on oxidative phosphorylation (OxPhos) and therefore targeting mitochondria may inhibit CSC function. We previously reported that small molecule ONC201, which is an agonist for the mitochondrial caseinolytic protease (ClpP), induces mitochondrial dysfunction in breast cancer cells. In this study, we report that ClpP agonists inhibit breast cancer cell proliferation and CSC function in vitro and in vivo . Mechanistically, we found that OxPhos inhibition downregulates multiple pathways required for CSC function, such as the mevalonate pathway, YAP, Myc, and the HIF pathway. ClpP agonists showed significantly greater inhibitory effect on CSC functions compared with other mitochondria-targeting drugs. Further studies showed that ClpP agonists deplete NAD(P)+ and NAD(P)H, induce redox imbalance, dysregulate one-carbon metabolism and proline biosynthesis. Downregulation of these pathways by ClpP agonists further contribute to the inhibition of CSC function. In conclusion, ClpP agonists inhibit breast CSC functions by disrupting mitochondrial homeostasis in breast cancer cells and inhibiting multiple pathways critical to CSC function., Significance: ClpP agonists disrupt mitochondrial homeostasis by activating mitochondrial matrix protease ClpP. We report that ClpP agonists inhibit cell growth and cancer stem cell functions in breast cancer models by modulating multiple metabolic pathways essential to cancer stem cell function., Competing Interests: Conflict of interest disclosure EJI has a financial interest in Madera Therapeutics. The other authors declare no potential conflicts of interest.

Advanced therapeutic medicinal products (ATMPs) have emerged as novel therapies for untreatable diseases, generating the need for large volumes of high-quality, clinically-compliant GMP cells to replace costly, high-risk and limited scale manual expansion processes. We present the design of a fully automated, robot-assisted platform incorporating the use of multiliter stirred tank bioreactors for scalable production of adherent human stem cells. The design addresses a needle-to-needle closed process incorporating automated bone marrow collection, cell isolation, expansion, and collection into cryovials for patient delivery. AUTOSTEM, a modular, adaptable, fully closed system ensures no direct operator interaction with biological material; all commands are performed through a graphic interface. Seeding of source material, process monitoring, feeding, sampling, harvesting and cryopreservation are automated within the closed platform, comprising two clean room levels enabling both open and closed processes. A bioprocess based on human MSCs expanded on microcarriers was used for proof of concept. Utilizing equivalent culture parameters, the AUTOSTEM robot-assisted platform successfully performed cell expansion at the liter scale, generating results comparable to manual production, while maintaining cell quality postprocessing., (© 2022 The Authors. Bioengineering & Translational Medicine published by Wiley Periodicals LLC on behalf of American Institute of Chemical Engineers.)

Psychiatry has a long history of being criticised for the pathologisation and medicalisation of ordinary experiences. One of the most prominent of these critiques is advanced by Allan Horwitz and Jerome Wakefield who argue that instances of ordinary sadness in response to events such as bereavement, heartbreak and misfortune, are being mistakenly diagnosed as depression due to an increasing lack of consideration for aetiology and contextual factors. Critiques concerning pathologisation and medicalisation have not been forthcoming for psychiatry's close cousin, psychotherapy. Using Cognitive Behavioural Therapy, one of the most prominent schools of contemporary psychotherapy as a case study, I demonstrate that psychotherapy also contributes to medicalising and pathologising bereavement, heartbreak and misfortune., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Third window disorders are structural abnormalities in the bony otic capsule that establish a connection between the middle/inner ear or the inner ear/cranial cavity. Investigated extensively in adults, they have hardly been studied in children. This study is a retrospective study of children (aged 5-17 years) diagnosed with rare third window disorders (third window disorders reported rarely or not reported in children) in a tertiary pediatric vestibular unit in the United Kingdom. It aimed to investigate audiovestibular function in these children. Final diagnosis was achieved by high resolution CT scan of the temporal bones. Of 920 children attending for audiovestibular assessment over a 42 month period, rare third windows were observed in 8 (<1%). These included posterior semicircular canal dehiscence ( n = 3, 0.3%), posterior semicircular canal thinning ( n = 2, 0.2%), X linked gusher ( n = 2, 0.2%), and a combination of dilated internal auditory meatus/irregular cochlear partition/deficient facial nerve canal ( n = 1, 0.1%). The majority of them (87.5%) demonstrated a mixed/conductive hearing loss with an air-bone gap in the presence of normal tympanometry (100%). Transient otoacoustic emissions were absent with a simultaneous cochlear pathology in 50% of the cohort. Features of disequilibrium were observed in 75% and about a third showed deranged vestibular function tests. Video head impulse test abnormalities were detected in 50% localizing to the side of the lesion. Cervical vestibular evoked myogenic potential test abnormalities were observed in all children in the cohort undergoing the test where low thresholds and high amplitudes classically found in third window disorders localized to the side of the defects in 28.5%. In the series, 71.4% also demonstrated absent responses/amplitude asymmetry, some of which did not localize to the ipsilesional side. Two children presented with typical third window symptoms. This study observes 2 new rare pediatric third window phenotypes and the presence of a cochlear hearing loss in these disorders. It emphasizes that these disorders should be considered as an etiology of hearing loss/disequilibrium in children. It also suggests that pediatric third window disorders may not present with classical third window features and are variable in their presentations/audiovestibular functions., (Copyright © 2020 Dasgupta, Ratnayake, Crunkhorn, Iqbal, Strachan and Avula.)

Bacillus anthracis is the causative agent of anthrax, a disease of livestock, wildlife, and humans. Here, we present the draft genome sequences of five historical B. anthracis strains that were preserved as lyophilates in glass vials for decades., (Copyright © 2020 Sommer et al.)

Background: Young onset colorectal cancer is on the rise, with a disproportionate increase in incidence among young people, both in Australia and internationally. Current national guidelines for bowel cancer screening in average risk individuals include only patients greater than 50 years of age. It is well recognized that colorectal cancer is a highly treatable malignancy when detected at an early stage, and timely diagnosis yields a greater than 90% chance of cure and survival. The aims of this study were to define the clinical presentations leading to colonoscopy in young patients and assess the incidence of malignancy in this group., Methods: This is a retrospective cohort study including all patients ≤35 years of age without any baseline indication for early bowel cancer surveillance that underwent colonoscopy at Caboolture Hospital from January 2017 to April 2018., Results: A total of 224 patients underwent colonoscopy in the study period. A total of 210 (93.8%) had symptoms including rectal bleeding (51.7%), altered bowel habit (25.9%), abdominal pain (10.3%) and symptomatic anaemia (6.7%) prior to colonoscopy. Two cases of invasive adenocarcinoma were identified (0.89%, P < 0.01), both of which were symptomatic and were defined as stage IIIB disease on histopathology., Conclusion: In a theoretically low-risk population, the incidence of malignancy was nearly 1%. More advanced disease at diagnosis may be due to a delay in investigating these patients due to an overall low suspicion of cancer in young individuals. As such, investigation should be offered early to young patients presenting with any warning symptoms., (© 2019 Royal Australasian College of Surgeons.)

The Indian Cormorant (Phalacrocorax fuscicollis) is a common avian piscivore that occurs throughout the Indian subcontinent and east to southern Vietnam. Its evolutionary relationships, however, have remained obscure, largely because of a lack of material available for either osteological or genetic analysis. Here we show using DNA-sequence data from both nuclear and mitochondrial genes that this species is sister to the allopatric Little Black Cormorant (P. sulcirostris), which occurs from Java in the west through southern Indonesia and New Guinea to Australia and New Zealand in the south. We estimate this split to have happened 2.5-3.2 million years ago, during the late Pliocene. We also report on genetic variation within the mitochondrial control region, which suggests that this part of the genome may be useful in investigating if there is genetic structure across the geographical range of the Indian Cormorant., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Introduction: Severe acute pancreatitis is associated with high morbidity and mortality. This is a result of the development of pancreatic and extra-pancreatic necrosis with subsequent infection which can lead to multiorgan failure. Complications include localized ileus, abscess formation, mechanical obstruction, rupture and perforation into the gastrointestinal tract and fistula formation (Aldridge et al., 1989; Bassi et al., 2001 [1,2])., Case Presentation: A 72 year old man attended the emergency department with acute epigastric pain. Biochemistry results were reviewed with a lipase of 1680 U/L (ref range <60 U/L). He was treated conservatively. He had a labile course throughout his admission and on day 7 he had significant deterioration. Abdominal CT scan demonstrated marked mechanical large bowel obstruction at the level of the sigmoid colon, caecum dilated with features suggestive of ischaemia in the caecal wall and backflow dilatation of the small bowel loops. The patient was transferred to a tertiary centre for subsequent laparotomy and bowel resection., Discussion: Colonic complications of acute pancreatitis are uncommon. An analysis of pooled data reports the incidence of colonic complications from acute pancreatitis to be 3.3% and those from severe acute pancreatitis 15% (Bassi et al., 2001 [2]). Knowledge about colonic perforation from acute pancreatitis has been limited to few case reports, thus diagnostic and management dilemmas continue to persist., Conclusions: We report a rare case of ascending colon perforation in severe acute pancreatitis. This is particularly unusual given the anatomical propensity for splenic flexure involvement or transverse colon involvement being noted in literature. This highlights the high index of suspicion required for colonic complications given the varied, non-specific and often delayed presentation of complications., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Mindfulness exercises are presented as being compatible with almost any spiritual, religious or philosophical beliefs. In this paper, we argue that they in fact involve imagining and conceptualising rather striking and controversial claims about the self, and the self's relationship to thoughts and feelings. For this reason, practising mindfulness exercises is likely to be in tension with many people's core beliefs and values, a tension that should be treated as a downside of therapeutic interventions involving mindfulness exercises, not unlike a side effect. Clients ought to be informed of these metaphysical aspects of the exercises, and mental health providers ought to take them into account in assessing which course of treatment to recommend. Given these concerns, the casual way in which mindfulness exercises are presently distributed by mental health providers to the general public is inappropriate., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

When performing bioforensic casework, it is important to be able to reliably detect the presence of a particular organism in a metagenomic sample, even if the organism is only present in a trace amount. For this task, it is common to use a sequence classification program that determines the taxonomic affiliation of individual sequence reads by comparing them to reference database sequences. As metagenomic data sets often consist of millions or billions of reads that need to be compared to reference databases containing millions of sequences, such sequence classification programs typically use search heuristics and databases with reduced sequence diversity to speed up the analysis, which can lead to incorrect assignments. Thus, in a bioforensic setting where correct assignments are paramount, assignments of interest made by "first-pass" classifiers should be confirmed using the most precise methods and comprehensive databases available. In this study we present a BLAST-based method for validating the assignments made by less precise sequence classification programs, with optimal parameters for filtering of BLAST results determined via simulation of sequence reads from genomes of interest, and we apply the method to the detection of four pathogenic organisms. The software implementing the method is open source and freely available., Competing Interests: The authors declare that they have no competing interests.

High throughput sequencing (HTS) has been used for a number of years in the field of paleogenomics to facilitate the recovery of small DNA fragments from ancient specimens. Recently, these techniques have also been applied in forensics, where they have been used for the recovery of mitochondrial DNA sequences from samples where traditional PCR-based assays fail because of the very short length of endogenous DNA molecules. Here, we describe the biological sexing of a ~4000-year-old Egyptian mummy using shotgun sequencing and two established methods of biological sex determination (R X and R Y ), by way of mitochondrial genome analysis as a means of sequence data authentication. This particular case of historical interest increases the potential utility of HTS techniques for forensic purposes by demonstrating that data from the more discriminatory nuclear genome can be recovered from the most damaged specimens, even in cases where mitochondrial DNA cannot be recovered with current PCR-based forensic technologies. Although additional work remains to be done before nuclear DNA recovered via these methods can be used routinely in operational casework for individual identification purposes, these results indicate substantial promise for the retrieval of probative individually identifying DNA data from the most limited and degraded forensic specimens., Competing Interests: Names of commercial manufacturers are provided for identification purposes only and inclusion does not imply endorsement of the manufacturer, or its products or services by the FBI. The views expressed are those of the authors and do not necessarily reflect the official policy or position of the FBI or the U.S. Government. This is FBI Laboratory publication #18-13. The views and conclusions contained in this document are those of the author and should not be interpreted as necessarily representing the official policies, either expressed or implied, of the DHS or S&T. In no event shall DHS, NBACC, S&T, or Battelle National Biodefense Institute have any responsibility or liability for any use, misuse, inability to use, or reliance upon the information contained herein. DHS does not endorse any products or commercial services mentioned in this publication.

The draft genome sequences of six Bacillus strains, isolated from the International Space Station and belonging to the Bacillus anthracis - B. cereus - B. thuringiensis group, are presented here. These strains were isolated from the Japanese Experiment Module (one strain), U.S. Harmony Node 2 (three strains), and Russian Segment Zvezda Module (two strains)., (Copyright © 2017 Venkateswaran et al.)

Background: The use of dipstick proteinuria to screen Chronic Kidney Disease of uncertain aetiology (CKDu) in Sri Lanka is a recently debated matter of dispute. The aim of this study was to assess the suitability of biomarkers: serum creatinine, cystatin C and urine albumin to creatinine ratio (ACR) for screening CKDu in Sri Lanka., Methods: Forty-four male CKDu patients and 49 healthy males from a CKDu-endemic region were selected. Meanwhile, 25 healthy males from a non-endemic region were selected as an absolute control. The diagnostic accuracy of each marker was compared using the above three study groups., Results: In receiver operating characteristics (ROC) plots for creatinine, cystatin C and ACR, values of area under the curve (AUC) were 0.926, 0.920 and 0.737 respectively when CKDu was compared to non-endemic control. When CKDu was compared to endemic control, AUCs of above three analytes were distinctly lower as 0.718, 0.808 and 0.678 respectively. Cystatin C exhibited the highest sensitivity for CKDu when analyzed against both control groups where respective sensitivities were 0.75 against endemic control and 0.89 against non-endemic control. ROC-optimal cutoff limits of creatinine, cystatin C and ACR in CKDu vs non-endemic control were 89.0 μmol/L, 1.01 mg/L and 6.06 mg/g-Cr respectively, whereas in CKDu vs endemic control the respective values were 111.5 μmol/L, 1.22 mg/L and 12.66 mg/g-Cr., Conclusions: Amongst the three biomarkers evaluated in this study, our data suggest that Cystatin C is the most accurate functional marker in detecting CKDu in endemic regions, yet the high cost hinders its usability on general population. Creatinine is favorable over dipstick proteinuria owing to its apparent accuracy and cost efficiency, while having the ability to complement the kidney damage marker (ACR) in screening. ACR may not be favorable as a standalone screening marker in place of dipstick proteinuria due to its significant decline in sensitivity against the CKDu-endemic population. However, creatinine and ACR in a complementary manner could overcome current shortcomings of dipstick proteinuria and such a dual marker tool could be commodious in screening CKDu-type tubulointerstital diseases. Furthermore, use of ACR may also increase the ability to clinically discriminate CKDu from other glomerular nephropathies.

Chitosan nanocomposite thin films were fabricated by incorporating MgO nanoparticles to significantly improve its physical properties for potential packaging applications. A novel in-situ method was developed to synthesise spherical shaped MgO nanoparticles by heat-treating magnesium carbonate/poly(methyl methacrylate) (PMMA) composite precursor. Optimum mechanical properties of chitosan composites were yielded at 5 (w/w%) of MgO concentration, where tensile stress and elastic modulus significantly improved by 86% and 38%, respectively, compared to those of pure chitosan films. These improvements are due to the interaction of hydroxyl and amine groups of chitosan with MgO as confirmed by FTIR spectroscopy. Fracture surface morphology indicated the interplay between MgO dispersion and aggregation on the mechanical properties at different MgO concentrations. Furthermore, the chitosan/MgO nanocomposites displayed remarkable thermal stability, flame retardant properties (satisfied V0 rating according to the UL-94 standards), UV shielding and moisture barrier properties, which could certainly add value to the packaging material., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

This protocol describes the specific techniques used for the characterization of reducing end (RE) and internal region glycosyl sequence(s) of heteroxylans. De-starched wheat endosperm cell walls were isolated as an alcohol-insoluble residue (AIR)(1) and sequentially extracted with water (W-sol Fr) and 1 M KOH containing 1% NaBH4 (KOH-sol Fr) as described by Ratnayake et al. (2014)(2). Two different approaches (see summary in Figure 1) are adopted. In the first, intact W-sol AXs are treated with 2AB to tag the original RE backbone chain sugar residue and then treated with an endoxylanase to generate a mixture of 2AB-labelled RE and internal region reducing oligosaccharides, respectively. In a second approach, the KOH-sol Fr is hydrolyzed with endoxylanase to first generate a mixture of oligosaccharides which are subsequently labelled with 2AB. The enzymically released ((un)tagged) oligosaccharides from both W- and KOH-sol Frs are then methylated and the detailed structural analysis of both the native and methylated oligosaccharides is performed using a combination of MALDI-TOF-MS, RP-HPLC-ESI-QTOF-MS and ESI-MS(n). Endoxylanase digested KOH-sol AXs are also characterized by nuclear magnetic resonance (NMR) that also provides information on the anomeric configuration. These techniques can be applied to other classes of polysaccharides using the appropriate endo-hydrolases.

We present a case of a 65-year-old Hispanic man with a history of disseminated cutaneous coccidioidomycosis who presented to the emergency room for progressively worsening abdominal pain associated with shortness of breath. The patient was found to have pleural effusion and moderate ascites on physical examination. Abdominal ultrasound and computed tomography scan were consistent with moderate ascites and portal hypertension but negative for both liver cirrhosis and for venous or arterial thrombosis. Cytology of ascitic fluid was suggestive of portal hypertension and was negative for infection. Subsequent, thoracentesis was suggestive of exudative effusion and also negative for infection. Liver biopsy confirmed the absence of cirrhosis. Complete blood count indicated pancytopenia, whereas bone marrow biopsy and flow cytometry were suggestive of marginal zone lymphoma (MZL). Clinically, the patient's shortness of breath was resolved by thoracentesis and paracentesis; however, his abdominal pain persisted. A diagnosis of idiopathic noncirrhotic portal hypertension in the setting of splenic MZL was made. The patient was transferred to a higher level of care for splenectomy; however, he missed multiple appointments. Since discharge, the patient has been seen in the outpatient setting and states that he is controlling his disease with diet and exercise; however, he continues to complain of intermittent shortness of breath with exertion.

Background: Weather variables affect dengue transmission. This study aimed to identify a dengue weather correlation pattern in Kandy, Sri Lanka, compare the results with results of similar studies, and establish ways for better control and prevention of dengue., Method: We collected data on reported dengue cases in Kandy and mid-year population data from 2003 to 2012, and calculated weekly incidences. We obtained daily weather data from two weather stations and converted it into weekly data. We studied correlation patterns between dengue incidence and weather variables using the wavelet time series analysis, and then calculated cross-correlation coefficients to find magnitudes of correlations., Results: We found a positive correlation between dengue incidence and rainfall in millimeters, the number of rainy and wet days, the minimum temperature, and the night and daytime, as well as average, humidity, mostly with a five- to seven-week lag. Additionally, we found correlations between dengue incidence and maximum and average temperatures, hours of sunshine, and wind, with longer lag periods. Dengue incidences showed a negative correlation with wind run., Conclusion: Our results showed that rainfall, temperature, humidity, hours of sunshine, and wind are correlated with local dengue incidence. We have suggested ways to improve dengue management routines and to control it in these times of global warming. We also noticed that the results of dengue weather correlation studies can vary depending on the data analysis.

Unintentional weight loss is a health risk for residents of aged care facilities, a concern for families and places demands on nursing staff. An existing weight loss framework to assess and manage residents' weight developed by a multidisciplinary team was implemented and evaluated with nurses and residents in aged care facilities within an area health service of Sydney, Australia. Thematic analysis generated seven binary concepts relating to relational, procedural, behavioural, physical, psychological, environmental and temporal aspects of feeding assistance provided by nurses to residents. Theoretical sampling was applied to the literature confirming those concepts which were organized as a model of feeding assistance labelled the Focus on Feeding! Decision Model. Nurses can play a pivotal role in the assessment of feeding difficulty and implementation of innovative mealtime programs. The Model aims to promote nurses' critical thinking and decision-making to improve nutritional intake of residents and avoid preventable weight loss., (© 2014 Wiley Publishing Asia Pty Ltd.)

Introduction: Stump appendicitis is one of the rare delayed complications post appendectomy with a reported incidence of 1 in 50,000 cases. Stump appendicitis can present as a diagnostic dilemma if the treating clinician is unfamiliar with this rare clinical entity. A PubMed search was conducted to identify cases of stump appendicitis following appendectomy. Sixty one cases of SA that were reported in English medical literature were analyzed., Presentation of Case: We report a case of stump appendicitis (SA) with a systematic review and challenges encountered during the management., Discussion: The interval from original appendectomy to stump appendicitis ranged from 4 days to 50 years. SA followed appendectomy in 58% of open and 31.6% of laparoscopic procedures. SA was frequently misdiagnosed as constipation, gastroenteritis or right sided diverticulitis, therefore leading to a significant delay to surgery. Computerized Tomography diagnosed SA in 56.3% of cases. Perforation with gangrene of the stump occurred in 60%., Conclusion: Stump appendicitis can represent a diagnostic dilemma if the treating physician is unfamiliar with this uncommon clinical entity. Radiological imaging is required to aid diagnosis and a completion appendectomy is the modality of treatment., (Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.)

Walls from wheat (Triticum aestivum L.) endosperm are composed primarily of hetero-(arabino)xylans (AXs) (70%) and (1→3)(1→4)-β-D-glucans (20%) with minor amounts of cellulose and heteromannans (2% each). To understand the differential solubility properties of the AXs, as well as aspects of their biosynthesis, we are sequencing the xylan backbone and examining the reducing end (RE) sequence(s) of wheat (monocot) AXs. A previous study of grass AXs (switchgrass, rice, Brachypodium, Miscanthus and foxtail millet) concluded that grasses lacked the comparable RE glycosyl sequence (4-β-D-Xylp-(1→4)-β-D-Xylp-(1→3)-α-L-Rhap-(1→2)-α-D-GalpA-(1→4)-D-Xylp) found in dicots and gymnosperms but the actual RE sequence was not determined. Here we report the isolation and structural characterisation of the RE oligosaccharide sequence(s) of wheat endosperm cell wall AXs. Walls were isolated as an alcohol-insoluble residue (AIR) and sequentially extracted with hot water (W-sol Fr) and 1M KOH containing 1% NaBH4 (KOH-sol Fr). Detailed structural analysis of the RE oligosaccharides was performed using a combination of methylation analysis, MALDI-TOF-MS, ESI-QTOF-MS, ESI-MS(n) and enzymic analysis. Analysis of RE oligosaccharides, both 2AB labelled (from W-sol Fr) and glycosyl-alditol (from KOH-sol Fr), revealed that the RE glycosyl sequence of wheat endosperm AX comprises a linear (1→4)-β-D-Xylp backbone which may be mono-substituted with either an α-L-Araf residue at the reducing end β-D-Xylp residue and/or penultimate RE β-D-Xyl residue; β-D-Xylp-(1→4)-[α-L-Araf-(1→3)](+/-)-β-D-Xylp-(1→4)-[α-L-Araf-(1→3)](+/-)-β-D-Xylp and/or an α-D-GlcpA residue at the reducing end β-D-Xylp residue; β-D-Xylp-(1→4)-[α-L-Araf-(1→3)](+/-)-β-D-Xylp-(1→4)-[α-D-GlcAp-(1→2)]-β-D-Xylp. Thus, wheat endosperm AX backbones lacks the RE sequence found in dicot and gymnosperm xylans; a finding consistent with previous reports from other grass species., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Oxidation and S-nitrosylation of cysteinyl thiols (Cys-SH) to sulfenic (Cys-SOH), sulfinic (Cys-SO2H), sulfonic acids (Cys-SO3H), disulphides and S-nitrosothiols are suggested as important post-translational modifications that can activate or deactivate the function of many proteins. Non-enzymatic post-translational modifications to cysteinyl thiols have been implicated in a wide variety of physiological and pathophysiological states but have been difficult to monitor in a physiological setting because of a lack of experimental tools. The purpose of this review is to bring together the approaches that have been developed for stably trapping cysteine either in its reduced or oxidised forms for enrichment and or subsequent mass spectrometric analysis. These tools are providing insight into potential targets for post-translational modifications to cysteine modification in vivo. This article is part of a Special Issue entitled: Special Issue: Posttranslational Protein modifications in biology and Medicine., (Crown Copyright © 2013. Published by Elsevier B.V. All rights reserved.)

Nicotiana alata pollen tubes are a widely used model for studies of polarized tip growth and cell wall synthesis in plants. To better understand these processes, RNA-Seq and de novo assembly methods were used to produce a transcriptome of N. alata pollen grains. Notable in the reconstructed transcriptome were sequences encoding proteins that are involved in the synthesis and remodelling of xyloglucan, a cell wall polysaccharide previously not thought to be deposited in Nicotiana pollen tube walls. Expression of several xyloglucan-related genes in actively growing pollen tubes was confirmed and xyloglucan epitopes were detected in the wall with carbohydrate-specific antibodies: the major xyloglucan oligosaccharides found in N. alata pollen grains and tubes were fucosylated, an unusual structure for the Solanaceae, the family to which Nicotiana belongs. Finally, carbohydrate linkages consistent with xyloglucan were identified chemically in the walls of N. alata pollen grains and pollen tubes grown in culture. The presence of a fucosylated xyloglucan in Nicotiana pollen tube walls was thus confirmed. The consequences of this discovery to models of pollen tube growth dynamics and more generally to polarised tip-growing cells in plants are discussed.

The aim of this study was to determine the effects of high-glucose, high-fructose and high-sucrose diets on weight gain, liver lipid metabolism and gene expression of proteins involved with hepatic fat metabolism. Rats were fed a diet containing either 60% glucose, 60% fructose, 60% sucrose, or a standard chow for 28 days. Results indicated that high-fructose and high-sucrose diets were associated with higher mRNA levels of gene transcripts involved with fat synthesis; ACC, FAS and ChREBP, with no change in SREBP-1C mRNA. The protein level of ChREBP and SREBP1c was similar in liver homogenates from all groups, but were higher in nuclear fractions from the liver of high-fructose and high-sucrose fed rats. The mRNA level of gene transcripts involved with fat oxidation was the same in all three diets, whilst a high-fructose diet was associated with greater amount of mRNA of the fat transporter CD36. Despite the changes in mRNA of lipogenic proteins, the body weight of animals from each group was the same and the livers from rats fed high-fructose and high-sucrose diets did not contain more fat than control diet livers. In conclusion, changing the composition of the principal monosaccharide in the diet to a fructose containing sugar elicits changes in the level of hepatic mRNA of lipogenic and fat transport proteins and protein levels of their transcriptional regulators; however this is not associated with any changes in body weight or liver fat content.

Here we report the use of a multi-genome DNA microarray to investigate the genome diversity of Bacillus cereus group members and elucidate the events associated with the emergence of Bacillus anthracis the causative agent of anthrax-a lethal zoonotic disease. We initially performed directed genome sequencing of seven diverse B. cereus strains to identify novel sequences encoded in those genomes. The novel genes identified, combined with those publicly available, allowed the design of a "species" DNA microarray. Comparative genomic hybridization analyses of 41 strains indicate that substantial heterogeneity exists with respect to the genes comprising functional role categories. While the acquisition of the plasmid-encoded pathogenicity island (pXO1) and capsule genes (pXO2) represents a crucial landmark dictating the emergence of B. anthracis, the evolution of this species and its close relatives was associated with an overall shift in the fraction of genes devoted to energy metabolism, cellular processes, transport, as well as virulence., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Here we report the use of a multi-genome DNA microarray to elucidate the genomic events associated with the emergence of the clonal variants of Haemophilus influenzae biogroup aegyptius causing Brazilian Purpuric Fever (BPF), an important pediatric disease with a high mortality rate. We performed directed genome sequencing of strain HK1212 unique loci to construct a species DNA microarray. Comparative genome hybridization using this microarray enabled us to determine and compare gene complements, and infer reliable phylogenomic relationships among members of the species. The higher genomic variability observed in the genomes of BPF-related strains (clones) and their close relatives may be characterized by significant gene flux related to a subset of functional role categories. We found that the acquisition of a large number of virulence determinants featuring numerous cell membrane proteins coupled to the loss of genes involved in transport, central biosynthetic pathways and in particular, energy production pathways to be characteristics of the BPF genomic variants., (Copyright © 2010 Elsevier Inc. All rights reserved.)

It has been consistently reported that vegetable oils including canola oil have a life shortening effect in Stroke-Prone Spontaneously Hypertensive Rats (SHRSP) and this toxic effect is not due to the fatty acid composition of the oil. Although it is possible that the phytosterol content or type of phytosterol present in vegetable oils may play some role in the life shortening effect observed in SHRSP rats this is still not completely resolved. Furthermore supercritical CO2 fractionation of canola oil with subsequent testing in SHRSP rats identified safe and toxic fractions however, the compounds responsible for life shortening effect were not characterised. The conventional approach to screen toxic substances in oils using rats takes more than six months and involves large number of animals. In this article we describe how rapid bioassay-guided screening could be used to identify toxic substances derived from vegetable oils and/or processed foods fortified with vegetable oils. The technique incorporates sequential fractionation of oils/processed foods and subsequent treatment of human cell lines that can be used in place of animal studies to determine cytotoxicity of the fractions with structural elucidation of compounds of interest determined via HPLC-MS and GC-MS. The rapid bioassay-guided screening proposed would require two weeks to test multiple fractions from oils, compared with six months if animal experiments were used to screen toxic effects. Fractionation of oil before bio-assay enhances the effectiveness of the detection of active compounds as fractionation increases the relative concentration of minor components.